Abstract
A heteroaromatic amide derivative or salt thereof showing high efficacy for diseases associated with Nav1.7 is represented by general formula (I)
##STR00001## [wherein, X.sup.1-X.sup.2 is N—C or C—N, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 are —CH.sub.2—, —CR.sup.4aH— or —O— and so on, Z.sup.1 is —O— and so on, ring A is a 3- to 7-membered monocyclic aromatic ring and so on, R.sup.1a and R.sup.1b are a hydrogen atom or a halogen atom and so on, R.sup.2 is a hydrogen atom and so on, R.sup.3a, R.sup.3b and R.sup.3c are a hydrogen atom or an optionally substituted C.sub.1-C.sub.6 haloalkyl group and so on, R.sup.4a, R.sup.4b and R.sup.4c are, an optionally substituted C.sub.1-C.sub.6 haloalkyl group or C.sub.1-C.sub.6 haloalkoxy group and so on, R.sup.5a is a hydrogen atom and so on, R.sup.5a and R.sup.5b together form —CH.sub.2O— and so on, R.sup.6a and R.sup.6b are a hydrogen atom and so on, n is 1 or 2.].
Claims
1. A heteroaromatic amide derivative represented by the general formula (I) or salt thereof: ##STR01159## [wherein, X.sup.1-X.sup.2 is N—C or C—N, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 are, independently each other, a single bond, —CH.sub.2—, —CH.sub.2CH.sub.2—, —CR.sup.4aR.sup.4b—, —CR.sup.4aH—, —CR.sup.4bH—, —CH.sub.2CR.sup.4aR.sup.4b—, —CH.sub.2CR.sup.4aH—, —NR.sup.4c—, —NH—, —S—, —SO.sub.2—, or —O—, Z.sup.1 is a single bond, —CR.sup.7aR.sup.7b—, —O—, —S—, —NH—, —NR.sup.7a—, —NR.sup.7aCH.sub.2—, —CH.sub.2NR.sup.7a—, —CO—, or —SO.sub.2—, ring A is a 3- to 7-membered monocyclic aromatic ring, or a 8- to 12-membered bicyclic aromatic ring, R.sup.1a and R.sup.1b are, independently each other, a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 alkoxy group, a C.sub.1-C.sub.4 haloalkoxy group, a C.sub.3-C.sub.7 cycloalkyl group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, R.sup.2 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, an optionally substituted C.sub.1-C.sub.6 alkyl group, an optionally substituted C.sub.1-C.sub.6 haloalkyl group, an optionally substituted C.sub.2-C.sub.6 alkenyl group, an optionally substituted C.sub.2-C.sub.6 alkynyl group, or an optionally substituted saturated, partially saturated or unsaturated 3- to 7-membered monocyclic ring, R.sup.3a, R.sup.3b and R.sup.3c are, independently each other, a hydrogen atom, a halogen atom, a cyano group, a cyanomethyl group, a formyl group, a nitro group, a carboxamide group, a hydroxy group, an optionally substituted C.sub.1-C.sub.6 alkyl group, an optionally substituted C.sub.1-C.sub.6 haloalkyl group, an optionally substituted C.sub.1-C.sub.6 alkoxy group, an optionally substituted C.sub.1-C.sub.6 haloalkoxy group, an optionally substituted C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.6 alkylcarbonyl group, an optionally substituted C.sub.1-C.sub.6 alkoxycarbonyl group, an optionally substituted C.sub.1-C.sub.6 alkylcarbonyloxy group, an optionally substituted C.sub.1-C.sub.6 haloalkylcarbonyl group, an optionally substituted C.sub.1-C.sub.6 haloalkoxycarbonyl group, an optionally substituted C.sub.1-C.sub.6 haloalkylcarbonyloxy group, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group, an optionally substituted heterocycloalkyl group, an optionally substituted C.sub.3-C.sub.7 cycloalkyloxy group, an optionally substituted heterocycloalkyloxy group, an optionally substituted C.sub.2-C.sub.6 alkenyl group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.2-C.sub.6 alkynyl group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 haloalkoxy group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 haloalkoxy group, an optionally substituted C.sub.1-C.sub.6 alkylthio group, an optionally substituted C.sub.1-C.sub.6 haloalkylthio group, an optionally substituted C.sub.1-C.sub.4 alkylthio-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkylthio-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 alkylthio-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkylthio-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.6 alkylsulfonyl group, —(CH.sub.2).sub.pNR.sup.a11R.sup.a2(R.sup.a1 and R.sup.a2 are, independently each other, a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group, and p is 0, 1, or 2.), or a group represented by the general formula (I-A) ##STR01160## {wherein, ring B is a saturated, partially saturated or unsaturated 3- to 7-membered monocyclic ring, L.sup.1 is a single bond, —CR.sup.a3R.sup.a4—, —O—, —NR.sup.a2—, —CR.sup.a3R.sup.a4O—, —OCR.sup.a3R.sup.a4—, —CH.sub.2CH.sub.2—, —CH═CH—, —C≡C—, or —CH.sub.2OCH.sub.2— (R.sup.a3 and R.sup.a4 are, independently each other, a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group.), R.sup.8a, R.sup.8b and R.sup.8c are, independently each other, a hydrogen atom, a halogen atom, a cyano group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.3-C.sub.7 cycloalkyl group, a C.sub.3-C.sub.7 cycloalkyloxy group, a heterocycloalkyl group, a heterocycloalkyloxy group, a C.sub.2-C.sub.6 alkenyl group, or a C.sub.2-C.sub.6 alkynyl group.}, R.sup.4a, R.sup.4b and R.sup.4c are, independently each other, a halogen atom, a cyano group, a cyanomethyl group, a formyl group, a nitro group, a carboxamide group, a hydroxy group, an optionally substituted C.sub.1-C.sub.6 alkyl group, an optionally substituted C.sub.1-C.sub.6 haloalkyl group, an optionally substituted C.sub.1-C.sub.6 alkoxy group, an optionally substituted C.sub.1-C.sub.6 haloalkoxy group, an optionally substituted C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.6 alkylcarbonyl group, an optionally substituted C.sub.1-C.sub.6 alkoxycarbonyl group, an optionally substituted C.sub.1-C.sub.6 alkylcarbonyloxy group, an optionally substituted C.sub.1-C.sub.6 haloalkylcarbonyl group, an optionally substituted C.sub.1-C.sub.6 haloalkoxycarbonyl group, an optionally substituted C.sub.1-C.sub.6 haloalkylcarbonyloxy group, an optionally substituted C.sub.3-C.sub.7 cycloalkyl group, an optionally substituted heterocycloalkyl group, an optionally substituted C.sub.3-C.sub.7 cycloalkyloxy group, an optionally substituted heterocycloalkyloxy group, an optionally substituted C.sub.2-C.sub.6 alkenyl group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.2-C.sub.6 alkynyl group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 alkoxy group, an optionally substituted C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 haloalkoxy group, an optionally substituted C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 haloalkoxy group, an optionally substituted C.sub.1-C.sub.6 alkylthio group, an optionally substituted C.sub.1-C.sub.6 haloalkylthio group, an optionally substituted C.sub.1-C.sub.4 alkylthio-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkylthio-C.sub.1-C.sub.4 alkyl group, an optionally substituted C.sub.1-C.sub.4 alkylthio-C.sub.1-C.sub.4 haloalkyl group, an optionally substituted C.sub.1-C.sub.4 haloalkylthio-C.sub.1-C.sub.4 haloalkyl group, a pentafluorosulfanyl group, —(CH.sub.2).sub.qNR.sup.b1R.sup.b2 (R.sup.b1 and R.sup.b2 are, independently each other, a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group, and q is 0, 1, 2, or 3.), or a group represented by the general formula (I-B) ##STR01161## {wherein, ring C is a saturated, partially saturated or unsaturated 3- to 7-membered monocyclic ring, or a saturated, partially saturated or unsaturated 7- to 12-membered bicyclic ring, L.sup.2 is a single bond, —CH═CH—, —C≡C—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2O(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2NR.sup.c(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2CO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2CONR.sup.c(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2NR.sup.cCO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2SCO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2SOCO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2SO.sub.2CO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2SO.sub.2NR.sup.c(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, or —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2NR.sup.cSO.sub.2(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sup.r4—, (R.sup.c is a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group, R.sup.10a, R.sup.10b, R.sup.10c, R.sup.10d, R.sup.10e, R.sup.10f, R.sup.10g, and R.sup.10h are, independently each other, a hydrogen atom, a halogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.3-C.sub.7 cycloalkyl group, R.sup.10a and R.sup.10b optionally form, together with the carbon atom bonded thereto, a 3- to 7-membered monocyclic ring, R.sup.10c and R.sup.10d optionally form, together with the carbon atom bonded thereto, a 3- to 7-membered monocyclic ring, R.sup.10e and R.sup.10f optionally form, together with the carbon atom bonded thereto, a 3- to 7-membered monocyclic ring, R.sup.10g and R.sup.10h optionally form, together with the carbon atom bonded thereto, a 3- to 7-membered monocyclic ring, r1, r2, r3 and r4 are, independently each other, 0, 1, or 2.), R.sup.9a, R.sup.9b and R.sup.9c are, independently each other, a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a formyl group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.6 alkylcarbonyl group, a C.sub.1-C.sub.6 alkoxycarbonyl group, a C.sub.1-C.sub.6 haloalkylcarbonyl group, a C.sub.3-C.sub.7 cycloalkyl group, a heterocycloalkyl group, a C.sub.3-C.sub.7 cycloalkyloxy group, a heterocycloalkyloxy group, a C.sub.2-C.sub.6 alkenyl group, —(CH.sub.2).sub.sNR.sup.d1R.sup.d2 (R.sup.d1 and R.sup.d2 are, independently each other, a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group, and s is 0, 1, or 2.), or the general formula (I-C) ##STR01162## {wherein, ring D is a 3- to 7-membered monocyclic ring optionally substituted by a halogen atom, a hydroxy group, a C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 alkoxy group, or a C.sub.1-C.sub.4 haloalkoxy group, L.sup.3 is a single bond, or an oxygen atom.}.} or R.sup.4aand R.sup.4b optionally form, together with the carbon atom bonded thereto, a 3- to 7-membered monocyclic ring, or R.sup.4aand R.sup.4b optionally together form the general formula (I-D): ##STR01163## (R.sup.4d and R.sup.4e are, independently each other, a hydrogen atom, a halogen atom, or a C.sub.1-C.sub.4 alkyl group, or R.sup.4d and R.sup.4e optionally form, together with the carbon atom bonded thereto, a 3- to 7-membered monocyclic ring) (with a proviso that at least one of Y.sup.1, Y.sup.2, Y.sup.3, and Y.sup.4 is —CR.sup.4aR.sup.4b—, —CR.sup.4aH—, —CH.sub.2CR.sup.4aR.sup.4b—, or —CH.sub.2CR.sup.4aH— when R.sup.2 is a hydrogen atom.), R.sup.5a, R.sup.5b, R.sup.5c, R.sup.6a, R.sup.6b, and n fulfill either one of the following constitutions (i) and (ii), {(i) R.sup.5b and R.sup.5c together form —OCH.sub.2—, —CH.sub.2O—, —CH.sub.2S—, —SCH.sub.2—, —CH.sub.2NR.sup.e1—, —NR.sup.e1CH.sub.2—, —CH.sub.2CH.sub.2—, —NR.sup.e1CO—, —CR.sup.e1R.sup.e2O—, or —OCR.sup.e1R.sup.e2— (R.sup.e1 and R.sup.e2 are a hydrogen atom or a C.sub.1-C.sub.4 alkyl group.), and R.sup.5a is a hydrogen atom, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.3-C.sub.7 cycloalkyl group, a heterocycloalkyl group, a C.sub.3-C.sub.7 cycloalkyl-C.sub.1-C.sub.4 alkyl group, a heterocycloalkyl-C.sub.1-C.sub.4 alkyl group, or an aralkyl group, and R.sup.6a and R.sup.6b, independently each other, are a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 alkoxy group, or a C.sub.1-C.sub.4 haloalkoxy group, and n is 1 or 2. (ii) R.sup.5a and R.sup.6a together form —CH.sub.2—, —CH.sub.2CH.sub.2—, —CH.sub.2CR.sup.e1R.sup.e2—, —CR.sup.e1R.sup.e2CH.sub.2—, —CH.sub.2CH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2O—, —CH.sub.2CH.sub.2CH.sub.2O— (R.sup.e1 and R.sup.e2 are the same as the definition given in the (i).), and R.sup.5b is a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group, R.sup.5c and R.sup.6b are a hydrogen atom, a halogen atom, a hydroxy group, a C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 alkoxy group, a C.sub.1-C.sub.4 haloalkoxy group or, alternatively, R.sup.5c and R.sup.6b together form —(CH.sub.2).sub.t—, —O(CH.sub.2).sub.t—, —(CH.sub.2).sub.tO—, —(CH.sub.2).sub.tO(CH.sub.2).sub.u—, —(CH.sub.2).sub.tNR.sup.e3(CH.sub.2).sub.u—, —(CH.sub.2).sub.tCONR.sup.e3(CH.sub.2).sub.u—, or —(CH.sub.2).sub.tNR.sup.e3CO(CH.sub.2).sub.u— (t and u are, independently each other, 0, 1, 2, or 3, R.sup.e3 is a hydrogen atom or a C.sub.1-C.sub.4 alkyl group.), and n is 1.} (with a proviso that Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 do not together form —CH.sub.2NR.sup.4aHCH.sub.2CH.sub.2— when R.sup.5a, R.sup.5b, R.sup.5c, R.sup.6a, R.sup.6b, and n fulfill the constitution in the (ii) above.), R.sup.7a and R.sup.7b are, independently each other, a hydrogen atom, a halogen atom, or a C.sub.1-C.sub.4 alkyl group.].
2. The heteroaromatic amide derivative or salt thereof according to claim 1, wherein in the general formula (I), Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —OCR.sup.4aHCH.sub.2CH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —OCH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2—, —OCH.sub.2CH.sub.2CH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2CH.sub.2CH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2CH.sub.2CH.sub.2—, —OCH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —OCH.sub.2CR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —CH.sub.2OCH.sub.2CH.sub.2—, —CH.sub.2OCH.sub.2CH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2OCH.sub.2—, —CH.sub.2CR.sup.4aHOCH.sub.2— —CH.sub.2CH.sub.2CH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2CR.sup.4aHCH.sub.2—, —CH.sub.2CH.sub.2CR.sup.4aR.sup.4bCH.sub.2—, —CH.sub.2SCH.sub.2CH.sub.2—, —CH.sub.2SO.sub.2CH.sub.2CH.sub.2—, —NHCH.sub.2CH.sub.2CH.sub.2—, —NR.sup.4cCH.sub.2CH.sub.2CH.sub.2—, —NR.sup.4cCR.sup.4aHCH.sub.2CH.sub.2—, —NHCR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2NR.sup.4cCH.sub.2CH.sub.2—, —CH.sub.2NR.sup.4cCR.sup.4aHCH.sub.2—, —CH.sub.2NHCR.sup.4aHCH.sub.2—, —CH.sub.2CH.sub.2NR.sup.4cCH.sub.2—, —CH.sub.2CR.sup.4aHNR.sup.4cCH.sub.2—, or —CH.sub.2CR.sup.4aHNHCH.sub.2— (R.sup.4a, R.sup.4b and R.sup.4c are the same as the definition given in claim 1.), R.sup.2 is a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, or an optionally substituted saturated, partially saturated or unsaturated 3- to 7-membered monocyclic ring (with a proviso that R.sup.2 is a hydrogen atom when X.sup.1-X.sup.2 is C-N and Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —OCR.sup.4aHCH.sub.2CH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2CH.sub.2—.), (with a proviso that ring C is not a phenyl ring when X.sup.1-X.sup.2 is N—C, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, R.sup.2 is a hydrogen atom, R.sup.4ais a group represented by the general formula (I-B), and L.sup.2 is a single bond.).
3. The heroaromatic amide derivative or salt thereof according to claim 1, wherein in the general formula (I), X.sup.1-X.sup.2 is C—N, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —OCR.sup.4aHCH.sub.2CH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —OCH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2—, —OCH.sub.2CH.sub.2CH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2CH.sub.2CH.sub.2—, —OCH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2OCH.sub.2CH.sub.2—, —CH.sub.2OCH.sub.2CH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2CR.sup.4aHCH.sub.2—, —NHCH.sub.2CH.sub.2CH.sub.2—, —NR.sup.4cCR.sup.4aHCH.sub.2CH.sub.2—, —NHCR.sup.4aHCH.sub.2CH.sub.2—, or —CH.sub.2NR.sup.4cCH.sub.2CH.sub.2— (R.sup.4a, R.sup.4b and R.sup.4c have the same definition as given in claim 1.), R.sup.5a, R.sup.5b, R.sup.5c, R.sup.6a, R.sup.6b, and n fulfill the constitution (i) in claim 1.
4. A heteroaromatic amide derivative or salt thereof represented by the general formula (I-E2): ##STR01164## [wherein, X.sup.1, X.sup.2, Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, R.sup.1a, R.sup.1b, R.sup.2 have the same definition as given in claim 1, Z.sup.2-Z.sup.3 is —OCH.sub.2—, —CH.sub.2O—, —SCH.sub.2—, —CH.sub.2S—, —CH.sub.2NR.sup.f1—, —NR.sup.f1CH.sub.2—, —CH.sub.2CH.sub.2—, —CONR.sup.f1—, —NR.sup.f1CO—, —OCR.sup.f1R.sup.f2—, or —CR.sup.f1R.sup.f2O— (R.sup.f1 and R.sup.f2 are a hydrogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 haloalkyl group.), R.sup.5a is a hydrogen atom, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.3-C.sub.7 cycloalkyl group, a heterocycloalkyl group, a C.sub.3-C.sub.7 cycloalkyl-C.sub.1-C.sub.4 alkyl group, a heterocycloalkyl-C.sub.1-C.sub.4 alkyl group, or an aralkyl group, R.sup.6a and R.sup.6b are, independently each other, a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 alkoxy group, or a C.sub.1-C.sub.4 haloalkoxy group, Z.sup.4 is C-R.sup.11a or a nitrogen atom, R.sup.11a is a hydrogen atom, a halogen atom, a cyano group, a cyanomethyl group, a formyl group, a nitro group, a carboxamide group, a hydroxy group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.3-C.sub.7 cycloalkyl group, a C.sub.2-C.sub.6 alkenyl group, a C.sub.2-C.sub.6 alkenyloxy group, a C.sub.2-C.sub.6 alkynyl group, or a C.sub.2-C.sub.6 alkynyloxy group, R.sup.11b has the same definition as given to R.sup.3b in claim 1, R.sup.11c has the same definition as given to R.sup.3c in claim 1 (with a proviso that at least one of Y.sup.1, Y.sup.2, Y.sup.3, or Y.sup.4, is —CR.sup.4aR.sup.4b—, —CR.sup.4aH—, —CH.sub.2CR.sup.4aR.sup.4b—, —CH.sub.2CR.sup.4aH—, or —NR.sup.4c— (R.sup.4a, R.sup.4b and R.sup.4c have the same definition as given in claim 1.) when R.sup.2 is a hydrogen atom.).].
5. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), X.sup.1-X.sup.2 is C—N, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —OCR.sup.4aHCH.sub.2CH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —OCH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2—, —OCR.sup.4aR.sup.4bCH.sub.2—, —OCH.sub.2CH.sub.2CH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2CH.sub.2CH.sub.2—, —OCH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2OCH.sub.2CH.sub.2—, —CH.sub.2OCH.sub.2CH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2CR.sup.4aHCH.sub.2—, —NHCH.sub.2CH.sub.2CH.sub.2—, —NR.sup.4cCR.sup.4aHCH.sub.2CH.sub.2—, —NHCR.sup.4aHCH.sub.2CH.sub.2—, or —CH.sub.2NR.sup.4cCH.sub.2CH.sub.2— (R.sup.4a, R.sup.4b and R.sup.4c have the same definition as given in claim 1.), (with a proviso that R.sup.2 is a hydrogen atom when X.sup.1-X.sup.2 is C—N and Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —OCR.sup.4aHCH.sub.2CH.sub.2— or —OCR.sup.4aR.sup.4bCH.sub.2CH.sub.2—.).
6. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), Z.sup.2-Z.sup.3 is —CH.sub.2O—, R.sup.6a and R.sup.6b, each independently, are a hydrogen atom, a fluorine atom, a hydroxy group or a methoxy group, R.sup.11a and R.sup.11c are each a hydrogen atom.
7. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), X.sup.1-X.sup.2 is C—N, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —OCR.sup.4aHCH.sub.2CH.sub.2—, —OCR.sup.4aHCH.sub.2—, —OCR.sup.4aHCH.sub.2CH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —NR.sup.4cCR.sup.4aHCH.sub.2CH.sub.2—, —NHCR.sup.4aHCH.sub.2CH.sub.2—, or —CH.sub.2NR.sup.4cCH.sub.2CH.sub.2—, R.sup.4a is a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 alkyl group optionally substituted by a hydroxy group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 haloalkyl group optionally substituted by a hydroxy group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group optionally substituted by a C.sub.1-C.sub.4 haloalkoxy group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.6 alkylcarbonyl group, a C.sub.1-C.sub.6 alkoxycarbonyl group, a C.sub.1-C.sub.6 haloalkylcarbonyl group, a C.sub.3-C.sub.7 cycloalkyl group, a C.sub.3-C.sub.7 cycloalkyl group optionally substituted by a halogen atom or a C.sub.1-C.sub.4 haloalkyl group, a heterocycloalkyl group, a C.sub.2-C.sub.6 alkenyl group, a C.sub.2-C.sub.6 alkenyloxy group, a C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkyl group, a C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkyl group optionally substituted by a halogen atom, a C.sub.2-C.sub.6 alkynyl group, a C.sub.2-C.sub.6 alkynyl group optionally substituted by a halogen atom or a methoxy group, a C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkoxy group, a C.sub.1-C.sub.6 alkylthio group, a C.sub.1-C.sub.6 haloalkylthio group, a C.sub.1-C.sub.4 alkylthio-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkylthio-C.sub.1-C.sub.4 alkyl group, —(CH.sub.2).sub.qNR.sup.b1R.sup.b2 (q, R.sup.b1 and R.sup.b2 have the same definition as given in claim 1.), or the general formula (I-B) ##STR01165## {wherein, ring C is a C.sub.3-C.sub.7 cycloalkyl, an azetidinyl, a pyrrolidinyl, a piperidyl, a piperazinyl, a morpholino, a phenyl, a pyrrolyl, a furyl, a thienyl, an imidazolyl, a pyrazolyl, an oxazolyl, a thiazolyl, a triazolyl, a pyridyl, a pyrazinyl, a pyridazinyl, or a pyrimidinyl, L.sup.2 is a single bond, —CH═CH—, —C≡C—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2O(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2NR.sup.c(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2CO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2S(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, or —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2SO(CR.sup.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4— (R.sup.10a, R.sup.10b, R.sup.10c, R.sup.10d, R.sup.10e, R.sup.10f, R.sup.10g, R.sup.10h, r1, r2, .sub.r3, .sub.r4 and RC have the same definition as given in claim 1.), R.sup.9a, R.sup.9b and R.sup.9c are, independently each other, a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.6 alkoxycarbonyl group, a heterocycloalkyloxy group, or —(CH.sub.2).sub.sNR.sup.d1R.sup.d2 (s, R.sup.d1 and R.sup.d2have the same definition as given in claim 1.). }
8. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), X.sup.1-X.sup.2 is N—C, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —CH.sub.2CR.sup.4aHOCH.sub.2—, —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2CR.sup.4aR.sup.4bCH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2NR.sup.4cCH.sub.2—, —CH.sub.2CR.sup.4aHNR.sup.4cCH.sub.2—, or —CH.sub.2CR.sup.4aHNHCH.sub.2— (R.sup.4a, R.sup.4b and R.sup.4c have the same definition as given in claim 1.), (with a proviso that ring C is not a phenyl ring when Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, R.sup.2 is a hydrogen atom, R.sup.4a is a group represented by the general formula (I-B), and L.sup.2 is a single bond.).
9. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), Z.sup.2-Z.sup.3 is —CH.sub.2O—, R.sup.6a, R.sup.6b, and R.sup.11c are each a hydrogen atom, R.sup.11a is a hydrogen atom or a halogen atom.
10. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), X.sup.1-X.sup.2 is N—C, Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 together form —CH.sub.2CR.sup.4aHOCH.sub.2—, —CH.sub.2CR.sup.4aHCH.sub.2CH.sub.2—, —CH.sub.2CH.sub.2NR.sup.4cCH.sub.2—, —CH.sub.2CR.sup.4aHNR.sup.4cCH.sub.2—, or —CH.sub.2CR.sup.4aHNHCH.sub.2—, R.sup.4a and R.sup.4c, each independently, are a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 alkyl group optionally substituted by a hydroxy group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 haloalkyl group optionally substituted by a hydroxy group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group optionally substituted by a C.sub.1-C.sub.4 haloalkoxy group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.6 alkylcarbonyl group, a C.sub.1-C.sub.6 alkoxycarbonyl group, a C.sub.1-C.sub.6 haloalkylcarbonyl group, a C.sub.3-C.sub.7 cycloalkyl group, a C.sub.3-C.sub.7 cycloalkyl group optionally substituted by a halogen atom or a C.sub.1-C.sub.4 haloalkyl group, a heterocycloalkyl group, a C.sub.2-C.sub.6 alkenyl group, a C.sub.2-C.sub.6 alkenyloxy group, a C.sub.2-C.sub.6 alkenyloxy-a C.sub.1-C.sub.4 alkyl group, a C.sub.2-C.sub.6 alkenyloxy-C.sub.1-C.sub.4 alkyl group optionally substituted by a halogen atom, a C.sub.2-C.sub.6 alkynyl group, a C.sub.2-C.sub.6 alkynyl group optionally substituted by a halogen atom or a methoxy group, a C.sub.2-C.sub.6 alkynyloxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkoxy group, a C.sub.1-C.sub.6 alkylthio group, a C.sub.1-C.sub.6 haloalkylthio group, a C.sub.1-C.sub.4 alkylthio-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 haloalkylthio-C.sub.1-C.sub.4 alkyl group, —(CH.sub.2).sub.qNR.sup.b1R.sup.b2 (q, R.sup.b1 and R.sup.b2 have the same definition as given in claim 1.), or the general formula (I-B) ##STR01166## {wherein, ring C is a C.sub.3-C.sub.7 cycloalkyl, an azetidinyl, a pyrrolidinyl, a piperidyl, a piperazinyl, a morpholino, a phenyl, a pyrrolyl, a furyl, a thienyl, an imidazolyl, a pyrazolyl, an oxazolyl, a thiazolyl, a triazolyl, a pyridyl, a pyrazinyl, a pyridazinyl, or a pyrimidinyl, L.sup.2 is a single bond, —CH═CH—, —C≡C—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2(CR.sub.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2O(CR.sub.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2NR.sup.c(CR.sub.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2CO(CR.sub.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2S(CR.sub.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4—, —(CR.sup.10aR.sup.10b).sub.r1(CR.sup.10cR.sup.10d).sub.r2SO(CR.sub.10eR.sup.10f).sub.r3(CR.sup.10gR.sup.10h).sub.r4— (R.sup.10a, R.sup.10b, R.sup.10c, R.sup.10d, R.sup.10e, R.sup.10f, R.sup.10g, R.sup.10h, r1, r2, r3, r4 and R.sup.c have the same definition as given in claim 1.), R.sup.9a, R.sup.9b and R.sup.9c are, independently each other, a hydrogen atom, a halogen atom, a hydroxy group, a cyano group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.6 alkoxycarbonyl group, a heterocycloalkyloxy group, or —(CH.sub.2).sub.sNR.sup.d1R.sup.d2 (s, R.sup.d1 and R.sup.d2have the same definition as given in claim 1.).}.
11. The heroaromatic amide derivative or salt thereof according to claim 4, wherein in the general formula (I-E2), R.sup.11b is a hydrogen atom, a halogen atom, a cyano group, a cyanomethyl group, a formyl group, a nitro group, a carboxamide group, a hydroxy group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 alkyl group optionally substituted by a dimethylaminocarbonyl group or a dimethylamino group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 alkyl group, a C.sub.1-C.sub.4 alkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.4 haloalkoxy-C.sub.1-C.sub.4 haloalkyl group, a C.sub.1-C.sub.6 alkylcarbonyl group, a C.sub.2-C.sub.6 alkenyl group, a C.sub.2-C.sub.6 alkynyl group, a C.sub.2-C.sub.6 alkynyl group optionally substituted by a halogen atom, a C.sub.1-C.sub.6 alkylthio group, a C.sub.1-C.sub.6 haloalkylthio group, —(CH.sub.2).sub.pNR.sup.a1R.sup.a2 (p, R.sup.a1 and R.sup.a2 have the same definition given in claim 1.), or a group represented by the general formula (I-A) ##STR01167## {wherein, ring B is a C.sub.3-C.sub.7 cycloalkyl, an azetidinyl, a pyrrolidinyl, a piperidyl, a piperazinyl, a morpholino, a phenyl, a pyrrolyl, a furyl, a thienyl, an imidazolyl, a pyrazolyl, an oxazolyl, an isoxazolyl, a thiazolyl, an isothiazolyl, a triazolyl, a tetrazolyl, a pyridyl, a pyrazinyl, a pyridazinyl, or a pyrimidinyl, L.sup.1 is a single bond, —CH.sub.2—, —CH.sub.2O—, —OCH.sub.2—, —CH.sub.2CH.sub.2—, or —CH.sub.2OCH.sub.2—, R.sup.8a, R.sup.8b and R.sup.8c are, independently each other, a hydrogen atom, a halogen atom, a cyano group, a C.sub.1-C.sub.6 alkyl group, a C.sub.1-C.sub.6 haloalkyl group, a C.sub.1-C.sub.6 alkoxy group, a C.sub.1-C.sub.6 haloalkoxy group, a C.sub.3-C.sub.7 cycloalkyl group, a C.sub.3-C.sub.7 cycloalkyloxy group, a heterocycloalkyl group, a heterocycloalkyloxy group, a C.sub.2-C.sub.6 alkenyl group, or a C.sub.2-C.sub.6 alkynyl group}.
12. The heroaromatic amide derivative or salt thereof according to claim 4, wherein the compound represented by the general formula (I-E2) (the asterisks (*) in the sturctural formulae denote that the stereo of the corresponding asymmetric carbon has a single steric structure.) is any one of the following: ##STR01168## ##STR01169## ##STR01170## ##STR01171## ##STR01172## ##STR01173## ##STR01174## ##STR01175## ##STR01176## ##STR01177## ##STR01178## ##STR01179## ##STR01180## ##STR01181## ##STR01182## ##STR01183## ##STR01184## ##STR01185## ##STR01186## ##STR01187## ##STR01188## ##STR01189## ##STR01190## ##STR01191## ##STR01192## ##STR01193## ##STR01194##
13. A pharmaceutical composition containing the heteroaromatic amide derivative or salt thereof according to claim 4.
14. (canceled)
15. (canceled)
16. (canceled)
17. (canceled)
18. (canceled)
19. (canceled)
20. (canceled)
21. A method for preventing or treating a disorder associated with voltage-gated sodium channel Nav1.7, containing as an active ingredient the heteroaromatic amide derivative or salt thereof according to claim 4.
22. A method for preventing or treating a disorder with pain, a disorder with pruritus, a disorder associated with autonomic nerves, containing as an active ingredient the heteroaromatic amide derivative or salt thereof according to claim 4.
23. A method for preventing or treating a disorder with pain, containing as an active ingredient the heteroaromatic amide derivative or salt thereof according to claim 4.
24. A method for preventing or treating a disorder with nociceptive pain or neuropathic pain, containing as an active ingredient the heteroaromatic amide derivative or salt thereof according to claim 4.
Description
EXAMPLE
[0672] Hereinbelow, features of the present invention will more specifically be explained by reciting examples and test examples.
[0673] The materials, the amount used, the ratios, the processing content, the processing procedures and so on indicated in the following Examples can appropriately be changed as long as not departing from the subject matter of the present invention.
[0674] Hence the scope of the present invention should not be interpreted limitatively by the specific examples shown hereinbelow.
[0675] The .sup.1H-NMR spectra shown hereinbelow were measured by a JNM-ECA400 type spectrometer (400 MHz, manufactured by JEOL Ltd.) or AVANCEIII HD400 type (400 MHz, manufactured by Bruker BioSpin Co., Ltd.), by using deuterated chloroform (CDCl.sub.3), deuterated dimethyl sulfoxide (DMSO-d.sub.6), deuterated methanol (CD.sub.3OD) as a solvent, and tetramethylsilane (TMS) as an internal standard. In the measurement results for the chemical shift, the δ value was expressed in ppm and the J value of the coupling constant was expressed in Hz. In the abbreviation, “s” means “singlet”, “d” means “doublet”, “t” means “triplet”, “q” means “quartert”, “m” means “multiplet” and “br” means “broad”. Mass spectrum (ESI-MS) was measured by electrospray ionization with Exactive (manufactured by Thermo Fisher Scientific Co., Ltd.). The chemical structural formulae and physical property values of the compound in each Example are shown in the tables shown below.
[0676] Ac: acetyl
[0677] ADDP: 1,1′-(azodicarbonyl) dipiperidine
[0678] (A.sup.taPhos).sub.2PdCl.sub.2: bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)
[0679] Bn: benzyl
[0680] Boc: tert-butoxycarbonyl
[0681] Bu: butyl
[0682] CAN: ammonium cerium (IV) nitrate
[0683] DAST: N,N-diethylaminosulfur trifluoride
[0684] DBU: diazabicycloundecene
[0685] DCE: 1,2-dichloroethane
[0686] DCM: dichloromethane
[0687] DDQ: 2,3-dichloro-5,6-dicyano-p-benzoquinone
[0688] DIAD: diisopropyl azodicarboxylate
[0689] DIEA: N,N-diisopropylethylamine
[0690] DMAP: N,N-dimethyl-4-aminopyridine
[0691] DME: 1,2-dimethoxyethane
[0692] DMF: N,N-dimethylformamide
[0693] DMSO: dimethyl sulfoxide
[0694] Et: ethyl
[0695] EDCI: 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide
[0696] HATU: O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate
[0697] HOBt: 1-hydroxybenzotriazole
[0698] HPLC: high performance liquid chromatography
[0699] i: iso
[0700] IPA: isopropyl alcohol
[0701] Me: methyl
[0702] Ms: methanesulfonyl
[0703] n: normal
[0704] NBS: N-bromosuccinimide
[0705] NCS: N-chlorosuccinimide
[0706] NIS: N-iodosuccinimide
[0707] NMM: N-methylmorpholine
[0708] nor-AZADO: 9-azanor adamantane N-oxyl
[0709] p: para
[0710] Ph: phenyl
[0711] PTSA: p-toluenesulfonic acid
[0712] TBAB: tetrabutylammonium bromide
[0713] TBA-HS: tetrabutylammonium hydrogen sulfate
[0714] TBAI: tetrabutylammonium iodide
[0715] TBAF: tetrabutylammonium fluoride
[0716] TBDPS: tert-butyldiphenylsilyl
[0717] tert: tertiary
[0718] tBuXphos: 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl
[0719] Tf: trifluoromethylsulfonyl
[0720] TEA: triethylamine
[0721] TFA: trifluoroacetic acid
[0722] TFAA: trifluoroacetic anhydride
[0723] THF: tetrahydrofuran
[0724] TMEDA: tetramethylethylenediamine
[0725] TMS: trimethylsilyl
[0726] TMG: 1,1,3,3-tetramethylguanidine
[0727] Ts: p-toluenesulfonyl
[0728] Xantphos Pd G3: [(4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene)-2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate
[0729] The asterisks (*) appearing in the structural formulae in the Examples denote that the corresponding asymmetric carbon has a single steric structure. Regarding the notations of “isomer A”, “isomer B”, “isomer C” and “isomer D”, among the plural compounds indicated by the same Example number, the isomers are specified as “isomer A”, “isomer B”, “isomer C” and “isomer D” in accordance with the order of collection by the high performance liquid chromatography in the Example.
Example 1
Production of N-(6-fluorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide
[0730] ##STR00103##
Step 1
[0731] To a mixed solution of 5-(trifluoromethyl)pyridin-2-amine (835 mg, 5.15 mmol) in 1,2-dimethoxyethane (12.9 mL) and methanol (12.9 mL) was added ethyl bromopyruvate (776 μL, 6.18 mmol), and the mixture was stirred for 14 hours at 80° C. After concentrating the reaction solution under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl 6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylate (amount 557 mg, yield 42%).
Step 2
[0732] To a mixed solution of ethyl 6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylate (5.96 g, 23.1 mmol) in tetrahydrofuran (100 mL), ethanol (100 mL) and acetic acid (11.9 mL) was added 20% palladium hydroxide on carbon (2.43 g). The mixture was stiffed under pressurized conditions (about 3 atm) at hydrogen atmospherefor 16 hours at room temperature. The reaction solution was filtered through celite and the solvent was evaporated off under reduced pressure. To the residue was added toluene, and the solvent was evaporated off under reduced pressure to give ethyl 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate (amount 6.42 g) as a crude product.
Step 3
[0733] To a solution of ethyl 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate (6.42 g, 24.5 mmol) in ethanol (49 mL) was added 4 mol/L aqueous solution of sodium hydroxide (24.5 mL, 98.0 mmol), and the mixture was stiffed for 3 hours at room temperature. To the reaction solution, 1 mol/L hydrochloric acid (98.0 mL, 98.0 mmol) was added, and then the solvent was evaporated off under reduced pressure. To the residue was added toluene, the solvent was evaporated off under reduced pressure, and the procedure was repeated three times to give 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid (amount 11.2 g, yield 98%) as a mixture with 4 equivalents of sodium chloride.
Step 4
[0734] To a suspension of 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (30.0 mg, 0.0641 mmol) in N,N-dimethylformamide (641 μL) were added HATU (29.2 mg, 0.0769 mmol), N,N-diisopropylethylamine (55 μL, 0.32 mmol) and 6-fluorochroman-3-amine hydrochloride (14.4 mg, 0.0705 mmol), and the mixture was stirred for 6 hours at 40° C. To the reaction solution, water and ethyl acetate were added, and the mixture was partitioned. Thereafter, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give N-(6-fluorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (amount 17.9 mg, yield 73%).
Reference Example 1
Production of (R)-6-chlorochroman-3-amine hydrochloride
[0735] ##STR00104##
Step 1
[0736] To a suspension of (R)-chroman-3-amine hydrochloride (200 mg, 1.08 mmol) in dichloromethane (11 mL) were added N,N-diisopropylethylamine (555 μL, 3.23 mmol) and trifluoroacetic anhydride (180 μL, 1.29 mmol), and the mixture was stirred for 2 hours at room temperature. After concentrating the reaction solution under reduced pressure, the residue was purified by silica gel column chromatography to give (R)-N-(chroman-3-yl)-2,2,2-trifluoroacetamide (amount 245 mg, yield 93%).
Step 2
[0737] To a solution of (R)-N-(chroman-3-yl)-2,2,2-trifluoroacetamide (4.00 g, 16.3 mmol) in acetonitrile (100 mL), N-chlorosuccineimide (2.60 g, 19.5 mmol) was added, and the mixture was stirred for 6 hours at 70° C. To the reaction solution were added saturated aqueous solution of sodium hydrogen carbonate and ethyl acetate, and the mixture was partitioned. Thereafter, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated off under reduced pressure to give (R)-N-(6-chlorochroman-3-yl)-2,2,2-trifluoroacetamide (amount 4.60 g, yield 100%).
Step 3
[0738] To a solution of (R)-N-(6-chlorochroman-3-yl)-2,2,2-trifluoroacetamide (297 mg, 1.06 mmol) in chloroform (2.7 mL), 4 mol/L aqueous solution of sodium hydroxide (2.7 mL, 10.8 mmol) was added, and the mixture was stirred for 17 hours at room temperature. Water and chloroform were added to the reaction solution, and the mixture was partitioned. The organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure and the residue was purified by silica gel column chromatography. To a solution of the purified compound in ethyl acetate, 4 mol/L hydrogen chloride-ethyl acetate solution was added, and then precipitated solid was filtered to give (R)-6-chlorochroman-3-amine hydrochloride (amount 60.9 mg, yield 67%).
Example 2
Production and isomeric separation of N-((R)-6-chlorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide
[0739] ##STR00105##
Step 1
[0740] To a suspension of 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (128 mg, 0.273 mmol) synthesized by a method described in Step 3 in Example 1 in N,N-dimethylformamide (2.27 mL) were added HATU (95.0 mg, 0.250 mmol), N,N-diisopropylethylamine (195 μL, 1.14 mmol) and (R)-6-chlorochroman-3-amine hydrochloride (50.0 mg, 0.227 mmol) synthesized by a method described in Reference Example 1, and the mixture was stirred for 15 hours at room temperature. Water was added to the reaction solution, and the precipitated solid was collected by filtration. The obtained solid was purified by silica gel column chromatography to give N-((R)-6-chlorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (amount 60.9 mg, yield 67%).
Step 2
[0741] N-((R)-6-Chlorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (50.0 mg, 0.125 mmol) was dissolved into ethanol (20 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK IB, developing solvent: ethanol/n-hexane=50/50, flow rate: 5.0 mL/min, room temperature)to give isomer A (amount 16.8 mg, yield 34%) and isomer B (amount 14.3 mg, yield 29%).
[0742] The compound of Example 3 was synthesized from the compound of Example 2 (isomer A) under the scheme depicted in the figure below.
##STR00106##
[0743] The compound of Example 4 was synthesized from the compound of Example 2 (isomer B) by a method similar to Example 3.
[0744] The compound of Reference Example 2 ((R)-6-bromochroman-3-amine hydrochloride) was synthesized under the scheme depicted in the figure below.
##STR00107##
[0745] The compound of Example 5 was synthesized by methods similar to those described in Example 1 and Reference Example 2.
Reference Example 3
Production of (R)-6-(difluoromethyl)chroman-3-amine hydrochloride
[0746] ##STR00108##
Step 1
[0747] A mixed suspension of (R)-N-(6-bromochroman-3-yl)-2,2,2-trifluoroacetamide (6.47 g, 20.0 mmol), potassium vinyl trifluoroborate (4.01 g, 29.9 mmol), cesium carbonate (13.0 g, 39.9 mmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium (II) (707 mg, 0.998 mmol) in 1,4-dioxane (167 mL) and water (33 mL) was stirred for 15 hours at 100° C. To the reaction solution, water and ethyl acetate were added, and the mixture was partitioned. Thereafter, the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to obtain (R)-2,2,2-trifluoro-N-(6-vinylchroman-3-yl)acetamide (amount 3.03 g, yield 56%).
Step 2
[0748] To a solution of (R)-2,2,2-trifluoro-N-(6-vinylchroman-3-yl)acetamide (3.03 g, 11.2 mmol) in 1,4-dioxane were added water (37 mL), 2,6-lutidine (2.6 mL, 22.3 mmol), sodium periodate (9.56 g, 44.7 mmol) and 2.5w/v% osmium tetroxide t-butanol solution (5.7 mL, 0.56 mmol), and the mixture was stirred for 3 hours at room temperature. Water and ethyl acetate was added to the reaction solution and the mixture was filtered. After the filtrate was partitioned, the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatographyto to obtain (R)-2,2,2-trifluoro-N-(6-formylchroman-3-yl)acetamide (amount 2.56 g, yield 84%).
Step 3
[0749] To (R)-2,2,2-trifluoro-N-(6-formylchroman-3-yl)acetamide (1.45 g, 5.31 mmol), N,N-diethylaminosulfur trifluoride (2.8 mL, 21.2 mmol) was added, and the mixture was stirred for 5 days at room temperature. The reaction solution was diluted with dichloromethane, added dropwise to a mixed liquid of chloroform and water, and then the mixture was partitioned. The organic layer was dried over anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-N-(6-(difluoromethyl)chroman-3-yl)-2,2,2-trifluoroacetamide (amount 1.11 g, yield 71%).
Step 4
[0750] (R)-6-(Difluoromethyl)chroman-3-amine hydrochloride was obtained by a method similar to Step 3 in Reference Example 1, using (R)-N-(6-(difluoromethyl)chroman-3-yl)-2,2,2-trifluoroacetamide instead of (R)-N-(6-chlorochroman-3-yl)-2,2,2-trifluoroacetamide
[0751] The compound of Example 6 was synthesized by methods similar to those described in Example 1 and Reference Example 3.
[0752] The compounds of Example 7 were obtained by separating the compound of Example 6.
[0753] The compound of Reference Example 4 (5-chlorochroman-3-amine hydrochloride) was synthesized under the scheme depicted in the figure below.
##STR00109##
[0754] The compound of Example 8 was synthesized by methods similar to those described in Example 1 and Reference Example 4.
[0755] The compounds of Example 9 (isomer A and isomer B) were synthesized by a method similar to Example 1.
[0756] The compound of Example 10 was synthesized from the compound of Example 9 under the scheme depicted in the figure below.
##STR00110##
[0757] The compound of Reference Example 5 ((R)-6-ethylchroman-3-amine hydrochloride) was synthesized under the scheme depicted in the figure below.
##STR00111##
[0758] The compound of Example 11 was synthesized by methods similar to those described in Example 1 and Reference Example 5.
[0759] The compound of Example 12 was synthesized by a method similar to Example 1.
[0760] The compound of Example 13 was synthesized from the compound of Example 12 under the scheme depicted in the figure below.
##STR00112##
[0761] The compound of Reference Example 7 (shown in the figure below.) was synthesized by a method similar to Example 1, using (R)-chroman-3-amine hydrochloride instead of 6-fluorochroman-3-amine hydrochloride in Step 4
##STR00113##
Example 14
Production of N-((R)-chroman-3-yl)-3-iodo-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide
[0762] ##STR00114##
[0763] To a solution of N-((R)-chroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide synthesized by the method described in Reference Example 7 (79.7 mg, 0.218 mmol) in N,N-dimethylformamide (2.2 mL), N-iodosuccineimide (73.6 mg, 0.327 mmol) was added, and the mixture was stirred for 14 hours at 80° C. In addition, N-iodosuccineimide (73.6 mg, 0.327 mmol) was added, and the mixture was stirred for 8 hours at 100° C. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. After the organic layer was washed with saturated brine, dried over anhydrous sodium sulfate and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give N-((R)-chroman-3-yl)-3-iodo-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (amount 97.5 mg, yield 91%).
[0764] The compound of Example 15 was synthesized from the compound of Example 14 under the scheme depicted in the figure below.
##STR00115##
[0765] The compound of Example 16 was synthesized from the compound of Reference Example 9 under the scheme depicted in the figure below.
##STR00116##
Example 17
Production of (R)-N-(6-chlorochroman-3-yl)-3-(6-methoxypyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide
[0766] ##STR00117##
Step 1
[0767] Ethyl 3-iodo-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate was obtained by a method similar to Example 14, using ethyl 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate instead of N-((R)-chroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide.
Step 2
[0768] Ethyl 3-(6-methoxypyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate was obtained by a method similar to Example 15, using ethyl 3-iodo-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate instead of N-((R)-chroman-3-yl)-3-iodo-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide.
Step 3
[0769] 3-(6-Methoxypyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid was obtained as a mixture with 4 equivalents of sodium chloride by a method similar to Step 3 in Example 1, using ethyl 3-(6-methoxypyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate instead of ethyl 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate.
Step 4
[0770] (R)-N-(6-Chlorochroman-3-yl)-3-(6-methoxypyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide was obtained by a method similar to Step 4 in Example 1, using 3-(6-methoxypyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid instead of 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid, and using (R)-6-chlorochroman-3-amine hydrochloride synthesized by a method described in Reference Example 1 instead of 6-fluorochroman-3-amine hydrochloride.
Example 18
Production of (R)-N-(6-chlorochroman-3-yl)-3-(pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide
[0771] ##STR00118##
Step 1
[0772] Ethyl 3-(6-chloropyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate was obtained by a method similar to Step 2 in Example 17, using 6-(chloropyridin-2-yl)boronic acid instead of 6-methoxypyridine-2- boronic acid.
Step 2
[0773] To a solution of ethyl 3-(6-chloropyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate (1.05 g, 3.43 mmol) in tetrahydrofuran (10 mL) were added ethanol (10 mL), acetic acid (1.8 mL) and 20% palladium hydroxide on carbon (0.72 g), and the mixture was stirred for 2 hours in hydrogen atmosphere (under balloon pressure) at 50° C. The reaction solution was filtered through Celite, and then the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 3-(pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate (amount 900 g, yield 97%).
Step 3
[0774] 3-(Pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid was obtained as a mixture with 4 equivalents of sodium chloride by a method similar to Step 3 in Example 1, using ethyl 3-(pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate instead of ethyl 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate.
Step 4
[0775] To suspension of 3-(pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid (4 equivalents sodium chloride mixture) (15 mg, 0.031 mmol), (R)-6-chlorochroman-3-amine hydrochloride synthesized by a method described in Reference Example 1 (6.9 mg, 0.031 mmol), 1-hydroxybenzotriazole (7.2 mg, 0.047 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (9.0 mg, 0.047 mmol) in dichloromethane (1 mL), 4-methylmorpholine (21 0.19 mmol) was added, and the mixture was stirred for 2 hours at room temperature. Water and ethyl acetate was added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-N-(6-chlorochroman-3-yl)-3-(pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (amount 8.0 mg, yield 62%).
[0776] The compound of Reference Example 8 (shown in the figure below.) was synthesized by a method similar to Step 2 to Step 3 in Example 17.
##STR00119##
[0777] The compound of Example 19 was synthesized from the compound of Reference Example 8 and the compound of Reference Example 43 by a method similar to Step 4 in Example 18.
[0778] The compound of Example 20 was synthesized from the compound of Reference Example 8 and the compound of Reference Example 44 by a method similar to Step 4 in Example 18.
[0779] The compound of Example 21 was synthesized by a method similar to Example 17.
[0780] The compound of Example 22 was synthesized by a method similar to Example 17.
[0781] The compound of Reference Example 9 (shown in the figure below.) was synthesized by a method similar to Step 4 in Example 1.
##STR00120##
[0782] The compound of Example 23 was synthesized from the compound of Reference Example 9 under the scheme depicted in the figure below.
##STR00121##
[0783] The compound of Example 24 was synthesized by a method similar to Example 23.
[0784] The compound of Reference Example 10 (shown in the figure below.) was synthesized by a method similar to Example 23.
##STR00122##
[0785] The compound of Example 25 was synthesized from the compound of Reference Example 10 under the scheme depicted in the figure below.
##STR00123##
[0786] The compound of Reference Example 11 (shown in the figure below.) was synthesized by a method similar to Reference Example 9.
##STR00124##
[0787] The compound of Example 26 was synthesized from the compound of Reference Example 11 by a method similar to Example 23.
[0788] The compound of Reference Example 12 (shown in the figure below.) was synthesized by a method similar to Step 4 in Example 1.
##STR00125##
[0789] The compound of Example 27 was synthesized from the compound of Reference Example 12 by a method similar to Example 23.
[0790] The compound of Reference Example 13 (shown in the figure below.) was synthesized by a method similar to Reference Example 12.
##STR00126##
[0791] The compound of Example 28 was synthesized from the compound of Reference Example 13 by a method similar to Example 23.
[0792] The compound of Reference Example 14 (shown in the figure below.) was synthesized by a method similar to Reference Example 12.
##STR00127##
[0793] The compound of Example 29 was synthesized from the compound of Reference Example 14 under the scheme depicted in the figure below.
##STR00128##
[0794] The compound of Example 30 was synthesized under the scheme depicted in the figure below.
##STR00129##
[0795] The compound of Example 31 was produced under the scheme depicted in the figure below.
##STR00130##
[0796] The compound of Reference Example 15 (2-(2,4-difluorophenyl)morpholine) was synthesized under the scheme depicted in the figure below.
##STR00131##
[0797] The compound of Example 32 was synthesized under the scheme depicted in the figure below.
##STR00132##
[0798] The compound of Example 33 was synthesized under the scheme depicted in the figure below.
##STR00133##
[0799] The compound of Example 34 was synthesized from the compound synthesized in Step 4 in Example 33 under the scheme depicted in the figure below.
##STR00134##
[0800] The compound of Example 35 was synthesized from the compound of Reference Example 9 under the scheme depicted in the figure below.
##STR00135##
[0801] The compound of Example 36 was synthesized under the scheme depicted in the figure below.
##STR00136##
Example 37
Production of N-((R)-chroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide
[0802] ##STR00137##
Step 1
[0803] Ethyl 6-hydroxyimidazo[1,2-a]pyridine-2-carboxylate was obtained by a method similar to Step 1 in Example 1, using 6-aminopyridin-3-ol instead of 5-(trifluoromethyl)pyridin-2-amine.
Step 2
[0804] To ice cold solution of ethyl 6-hydroxyimidazo[1,2-a]pyridine-2-carboxylate (1.38 g, 6.69 mmol) in N,N-dimethylformamide (34 mL), sodium hydride (60% in oil) (535 mg, 13.4 mmol) was added. After stirring for 5 minutes, 2,2,2-trifluoroethyl trifluoromethanesulphonate (1.93 mL, 13.4 mmol) was added, and the mixture was stirred for 1 hour at 80° C. Water and ethyl acetate were added to the reaction solution, and then the mixture was partitioned. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 6-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate (amount 1.55 g, yield 80%).
Step 3
[0805] Ethyl 6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate was obtained by a method similar to Step 2 in Example 1, using ethyl 6-(2,2,2-trifluoroethoxy)imidazo[1,2-a]pyridine-2-carboxylate instead of ethyl 6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylate.
Step 4
[0806] 6-(2,2,2-Trifluoroethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid was obtained by a method similar to Step 3 in Example 1, using ethyl 6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate instead of ethyl 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate.
Step 5
[0807] N-((R)-Chroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide was obtained by a method similar to Step 4 in Example 1, using 6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid instead of 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid, and, using (R)-chroman-3-amine hydrochloride instead of 6-fluorochroman-3-amine hydrochloride.
[0808] The compound of Example 38 was synthesized from the compound synthesized in Step 4 in Example 37 and the compound of Reference Example 1 by a method similar to Step 4 in Example 1.
[0809] The compounds of Example 39 were obtained by separating the compound of Example 38.
[0810] The compound of Example 40 was synthesized from the compound synthesized in Step 4 in Example 37 and the compound of Reference Example 3 by a method similar to Step 4 in Example 1.
[0811] The compound of Example 41 was synthesized under the scheme depicted in the figure below.
##STR00138##
[0812] The compound of Reference Example 16 (shown in the figure below.) was synthesized by a method similar to Step 1 in Example 1.
##STR00139##
[0813] The compound of Reference Example 17 (shown in the figure below.) was synthesized from the compound of Reference Example 16 by a method similar to Step 1 to Step 2 in Example 41.
##STR00140##
[0814] The compound of Example 42 was synthesized under the scheme depicted in the figure below.
##STR00141##
[0815] The compound of Example 43 was synthesized under the scheme depicted in the figure below.
##STR00142##
[0816] The compound of Example 44 was synthesized by a method similar to Example 43.
[0817] The compound of Example 45 was synthesized from the compound of Example 44 under the scheme depicted in the figure below.
##STR00143##
[0818] The compound of Example 46 was synthesized by a method similar to Example 43.
[0819] The compound of Example 47 was synthesized from the compound of Example 46 by a method similar to Example 45.
[0820] The compound of Example 48 was synthesized by a method similar to Example 43.
[0821] The compound of Example 49 was synthesized under the scheme depicted in the figure below.
##STR00144##
[0822] The compound of Example 50 was synthesized from the compound of Example 49 by a method similar to Example 45.
[0823] The compound of Example 51 was synthesized by a method similar to Example 49.
[0824] The compound of Example 52 was synthesized from the compound of Example 51 by a method similar to Example 45.
[0825] The compound of Example 53 was synthesized by a method similar to Example 49.
[0826] The compound of Example 54 was synthesized from the compound of Example 53 by a method similar to Example 45.
[0827] The compound of Example 55 was synthesized by a method similar to Example 49.
[0828] The compound of Example 56 was synthesized under the scheme depicted in the figure below.
##STR00145##
[0829] The compound of Example 57 was synthesized from the compound of Example 56 by a method similar to Example 45.
[0830] The compound of Reference Example 18 (shown in the figure below.) was synthesized by a method similar to Example 56.
##STR00146##
[0831] The compound of Example 58 was synthesized from the compound of Reference Example 18 by a method similar to Example 45.
[0832] The compound of Example 59 was synthesized under the scheme depicted in the figure below.
##STR00147##
[0833] The compound of Reference Example 19 was synthesized from the compound synthesized in Step 1 in Example 56 under the scheme depicted in the figure below.
##STR00148##
[0834] The compound of Example 60 was synthesized from the compound of Reference Example 19 by a method similar to Step 4 in Example 59.
[0835] The compound of Reference Example 20 (shown in the figure below.) was synthesized by a method similar to Reference Example 15.
##STR00149##
[0836] The compound of Example 61 was synthesized from the compound of Reference Example 19 and the compound of Reference Example 20 by a method similar to Step 4 in Example 59.
[0837] The compound of Reference Example 21 (shown in the figure below.) was synthesized from the compound synthesized in Step 1 in Reference Example 19 by methods similar to those described in Example 45 and Step 2 in Reference Example 19.
##STR00150##
[0838] The compound of Reference Example 22 was synthesized under the scheme depicted in the figure below.
##STR00151##
[0839] The compound of Example 62 was synthesized from the compound Reference Example 21 and the compound Reference Example 22 by a method similar to Step 3 in Example 56.
[0840] The compound of Reference Example 23 (2-(azetidin-3-yloxy)-6-(trifluoromethyl)pyridine dihydrochloride) was synthesized under the scheme depicted in the figure below.
##STR00152##
[0841] The compound of Example 63 was synthesized from the compound of Reference Example 21 and the compound of Reference Example 23 by a method similar to Step 3 in Example 56.
[0842] The compound of Example 64 was synthesized under the scheme depicted in the figure below.
##STR00153##
[0843] The compound of Example 65 was synthesized by methods similar to those described in Example 64 and Reference Example 1.
[0844] The compound of Example 66 was synthesized under the scheme depicted in the figure below.
##STR00154##
[0845] The compound of Example 67 was synthesized from the compound synthesized in Step 4 in Example 66 and the compound of Reference Example 43 by a method similar to Step 4 in Reference Example 18.
[0846] The compound of Example 68 was synthesized by a method similar to Example 32.
[0847] The compound of Example 69 was synthesized under the scheme depicted in the figure below.
##STR00155##
Reference Example 24
Production of (R)-3-aminochroman-6-carbonitrile
[0848] ##STR00156##
Step 1
[0849] To a solution of (R)-2,2,2-trifluoro-N-(6-formylchroman-3-yl)acetamide (1.43 g, 5.23 mmol) synthesized by a method described in Step 2 in Reference Example 3 in acetonitrile (52.3 mL) were added sodium azide (524 mg, 8.06 mmol) and trifluoromethanesulfonic acid (1.61 mL, 18.3 mmol), and the mixture was stirred for 2 hours at room temperature. Saturated aqueous solution of sodium hydrogen carbonate, water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-N-(6-cyanochroman-3-yl)-2,2,2-trifluoroacetamide (amount 1.40 g, yield 99%).
Step 2
[0850] To a solution of (R)-N-(6-cyanochroman-3-yl)-2,2,2-trifluoroacetamide (1.40 g, 5.18 mmol) in chloroform (13 mL), 4 mol/L aqueous solution of sodium hydroxide (13.0 mL, 51.8 mmol) was added, and the mixture was stirred for 13 hours at room temperature. Water and chloroform were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure to give (R)-3-aminochroman-6-carbonitrile (amount 505 mg, yield 56%).
Example 70
Production of N-((R)-6-cyanochroman-3-yl)-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0851] ##STR00157## ##STR00158##
Step 1
[0852] To a solution of 2-fluorobenzaldehyde (2.00 g, 16.1 mmol) in chloroform (32.2 mL) were added 1,1,3,3-tetramethylguanidine (3.03 mL, 24.2 mmol) and diethylphosphonoethyl acetate (3.52 mL, 17.7 mmol), and the mixture was stirred for 4 hours at 50° C. After evaporating off the solvent under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl 3-(2-fluorophenyl)acrylate (amount 2.98 g, yield 95%).
Step 2
[0853] To a solution of ethyl 3-(2-fluorophenyl)acrylate (2.98 g, 15.3 mmol) in ethanol (76.7 mL), 20% palladium hydroxide on carbon (539 mg) was added, and the mixture was stirred under pressurized conditions (about 3 atm) in hydrogen atmosphere for 3 hours at 50° C. After the reaction solution was filtered through celite, the solvent was evaporated off under reduced pressure to give ethyl 3-(2-fluorophenyl)propanoate (amount 2.79 g, yield 93%).
Step 3
[0854] To a solution of ethyl 3-(2-fluorophenyl)propanoate (2.79 g, 14.2 mmol) in tetrahydrofuran (71.1 mL), lithium borohydride (774 mg, 35.5 mmol) was added, and the mixture was stirred for 5 hours at room temperature. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give 3-(2-fluorophenyl)propan-1-ol (amount 2.17 g, yield 99%).
Step 4
[0855] To a solution of cyanuric chloride (2.86 g, 15.5 mL) in N,N-dimethylformamide (3.3 mL) was added a solution of 3-(2-fluorophenyl)propan-1-ol (2.17 g, 14.1 mmol) in dichloromethane (70.4 mL), and the mixture was stirred for 13 hours at room temperature. Water and chloroform were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give 1-(3-chloropropyl)-2-fluorobenzene (amount 2.00 g, yield 82%).
Step 5
[0856] To a solution of 1-(3-chloropropyl)-2-fluorobenzene (2.00 g, 11.6 mmol) in carbon tetrachloride (39 mL) were added N-bromosuccineimide (2.27 g, 12.7 mmol) and 2,2′-azobis(isobutyropionitrile) (168 1.16 mmol), and the mixture was stirred for 2 hours at 90° C. Water and chloroform were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give 1-(1-bromo-3-chloropropyl)-2-fluorobenzene (amount 2.36 g, yield 81%).
Step 6
[0857] To a solution of 1-(1-bromo-3-chloropropyl)-2-fluorobenzene (2.36 g, 9.38 mmol) in acetonitrile (31.3 mL) were added ethyl 5-hydroxy-1H-pyrazole-3-carboxylate (1.47 g, 9.38 mmol) and potassium carbonate (3.89 g, 28.1 mmol), and the mixture was stirred for 15 hours at 100° C. After concentrating the reaction solution under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl 5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (amount 2.30 g, yield 84%).
Step 7
[0858] To a solution of ethyl 5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (2.30 g, 7.92 mmol) in ethanol (15.8 mL) was added 4 mol/L aqueous solution of sodium hydroxide (7.92 mL, 31.7 mmol), and the mixture was stirred for 24 hours at room temperature. To the reaction solution, 2 mol/L hydrochloric acid was added, and then the solvent was evaporated off under reduced pressure. Water and ethyl acetate were added to the residue, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate, and the solvent was evaporated off under reduced pressure to give 5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (amount 1.80 g, yield 87%) as a mixture with 4 equivalents of sodium chloride.
Step 8
[0859] To a suspension of 5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (36.1 mg, 0.138 mmol) in dichloromethane (1.2 mL) were added HATU (48.0 mg, 0.126 mmol), N,N-diisopropylethylamine (99 0.57 mmol) and (R)-3-aminochroman-6-carbonitrile (20.0 mg, 0.115 mmol), and the mixture was stirred for 2 hours at room temperature. The reaction solution was purified by silica gel column chromatography to give N-((R)-6-cyanochroman-3-yl)-5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (amount 47.9 mg, yield 100%).
[0860] The compound of Example 71 was synthesized by methods similar to those described in Example 70 and Reference Example 2.
[0861] The compound of Example 72 was synthesized by a method similar to Example 70.
[0862] The compound of Example 73 was synthesized by a method similar to Example 70.
[0863] The compounds of Example 74 were obtained by separating the compound of Example 73.
[0864] The compound of Example 75 was synthesized by a method similar to Example 70.
[0865] The compound of Example 76 was synthesized by methods similar to those described in Example 70 and Reference Example 5.
[0866] The compound of Example 77 was synthesized by a method similar to those described in Step 6 to Step 8 in Example 70 and Reference Example 4.
[0867] The compound of Reference Example 25 (shown in the figure below.) was synthesized by a method similar to Reference Example 4.
##STR00159##
[0868] The compound of Example 78 was synthesized by methods similar to those described in Example 77 and Reference Example 25.
[0869] The compound of Example 79 was synthesized by a method similar to Example 77.
[0870] The compound of Reference Example 27 was synthesized under the scheme depicted in the figure below.
##STR00160##
[0871] The compound of Example 80 was synthesized by methods similar to those described in Example 70 and Reference Example 27.
Reference Example 28
Production of (R)-6-(pyridin-2-yl)chroman-3-amine dihydrochloride
[0872] ##STR00161##
Step 1
[0873] To a solution of (R)-N-(6-bromochroman-3-yl)-2,2,2,-trifluoroacetamide (500 mg, 1.54 mmol) synthesized by a method described in Step 1 in Reference Example 2 in 1,4-dioxane (10 mL) were added bis(pinacolato)diboron (800 mg, 3.15 mmol), potassium acetate (300 mg, 7.87 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (100 mg, 0.14 mmol). The mixture was stirred for 15 hours at 90° C. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-2,2,2-trifluoro-N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman-3-yl)acetamide (amount 570 mg, yield 100%).
Step 2
[0874] A mixture suspension of (R)-2,2,2-trifluoro-N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman-3-yl)acetamide (200 mg, 0.539 mmol), 2-bromopyridine (130 mg, 0.823 mmol), cesium carbonate (350 mg, 1.07 mmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium (II) (38.0 mg, 0.0537 mmol) in 1,4-dioxane (2.5 mL) and water (0.5 mL) was stirred for 5 hours at 100° C. To the reaction solution, an aqueous solution of saturated ammonium chloride and ethyl acetate were added, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-2,2,2-trifluoro-N-(6-(pyridin-2-yl)chroman-3-yl)acetamide (amount 82.0 mg, yield 47%).
Step 3
[0875] (R)-6-(Pyridin-2-yl)chroman-3-amine dihydrochloride was obtained by a method similar to Step 3 in Reference Example 1, using (R)-2,2,2-trifluoro-N-(6-(pyridin-2-yl)chroman-3-yl)acetamide instead of (R)-N-(6-chlorochroman-3-yl)-2,2,2,-trifluoroacetamide.
[0876] The compound of Example 81 was synthesized by methods similar to those described in Example 70 and Reference Example 28.
[0877] The compound of e Example 82 was synthesized under the scheme depicted in the figure below.
##STR00162##
[0878] The compound of Example 83 was synthesized under the scheme depicted in the figure below.
##STR00163##
[0879] The compound of Example 84 was synthesized under the scheme depicted in the figure below.
##STR00164##
[0880] The compound of Example 85 was synthesized under the scheme depicted in the figure below.
##STR00165##
[0881] The compound of Example 86 was synthesized by a method similar to Example 85.
[0882] The compound of Example 87 was synthesized by a method similar to Example 85.
[0883] The compound of Example 88 was synthesized by methods similar to those described in Example 85 and Reference Example 2.
[0884] The compound of Example 89 was synthesized by methods similar to those described in Example 85 and Reference Example 2.
[0885] The compound of Example 90 was synthesized by a method similar to Example 85.
[0886] The compound of Example 91 was synthesized by methods similar to those described in Example 85 and Reference Example 24.
[0887] The compounds of Example 92 were obtained by separating the compound of Example 91.
[0888] The compound of Reference Example 29 (shown in the figure below.) was synthesized by a method similar to Reference Example 27.
##STR00166##
[0889] The compound of Example 93 was synthesized by methods similar to those described in Example 85 and Reference Example 29.
[0890] The compound of Example 94 was synthesized by methods similar to those described in Example 85 and Reference Example 24.
[0891] The compounds of Example 95 were obtained by separating the compound of Example 94.
[0892] The compound of Reference Example 30 (4-cyclopropylbutan-1,3-diol) was synthesized under the scheme depicted in the figure below.
##STR00167##
[0893] The compound of Example 96 was synthesized by methods similar to those described in Reference Example 30, Example 85 and Reference Example 24.
[0894] The compounds of Example 97 were obtained by separating the compound of Example 96.
Reference Example 31
Production of ethyl 5-((benzyloxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
[0895] ##STR00168##
[0896] Ethyl 5-((benzyloxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate was obtained by a method similar to Step 1 to Step 4 in Example 85, using 4-(benzyloxy)butan-1,3-diol instead of butan-1,3-diol in Step 1.
[0897] The compound of Example 98 was synthesized from the compound of Reference Example 31 by methods similar to Step 5 and Step 6 in Example 85.
[0898] The compound of Example 99 was synthesized by methods similar to Reference Example 31, Step 5 and Step 6 in Example 85 and Example 24.
Example 100
Production of N-((R)-6-cyanochroman-3-yl)-5-(propoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0899] ##STR00169##
Step 1
[0900] To a solution of ethyl 5-((benzyloxy)methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (12.4 g, 18.4 mmol) synthesized by a method described in Reference Example 31 in ethanol (61 mL), 20% palladium hydroxide on carbon (2.59 mg) was added. The mixture was stirred for 23 hours at 40° C. under pressurized conditions (about 3 atm) in hydrogen atmosphere. After the reaction solution was filtered through celite, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (amount 2.47 g, yield 59%).
Step 2
[0901] To a solution of ethyl 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (1.97 g, 8.71 mmol) in ethanol (44 mL), 4 mol/L aqueous solution of sodium hydroxide (8.7 mL, 35 mmol) was added, and the mixture was stirred for 15 hours at room temperature. To the reaction solution, 2 mol/L hydrochloric acid was added, and then the solvent was evaporated off under reduced pressure to give 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (amount 3.68 g, yield 98%) as a mixture with 4 equivalents of sodium chloride.
Step 3
[0902] To a suspension of 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (450 mg, 1.04 mmol), (R)-3-aminochroman-6-carbonitrile (200 mg, 1.15 mmol) synthesized by a method described in Reference Example 24, 1-hydroxybenzotriazole (169 mg, 1.25 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (240 mg, 1.25 mmol) in dichloromethane (10 mL), 4-methylmorpholine (573 5.21 mmol) was added, and the mixture was stirred for 24 hours at room temperature. To the reaction solution, 1 mol/L hydrochloric acid and chloroform was added, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (amount 300 mg, yield 81%).
Step 4
[0903] To a solution of N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (330 mg, 0.931 mmol) in N,N-dimethylformamide (8.8 mL) was added sodium hydride (60% in oil) and 1-iodopropane (136 1.39 mmol). The mixture was stirred for 13 hours at 90° C. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give N-((R)-6-cyanochroman-3-yl)-5-(propoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (amount 73.3 mg, yield 20%).
Example 101
[0904] Isomeric separation of N-((R)-6-cyanochroman-3-yl)-5-(propoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
##STR00170##
[0905] N-((R)-6-Cyanochroman-3-yl)-5-(propoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (150 mg, 0.378 mmol) synthesized by a method described in Example 100 was dissolved in ethanol (15 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK IB, developing solvent: ethanol, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 59.9 mg, yield 40%) and isomer B (amount 61.4 mg, yield 41%).
Example 102
Production of N-((R)-6-cyanochroman-3-yl)-5-((cyclopropylmethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0906] ##STR00171##
[0907] To a solution of N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (397 mg, 1.12 mmol) synthesized by a method described in Step 3 in Example 100 in N,N-dimethylformamide (11.2 mL), sodium hydride (60% in oil) (179 mg, 4.48 mmol) was added. The mixture was stirred for 10 minutes at room temperature. In addition, (bromomethyl)cyclopropane (215 2.24 mmol) was added, and the mixture was stirred for 16 hours at 90° C. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give N-((R)-6-cyanochroman-3-yl)-5-((cyclopropylmethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (amount 136 mg, yield 30%).
Example 103
Isomeric separation of N-((R)-6-cyanochroman-3-yl)-5-((cyclopropylmethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0908] ##STR00172##
[0909] N-((R)-6-Cyanochroman-3-yl)-5-((cyclopropylmethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (134 mg, 0.328 mmol) synthesized by a method described in Example 102 was dissolved in ethanol (13 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK IB, developing solvent: ethanol, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 49.3 mg, yield 37%) and isomer B (amount 48.9 mg, yield 37%).
[0910] The compound of Example 104 was synthesized by a method similar to Example 100.
[0911] The compound of Example 105 was synthesized by methods similar to those described in Example 100 and Reference Example 1.
[0912] The compound of Example 106 was synthesized by methods similar to those described in Example 100 and Reference Example 1.
[0913] The compound of Reference Example 32 (shown in the figure below.) was synthesized by a method similar to Reference Example 27.
##STR00173##
[0914] The compound of Example 107 was synthesized by methods similar to those described in Example 100 and Reference Example 32.
[0915] The compound of Reference Example 33 (shown in the figure below.) was synthesized by a method similar to Example 100.
##STR00174##
[0916] The compound of Example 108 was synthesized from the compound of Reference Example 33 and the compound of Reference Example 48 by a method similar to Step 3 in Example 100.
[0917] The compounds of Example 109 were obtained by separating the compound of Example 108.
[0918] The compound of Example 110 was synthesized from the compound of Reference Example 33 and the compound of Reference Example 28 by a method similar to Step 3 in Example 100.
[0919] The compounds of Example 111 were obtained by separating the compound of Example 110.
[0920] The compound of Reference Example 34 (4-((1-methylcyclopropyl)methoxy)butan-1,3-diol) was synthesized under the scheme depicted in the figure below.
##STR00175##
[0921] The compound of Example 112 was synthesized by methods similar to those described in Reference Example 34, Example 85 and Reference Example 24.
[0922] The compounds of Example 113 were obtained by separating the compound of Example 112.
Example 114
Production of N-((R)-6-cyanochroman-3-yl)-5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0923] ##STR00176##
[0924] To a solution of N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (20.0 mg, 0.0564 mmol) synthesized by a method described in Step 3 in Example 100 in toluene (1.1 mL) were added tributylphosphine (28.2 μL, 0.113 mmol), 2,2,2-trifluoroethanol (40.6 μL, 0.564 mmol) and 1,1′-(azodicarbonyl)dipiperizine (28.5 mg, 0.113 mmol). The mixture was stirred for 15 hours at 80° C. The reaction solution was purified by silica gel column chromatography to give N-((R)-6-cyanochroman-3-yl)-5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide.
Example 115
Isomeric separation of N-((R)-6-cyanochroman-3-yl)-5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0925] ##STR00177##
[0926] N-((R)-6-Cyanochroman-3-yl)-5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (178 mg, 0.408 mmol) synthesized by a method described in Example 114 was dissolved in ethanol (18 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK IB, developing solvent: ethanol, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 74.7 mg, yield 42%) and isomer B (amount 70.5 mg, yield 40%).
[0927] The compound of Example 116 was synthesized by a method similar to Example 114.
[0928] The compound of Example 117 was synthesized under the scheme depicted in the figure below.
##STR00178##
[0929] The compound of Example 118 was synthesized from the compound synthesized in Step 3 in Example 100 by a method similar to Step 2 in Example 117.
[0930] The compound of Example 119 was synthesized under the scheme depicted in the figure below.
##STR00179##
[0931] The compound of Example 120 was synthesized from the compound synthesized in Step 1 in Example 117 by a method similar to Example 119.
[0932] The compound of Example 121 was synthesized under the scheme depicted in the figure below.
##STR00180##
[0933] The compound of Example 122 was synthesized under the scheme depicted in the figure below.
##STR00181##
[0934] The compound of Reference Example 35 was synthesized from the compound of synthesized in Step 1 in Example 122 under the scheme depicted in the figure below.
##STR00182##
[0935] The compound of Example 123 was synthesized from the compound of Reference Example 35 and the compound of Reference Example 28 by methods similar to Step 3 and Step 4 in Example 122.
[0936] The compounds of Example 124 were obtained by separating the compound of Example 123.
[0937] The compound of Example 125 was synthesized from the compound of Reference Example 35 and the compound of Reference Example 32 by methods similar to Step 3 and Step 4 in Example 122.
Reference Example 36
Ethyl 5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
[0938] ##STR00183##
[0939] Ethyl 5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate was obtained by a method similar to Example 114, using ethyl 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate synthesized by a method described in Step 1 in Example 100 instead of N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide.
[0940] The compound of Example 126 was synthesized from the compound of Reference Example 36 and Reference Example 48 by methods similar to Step 2 and Step 3 in Example 100.
[0941] The compounds of Example 127 were obtained by separating the compound of Example 126.
Example 128
Production of 5-((2,2,2-trifluoroethoxy)methyl)-N-((R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0942] ##STR00184##
[0943] 5-((2,2,2-Trifluoroethoxy)methyl)-N-((R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide was obtained by a method similar to Step 3 and Step 4 in Example 1, using ethyl 5-((2,2,2-trifluoroethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate synthesized by a method described in Reference Example 36 instead of ethyl 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate in Step 3, and using (R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-amine hydrochloride synthesized by a method described in Reference Example 44 instead of 6-fluorochroman-3-amine hydrochloride in Step 4.
Example 129
Isomeric separation of 5-((2,2,2-trifluoroethoxy)methyl)-N-((R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0944] ##STR00185##
[0945] 5-((2,2,2-Trifluoroethoxy)methyl)-N-((R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide synthesized by a method described in Example 128 was dissolved in ethanol, and the solution was subjected to HPLC fractionation (column: CHIRALPAK IC, developing solvent: ethanol/n-hexane=50/50, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 3.7 mg) and isomer B (amount 3.6 mg).
[0946] The compound of Example 130 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 28 by methods similar to Step 2 and Step 3 in Example 100.
[0947] The compounds of Example 131 were obtained by separating the compound of Example 130.
[0948] The compound of Example 132 was synthesized from the compound of Reference Example 36 and Reference Example 32 by methods similar to Step 3 and Step 4 in Example 122.
[0949] The compound of Reference Example 37 (5-((trifluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00186##
Example 133
Production of N-((R)-6-cyanochroman-3-yl)-5-((trifluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0950] ##STR00187##
[0951] To a suspension of 5-((trifluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (267 mg, 0.534 mmol) synthesized by a method described in Reference Example 37, (R)-3-aminochroman-6-carbonitrile (140 mg, 0.804 mmol) synthesized by a method described in Reference Example 24, 1-hydroxybenzotriazole (123 mg, 0.804 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (154 mg, 0.804 mmol) in N,N-dimethylformamide (5 mL), 4-methylmorpholine (353 μL, 3.21 mmol) was added. The mixture was stirred for 15 hours at 40° C. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give N-((R)-6-cyanochroman-3-yl)-5-((trifluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (amount 182 mg, yield 81%).
Example 134
Isomeric separation of N-((R)-6-cyanochroman-3-yl)-5-((trifluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0952] ##STR00188##
[0953] N-((R)-6-Cyanochroman-3-yl)-5-((trifluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (20 mg) synthesized by a method described in Example 133 was dissolved in ethanol (2 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK IB, developing solvent: ethanol, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 9.4 mg, yield 47%) and isomer B (amount 8.2 mg, yield 41%).
[0954] The compound of Example 135 was synthesized from the compound of Reference Example 37 and the compound of Reference Example 48 by a method similar to Step 3 in Example 100.
[0955] The compounds of Example 136 were obtained by separating the compound of Example 135.
[0956] The compound of Reference Example 38 (5-((difluoromethoxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid) was synthesized from the compound synthesized in Step 1 in Example 100 under the scheme depicted in the figure below.
##STR00189##
[0957] The compound of Example 137 was synthesized from the compound of Reference Example 38 and the compound of Reference Example 48 by a method similar to Step 3 in Example 100.
[0958] The compounds of Example 138 were obtained by separating the compound of Example 137.
[0959] The compound of Example 139 was synthesized from the compound of Reference Example 38 and the compound of Reference Example 44 by a method similar to Step 3 in Example 100.
[0960] The compounds of Example 140 were obtained by separating the compound of Example 139.
[0961] The compound of Example 141 was synthesized from the compound of Reference Example 38 and the compound of Reference Example 45 by a method similar to Step 3 in Example 100.
[0962] The compounds of Example 142 were obtained by separating the compound of Example 141.
Reference Example 39
Ethyl -(2-(benzyloxy)ethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
[0963] ##STR00190##
[0964] Ethyl 5-(2-(benzyloxy)ethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate was obtained by a method similar to Step 1 to Step 4 in Example 85, using 5-(benzyloxy)pentane-1,3-diol instead of butan-1,3-diol in Step 1.
Reference Example 40
5-(2-(Trifluoromethoxy)ethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid
[0965] ##STR00191##
Step 1
[0966] Ethyl 5-(2-hydroxyethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate was obtained by a method similar to Step 1 in Example 100, using ethyl 5-(2-(benzyloxy)ethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate synthesized by a method described in Reference Example 39 instead of ethyl 5-((benzyloxy)methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate.
Step 2, Step 3
[0967] 5-(2-(Trifluoromethoxy)ethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid was obtained as a mixture with 2 equivalents of sodium chloride by a method similar to Step 1 and Step 2 in Reference Example 37, using ethyl5-(2-hydroxyethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate instead of ethyl5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate in Step 1.
[0968] The compound of Example 143 was synthesized, from the compound of Reference Example 40 and the compound of Reference Example 24 by a method similar to Step 4 in Example 1.
[0969] The compounds of Example 144 were obtained by separating the compound of Example 143.
[0970] The compound of Reference Example 41 (shown in the figure below.) was synthesized from the compound synthesized in Step 1 in Reference Example 40 by a method similar to Step 1 to Step 2 in Reference Example 38.
##STR00192##
[0971] The compound of Example 145 was synthesized from the compound of Reference Example 41 and the compound of Reference Example 24 by a method similar to Step 4 in Example 1.
[0972] The compounds of Example 146 were obtained by separating the compound of Example 145.
[0973] The compound of Example 147 was synthesized from the compound of Reference Example 41 and the compound of Reference Example 48 by a method similar to Step 4 in Example 1.
[0974] The compounds of Example 148 were obtained by separating the compound of Example 147.
[0975] The compound of Example 149 was synthesized from the compound of Reference Example 41 and the compound of Reference Example 44 by a method similar to Step 4 in Example 1.
[0976] The compounds of Example 150 were obtained by separating the compound of Example 149.
[0977] The compound of Reference Example 151 was synthesized from the compound synthesized in Step 1 in Example 117 under the scheme depicted in the figure below.
##STR00193##
[0978] The compounds of Example 152 were obtained by separating the compound of Example 151.
[0979] The compound of Reference Example 42 (shown in the figure below.) was synthesized by a method similar to Step 2 to Step 3 in Example 122.
##STR00194##
[0980] The compound of Example 153 was synthesized from the compound of Reference Example 42 under the scheme depicted in the figure below.
##STR00195##
[0981] The compound of Example 154 was synthesized from the compound of Reference Example 42 under the scheme depicted in the figure below.
##STR00196##
[0982] The compound of Example 155 was synthesized under the scheme depicted in the figure below.
##STR00197##
[0983] The compounds of Example 156 were obtained by separating the compound of Example 155.
[0984] The compound of Reference Example 157 was synthesized from the compound synthesized in Step 1 in Example 151 under the scheme depicted in the figure below.
##STR00198##
[0985] The compounds of Example 158 were obtained by separating the compound of Example 157.
Example 159
Production of N-((R)-6-bromochroman-3-yl)-5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0986] ##STR00199##
Step 1
[0987] To a solution of ethyl 4,4-difluoro3-oxo-butanoate (10.0 g, 60.2 mmol) in tetrahydrofuran (300 mL), lithium borohydride (4.34 g, 199 mmol) was added, and the mixture was stirred for 15 hours at room temperature. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give 4,4-difluorobutan-1,3-diol (amount 3.37 g, yield 44%).
Step 2
[0988] To a solution of 4,4-difluorobutan-1,3-diol (128 mg, 1.02 mmol) in dichloromethane (3.4 mL) were added imidazole (346 mg, 5.08 mmol) and tert-butylchlorodiphenylsilane (263 μL, 1.01 mmol), and the mixture was stirred for 6 hours at room temperature. After the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give 4-(tert-butyl (diphenyl)silyl)oxy-1,1-difluorobutan-2-ol (amount 299 mg, yield 81%).
Step 3
[0989] To a solution of 4-(tert-butyl (diphenyl)silyl)oxy-1,1-difluorobutan-2-ol (100 mg, 0.274 mmol) in tetrahydrofuran (1.0 mL) were added ethyl 5-hydroxy-1H-pyrazole-3-carboxylate (42.8 mg, 0.274 mmol), triphenylphosphine (93.6 mg, 0.357 mmol) and 1.9 mol/L azodicarboxylic acid diisopropyl-toluene solution (190 μL, 0.36 mmol). The mixture was stirred for 13 hours at room temperature. The reaction solution was purified by silica gel column chromatography to give ethyl 5-(3-(tert-butyl(diphenylsilyl)oxy)-1-(difluoromethyl)propoxy)-1H-pyrazole-3-carboxylate (amount 33.3 mg, yield 24%).
Step 4
[0990] To a solution of ethyl 5-(3-(tert-butyl (diphenylsilyl)oxy)-1-(difluoromethyl)propoxy)-1H-pyrazole-3-carboxylate (9.16 g, 18.2 mmol) in tetrahydrofuran (180 mL), 1 mol/L tetrahydroammoniumfluoride-tetrahydrofuran solution (37 mL, 37 mmol) was added, and the mixture was stirred for 1 hour at room temperature. After concentrating the reaction solution under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl 5-(1-(difluoromethyl)-3-hydroxypropoxy)-1H-pyrazole-3-carboxylate (amount 4.75 g, yield 99%).
Step 5
[0991] To a solution of ethyl 5-(1-(difluoromethyl)-3-hydroxypropoxy)-1H-pyrazole-3-carboxylate (93.0 mg, 5.91 mmol) in dichloromethane (3.5 mL) were added N,N-diisopropylethylamine (363 mL, 2.11 mmol), carbon tetrabromide (233 mg, 0.703 mmol) and triphenylphosphine (120 mg, 0.703 mmol). The mixture was stirred for 22 hours at room temperature. 1 mol/L Hydrochloric acid and chloroform were added, and the mixture was partitioned. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl 5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate (219 mg) as a mixture with triphenylphosphine oxide.
Step 6
[0992] To a solution of mixture of ethyl 5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate and triphenylphosphine oxide (213 mg) in ethanol (1.7 mL), 4 mol/L aqueous solution of sodium hydroxide (346 1.38 mmol) was added, and the mixture was stirred for 1 hours at room temperature. 2 mol/L Hydrochloric acid and toluene were added. After the solvent being evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give 5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (20.1 mg).
Step 7
[0993] N-((R)-6-bromochroman-3-yl)-5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide was obtained by a method similar to Step 3 in Example 100, using 5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid instead of 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid, and using (R)-6-bromochroman-3-amine hydrochloride synthesized by a method described in Reference Example 2 instead of (R)-3-aminochroman-6-carbonitrile.
Reference Example 43
Production of (R)-6-(trifluoromethyl)chroman-3-amine hydrochloride
[0994] ##STR00200##
Step 1
[0995] To a solution of (R)-N-(chroman-3-yl)-2,2,2-trifluoroacetamide (2.50 g, 16.3 mmol) synthesized by a method described in Step 1 in Reference Example 1 in acetonitrile (26 mL), para-toluene sulfonic acid monohydrate (2.13 g, 11.2 mmol) was added. The mixture was stirred for 10 minutes at room temperature. In addition, a solution of N-iodosuccineimide (2.52 g, 11.2 mmol) in acetonitrile (40 mL) was added, and the mixture was stirred for 16 hours at room temperature. Thereafter, saturated aqueous solution of sodium hydrogen carbonate, an aqueous solution of saturated sodium thiosulfate and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. n-Hexane and ethyl acetate were added to the residue,and the residue was dissolved by heating, and then the solution was allowed to cool to room temperature. The precipitated solid was collected by filtration to give (R)-2,2,2-trifluoro-N-(6-iodochroman-3-yl)acetamide (amount 1.19 g, yield 32%).
Step 2
[0996] To a solution of (R)-2,2,2-trifluoro-N-(6-iodochroman-3-yl)acetamide (1.19 g, 3.21 mmol) in N,N-dimethylformamide (100 mL) were added copper iodide (I) (0.73 g, 3.8 mmol), methyl 2,2-difluoro2-(fluorosulfonyl)acetate (2.04 mL, 16 mmol). The mixture was stirred for 16 hours at 120° C. The reaction solution was allowed to cooled to room temperature thereafter filtered through celite. Thereafter, ethyl acetate, n-hexane and saturated aqueous solution of sodium hydrogen carbonate were added, and the mixture was partitioned. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. After the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give (R)-2,2,2-trifluoro-N-(6-(trifluoromethyl)chroman-3-yl)acetamide (amount 949 mg, yield 95%).
Step 3
[0997] To a solution of (R)-2,2,2-trifluoro-N-(6-(trifluoromethyl)chroman-3-yl)acetamide (133 mg, 0.425 mmol) in methanol (1.1 mL), 2 mol/L aqueous solution of sodium hydroxide (1.1 mL, 2.2 mmol) was added, and the mixture was stirred for 3 hours at room temperature. Water and chloroform was added to the reaction solution, and the mixture was partitioned. Thereafter, the organic layer was dried over anhydrous sodium sulfate. The solvent was evaporated off under reduced pressure, the residue was dissolved in ethyl acetate, 4 mol/L hydrogen chloride-ethyl acetate solution was added, and the mixture was stirred for 1 hour. Under reduced pressure, the solvent was evaporated off to give ((R)-6-(trifluoromethyl)chroman-3-amine hydrochloride (amount 93.8 mg, yield 87%).
Example 160
Production of 5-(difluoromethyl)-N-((R)-6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[0998] ##STR00201##
[0999] To a solution of 5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (51.5 mg, 0.236 mmol) synthesized by a method described in Step 6 in Example 159, (R)-6-(trifluoromethyl)chroman-3-amine hydrochloride (72.0 mg, 0.284 mmol) synthesized by a method described in Reference Example 43, 1-hydroxybenzotriazole (43.4 mg, 0.283 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (54.5 mg, 0.284 mmol) in N,N-dimethylformamide (787 4-methylmorpholine (158 1.44 mmol) was added. The mixture was stirred for 4 hours at room temperature. Water and ethyl acetate was added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give 5-(difluoromethyl)-N-((R)-6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (amount 91.1 mg, yield 93%).
Example 161
Isomeric separation of 5-(difluoromethyl)-N-((R)-6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide
[1000] ##STR00202##
[1001] 5-(Difluoromethyl)-N-((R)-6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide (14.7 mg, 0.035 mmol) synthesized by a method described in Example 160 was dissolved in ethanol (7 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK IC, developing solvent: ethanol/n-hexane=50/50, flow rate: 20.0 mL/min) to give isomer A (amount 6.2 mg, yield 42%) and isomer B (amount 5.2 mg, yield 35%).
Reference Example 44
Production of (R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-amine hydrochloride
[1002] ##STR00203##
Step 1
[1003] To ice cold (R)-2,2,2-trifluoro-N-(6-formylchroman-3-yl)acetamide (3.89 g, 14.2 mmol) synthesized by a method described in Step 2 in Reference Example 3 in methanol (70 mL), sodium borohydride (1.08 g, 28.5 mmol) was added, and the mixture was stirred for 15 minutes under ice cooling. To the reaction solution, 1 mol/L hydrochloric acid and chloroform were added, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-2,2,2-trifluoro-N-(6-(hydroxymethyl)chroman-3-yl)acetamide (amount 2.34 g, yield 60%).
Step 2
[1004] To a solution of (R)-2,2,2-trifluoro-N-(6-(hydroxymethyl)chroman-3-yl)acetamide (500 mg, 1.82 mmol) in toluene (18 mL) were added tributylphosphine (908 μL, 3.64 mmol), 2,2,2-trifluoroethanol (1.3 mL, 18 mmol) and 1,1′-(azodicarbonyl)dipiperidine (919 mg, 3.64 mmol). The mixture was stirred for 1 hours at 80° C. The reaction solution was allowed to cool to room temperature, water and ethyl acetate were added, and the mixture was partitioned. The organic layer was washed with saturated brine, and then dried over anhydrous magnesium sulfate, and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-2,2,2-trifluoro-N-(6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)acetamide (amount 409 mg, yield 63%).
Step 3
[1005] (R)-6-((2,2,2-Trifluoroethoxy)methyl)chroman-3-amine hydrochloride was obtained by a method similar to Step 3 in Reference Example 1, using (R)-2,2,2-trifluoro-N-(6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)acetamide instead of (R)-N-(6-chlorochroman-3-yl)-2,2,2-trifluoroacetamide.
[1006] The compound of Example 162 was synthesized by methods similar to those described in Example 159 and Reference Example 44.
[1007] The compounds of Example 163 were obtained by separating the compound of Example 162.
[1008] The compound of Reference Example 45 ((R)-6-(2-(difluoromethoxy)ethyl)chroman-3-amine hydrochloride) was synthesized from the compound synthesized in Step 1 in Reference Example 3 under the scheme depicted in the figure below.
##STR00204##
[1009] The compound of Example 164 was synthesized by methods similar to those described in Example 159 and Reference Example 45.
[1010] The compounds of Example 165 were obtained by separating the compound of Example 164.
[1011] The compounds of Reference Example 46 (N-((R)-6-chlorochroman-3-yl)-5-(2-hydroxypropan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide, and 5-acetyl-N-((R)-6-chlorochroman-3-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide) were synthesized from the compound synthesized in Step 1 in Example 117 under the scheme depicted in the figure below.
##STR00205##
[1012] The compound of Example 166 was synthesized from the compound of Reference Example 46 (N-((R)-6-chlorochroman-3-yl)-5-(2-hydroxypropan-2-yl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide) by a method similar to Example 157.
[1013] The compound of Example 167 was synthesized from the compound of Reference Example 46 (5-acetyl -N-((R)-6-chlorochroman-3-yl)-6,7-dihydro-5H-pyrazolo[5, 1-b][1,3]oxazine-2-carboxamide) by a method similar to Example 157.
[1014] The compound of Example 168 was synthesized from the compound synthesized in Step 2 in Reference Example 46 under the scheme depicted in the figure below.
##STR00206##
[1015] The compound of Example 169 was synthesized under the scheme depicted in the figure below.
##STR00207##
[1016] The compounds of Example 170 were obtained by separating the compound of Example 169.
[1017] The compound of Example 171 was synthesized by methods similar to those described in Example 169 and Reference Example 2.
[1018] The compound of Reference Example 47 (shown in the figure below.) was synthesized by a method similar to Reference Example 4.
##STR00208##
[1019] The compound of Reference Example 48 ((R)-6-(2,2-difluoroethyl)chroman-3-amine hydrochloride) was synthesized from the compound synthesized in Step 1 in Reference Example 45 under the scheme depicted in the figure below.
##STR00209##
[1020] The compound of Example 172 was synthesized by methods similar to those described in Example 169 and Reference Example 48.
[1021] The compounds of Example 173 were obtained by separating the compound of Example 172.
[1022] The compound of Example 174 was synthesized from the compound of Example 171 by a method similar to Step 1 in Reference Example 27.
[1023] The compound of Example 175 was synthesized by a method similar to Example 174.
[1024] The compound of Example 176 was synthesized by a method similar to Example 174.
[1025] The compound of Example 177 was synthesized under the scheme depicted in the figure below.
##STR00210##
[1026] The compound of Example 178 was synthesized by methods similar to those described in Example 177 and Reference Example 24.
[1027] The compound of Example 179 was synthesized by methods similar to those described in Example 177 and Reference Example 32.
[1028] The compound of Example 180 was synthesized by methods similar to those described in Example 177 and Reference Example 24.
[1029] The compound of Example 181 was synthesized by a method similar to Step 6 to Step 8 in Example 70.
[1030] The compound of Example 182 was synthesized by methods similar to those described in Example 181 and Reference Example 24.
[1031] The compound of Example 183 was synthesized by methods similar to those described in Example 169 and Reference Example 44.
[1032] The compounds of Example 184 were obtained by separating the compound of Example 183.
[1033] The Reference Example 49 (3-(cyclopropylmethoxy)propane-1,2-diol) was synthesized under the scheme depicted in the figure below.
##STR00211##
[1034] The compound of Reference Example 50 (shown in the figure below.) was synthesized from the compound of Reference Example 49 by a method similar to Step 1 to Step 5 in Example 85.
##STR00212##
[1035] The compound of Example 185 was synthesized from the compound of Reference Example 50 and the compound of Reference Example 44 by a method similar to Step 3 in Example 100.
[1036] The compounds of Example 186 were obtained by separating the compound of Example 185.
[1037] The compound of Reference Example 51 (shown in the figure below.) was synthesized by a method similar to Step 1 to Step 4 in Example 85.
##STR00213##
Example 187
Production of 2-((2,2,2-trifluoroethoxy)methyl)-N-((R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide
[1038] ##STR00214##
Step 1
[1039] Ethyl 2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate was obtained by a method similar to Step 1 in Example 100, using ethyl 2-((benzyloxy)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate synthesized by a method described in Reference Example 51 instead of ethyl 5-((benzyloxy)methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate.
Step 2
[1040] Ethyl 2-((2,2,2-trifluoroethoxy)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate was obtained by a method similar to Example 114, using ethyl 2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate instead of N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide.
Step 3
[1041] 2-((2,2,2-Trifluoroethoxy)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid was obtained as a mixture with 4 equivalents of sodium chloride by a method similar to Step 2 in Example 100, using ethyl 2-((2,2,2-trifluoroethoxy)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate instead of ethyl 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate.
Step 4
[1042] 2-((2,2,2-Trifluoroethoxy)methyl)-N-((R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-yl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide was obtained by a method similar to Step 3 in Example 100, using 2-((2,2,2-trifluoroethoxy)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid instead of 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid, and using (R)-6-((2,2,2-trifluoroethoxy)methyl)chroman-3-amine hydrochloride synthesized by a method described in Reference Example 44 instead of (R)-3-aminochroman-6-carbonitrile.
[1043] The compounds of Example 188 were obtained by separating the compound of Example 187.
[1044] The compound of Example 189 was synthesized by methods similar to those described in Example 187 and Reference Example 45.
[1045] The compounds of Example 190 were obtained by separating the compound of Example 189.
[1046] The compound of Reference Example 52 ((R)-6-(2,2,2-trifluoroethyl)chroman-3-amine hydrochloride) was synthesized from the compound synthesized in Step 2 in Reference Example 3 under the scheme depicted in the figure below.
##STR00215##
[1047] The compound of Example 191 was synthesized by methods similar to those described in Example 187 and Reference Example 52.
[1048] The compounds of Example 192 were obtained by separating the compound of Example 191.
Reference Example 53
Production of (R)-6-(5-methylpyrazine-2-yl)chroman-3-amine
[1049] ##STR00216##
Step 1
[1050] To a suspension of (R)-2,2,2-trifluoro-N-(6-(4,4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl)chroman-3-yl)acetamide (600 mg, 1.62 mmol) synthesized by a method described in Step 1 in Reference Example 28, 2-bromo-5-methylpyrazine (336 mg, 1.94 mmol) cesium carbonate (1.00 g, 3.07 mmol) in 1,4-dioxane (20 mL), Xantphos Pd G3 (15.0 mg, 0.0158 mmol) was added. The mixture was stirred for 4 hours at 125° C. Water and ethyl acetate was added to the reaction solution, and the mixture was partitioned. Thereafter, the organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-2,2,2-trifluoro-N-(6-(5-methylpyrazine-2-yl)chroman-3-yl)acetamide (amount 224 mg, yield 41%).
Step 2
[1051] (R)-6-(5-Methylpyrazine-2-yl)chroman-3-amine was obtained by a method similar to Step 3 in Reference Example 1, using (R)-2,2,2-trifluoro-N-(6-(5-methylpyrazine-2-yl)chroman-3-yl)acetamide instead of (R)-N-(6-chlorochroman-3-yl)-2,2,2-trifluoroacetamide.
[1052] The compound of Example 193 was synthesized by methods similar to those described in Example 187 and Reference Example 52.
[1053] The compounds of Example 194 were obtained by separating the compound of Example 193.
[1054] The compound of Reference Example 54 (shown in the figure below.) was synthesized from the compound synthesized in Step 1 in Example 187 by a method similar to Reference Example 37.
##STR00217##
[1055] The compound of Example 195 was synthesized from the compound of Reference Example 54 and the compound of Reference Example 44 by a method similar to Step 3 in Example 100.
[1056] The compounds of Example 196 were obtained by separating the compound of Example 195.
[1057] The compound of Example 197 was synthesized from the compound of Reference Example54 and the compound of Reference Example 48 by a method similar to Step 3 in Example 100.
[1058] The compounds of Example 198 were obtained by separating the compound of Example 197.
[1059] The compound of Example 199 was synthesized by methods similar to those described in Example 187 and Reference Example 24.
[1060] The compounds of Example 200 were obtained by separating the compound of Example 199.
Example 201
Production of N-((R)-6-cyanochroman-3-yl)-2-(2-(cyclopropylmethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide
[1061] ##STR00218##
Step 1
[1062] To 4 mol/L aqueous solution of sodium hydroxide (1 mL) were added tetrabutylammonium bromide (16.4 mg, 0.0509 mmol), 4-benzyloxybutan-1,3-diol (100 mg, 0.510 mmol) and (bromomethyl)cyclopropane (0.15 mL, 1.6 mmol). The mixture was stirred for 2 hours at 50° C. To the reaction solution, aqueous solution of saturated ammonium chloride and ethyl acetate were added, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give 1-benzyloxy-4-(cyclopropylmethoxy)butan-2-ol (amount 58 mg, yield 45%).
Step 2
[1063] Ethyl 5-(1-benzyloxymethyl)-3-(cyclopropylmethoxy)propoxy)-1H-pyrazole-3-carboxylate was obtained by a method similar to Example 85, using 1-benzyloxy-4-(cyclopropylmethoxy)butan-2-ol instead of 4-((tert-butyldiphenylsilyl)oxy)butan-2-ol.
Step 3
[1064] To a solution of ethyl 5-(1-benzyloxymethyl)-3-(cyclopropylmethoxy)propoxy)-1H-pyrazole-3-carboxylate (1.3 g, 3.3 mmol) in ethanol (50 mL), 5% palladium on carbon (0.71 g) was added, and the mixture was stirred under hydrogen atmosphere (balloon pressure) for 3 hours at room temperature. After the reaction solution was filtered through celite, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 5-(3-(cyclopropylmethoxy)-1-(hydroxymethyl)propoxy)-1H-pyrazole-3-carboxylate (amount 0.91 g, yield 91%).
Step 4
[1065] To a solution of ethyl 5-(3-(cyclopropylmethoxy)-1-(hydroxymethyl)propoxy)-1H-pyrazole-3-carboxylate (0.91 g, 3.1 mmol) in dichloromethane (20 mL) were added N,N-diisopropylethylamine (3.1 mL, 18 mmol), carbon tetrabromide (3.0 g, 9.0 mmol) and triphenylphosphine (1.6 g, 6.1 mmol). The mixture was stirred for 15 hours at room temperature. After concentrating the reaction solution under reduced pressure, the residue was purified by silica gel column chromatography to give ethyl 5-(1-(bromomethyl)-3-(cyclopropylmethoxy)propoxy)-1H-pyrazole-3-carboxylate (amount 0.42 g, yield 38%).
Step 5
[1066] To a solution of ethyl 5-(1-(bromomethyl)-3-(cyclopropylmethoxy)propoxy)-1H-pyrazole-3-carboxylate (0.42 g, 1.2 mmol) in N,N-dimethylformamide (12 mL), potassium carbonate (0.40 g, 2.9 mmol) was added, and the mixture was stirred for 3 hours at room temperature. Water and chloroform was added to the reaction solution, and the mixture was partitioned. After the organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated off under reduced pressure. Ethyl 2-(2-(cyclopropylmethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate (amount 195 mg, yield 60%) was obtained.
Step 6
[1067] 2-(2-(Cyclopropylmethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid was obtained as a mixture with 4 equivalents of sodium chloride by a method similar to Step 5 in Example 85, using ethyl 2-(2-(cyclopropylmethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate instead of ethyl 5-(2-fluorophenyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate.
Step 7
[1068] N-((R)-6-Cyanochroman-3-yl)-2-(2-(cyclopropylmethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide was obtained by a method similar to Step 4 in Example 1, using 2-(2-(cyclopropylmethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid instead of 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid, and using (R)-3-aminochroman-6-carbonitrile synthesized by a method described in Reference Example 24 instead of 6-fluorochroman-3-amine hydrochloride.
[1069] The compounds of Example 202 were obtained by separating the compound of Example 201.
Example 203
Production of 2-(2-(cyclopropylmethoxy)ethyl)-N-((R)-6-(2-methoxypyrimidin-5-yl)chroman-3-yl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide
[1070] ##STR00219##
[1071] 2,2-(2-(Cyclopropylmethoxy)ethyl)-N-((R)-6-(2-methoxypyrimidin-5-yl)chroman-3-yl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide was obtained by a method similar to Example 201, using (R)-6-(2-methoxypyrimidin-5-yl)chroman-3-amine synthesized by a method described in Reference Example 29 instead of (R)-3-aminochroman-6-carbonitrile.
Example 204
Isomeric separation of 2-(2-(cyclopropylmethoxy)ethyl)-N-((R)-6-(2-methoxypyrimidin-5-yl)chroman-3-yl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide
[1072] ##STR00220##
[1073] 2-(2-(Cyclopropylmethoxy)ethyl)-N-((R)-6-(2-methoxypyrimidin-5-yl)chroman-3-yl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide (22.0 mg, 0.045 mmol) synthesized by a method described in Example 203 was dissolved in ethanol (7 mL), the solution was subjected to HPLC fractionation (column: CHIRALPAK IB, developing solvent: ethanol, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 6.4 mg, yield 29%) and isomer B (amount 8.5 mg, yield 39%).
[1074] The compound of Reference Example 55 (2-(2-(2,2,2-trifluoroethoxy)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00221##
[1075] The compound of Reference Example 56 (shown in the figure below.) was synthesized by a method similar to Reference Example 53.
##STR00222##
[1076] The compound of Example 205 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 56 by a method similar to Step 3 in Example 100.
[1077] The compounds of Example 206 were obtained by separating the compound of Example 205.
[1078] The compound of Example 207 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 28 under the scheme depicted in the figure below.
##STR00223##
[1079] The compound of Reference Example 57 (shown in the figure below.) was synthesized from the compound synthesized in Step 5 in Reference Example 55 by a method similar to Reference Example 37.
##STR00224##
[1080] The compound of Example 208 was synthesized from the compound of Reference Example 57 and the compound of Reference Example 24 by a method similar to Step 4 in Example 1.
[1081] The compounds of Example 209 were obtained by separating the compound of Example 208.
[1082] The compound of Example 210 was synthesized from the compound of Reference Example 57 and the compound of Reference Example 48 by a method similar to Step 4 in Example 1.
[1083] The compounds of Example 211 were obtained by separating the compound of Example 210.
[1084] The compound of Example 212 was synthesized from the compound of Reference Example 57 and the compound of Reference Example 56 by a method similar to Step 4 in Example 1.
[1085] The compounds of Example 213 were obtained by separating the compound of Example 212.
[1086] The compound of Reference Example 58 (shown in the figure below.) was synthesized from the compound synthesized in Step 5 in Reference Example 55 by a method similar to Reference Example 38.
##STR00225##
[1087] The compound of Example 214 was synthesized from the compound of Reference Example 58 and the compound of Reference Example 44 by a method similar to Step 4 in Example 1.
[1088] The compounds of Example 215 were obtained by separating the compound of Example 214.
[1089] The compound of Example 216 was synthesized from the compound of Reference Example 58 and the compound of Reference Example 45 by a method similar to Step 4 in Example 1.
[1090] The compounds of Example 217 were obtained by separating the compound of Example 216.
[1091] The compound of Example 218 was synthesized from the compound of Reference Example 58 and the compound of Reference Example 48 by a method similar to Step 4 in Example 1.
[1092] The compounds of Example 219 were obtained by separating the compound of Example 218.
[1093] The compound of Reference Example 59 (shown in the figure below.) was synthesized by a method similar to Example 53.
##STR00226##
[1094] The compound of Example 220 was synthesized from the compound of Reference Example 58 and the compound of Reference Example 59 by a method similar to Step 4 in Example 1.
[1095] The compounds of Example 221 were obtained by separating the compound of Example 220.
[1096] The compound of Reference Example 60 (shown in the figure below.) was synthesized by a method similar to Reference Example 53.
##STR00227##
[1097] The compound of Example 222 was synthesized from the compound of Reference Example 58 and the compound of Reference Example 60 by a method similar to Step 4 in Example 1.
[1098] The compounds of Example 223 were obtained by separating the compound of Example 222.
[1099] The compound of Reference Example 61 was synthesized under the scheme depicted in the figure below.
##STR00228##
[1100] The compound of Reference Example 62 (shown in the figure below.) was synthesized from the compound of Reference Example 61 by a method similar to Step 2 to Step 6 in Example 201.
##STR00229##
[1101] The compound of Example 224 was synthesized from the compound of Reference Example 62 and the compound of Reference Example 44 under the scheme depicted in the figure below.
##STR00230##
[1102] The compound of Example 225 was synthesized from the compound synthesized in Step 5 in Reference Example 55 under the scheme depicted in the figure below.
##STR00231##
[1103] The compounds of Example 226 were obtained by separating the compound of Example 225
[1104] The compound of Reference Example 63 (shown in the figure below.) was synthesized by a method similar to Reference Example 27.
##STR00232##
[1105] The compound of Example 227 was synthesized by methods similar to those described in Example 225 and Reference Example 63.
[1106] The compounds of Example 228 were obtained by separating the compound of Example 227.
[1107] The compound of Example 229 was synthesized by methods similar to those described in Example 225 and Reference Example 43.
[1108] The compounds of Example 230 were obtained by separating the compound of Example 229.
[1109] The compound of Example 231 was synthesized by methods similar to those described in Example 225 and Reference Example 44.
[1110] The compounds of Example 232 were obtained by separating the compound of Example 231.
[1111] The compound of Reference Example 64 (2-(2-(3,3-difluoroazetidin-1-yl)ethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid) was synthesized from the compound synthesized in Step 1 in Example 225 under the scheme depicted in the figure below.
##STR00233##
[1112] The compound of Example 233 was synthesized from the compound of Reference Example 64 and the compound of Reference Example 1 by a method similar to Step 3 in Example 100.
[1113] The compounds of Example 234 were obtained by separating the compound of Example 233.
[1114] The compound of Example 235 was synthesized from the compound of Reference Example 64 and the compound of Reference Example 43 by a method similar to Step 3 in Example 100.
[1115] The compounds of Example 236 were obtained by separating the compound of Example 235.
[1116] The compound of Example 237 was synthesized from the compound of Reference Example 64 and the compound of Reference Example 45 by a method similar to Step 3 in Example 100.
[1117] The compounds of Example 238 were obtained by separating the compound of Example 237.
[1118] The compound of Reference Example 65 ((R)-6-(2-(trifluoromethoxy)ethyl)chroman-3-amine hydrochloride) was synthesized from the compound synthesized in Step 1 in Reference Example 45 under the scheme depicted in the figure below.
##STR00234##
[1119] The compound of Example 239 was synthesized by methods similar to those described in Example 233 and Reference Example 65.
[1120] The compounds of Example 240 were obtained by separating the compound of Example 239.
[1121] The compound of Reference Example 66 (shown in the figure below.) was synthesized by a method similar to Reference Example 64.
##STR00235##
[1122] The compound of Example 241 was synthesized from the compound of Reference Example 66 under the scheme depicted in the figure below.
##STR00236##
[1123] The compound of Reference Example 67 (shown in the figure below.) was synthesized by a method similar to Reference Example 64.
##STR00237##
[1124] The compound of Example 242 was synthesized from the compound of Reference Example 67 under the scheme depicted in the figure below.
##STR00238##
[1125] The compound of Example 243 was synthesized from the compound synthesized in Step 5 in Reference Example 55 and the compound of Reference Example 24 by a method similar to Step 2 to Step 4 in Example 187.
[1126] The compounds of Example 244 were obtained by separating the compound of Example 243.
[1127] The compound of Example 245 was synthesized under the scheme depicted in the figure below.
##STR00239##
[1128] The compounds of Example 246 were obtained by separating the compound of Example 245.
Example 247
Production and isomeric separation of N-((R)-6-cyanochroman-3-yl)-2-(3-(trifluoromethoxy)propyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide
[1129] ##STR00240##
Step 1 to Step 2
[1130] 2-(3-(Trifluoromethoxy)propyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid was obtained by a method similar to Step 1 to Step 2 in Reference Example 37, using ethyl 2-(3-hydroxypropyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate synthesized by a method described in Step 7 in Example 245 instead of ethyl 5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate in Step 1.
Step 3
[1131] N-((R)-6-Cyanochroman-3-yl)-2-(3-(trifluoromethoxy)propyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide was obtained by a method similar to Step 4 in Example 1, using 2-(3-(trifluoromethoxy)propyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid instead of 6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylic acid, and using (R)-3-aminochroman-6-carbonitrile synthesized by a method described in Reference Example 24 instead of 6-fluorochroman-3-amine hydrochloride.
Step 4
[1132] N-((R)-6-Cyanochroman-3-yl)-2-(3-(trifluoromethoxy)propyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxamide (126 mg, 0.289 mmol) was dissolved in ethanol (12 mL), and the solution was subjected to HPLC fractionation (column: CHIRALPAK D3 N-5, developing solvent: ethanol, flow rate: 8.0 mL/min, room temperature) to give isomer A (amount 57.7 mg, yield 46%) and isomer B (amount 52.5 mg, yield 42%).
[1133] The compound of Reference Example 248 was synthesized from the compound synthesized in Step 7 in Example 245 under the scheme depicted in the figure below.
##STR00241##
[1134] The compound of Example 249 was synthesized under the scheme depicted in the figure below.
##STR00242##
[1135] The compound of Reference Example 68 (ethyl 2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate) was synthesized under the scheme depicted in the figure below.
##STR00243##
[1136] The compound of Example 250 was synthesized from the compound of Reference Example 68 by a method similar to Step 2 to Step 5 in Example 249.
[1137] The compound of Example 251 was synthesized by a method similar to Step 5 to Step 8 in Example 70.
Example 252
Production of N-((R)-6-cyanochroman-3-yl)-6-(trifluoromethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide
[1138] ##STR00244##
Step 1
[1139] 1-(Benzyloxy)-4-((tert-butyldiphenylsilyl)oxy)butan-2-ol was obtained by a method similar to Step 1 in Example 85, using 4-(benzyloxy)butan-1,3-diol instead of butan-1,3-diol.
Step 2
[1140] 4-((tert-Butyldiphenylsilyl)oxy)butan-1,2-diol was obtained by a method similar to Step 1 in Example 100, using 1-(benzyloxy)-4-((tert-butyldiphenylsilyl)oxy)butan-2-ol instead of ethyl 5-((benzyloxy)methyl-6,7-dihydro-5H-pyrazolo[5, 1-b][1,3]oxazine-2-carboxylate.
Step 3
[1141] To a solution of 4-((tert-butyldiphenylsilyl)oxy)butan-1,2-diol (2.00 g, 5.81 mmol) in dichloromethane (24 mL) were was added p-toluene sulfonic acid (55 mg, 0.29 mmol) and 4-methoxybenzaldehyde (2.37 g, 17.4 mmol), and the mixture was stirred for 1 hour at room temperature. Saturated aqueous solution of sodium hydrogen carbonate and chloroform was added to the reaction solution, and the mixture was partitioned. After the organic layer was washed with saturated brine and the solvent was evaporated off under reduced pressure, the residue was purified by silica gel column chromatography to give tert-butyl (2-(2-(4-methoxyphenyl)-1,3-dioxolan-4-yl)ethoxy)diphenylsilane (amount 1.76 g, yield 66%).
Step 4
[1142] A solution of tert-butyl (2-(2-(4-methoxyphenyl)-1,3-dioxolan-4-yl)ethoxy)diphenylsilane (1.76 g, 3.80 mmol) in dichloromethane (20 mL) was cooled to −78° C., and 1 mol/L diisobutylaluminum hydride/n-hexane solution (5.33 mL, 5.33 mmol) was added to the solution. After stirring for 15 minutes, the mixture was warmed to 0° C. To the reaction solution, an aqueous solution of potassium sodium tartarate and chloroform were added, and the mixture was partitioned. Thereafter, the organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give 4-(tert-butyl (diphenyl)silyl)oxy-2-((4-methoxyphenyl)methoxy)butan-1-ol (amount 427 mg, yield 24%).
Step 5 to Step 6
[1143] Ethyl 5-(4-hydroxy-2-((4-methoxybenzyl)oxy)butoxy)-1H-pyrazole-3-carboxylate was obtained by a method similar to Step 2 to Step 3 in Example 85, using 4-(tert-butyl (diphenyl)silyl)oxy-2-((4-methoxyphenyl)methoxy)butan-1-ol instead of 4-((tert-butyldiphenylsilyl)oxy)butan-2-ol in Step 2.
Step 7
[1144] To a solution of ethyl 5-(4-hydroxy-2-((4-methoxybenzyl)oxy)butoxy)-1H-pyrazole-3-carboxylate (274 mg, 0.752 mmol) in toluene (15 mL) were added tri-N-butylphosphine (376 μL, 1.51 mmol) and 1,1′-(azodicarbonyl)dipiperidine (379 mg, 1.50 mmol), and the mixture was stirred for 1.5 hours at 80° C. The reaction solution was allowed to cool to room temperature, and water and ethyl acetate was added, and the mixture was partitioned. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 6-((4-methoxybenzyl)oxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate (amount 198 mg, yield 76%).
Step 8
[1145] Ethyl 6-hydroxy-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxyl ate was obtained by a method similar to Step 1 in Example 100, using 6-((4-methoxybenzyl)oxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate instead of ethyl 5-((benzyloxy)methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate.
Step 9 to Step 11
[1146] By a method similar to Example 247, N-((R)-6-cyanochroman-3-yl)-6-(trifluoromethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide was obtained, using ethyl 6-hydroxy-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate instead of ethyl 2-(3-hydroxypropyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate in Step 1.
[1147] The compounds of Example 253 were obtained by separating the compound of Example 252.
Example 254
Production of N-((R)-6-cyanochroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide
[1148] ##STR00245##
Step 1
[1149] By a method similar to Example 114, (4-(benzyloxy)-3-(2,2,2-trifluoroethoxy)butoxy) (tert-butyl)diphenylsilane was obtained, using 1-(benzyloxy)-4-((tert-butyldiphenylsilyl)oxy)butan-2-ol synthesized by a method described in Step 1 in Example 252 instead of N-((R)-6-cyanochroman-3-yl)-5-(hydroxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxamide.
Step 2
[1150] By a method similar to Step 2 in Example 252, 4-(tert-butyldiphenylsilyl)oxy)-2-(2,2,2-trifluoroethoxy)butan-1-ol was obtained, using (4-(benzyloxy)-3-(2,2,2-trifluoroethoxy)butoxy) (tert-butyl)diphenylsilane instead of 1-(benzyloxy)-4-((tert-butyldiphenylsilyl)oxy)butan-2-ol.
Step 3 to Step 5
[1151] By a method similar to Step 5 to Step 7 in Example 252, ethyl 6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate was obtained, using 4-(tert-butyldiphenylsilyl)oxy)-2-(2,2,2-trifluoroethoxy)butan-1-ol instead of 4-(tert-butyl (diphenyl)silyl)oxy-2-((4-methoxyphenyl)methoxy)butan-1-ol in Step 5.
Step 6 to Step 7
[1152] By a method similar to Step 10 to Step 11 in Example 252, N-((R)-6-cyanochroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide was obtained, using ethyl 6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate instead of ethyl 6-(trifluoromethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate in Step 10.
[1153] The compounds of Example 255 were obtained by separating the compound of Example 254.
Example 256
Production of N-((R)-6-chlorochroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide (isomer A and isomer B)
[1154] ##STR00246##
[1155] To a suspension of 6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (26.0 mg, 0.0591 mmol) synthesized by a method described in Step 6 in Example 254, (R)-6-chlorochroman-3-amine (14.1 mg, 0.0768 mmol), 1-hydroxybenzotriazole (14.2 mg, 0.0927 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (17.8 mg, 0.0929 mmol) in N,N-dimethylformamide (0.5 mL), 4-methylmorpholine (41 μL, 0.373 mmol) was added. The mixture was stirred for 2 hours at room temperature. Water and ethyl acetate was added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography and the diastereomers were separated to give N-((R)-6-chlorochroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide (isomer A) (amount 2.7 mg, yield 10%) and N-((R)-6-chlorochroman-3-yl)-6-(2,2,2-trifluoroethoxy)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide (isomer B) (amount 2.9 mg, yield 11%).
[1156] The compound of Example 257 was synthesized from the compound synthesized in Step 6 in Example 254 under the scheme depicted in the figure below.
##STR00247##
Example 258
Production of (R)-3-(1H-pyrazol-5-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide
[1157] ##STR00248##
Step 1
[1158] To a solution of ethyl 5-hydroxy-1H-pyrazole-3-carboxylate (1.00 g, 6.40 mmol) in acetonitrile (13 mL) was added potassium carbonate (2.66 g, 19.2 mmol) and 1,4-dibromobutane (804 μL, 6.73 mmol). After sealing, the mixture was stirred for 15 hours at 100° C. The reaction solution was allowed to cool to room temperature, and after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate (amount 574 mg, yield 43%).
Step 2
[1159] Ethyl 3-iodo-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate was obtained by a method similar to Example 14, using ethyl 5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate instead of N-((R)-chroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide.
Step 3 to Step 4
[1160] (R)-3-Iodo-N-(6-(trifluoromethyl)chroman-3-yl)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide was obtained by a method similar to Step 3 to Step 4 in Example 18, using ethyl 3-iodo-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate instead of ethyl 3-(pyridin-2-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxylate in Step 3, and using (R)-6-(trifluoromethyl)chroman-3-amine hydrochloride synthesized by a method described in Reference Example 43 instead of (R)-6-chlorochroman-3-amine hydrochloride in Step 4.
Step 5
[1161] To a solution of (R)-3-iodo-N-(6-(trifluoromethyl)chroman-3-yl)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide (20 mg, 0.039 mmol) in n-butanol (800 μL) were added 1H-pyrazol-5-ylboronic acid (8.8 mg, 0.079 mmol), triethylamine (22 μL, 0.16 mmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium (II) (2.8 mg, 0.0040 mmol). The mixture was stirred for 1 hour at 120° C. under microwave irradiation. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography to give (R)-3-(1H-pyrazol-5-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxamide (amount 13.6 mg, yield 77%).
Example 259
Production of (R)-3-(1H-pyrazol-5-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide
[1162] ##STR00249##
Step 1 to Step 4
[1163] (R)-3-(1H-Pyrazol-5-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide was obtained by a method similar to Step 2 to Step 5 in Example 258, using ethyl 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylate instead of ethyl 5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylate in Step 2.
Example 260
Production of (R)-3-(pyridin-2-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide
[1164] ##STR00250##
Step 1
[1165] To a solution of ethyl 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylate (400 mg, 2.04 mmol) in acetonitrile (6.8 mL), N-iodosuccineimide (1.38 g, 6.13 mmol) was added, and the mixture was stirred for 14 hours at 70° C. An aqueous solution of sodium thiosulfate and ethyl acetate were added to the reaction solution, and the mixture was partitioned. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give ethyl 3-iodo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylate (amount 650 mg, yield 99%).
Step 2
[1166] To a solution of ethyl 3-iodo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylate (200 mg, 0.621 mmol) in ethanol (6.2 mL), 4 mol/L aqueous solution of sodium hydroxide (0.62 mL, 2.5 mmol) was added, and the mixture was stirred for 2 hours at room temperature. To the reaction solution, 2 mol/L hydrochloric acid was added, and then the solvent was evaporated off under reduced pressure. Toluene was added to the residue and the solvent was evaporated off under reduced pressure to give 3-iodo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylic acid (amount 325 mg, yield 99%) as a mixture with 4 equivalents of sodium chloride.
Step 3
[1167] To a suspension of 3-iodo-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylic acid (a mixture with 4 equivalents of sodium chloride) (325 mg, 0.616 mmol), (R)-6-(trifluoromethyl)chroman-3-amine hydrochloride (156 mg, 0.616 mmol) synthesized by a method described in Reference Example 43, 1-hydroxybenzotriazole (10.0 mg, 0.0739 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (142 mg, 0.0739 mmol) in dichloromethane (10 mL), 4-methylmorpholine (203 μL, 1.85 mmol) was added, and the mixture was stirred for 12 hours at room temperature. Water and ethyl acetate were added to the reaction solution, and the mixture was partitioned. After drying the organic layer with anhydrous sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-3-iodo-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide (amount 267 mg, yield 88%).
Step 4
[1168] To a mixed solution of (R)-3-iodo-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide (60.0 mg, 0.122 mmol) and (6-chloropyridin-2-yl)boronic acid (28.7 mg, 0.182 mmol) in 1,4-dioxane (1 mL) and water (1 mL) were added cesium carbonate (119 mg, 0.365 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium (II) (8.6 mg, 0.012 mmol). The mixture was stirred for 1 hour at 140° C. under microwave irradiation. Water and ethyl acetate was added to the reaction solution, and the mixture was partitioned. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-3-(6-chloropyridin-2-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide (amount 9.4 mg, yield 33%).
Step 5
[1169] To a solution of (R)-3-(6-chloropyridin-2-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide (290 mg, 0.606 mmol) in tetrahydrofuran (6 mL) were added ethanol (6 mL) and 20% palladium hydroxide on carbon (128 mg). The mixture was stirred under pressurized conditions (balloon pressure) in hydrogen atmosphere for 2 hours at 50° C. After the reaction solution was filtered through celite, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-3-(pyridin-2-yl)-N-(6-(trifluoromethyl)chroman-3-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxamide (amount 204 mg, yield 76%).
[1170] The compound of Example 261 was synthesized under the scheme depicted in the figure below.
##STR00251##
[1171] The compound of Example 262 was synthesized by a method similar to Example 261.
[1172] The compound of Reference Example 69 was synthesized under the scheme depicted in the figure below.
##STR00252##
[1173] The compound of Example 263 was synthesized using the compound of Reference Example 69 and the compound of Reference Example 1 by methods similar to Step 2 and Step 3 in Example 261.
[1174] The compound of Example 264 was synthesized using the compound of Reference Example 69 and the compound of Reference Example 47 by methods similar to Step 2 and Step 3 in Example 261.
[1175] The compound of Reference Example 70 (shown in the figure below.) was synthesized by a method similar to Reference Example 69.
##STR00253##
[1176] The compound of Example 265 was synthesized using the compound of Reference Example 70 and the compound of Reference Example 43 by methods similar to Step 2 and Step 3 in Example 261.
[1177] The compound of Example 266 was synthesized using the compound of Reference Example 70 and the compound of Reference Example 44 by methods similar to Step 2 and Step 3 in Example 261.
[1178] The compound of Example 267 was synthesized under the scheme depicted in the figure below.
##STR00254##
Example 268
Production of (R)-N-(6-cyanochroman-3-yl)-5-(4-fluorobenzyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamide
[1179] ##STR00255##
Step 1
[1180] To a solution of 5-(tert-butoxycarbonyl)-4,5,6,7-tetrahydropyrazolo[1, 5-a]pyrazine-2-carboxylic acid (120 mg, 0.449 mmol) in dichloromethane (3 mL) were added HATU (188 mg, 0.494 mmol), N,N-diisopropylethylamine (386 μL, 2.24 mmol) and (R)-3-aminochroman-6-carbonitrile (104 mg, 0.494 mmol) synthesized by a method described in Reference Example 24.
[1181] The mixture was stirred for 12 hours at room temperature. The reaction solution was purified by silica gel column chromatography to give (R)-tert-butyl 2-((6-cyanochroman-3-yl)carbamoyl)-6,7-dihydropyrazolo[1, 5-a]pyrazine-5 (4H)-carboxylate (amount 210 mg).
Step 2
[1182] To a solution of (R)-tert-butyl 2-((6-cyanochroman-3-yl) carbamoyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-5 (4H)-carboxylate (210 mg, 0.496 mmol) in ethyl acetate (8 mL), 4 mol/L hydrogen chloride-ethyl acetate solution (8.0 mL, 32 mmol) was added, and the mixture was stirred for 2 hours at room temperature. The solvent was evaporated off under reduced pressure to give (R)-N-(6-cyanochroman-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamide hydrochloride (amount 178 mg, yield 100%).
Step 3
[1183] To a solution of (R)-N-(6-cyanochroman-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamide (15.0 mg, 0.0417 mmol) in N,N-dimethylformamide (208 μL) were added N,N-diisopropylethylamine (36 μL, 0.21 mmol) and 1-(bromomethyl)-4-fluorobenzene (15.8 mg, 0.0834 mmol). The mixture was stirred for 12 hours at 100° C. Water and chloroform was added to the reaction soltion, and the mixture was partitioned. After the organic layer was dried over sodium sulfate, the solvent was evaporated off under reduced pressure. The residue was purified by silica gel column chromatography to give (R)-N-(6-cyanochroman-3-yl)-5-(4-fluorobenzyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamide (amount 16.0 mg, yield 89%).
[1184] The compound of Example 269 was synthesized by a method similar to Example 268.
[1185] The compound of Example 270 was synthesized by a method similar to Example 268.
[1186] The compound of Example 271 was synthesized by a method similar to Example 268.
[1187] The compound of Example 272 was synthesized by methods similar to those described in Example 268 and Reference Example 3.
[1188] The compound of Reference Example 71 (shown in the figure below.) was synthesized by methods similar to those described in Step 1 to Step 2 in Example 268 and in Reference Example 1.
##STR00256##
[1189] The compound of Example 273 was synthesized from the compound of Reference Example 71 by a method similar to Step 3 in Example 268.
[1190] The compound of Example 274 was synthesized from the compound of Reference Example 71 under the scheme depicted in the figure below.
##STR00257##
[1191] The compound of Example 275 was synthesized under the scheme depicted in the figure below.
##STR00258##
[1192] The compound of Reference Example 72 (shown in the figure below.) was synthesized by a method similar to Step 1 to Step 2 in Example 268.
##STR00259##
[1193] The compound of Example 276 was synthesized from the compound of Reference Example 72 under the scheme depicted in the figure below.
##STR00260##
[1194] The compound of Example 277 was synthesized from the compound of Reference Example 72 under the scheme depicted in the figure below.
##STR00261##
[1195] Example 278 was synthesized under the scheme depicted in the figure below.
##STR00262##
[1196] The compound of Reference Example 73 (shown in the figure below.) was synthesized by a method similar to Reference Example 27.
##STR00263##
[1197] The compound of Example 279 was synthesized by methods similar to those described in Example 278 and Reference Example 73.
[1198] The compound of Example 280 was synthesized from the compound of Reference Example 71 under the scheme depicted in the figure below.
##STR00264##
[1199] The compound of Example 281 was synthesized under the scheme depicted in the figure below.
##STR00265##
[1200] The compound of Example 282 was synthesized by methods similar to those described in Example 281 and Reference Example 24.
[1201] The compound of Example 283 was synthesized under the scheme depicted in the figure below.
##STR00266##
[1202] The compound of Example 284 was synthesized by a method similar to Example 283.
[1203] The compound of Example 285 was synthesized by a method similar to Example 283.
[1204] The compound of Reference Example 74 was synthesized under the scheme depicted in the figure below.
##STR00267##
[1205] The compound of Example 286 was synthesized by a method similar to Example 283, using the compound of Reference Example 74 and the compound of Reference Example 24.
[1206] The compound of Example 287 was synthesized by a method similar to Step 6 to Step 8 in Example 70.
Example 288
Production of N-((R)-6-chlorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (isomer A) hydrochloride
[1207] ##STR00268##
[1208] To a solution of N-((R)-6-chlorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (isomer A) (170 mg, 0.425 mmol) synthesized by a method described in Example 2 in ethyl acetate (1 mL), 4 mol/L hydrogen chloride-ethyl acetate solution (1 mL, 4 mmol) was added, and the mixture was stirred for 10 minutes. The solvent was evaporated off under reduced pressure to give N-((R)-6-chlorochroman-3-yl)-6-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine-2-carboxamide (isomer A) hydrochloride (amount 185 mg, yield 100%).
[1209] The compound of Example 289 was synthesized from the compound of Example 81 under the scheme depicted in the figure below.
##STR00269##
Example 290
Production of (R)-N-(6-cyanochroman-3-yl)-5-(4-fluorobenzyl)-4,5,6,7-tetrahydropyrazolo[1, 5-a]pyrazine-2-carboxamide hydrochloride
[1210] ##STR00270##
[1211] To a solution of (R)-N-(6-cyanochroman-3-yl)-5-(4-fluorobenzyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamide (122 mg, 0.283 mmol) synthesized by a method described in Example 268 in ethyl acetate (2 mL), 4 mol/L hydrogen chloride-ethyl acetate solution (141 μL, 0.563 mmol) was added, and the mixture was stirred. n-Hexane (2 mL) was added, the precipitated solid was filtered, and then the solid was dried under reduced pressure to give (R)-N-(6-cyanochroman-3-yl)-5-(4-fluorobenzyl)-4,5,6,7-tetrahydropyrazolo[1, 5-a]pyrazine-2-carboxamide hydrochloride (amount 96.4 mg, yield 73%).
[1212] In the tables below, on the compounds synthesized in Example 1 to Example 287, the chemical structures and instrumentall analysis data are shown. Meanwhile, n the tables below, the asterisks (*) appearing in the structural formulae in the Examples denote that the corresponding asymmetric carbon has a single steric structure. Unless specifically stated otherwise, “Example” in the tables refers to the compound intended for production in each Example; for example, the data given for Example 1 shows the data of the compound intended for production in Example 1.
TABLE-US-00001 TABLE 1 Example Structural formula NMR MS 1 [00271]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.93-1.99 (1H, m), 2.32-2.36 (1H, m, 2.75-2.88 (3H,m), 3.03-3.08 (1H, m), 3.14-3.19 (1H, m), 3.96-4.03 (1H, m), 4.12-4.18 (2H, m), 4.26-4.30 (1H, m), 4.56-4.62 (1H, m), 6.74 (1H, d, J = 9.0 Hz), 6.80-6.83 (2H, m), 7.18 (1H, d, J = 7.6 Hz), 7.46 (1H, s). 2 (isomer A) [00272]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (1H, m), 2.34 (1H, m), 2.74- 2.87 (3H, m), 3.02-3.19 (2H, m), 3.99 (1H, m), 4.13-4.22 (2H, m), 4.28 (1H, m), 4.60 (1H, m), 6.80 (1H, d, J = ![text missing or illegible when filed]()
.7 Hz), 7.03 (1H, m), 7.07 (1H, dd, J = 8.9, 2.7 Hz), 7.17 (1H, d, J = 7.8 Hz), 7.46 (1H, s). ESI-MS m/z: 400 [M + H]+ 2 (isomer B) [00273]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.34 (1H, m), 2.73- 2.87 (3H, m), 3.06 (1H, m), 3.15 (1H, m), 47.00 (1H, m), 4.13-4.23 (2H, m), 4.26 (1H, m), 4.60 (1H, m), 6.80 (1H, d, J = 6.7 Hz), 7.03 (1H, d, J = 2.5 Hz), 7.07 (1H, dd, J = 8.7, 2.6 Hz), 7.17 (1H, d, J = 6.2 Hz), 7.46 (1H, s). ESI-MS m/z: 400 [M + H]+ 3 [00274]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.34 (1H, m), 2.72- 2.88 (2H, m), 2.96-3.35 (6H, m), 3.99 (1H, m), 4.15 (1H, m), 4.26-4.31 (2H, m), 5.27 (1H, m), 6.77 (1H, d, J = 9.7 Hz), 7.05-7.07 (2H, m), 7.43 (1H, s). ESI-MS m/z: 414 [M + H]+ 4 [00275]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.97 (1H, m), 2.34 (1H, m), 2.73- 2.87 (2H, m), 3.0 ![text missing or illegible when filed]()
-3.27 (6H, m), 3.99 (1H, m), 4.14 (1H, m), 4.26-4.32 (2H, m), 5.27 (1H, m), 6.77 (1H, d, J = 9.4 Hz), 7.06-7.07 (2H, m), 7.43 (1H, s). ESI-MS m/z: 414 [M + H]+ 5 [00276]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.34 (1H, m), 2.76- 2.88 (3H, m), 3.06 (1H, m), 3.15 (1H, m), 3. ![text missing or illegible when filed]()
(1H, m), 4.13-4.22 (2H, m), 4.28 (1H, m), 4.60 (1H, m), 6.75 (1H, d, J = 8.6 Hz), 7.15-7.18 (2H, m), 7.21 (1H, dd, J = 8.6, 2.4 Hz), 7.46 (1H, s). ESI-MS m/z: 444, 446 [M + H]+ 6 [00277]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (1H, m), 2.33 (1H, m), 2.76- 2.84 (2H, m), 2.91 (1H, m), 3.05 (1H, m), 3.20 (1H, m), 3.99 (1H, m), 4.19 (1H, m), 4.25-4.30 (2H, m), 4.63 (1H, m), 6.56 (1H, t, J = 56.7 Hz), 6.93 (1H, d, J = ![text missing or illegible when filed]()
.4 Hz), 7.18 (1H, d, J = 7.9 Hz), 7.21 (1H, s), 7.27 (1H, m), 7.46 (1H, s). 7 (isomer A) [00278]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (1H, m), 2.33 (1H, m), 2.76- 2.84 (2H, m), 2.91 (1H, m), 3.05 (1H, m), 3.16 (1H, m), 3.99 (1H, m), 4.17-4.30 (3H, m), 4.63 (1H, m), 6.5 ![text missing or illegible when filed]()
(1H, t, J = 56.7 Hz), 6.93 (1H, d, J = 8.4 Hz), 7.16 (1H, d, J = 7.8 Hz), 7.21 (1H, s), 7.27 (1H, m), 7.46 (1H, s). ESI-MS m/z: 416 [M + H]+ 7 (isomer B) [00279]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.33 (1H, m), 2.75- 2.83 (2H, m), 2.90 (1H, m), 3.06 (1H, m), 3.20 (1H, m), 4.00 (1H, m), 4.19 (1H, m), 4.25-4.30 (2H, m), 4.63 (1H, m), 6.56 (1H, t, J = 56.7 Hz), 6.93 (1H, d, J = 8.4 Hz), 7.16 (1H, d, J = 7.8 Hz), 7.21 (1H, s), 7.27 (1H, m), 7.46 (1H, s). ESI-MS m/z: 416 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00002 TABLE 2 Ex- ample Structural formula NMR MS 8 [00280]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.98 (m, 1H), 2.36 (1H, m), 2.74- 2.91 (3H, m), 3.04-3.17 (2H, m), 4.00 (1H, t, J = 11.5 Hz), 4.11-4.20 (2H, m), 4.28 (1H, dd, J = 4.2, 12.4 Hz), 4.68 (1H, m), 6.80 (1H, d, J = 8.0 Hz), 6.98 (1H, dd, J = 8.0, 1.2 Hz), 7.07 (1H, t, J = 8.0 Hz), 7.17 (1H, d, J = 7.9 Hz), 7.47 (1H, s). ESI-MS m/z: 400 [M + H]+ 9 (iso- mer A) [00281]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96 (1H, m), 2.36 (1H, m), 2.76- 2.88 (3H, m), 3.05-3.14 (2H, m), 4.00 (1H, m), 4.10-4.20 12H, m), 4.28 (1H, m), 4.67 (1H, m), 6.85 (1H, dd, J = 6.2, 1.0 Hz), 7.01 (1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 7.16-7.18 (2H, m), 7.48 (1H, s). ESI-MS m/z: 444, 446 [M + H]+ 9 (iso- mer B) [00282]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.35 (1H, m), 2.77- 2.68 (3H, m), 3.04-3.14 (2H, m), 4.00 (1H, m), 4.10-4.20 (2H, m), 4.28 (1H, m), 4.67 (1H, m), 6.85 (1H, dd, J = 8.2, 1.0 Hz), 7.01 (1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 7.16-7.19 (2H, m), 7.47 (1H, s). ESI-MS m/z: 444, 446 [M + H]+ 10 [00283]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.50-5.64 (2H, m), 0.85-![text missing or illegible when filed]()
(2H, m), 1.70-1.79 (1H, m), 1.90-![text missing or illegible when filed]()
.01 (1H, m), 2.32-2.41 (1H, m), 2.71-2.68 (2H, m), 2.95 (1H, dd, J = 17.0, 4.7 Hz), 3.02-3.12 (1H, m), 3.24 (1H, dd, J = 17.0, 6.1 Hz), 4.00 (1H, t, J = 10.6 Hz), 4.08-4.12 (1H, m), 4.20 (1H, dd, J = 10.6, 2.4 Hz), 4.28 (1H, dd, J = 12.6, 5.4 Hz), 4.67-4.70 (1H, m), 6.62 (1H, d, J = 7.5 Hz), 6.74 (1H, d, J = 8.6 Hz), 7.06 (1H, t, J = 7.8 Hz), 7.20-7.26 (1H, m), 7.47 (1H, s). ESI-MS m/z: 406 [M + H]+ 11 [00284]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.20 (3H, t, J = 7.6 Hz, 1H), 1.95 (1H, m), 2.34 (1H, m), 2.55 (2H, q, J = 7.6 Hz), 1.74-1.86 (3H, m), 3.06 (1H, m), 3.17 (1H, m), 3.99 (1H, m), 4.12 (1H, m), 4.19 (1H, m), 4.27 (1H, m), 4.61 (1H, m), 4.67 (1H, d, J = 6.3 Hz), 6.87 (1H, s), 6.95 (1H, dd, J = 6.3, 2.1 Hz), 7.29 (1H, d, J = 8.4 Hz), 7.45 (1H, s). ESI-MS m/z: 394 [M + H]+ 12 [00285]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.34 (1H, m), 2.75- 2.89 (3H, m), 3.06 (1H, m), 3.15 (1H, m), 3.99 (1H, m), 4.13-4.22 (2H, m), 4.2![text missing or illegible when filed]()
(1H, m), 4.60 (1H, m), 6.75 (1H, d, J = 5.6 Hz), 7.15-7.16 (2H, m), 7.21 (1H, dd, J = 6.6, 2.4 Hz), 7.46 (1H, s). ESI-MS m/z: 444, 446 [M + H]+ 13 [00286]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (1H, m), 2.43 (1H, m), 2.74- 2.![text missing or illegible when filed]()
7 (3H, m), 3.05 (1H, m), 3.17 (1H, m), 3.74 (3H, s), 3.99 (1H, m), 4.10-4.1![text missing or illegible when filed]()
(2H, m), 4.27 (1H, m), 4.60 (1H, m), 6.56 (1H, d, J = 2.7 Hz), 6.79 (1H, dd, J = ![text missing or illegible when filed]()
.9, 3.0 Hz), 6.80 (1H, d, J = 8.9 Hz), 7.22 (1H, d, J = 7.6 Hz), 7.45 (1H, s). ESI-MS m/z: 396 [M + H]+ 14 [00287]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.92 (1H, m), 2.35 (1H, m), 2.72- 2.90 (3H, m), 3.98 (1H, m), 3.19 (1H, dd, J = 16.9, 5.4 Hz), 3.74 (1H, m), 4.14-4.24 (3H, m), 4.61 (1H, m), 6.86-6.91 (2H, m), 7.06 (1H, d, J = 7.4 Hz), 7.13 (1H, m), 7.31 (1H, d, J = 7.8 Hz). ESI-MS m/z: 492 [M + H]+ 15 [00288]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96 (1H, m), 2.33 (1H, m), 2.72 (1H, m), 2.80-2.90 (2H, m), 3.10-3.20 (2H, m), 3.89 (3H, d, J = 1.0 Hz), 4.09-4.23 (3H, m), 4.48 (1H, m), 4.55 (1H, m), 6.75 (1H, m), 6.86-6.91 (2H, m), 7.05 (1H, m), 7.12 (1H, m), 7.48 (1H, d, J = 8.2 Hz), 7.64-7.71 (2H, m). ESI-MS m/z: 473 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00003 TABLE 3 Ex- am- ple Structural formula NMR MS 16 [00289]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.92-1.93 (4H, m), 2.81-2.90 (3H, m), 3.12 (1H, dd, J = 16.6, 5.6 Hz), 3.68-3.70 (2H, m), 4.07-4.21 (2H, m), 4.54 (1H, m), 6.84-6.89 (2H, m), 7.03 (1H, d, J = 7.4 Hz), 7.11 (1H, m), 7.30 (1H, m), 7.39-7.44 (5H, m). ESI- MS m/z: 374 [M + H]+ 17 [00290]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.93-1.95 (4H, m), 2.81-2.92 (3H, m), 3.10 (1H, dd, J = 16.7, 5.6 Hz), 3.91 (3H, s), 4.05 (2H, s), 4.11 (1H, m), 4.19 (1H, dd, J = 10.8, 2.0 Hz), 4.53 (1H, m), 6.72 (1H, d, J = 8.2 Hz), 6.79 (1H, d, J = 8.7 Hz), 7.01 (1H, d, J = 2.3 Hz), 7.06 (1H, dd, J = 8.7, 2.4 Hz), 7.42 (1H, Hz), ESI- MS m/z: 439 [M + H]+ 18 [00291]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (4H, s), 2.81-2.86 (3H, m), 3.11 (1H, dd, J = 1![text missing or illegible when filed]()
.7, 5.8 Hz), 4.01 (2H, m), 4.09-4.20 (2H, m), 4.53 (1H, m), 6.79 (1H, d, J = 8.7 Hz), 7.02 (1H, s), 7.07 (1H, d, J = 7.4 Hz), 7.47 (1H, d, J = 8.5 Hz), 7.78 (1H, t, J = 7.7 Hz), 7.91 (1H, d, J = 8.0 Hz), 8.63 (1H, d, J = 4.0 Hz). ESI- MS m/z: 409 [M + H]+ 19 [00292]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (2H, m), 2.05 (2H, m), 2.87 (2H, q, J = 6.1 Hz), 2.97 (1H, dt, J = 16.7, 4.9 Hz), 3.23 (1H, dt, J = 16.7, 4.9 Hz), 4.15 (2H, q, J = 5.8 Hz), 4.28 (2H, m), 4.64 (1H, m), 6.52 (1H, d, J = 4.3 Hz), 6.95 (1H, m), 7.33 (1H, d, J = 2.9 Hz), 7.38 (1H, m), 7.66 (1H, d, J = 4.4 Hz), 7.70 (1H, m), 14.4 (1H, brs). ESI- MS m/z: 432 [M + H]+ 20 [00293]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94 (2H, m), 2.06 (2H, m), 2.87 (2H, t, J = 6.4 Hz), 2.93 (1H, dd, J = 10.8, 4.5 Hz), 3.21 (1H, dt, J = 15.5, 5.3 Hz), 3.82 (2H, q, J = 8.7 Hz), 4.15 (2H, d, J = 6.0 Hz), 4.20-4.27 (2H, m), 4.57 (2H, s), 4.64 (1H, m), 6.52 (1H, s), 6.89 (1H, d, J = 8.3 Hz), 7.06 (1H, s), 7.12 (1H, d, J = 8.4 Hz), 7.![text missing or illegible when filed]()
7 (1H, s), 7.74 (1H, d, J = 7.6=8 Hz), 14.5 (1H, brs). ESI- MS m/z: 476 [M + H]+ 21 [00294]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91-1.97 (2H, m), 2.04-2.10 (2H, m), 2.86-2.93 (3H, m), 3.18 (1H, dd, J = 16.9, 5.3 Hz), 4.16 (2H, t, J = 6.1 Hz), 4.21-4.23 (2H, m), 4.62 (1H, m), 6.![text missing or illegible when filed]()
3 (1H, d, J = 1.9 Hz), 6.62 (1H, d, J = 6.7 Hz), 7.05 (1H, d, J = 2.4 Hz), 7.09 (1H, dd, J = 8.7, 2.5 Hz), 7.67 (1H, d, J = 1.9 Hz), 7.72 (1H, d, J = 7.9 Hz). ESI- MS m/z: 397 [M + H]+ 22 [00295]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.94-1.95 (4H, m), 2.56-2.94 (4H, m), 3.58 (2H, q, J = 7.1 Hz), 3.71 (2H, t, J = 5.4 Hz, 7.38-7.46 (9H, m). ESI- MS m/z: 414 [M + H]+ 23 [00296]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05-2.15 (8H, m), 2.28 (1H, m), 2.93 (1H, m), 3.10 (1H, m), 3.23 (1H, m), 3.80 (1H, t, J = 11.7 Hz), 3.92 (1H, t, J = 12.7 Hz), 4.11 (1H, m), 4.24 (1H, dd, J = 12.6, 4.4 Hz), 4.57 (1H, m), 6.98- 7.20 (4H, s), 7.33 (1H, m), 7.48 (1H, s). ESI- MS m/z: 326 [M + H]+ 24 [00297]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.15-1.88 (12H, m), 2.11 (1H, m), 2.72 (1H, m), 2.85-2.96 (2H, m), 3.17 (1H, m), 3.61 (1H, m), 4.06-4.13 (2H, m), 4.25 (1H, m), 4.62 (1H, m), 6.85-6.89 (2H, m), 7.05 (1H, d, J = 6.6 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.41 (1H, s). ESI- MS m/z: 3![text missing or illegible when filed]()
[M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00004 TABLE 4 Ex- am- ple Structural formula NMR MS 25 [00298]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.08-2.14 (1H, m), 2.24-2.28 (1H, m), 2.81-2.91 (2H, m), 2.97-3.02 (1H, m), 3.17-3.22 (2H, m), 3.75 (1H, t, J = 8.0 Hz), 4.11-4.25 (3H, m), 4.56-4.66 (1H, m), 6.80-6.91 (2H, m), 7.03-7.40 (8H, m). ESI- MS m/z: 408 [M + H]+ 26 [00299]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05 (2H, m), 2.20 (2H, m), 2.34 (1H, m), 2.85-3.11 (3H, m), 3.41 (1H, m), 3.52 (1H, m), 3.69 (1H, m), 3.89 (2H, m), 3.98 (3H, s), 4.33 (1H, m), 6.89 (1H, m), 7.23-7.35 (5H, m), 7.41 (1H, m), 7.48 (1H, d, J = 11.8 Hz), 8.10 (1H, s). ESI- MS m/z: 403 [M + H]+ 27 [00300]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (2H, m), 2.81-3.01 (3H, m), 3.16 (1H, dd, J = 16.4, 5.4 Hz), 3.29 (1H, m), 3.66 (3H, s), 4.14 (1H, m), 4.24-4.33 (3H, m), 4.63 (1H, m), 6.63 (1H, d, J = 8.3 Hz), 6.79 (1H, d, J = 7.2 Hz), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 7.4 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.21 (1H, d, J = ![text missing or illegible when filed]()
.1 Hz), 7.48 (1H, s), 7.54 (1H, t, J = 7.8 Hz). ESI- MS m/z: 405 [M + H]+ 28 [00301]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.16-1.28 (2H, m), 1.56-1.91 (9H, m), 2.12-2.31 (3H, m), 2.69-2.81 (1H, m), 2.93-3.02 (1H, m), 3.56-3.64 (1H, m), 3.77-3.85 (1H, m), 3.90- 3.99 (4H, m), 4.07-4.25 (2H, m), 4.33-4.39 (1H, m), 5.56-5.58 (1H, m), 6.24-6.30 (2H, m), 7.41-7.48 (2H, m). ESI- MS m/z: 411 [M + H]+ 29 [00302]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.55-1.76 (4H, m), 2.01 (1H, m), 2.14-2.28 (3H, m), 2.55-2.83 (3H, m), 2.93-3.03 (1H, m), 3.54-3.62 (1H, m), 3.77-3.97 (2H, m), 4.05-4.38 (3H, m), 5.64 (1H, m), 6.68 (1H, dd, J = ![text missing or illegible when filed]()
, 2.4 Hz), 6.85 (1H, t, J = 5.8 Hz), 7.18-7.32 (4H, m), 7.42 (1H, d, J = 10.2 Hz), 7.55 (1H, t, J = 7.7 Hz), 8.14 (1H, m). ESI- MS m/z: 417 [M + H]+ 30 [00303]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.01 (1H, m), 2.20-2.43 (3H, m), 2.88-3.17 (3H, m), 3.48-3.50 (2H, m), 3.98 (1H, m), 4.30-4.39 (3H, m), 4.79 (0.6H, m), 5.23 (0.4H, m), 7.20-7.32 (5H, m), 7.45-7.52 (2H, m), 7.61 (1H, d, J = 7.3 Hz), 7.68 (1H, t, J = 7.8 Hz). ESI- MS m/z: 441 [M + H]+ 31 [00304]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.01-1.31 (6H, m), 1.68-1.84 (6H, m), 1.94-2.11 (2H, m), 2.26-2.35 (1H, m), 2.63-2.74 (1H, m), 2.99-3.07 (2H, m), 3.46-3.69 (1H, m), 3.64- 3.69 (1H, m), 3.94-4.09 (2H, m), 4.31-4.41 (1H, m), 4.71-4.82 (1H, m), 5.20-5.23 (1H, m), 7.20-7.31 (5H, m), 7.39-7.45 (1H, m). ESI- MS m/z: 378 [M + H]+ 32 [00305]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.83 (2H, m), 2.23 (3H, m), 3.11 (1H, m), 3.38 (1H, m), 3.54 (1H, m), 3.7![text missing or illegible when filed]()
3.89 (2H, m), 4.05 (3H, s), 4.35 (1H, dd, J = 12.1, 5.0 Hz), 4.63 (1H, m), 4.93 (1H, d, J = 11.0 Hz), 5.35 (1H, m), 6.83-6.95 (2H, m), 7.47 (1H, s), 7.49-7.53 (1H, s), 7.63 (1H, s), 8.40 (1H, s). ESI- MS m/z: 523 [M + H]+ 33 [00306]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.76-1.87 (1H, m), 2.12-2.17 (1H, m), 2.49-2.58 (1H, m), 2.76-2.90 (2H, m), 2.95-3.02 (1H, m), 3.15-3.20 (1H, m), 3.61-3.87 (1H, m), 3.90- 3.95 (1H, m), 4.03-4.07 (1H, m), 4.11-4.15 (1H, m), 4.22-4.29 (2H, m), 4.58-4.64 (1H, m), 6.85-6.90 (4H, m), 6.96-7.00 (1H, m), 7.05 (1H, d, J = 6.6 Hz), 7.1![text missing or illegible when filed]()
-7.14 (1H, m), 7.19 (1H, d, J = 8.0 Hz), 7.28- 7.32 (2H, m), 7.45 (1H, s). ESI- MS m/z: 404 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00005 TABLE 5 Ex- am- ple Structural formula NMR MS 34 [00307]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.15 (9H, m), 1.65 (1H, m), 2.02 (1H, m), 2.20 (1H, m), 2.75 (1H, m), 2.84-2.94 (2H, m), 3.18 (1H, m), 3.29 (1H, m), 3.43 (1H, m), 3.68 (1H, m), 4.10-4.16 (2H, m), 4.24 (1H, m), 4.62 (1H, m), 6.85- 6.90 (2H, m), 7.05 (1H, d, J = 7.4 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.16 (1H, d, J = 7.9 Hz), 7.42 (1H, s). ESI- MS m/z: 384 [M + H]+ 35 [00308]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.94 (1H, m), 1.60-1.78 (3H, m), 2.02 (1H, m), 2.13 (1H, m), 2.24-2.45 (3H, m), 2.87- 2.90 (3H, m), 3.18 (1H, m), 3.81 (1H, m), 4.09-4.16 (2H, m), 4.24 (1H, m), 4.61 (1H, m), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 7.2 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.19 (1H, d, J = 8.1 Hz), 7.44 (1H, s). ESI- MS m/z: 370 [M + H]+ 36 [00309]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.96 (9H, s), 1.47-1.56 (1H, m), 1.57-1.76 (1H, m), 2.09-2.15 (1H, m), 2.61-2.70 (1H, m), 2.86 (1H, dd, J = 16.6, 5.4 Hz), 2.93-3.00 (1H, m), 3.17 (1H, dd, J = 1![text missing or illegible when filed]()
.5, 5.5 Hz), 3.66 (1H, dt, J = 12.0, 1.5 Hz), 4.05-4.14 (2H, m), 4.23-4.26 (1H, m), 4.62 (1H, m), 6.85-6.90 (2H, m), 7.04-7.06 (1H, m), 7.09- 7.17 (2H, m), 7.41 (1H, s). ESI- MS m/z: 354 [M + H]+ 37 [00310]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.99-2.06 (1H, m), 2.20-2.28 (1H, m), 2.78-3.01 (3H, m), 3.15-3.21 (1H, m), 3.84-3.98 (2H, m), 4.06-4.16 (4H, m), 4.22-4.25 (1H, m), 4.5![text missing or illegible when filed]()
- 4.65 (1H, m), 6.65-6.90 (2H, m), 7.05 (1H, d, J = 7.3 Hz), 7.10-7.14 (1H, m), 7.19 (1H, d, J = 7.9 Hz), 7.42 (1H, s). ESI- MS m/z: 396 [M + H]+ 38 [00311]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03 (1H, m), 2.24 (1H, m), 2.![text missing or illegible when filed]()
0- 2.8![text missing or illegible when filed]()
(2H, m), 2.91-3.01 (1H, m), 3.14 (1H, m), 3.65- 3.9![text missing or illegible when filed]()
(2H, m), 4.1![text missing or illegible when filed]()
-4.23 (5H, m), 4.60 (1H, m), 6.80 (1H, d, J = 8.6 Hz), 7.03 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 8.9, 2.6 Hz), 7.17 (1H, d, J = 8.0 Hz), 7.42 (1H, s). ESI- MS m/z: 430 [M + H]+ 39 (iso- mer A) [00312]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03 (1H, m), 2.24 (1H, m), 2.80- 2.![text missing or illegible when filed]()
7 (2H, m), 2.96 (1H, m), 3.14 (1H, m), 3.86-3.96 (2H, m), 4.11-4.23 (5H, m), 4.60 (1H, m), 6.79 (1H, d, J = 8.6 Hz), 7.![text missing or illegible when filed]()
3 (1H, d, J = 2.4 Hz), 7.07 (1H, dd, J = 8.7, 2.6 Hz), 7.17 (1H, d, J = 6.1 Hz), 7.42 (1H, s). ESI- MS m/z: 430 [M + H]+ 39 (iso- mer B) [00313]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03 (1H, m), 2.24 (1H, m), 2.79- 2.87 (2H, m), 2.92-3.01 (1H, m), 3.14 (1H, m), 3.86- 3.96 (2H, m), 4.10-4.23 (5H, m), 4.60 (1H, m), 6.80 (1H, d, J = 8.7 Hz), 7.02 (1H, d, J = 2.5 Hz), 7.07 (1H, dd, J = 8.7, 2.6 Hz), 7.17 (1H, d, J = 7.7 Hz), 7.42 (1H, s). ESI- MS m/z: 430 [M + H]+ 40 [00314]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03 (1H, m), 2.24 (1H, m), 2.79- 3.00 (3H, m), 3.19 (1H, m), 3.86-3.96 (2H, m), 4.11- 4.20 (4H, m), 4.27 (1H, m), 4.63 (1H, m), 6.56 (1H, t, J = 56.8 Hz), 6.92 (1H, d, J = 8.4 Hz), 7.17 (1H, d, J = 8.0 Hz), 7.21 (1H, s), 7.26 (1H, m), 7.43 (1H, s). ESI- MS m/z: 446 [M + H]+ 41 [00315]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.85-0.89 (6H, m), 1.81 (1H, m), 1.95 (1H, m), 2.17 (1H, m), 2.73-2.99 (3H, m), 3.15- 3.31 (3H, m), 3.88 (1H, m), 4.03 (2H, d, J = 4.0 Hz), 4.13 (1H, m), 4.24 (1H, m), 4.62 (1H, m), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 6.4 Hz), 7.12 (1H, m), 7.18 (1H, d, J = 7.8 Hz), 7.41 (1H, s). ESI- MS m/z: 370 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00006 TABLE 6 Ex- am- ple Structural formula NMR MS 42 [00316]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.85-1.94 (1H, m), 2.09-2.16 (1H, m), 2.73-3.01 (3H, m), 3.15-3.25 (2H, m), 3.73-3.78 (1H, m), 3.83-3.91 (2H, m), 4.09-4.15 (2H, m), 4.22-4.25 (1H, m), 4.58-4.65 (1H, m), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 7.3 Hz), 7.10-7.14 (1H, m), 7.17 (1H, d, J = 8.0 Hz, 7.25-7.36 (5H, m), 7.38 (1H, s). ESI- MS m/z: 403 [M + H]+ 43 [00317]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.47 (3H, m), 2.86-2.90 (1H, m), 3.17-3.22 (1H, m), 3.99-4.06 (1H, m), 4.11-4.17 (3H, m), 4.19-4.25 (3H, m), 4.41-4.45 (1H, m), 4.58-4.65 (1H, m), 6.64 (1H, m), 6.81 (1H, d, J = ![text missing or illegible when filed]()
.6 Hz), 6.86-6.91 (2H, m). 44 [00318]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.88 (1H, dd, J = 16.3, 5.0 Hz), 3.20 (1H, dd, J = 16.3, 5.0 Hz), 3.91 (1H, t, J = 12.2 Hz), 4.05- 4.19 (4H, m), 4.23-4.28 (2H, m), 4.61-4.65 (1H, m), 6.86- 6.91 (2H, m), 7.05 (1H, d, J = 7.6 Hz), 7.11-7.23 (4H, m), 7.31 (1H, ddd, J = 10.7, 7.6, 2.2 Hz), 7.4![text missing or illegible when filed]()
(1H, s). ESI- MS m/z: 411 [M + H]+ 45 [00319]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17 (3H, s), 2.88 (1H, dd, J = 16.3, 5.0 Hz), 3.20 (1H, dd, J = 16.3, 5.0 Hz), 3.49 (1H, t, J = 12.2 Hz), 4.![text missing or illegible when filed]()
5-4.18 (4H, m), 4.21-4.26 (2H, m), 4.61- 4.64 (1H, m), 6.86-6.91 (2H, m), 7.05-7.22 (6H, m), 7.44 (1H, s). ESI- MS m/z: 425 [M + H]+ 46 [00320]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.27 (1H, brs), 2.55-2.91 (1H, m), 3.17-3.22 (1H, m), 4.11-4.29 (5H, m), 4.41-4.46 (2H, m), 4.60-4.65 (1H, m), 6.86-6.91 (2H, m), 7.06 (1H, d, J = 7.2 Hz), 7.13 (1H, t, J = 7.8 Hz), 7.20-7.23 (1H, m), 7.52 (1H, s), 7.66-7.72 (2H, m), 7.94 (1H, t, J = 7.8 Hz). ESI- MS m/z: 444 [M + H]+ 47 [00321]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (3H, s), 2.87 (1H, dd, J = 17.5, 5.7 Hz), 3.08-3.14 (1H, m), 3.84 (1H, dd, J = 16.4, 3.7 Hz), 4.02 (1H, dd, J = 16.1, 2.![text missing or illegible when filed]()
Hz), 4.11-4.24 (3H, m), 4.31- 4.36 (1H, m), 4.38-4.45 (1H, m), 4.63-4.67 (1H, m), 6.![text missing or illegible when filed]()
2- 6.7![text missing or illegible when filed]()
(2H, m), 7.05-7.09 (1H, m), 7.17-7.20 (1H, m), 7.52 (1H, d, J = 2.9 Hz), 7.66-7.71 (2H, m), 7.94 (1H, t, J = 7.8 Hz). ESI- MS m/z: 476 [M + H]+ 48 [00322]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.97 (2H, t, J = 7.3 Hz), 3.67 (2H, q, J = 7.0 Hz), 3.98 (1H, m), 4.13-4.30 (4H, m), 7.11 (1H, m), 7.34-7.49 (10H, m). ESI- MS m/z: 415 [M + H]+ 49 [00323]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.92 (6H, d, J = 7.3 Hz), 1.22-1.41 (3H, m), 1.51-1.56 (2H, m), 2.87 (1H, dd, J = 16.3, 5.5 Hz), 3.00-3.04 (1H, m), 3.18 (1H, dd, J = 16.3, 5.5 Hz), 3.60 (1H, t, J = 12.4 Hz), 3.95-4.03 (2H, m), 4.11-4.16 (2H, m), 4.24 (1H, d, J = 10.7 Hz), 4.60-4.64 (1H, m), 6.85-6.90 (2H, m), 7![text missing or illegible when filed]()
5 (1H, d, J = 7.3 Hz), 7.12 (1H, t, J = 7.3 Hz), 7.17 (1H, d, J = 7.3 Hz), 7.43 (1H, s) ESI- MS m/z: 369 [M + H]+ 50 [00324]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.90 (3H, d, J = 6.6 Hz), 0.91 2H, d, J = 7.3 Hz), 1.20-1.32 (2H, m), 1.35-1.44 (1H, m), 1.50-1.57 (1H, m), 1.63-1.71 (1H, m), 2.38 (3H, s), 2.54- 2.90 (2H, m), 3.18 (1H, dd, J = 15.3, 8.5 Hz), 3.70 (1H, dd, J = 12.4, 4.2 Hz), 3.79 (1H, ![text missing or illegible when filed]()
dd, J = 12.4, 8.2, 1.5 Hz), 3.![text missing or illegible when filed]()
5 (1H, dd, J = 16.![text missing or illegible when filed]()
, 3.8 Hz), 3.![text missing or illegible when filed]()
(1H, dd, J = 12.4, 4.2 Hz), 4.14 (1H, ddd, J = 10.7, 5.4, 1.5 Hz), 4.24 (1H, d, J = 10.7 Hz), 4.5![text missing or illegible when filed]()
-4.69 (1H, m), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 7.3 Hz), 7.12 (1H, t, J = 7.3 Hz), ![text missing or illegible when filed]()
.17 (1H, d, J = 8.5 Hz), ,7.49 (1H, s) ESI- MS m/z: 383 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00007 TABLE 7 Ex- am- ple Structural formula NMR MS 51 [00325]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.08-1.13 (3H, m), 1.39-1.44 (2H, m), 1.46-1.57 (5H, m), 1.72- 1.77 (3H, m), 2.66 (1H, dd, J = 16.3, 5.5 Hz), 3.00-3.05 (1H, m), 3.18 (1H, dd, J = 16.3 5.5 Hz), 3.5![text missing or illegible when filed]()
(1H, t, J = 12.4 Hz), 3.9![text missing or illegible when filed]()
-4.03 (2H, m), 4.10-4.15 (2H, m), 4.24 (1H, d, J = 10.7 Hz), 4.59-4.64 (1H, m). ESI- MS m/z: 395 [M + H]+ 52 [00326]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06-1.11 (3H, m), 1.35- 1.42 (3H, m), 1.51-1.56 (4H, m), 1.72-1.76 (3H, m), 2.38 (3H, s), 2.![text missing or illegible when filed]()
-2.9![text missing or illegible when filed]()
(2H, m), 3.18 (1H, dd, J = 16.3, 5.5 Hz), ![text missing or illegible when filed]()
.69 (1H, dd, J = 12.4, 4.2 Hz), 3.79 (1H, ddd, J = 12.4, 8.2, 1.![text missing or illegible when filed]()
Hz), 3.85 (1H, dd, J = 16.2, 3.8 Hz), 3.98 (1H, dd, J = 12.4, 4.2 Hz), 4.14 (1H, ddd, J = 1![text missing or illegible when filed]()
.7, 5.4, 1.6 Hz), 4.24 (1H, d, J = 10.7 Hz), 4.50-4.84 (1H, m), 6.85- 6.90 (2H, m), 7.05 (1H, d, J = 7.3 Hz), 7.12 (1H, t, J = 7.3 Hz), 7.18 (1H, d, J = 7.3 Hz), 7.43 (1H, s). ESI- MS m/z: 409 [M + H]+ 53 [00327]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80-1.85 (2H, m), 2.70- 2.81 (2H, m), 2.86 (1H, dd, J = 16.3, 5.0 Hz), 3.01-3.09 (1H, m), 3.18 (1H, dd, J = 16.3, 5.0 Hz), 3.63 (1H, t, J = 10.2 Hz), 3.95 (1H, dd, J = 16.3, 5.0 Hz), 4.00 (1H, dd, J = 12.4, 3.1 Hz), 4.11-4.16 (2H, m), 4.23 (1H, d, J = 10.7 Hz), 4.58- 4.65 (1H, m), 6.85-6.90 (2H, m), 6.99 (2H, t, J = 8.7 Hz), 7.05 (1H, d, J = 7.3 Hz), 7.10-7.18 (4H, m), 7.42 (1H, s). ESI- MS m/z: 421 [M + H]+ 54 [00328]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.63-1.72 (1H, m), 1.92- 1.97 (1H, m), 2.3![text missing or illegible when filed]()
(![text missing or illegible when filed]()
H, s), 2.66-2.74 (2H, m), 2.87 (1H, dd, J = 16.3, 5.0 Hz), 2.95-2.97 (1H, m), 3.15 (1H, dd, J = 16.3, ![text missing or illegible when filed]()
Hz), 3.74-3.88 (3H, m), 3.95 (1H, dd, J = 12.4, 3.1 Hz), 4.14 (1H, ddd, J = 10.7, 5.4, 1.![text missing or illegible when filed]()
Hz), 4.23 (1H, d, J = 10.7 Hz), 4.59- 4.65 (1H, m), 5.86-5.90 (2H, m), 5.98 (2H, t, J = 8.7 Hz), 7.05 (1H, d, J = 7.3 Hz), 7.11-7.19 (4H, m), 7.43 (1H, s). ESI- MS m/z: 435 [M + H]+ 55 [00329]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.56 (1H, q, J = 7.5 Hz), 1.69-1.85 (2H, m), 2.05 (2H, s), 2.67 (2H, t, J = 7.5 Hz), 2.87 (1H, dd, J = 16.6, 5.3 Hz), 3.02-3.09 (1H, m), 3.16 (1H, dd, J = 16.5, 5.4 Hz), 3.57 (1H, t, J = 11.3 Hz), 3.92-4.09 (2H, m), 4.09-4.15 (2H, m), 4.23 (1H, d, J = 10.7 Hz), 4.58-4.64 (1H, m), 6.54-6.![text missing or illegible when filed]()
9 (2H, m), 7.![text missing or illegible when filed]()
9- 7.29 (8H, m), 7.43 (1H, s). ESI- MS m/z: 417 [M + H]+ 56 [00330]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00 (1H, brs), 2.68 (1H, dd, J = 16.7, 4.9 Hz), 3.71-3.22 (1H, m), 3.97 (1H, t, J = 11.3 Hz), 4.11-4.27 (6H, m), 4.63 (1H, s), 6.89 (2H, t, J = 9.4 Hz), 7.06 (1H, d, J = 7.4 Hz), 7.1![text missing or illegible when filed]()
(1H, t, J = 7.6 Hz), 7.21 (1H, m), 7.36-7.48 (6H, m). ESI- MS m/z: 375 [M + H]+ 57 [00331]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16 (3H, s), 2.89 (1H, dd, J = 16.7, 5.1 Hz), 3.20 (1H, d, J = 16.3 Hz), 3.49 (1H, dd, J = 15.7, 4.9 Hz), 3.57 (1H, m), 4.07-4.10 (3H, m), 4.14-4.17 (1H, m), 4.25 (1H, d, J = 10.6 Hz), 4.63 (1H, m), 6.89 (2H, t, J = 9.0 Hz), 7.06 (1H, d, J = 7.1 Hz), 7.13 (1H, t, J = 7.5 Hz), 7.22 (1H, m), 7.32-7.39 (5H, m), 7.45 (1H, s). ESI- MS m/z: 389 [M + H]+ 58 [00332]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (3H, s), 2.91 (2H, t, J = 7.5 Hz), 3.52 (1H, d, J = 16.6 Hz), 3.59 (1H, t, J = 7.1 Hz), 3.68 (2H, q, J = 7.0 Hz), 4.07-4.13 (3H, m), 7.11 (1H, t, J = 7.9 Hz), 7.20-7.46 (11H, m). ESI- MS m/z: 361 [M + H]+ 59 [00333]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.23-1.38 (2H, m), 1.60-1.70 (4H, m), 1.79-1.93 (3H, m), 2.17 (1H, s), 2.78-2.89 (2H, m), 3.15-3.21 (1H, m), 3.66 (1H, t, J = 11.0 Hz), 3.94- 4.05 (2H, m), 4.12-4.17 (2H, m), 4.24 (1H, d, J = 10.7 Hz), 4.61 (1H, m), 6.85- 6.90 (2H, m), 7.![text missing or illegible when filed]()
5 (1H, d, J = 7.5 Hz), 7.10-7.17 (2H, m), 7.43 (1H, s). ESI- MS m/z: 367 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00008 TABLE 8 Ex- am- ple Structural formula NMR MS 60 [00334]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00-2.14 (2H, m), 2.33-2.41 (1H, m), 3.44-3.52 (1H, m), 3.64-3.77 (1H, m), 3.87-4.02 (2H, m), 4.13-4.41 (4H, m), 4.65 (1H, m), 7.36-7.54 (10H, m). ESI- MS m/z: 441 [M + H]+ 61 [00335]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.07 (1H, brs), 2.79-3.50 (2H, m), 3.79-3.85 (1H, m), 3.99 (1H, t, J = 11.1 Hz), 4.14-4.35 (5H, m), 4.61-4.84 (2H, m), 5.39-5.57 (1H, m), 7.37-7.50 (7H, m), 7.56-7.62 (2H, m), 7.73 (1H, s). ESI- MS m/z: 457 [M + H]+ 62 [00336]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (3H, s), 2.87 (2H, t, J = 7.1 Hz), 3.15-3.17 (4H, m), 3.48-3.53 (1H, m), 3.57-3.68 (3H, m), 3.85-3.87 (4H, m), 4.08-4.12 (3H, m), 6.75-6.80 (3H, m), 7.17-7.24 (2H, m), 7.33-7.43 (6H, m). ESI- MS m/z: 446 [M + H]+ 63 [00337]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16 (3H, s), 3.51-3.61 (2H, m), 4.0![text missing or illegible when filed]()
(2H, d, J = 6.7 Hz), 4.11-4.23 (2H, m), 4.58-4.60 (2H, m), 5.01-5.![text missing or illegible when filed]()
9 (1H, m), 5.47-5.53 (1H, m), 6.98 (1H, d, J = 8.4 Hz), 7.28-7.41 (6H, m), 7.46 (1H, s), 7.7![text missing or illegible when filed]()
(1H, t, J = 7.5 Hz). ESI- MS m/z: 458 [M + H]+ 64 [00338]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.84 (1H, dd, J = 16.6, 4.5 Hz), 3.14 (1H, dd, J = 16.6, 5.4 Hz), 3.80 (2H, t, J = 5.1 Hz), 3.99 (2H, t, J = 5.1 Hz), 4.09-4.20 (2H, m), 4.54 (1H, m), 4.83 (2H, s), 6.85-6.90 (2H, m), 7.04 (1H, d, J = 7.4 Hz), 7.12 (1H, m), 7.30 (1H, m), 7.40-7.45 (5H, m). ESI- MS m/z: 376 [M + H]+ 65 [00339]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (1H, dd, J = 17.0, 4.4 Hz), 3.12 (1H, dd, J = 16.6, 5.4 Hz), 3.91 (3H, s), 4.02 (2H, t, J = 5.0 Hz), 4.13-4.24 (4H, m), 4.54 (1H, m), 4.84 (2H, s), 6.74 (1H, d, J = 7.7 Hz), 6.80 (1H, d, J = 8.7 Hz), 7.03 (1H, s), 7.07 (1H, d, J = 8.8 Hz), 7.45 (1H, d, J = 7.6 Hz), 7.66-7.73 (2H, m). ESI- MS m/z: 441 [M + H]+ 66 [00340]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.84 (1H, dd, J = 16.7, 4.6 Hz), 3.13 (1H, dd, J = 17.0, 5.4 Hz), 4.02 (2H, t, J = 4.8 Hz), 4.13- 4.20 (4H, m), 4.54 (1H, m), 4.84 (2H, s), 6.81 (1H, d, J = ![text missing or illegible when filed]()
.7 Hz), 7.03 (1H, s), 7.08 (1H, d, J = 6.9 Hz), 7.29 (1H, m), 7.51 (1H, d, J = 7.8 Hz), 7.![text missing or illegible when filed]()
0 (1H, t, J = 7.8 Hz), 8.07 (1H, d, J = 7.8 Hz), 8.63 (1H, d, J = 4.2 Hz). ESI- MS m/z: 411 [M + H]+ 67 [00341]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.92 (1H, dd, J = 16.7, 4.9 Hz), 3.18 (1H, dd, J = 16.8, 5.3 Hz), 4.02 (2H, t, J = 5.0 Hz), 4.17- 4.28 (4H, m), 4.56 (1H, m), 4.84 (2H, s), 6.94 (1H, d, J = 8.5 Hz), 7.28 (1H, m), 7.32 (1H, s), 7.38 (1H, d, J = 8.6 Hz), 7.50 (1H, d, J = 8.0 Hz), 7.80 (1H dt, J = 1.8, 7.6 Hz), 8.07 (1H, dt, J = 1.0, ![text missing or illegible when filed]()
.0 Hz), 8.62 (1H, m). ESI- MS m/z: 445 [M + H]+ 68 [00342]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.21-2.30 (2H, m), 2.37 (3H, s), 2.80-2.92 (2H, m), 3.12 (1H, dd, J = 16.6, 4.5 Hz), 3.20 (1H, dd, J = 16.6, 5.5 Hz), 3.32 (1H, m), 4.09-4.30 (4H, m), 4.65 (1H, m), 6.55 (1H, s), 6.87-6.92 (2H, m), 7.06-7.19 (7H, m). ESI- MS m/z: 388 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00009 TABLE 9 Ex- am- ple Structural formula NMR MS 69 [00343]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.62-1.66 (2H, m), 2.01-2.08 (2H, m), 2.86 (1H, dd, J = 16.6, 4.6 Hz), 2.96-3.01 (2H, m), 3.16 (1H, dd, J = 16.7, 5.5 Hz), 3.90 (3H, s), 4.12-4.19 (4H, m), 4.57-4.65 (1H, m), 6.60 (1H, dd, J = 8.2, 0.68 Hz), 6.83-6.90 (2H, m), 7.04 (1H, d, J = 7.5 Hz), 7.09-7.14 (1H, m), 7.21-7.29 (1H, m), 7.40 (1H, dd, J = 7.4, 0.70 Hz), 7.54-7.59 (1H, m). ESI- MS m/z: 405 [M + H]+ 70 [00344]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.34-2.50 (2H, m), 2.92 (1H, m), 3.18 (1H, m), 4.14-4.32 (4H, m), 4.65 (1H, m), 5.56 (1H, m), 6.12 (1H, s), 6.93-6.95 (2H, m), 7.11 (1H, m), 7.21 (1H, t, J = 7.6 Hz), 7.34-7.49 (4H, m). ESI- MS m/z: 419 [M + H]+ 71 [00345]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.39-2.48 (2H, m), 2.87 (1H, m), 3.16 (1H, m), 4.15-4.28 (4H, m), 4.63 (1H, m), 5.![text missing or illegible when filed]()
6 (1H, m), 6.11 (1H, s), 6.77 (1H, d, J = 6.7 Hz), 7.02 (1H, m), 7.10 (1H, m), 7.19-7.27 (3H, m), 7.36 (1H, m), 7.47 (1H, m). ESI- MS m/z: 472, 474 [M + H]+ 72 [00346]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.32-2.43 (1H, m), 2.53- 2.57 (1H, m), 2.93 (1H, dd, J = 17.1, 4.7 Hz), 3.19 (1H, dt, J = 16.6, 4.9 Hz), 4.21-4.35 (4H, m), 4.63-4.67 (1H, m), 5.59-5.62 (1H, m), 6.14 (1H, s), 6.90-6.96 (2H, m), 7.39-7.44 (2H, m), 7.49-7.55 (1H, m), 7.67-7.74 (3H, m). ESI- MS m/z: 426 [M + H]+ 73 [00347]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.30-2.49 (2H, m), 2.91 (1H, dd, J = 16.9, 4.8 Hz), 3.1![text missing or illegible when filed]()
(1H, dd, J = 16.6, 5.2 Hz), 3.95 (3H, s), 4.09-4.32 (4H, m), 4.65 (1H, m), 5.24 (1H, d, J = 9.2 Hz), 6.13 (1H, s), 6.75 (1H, s), 6.86 (1H, d, J = 5.3 Hz), 6.93 (2H, d, J = ![text missing or illegible when filed]()
.4 Hz), 7.37-7.43 (2H, m), ![text missing or illegible when filed]()
.20 (1H, d, J = 5.3 Hz). ESI- MS m/z: 432 [M + H]+ 74 (iso- mer A) [00348]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.36 (1H, m), 2.44 (1H, m), 2.91 (1H, dd, J = 16.7, 4.3 Hz), 3.18 (1H, dd, J = 16.8, 5.3 Hz), 3.95 (3H, s), 4.09-4.32 (4H, m), 4.64 (1H, m), 5.24 (1H, dd, J = 9.3, 2.5 Hz), 6.13 (1H, s), 6.75 (1H, s), 6.![text missing or illegible when filed]()
6 (1H, d, J = 4.4 Hz), 6.93 (2H, d, J = 8.4 Hz), 7.39 (1H, s), 7.41 (1H, dd, J = 16.8, 1.6 Hz), 8.19 (1H, d, J = 5.3 Hz). ESI- MS m/z: 432 [M + H]+ 74 (iso- mer B) [00349]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.36 (1H, m), 2.44 (1H, m), 2.91 (1H, dd, J = 16.7, 4.3 Hz), 3.18 (1H, dd, J = 16.8, 5.3 Hz), 3.95 (3H, s), 4.11-4.30 (4H, m), 4.64 (1H, m), 5.24 (1H, dd, J = 9.3, 2.5 Hz), 6.13 (1H, s), 6.75 (1H, s), 6.56 (1H, d, J = 4.4 Hz), 6.93 (2H, d, J = 8.4 Hz), 7.39 (1H, s), 7.41 (1H, dd, J = 16.8, 1.6 Hz), 8.19 (1H, d, J = 5.3 Hz). ESI- MS m/z: 432 [M + H]+ 75 [00350]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24 (1H, m), 2.54 (1H, m), 2.92 (1H, dd, J = 16.9, 4.![text missing or illegible when filed]()
Hz), 3.18 (1H, dd, J = 16.6, 5.0 Hz), 3.99 (3H, s), 4.12 (1H, s), 4.18-4.32 (3H, m), 4.65 (1H, m), 5.47 (1H, d, J = 9.6 Hz), 6.11 (1H, s), 6.93-6.97 (3H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.5 Hz), 7.78 (1H, d, J = 7.4 Hz), 8.16 (1H, dd, J = 5.0, 1.4 Hz). ESI- MS m/z: 432 [M + H]+ 76 [00351]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.20 (3H, t, J = 7.6 Hz), 2.3-2.49 (2H, m), 2.56 (2H, q, J = 7.6 Hz), 2.86 (1H, m), 3.17 (1H, m), 4.12-4.27 (4H, m), 4.64 (1H, m), 5.55 (1H, m), 6.11 (1H, s), 6.80 (1H, d, J = 8.3 Hz), 6.89 (1H, s), 6.96 (1H, d, J = 8.3 Hz), 7.07-7.12 (2H, m), 7.20 (1H, m), 7.35 (1H, m), 7.4 (1H, m). ESI- MS m/z: 422 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00010 TABLE 10 Ex- am- ple Structural formula NMR MS 77 [00352]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41-2.47 (2H, m), 2.91 (1H, dd, J = 17.5, 4.4 Hz), 3.13 (1H, dd, J = 17.6, ![text missing or illegible when filed]()
.9 Hz), 4.15-4.24 (4H, m), 4.68 (1H, m), 5.27 (1H, m), 6.11 (1H, s), 6.82 (1H, dd, J = 8.2, 1.1 Hz), 6.99-7.03 (2H, m), 7.08 (1H, t, J = 8.0 Hz), 7.36- 7.44 (5H, m). ESI- MS m/z: 410 [M + H]+ 78 [00353]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41-2.47 (2H, m), 2.90 (1H, m), 3.12 (1H, dd, J = 17.4, 5.7 Hz), 4.14-4.19 (4H, m), 4.65 (1H, m), 5.27 (1H, m), 6.11 (1H, s), 6.63-6.66 (2H, m), 6.98 (1H, d, J = 8.1 Hz), 7.15 (1H, t, J = 8.3 Hz), 7.35-7.44 (5H, m). ESI- MS m/z: 460 [M + H]+ 79 [00354]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.41 (3H, t, J = 6.6 Hz), 2.41-2.49 (2H, m), 2.66 (2H, t, J = 7.2 Hz), 3.66 (2H, q, J = 7.2 Hz), 4.03 (2H, q, J = 7.0 Hz), 4.16-4.26 (2H, m), 5.28 (1H, dd, J = 9.0, 3.6 Hz), 6.09 (1H, s), 6.75-6.![text missing or illegible when filed]()
(4H, m), 7.21 (1H, t, J = 6.1 Hz), 7.35-7.45 (5H, m). ESI- MS m/z: 392 [M + H]+ 80 [00355]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.33-2.50 (2H, m), 2.98 (1H, dd, J = 16.8, 4.4 Hz), 3.26 (1H, dd, J = 16.7, 5.3 Hz), 4.13-4.3![text missing or illegible when filed]()
(4H, m), 4.69 (1H, m), 5.56 (1H, m), 6.12 (1H, s), 6.99 (1H, d, J = 8.5 Hz), 7.05-7.12 (2H, m), 7.26 (1H, m), 7.32-7.39 (2H, m), 7.43-7.49 (4H, m), 8.61 (2H, d, J = 5.2 Hz). ESI- MS m/z: 471 [M + H]+ 81 [00356]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.36-2.47 (2H, m), 2.97 (1H, dd, J = 16.5, 3.5 Hz), 3.27 (1H, dd, J = 16.4, 5.3 Hz), 4.13-4.28 (4H, m), 4.![text missing or illegible when filed]()
8 (1H, m), 5.55 (1H, d, J = 9.4 Hz), 6.11 (1H, s), 6.98 (1H, d, J = ![text missing or illegible when filed]()
.3 Hz), 7.04-7.12 (2H, m), 7.16-7.22 (2H, m), 7.35 (1H, m), 7.46 (1H, m), 7.64-7.77 (4H, m), 8.64 (1H, d, J = 3.![text missing or illegible when filed]()
Hz). ESI- MS m/z: 471 [M + H]+ 82 [00357]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.66 (1H, m), 2.33- 2.49 (2H, m), 2.86 (1H, dd, J = 16.7, 4.2 Hz), 3.19 (1H, dd, J = 16.9, 5.3 Hz), 4.12- 4.27 (4H, m), 4.59-4.65 (3H, m), 5.55 (1H, td, J = 9.5, 3.0 Hz), 6.11 (1H, s), 6.87 (1H, d, J = 6.3 Hz), 7.05-7.14 (4H, m), 7.20 (1H, tt, J = 7.5, 1.6 Hz), 7.35 (1H, m), 7.46 (1H, tt, J = 11.4, 1.9 Hz). ESI- MS m/z: 424 [M + H]+ 83 [00358]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.24 (3H, t, J = 6.8 Hz), 2.34-2.48 (2H, m), 2.87 (1H, m), 3.19 (1H, dd, J = 5.3, 17.1 Hz), 3.55 (2H, q, J = 7.0 Hz), 4.14-4.27 (4H, m), 4.39 (2H, s), 4.63 (1H, m), 5.56 (1H, d, J = 9.5 Hz), 6.10 (1H, s), 6.85 (1H, d, J = 8.3 Hz), 7.03-7.12 (4H, m), 7.2![text missing or illegible when filed]()
(1H, t, J = 7.6 Hz), 7.35 (1H, q, J = 6.9 Hz), 7.47 (1H, t, J = 7.4 Hz). ESI- MS m/z: 452 [M + H]+ 84 [00359]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.59-1.70 (2H, m), 1.![text missing or illegible when filed]()
9-1.96 (2H, m), 2.38-2.49 (2H, m), 2.88 (1H, dd, J = 16.2, 3.![text missing or illegible when filed]()
Hz), 3.19 (1H, dd, J = 16.8, 5.6 Hz), 3.44 (2H, m), 3.59 (1H, m), 3.95-4.00 (2H, m), 4.10- 4.27 (4H, m), 4.45 (2H, s), 4.64 (1H, m), 5.56 (1H, d, J = 9.5 Hz), 6.11 (1H, s), 6.86 (1H, d, J = 8.3 Hz), 7.04-7.13 (4H, m), 7.21 (1H, t, J = 7.2 Hz), 7.36 (1H, q, J = 6.9 Hz), 7.47 (1H, t, J = 7.6 Hz). ESI- MS m/z: 506 [M + H]+ 85 [00360]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46 (3H, d, J = 6.3 Hz), 2.06 (1H, m), 2.17 (1H, m), 2.84 (1H, dd, J = 16.8, 4.3 Hz), 3.14 (1H, dd, J = 16.8, 5.4 Hz), 4.02-4.19 (4H, m), 4.34 (1H, m), 4.60 (1H, m), 5.98 (1H, s), 6.80 (1H, d, J = 6.8 Hz), 6.99 (1H, d, J = 8.3 Hz), 7.03 (1H, d, J = 2.2 Hz), 7.08 (1H, dd, J = 8.7, 2.4 Hz). ESI- MS m/z: 348 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00011 TABLE 11 Ex- am- ple Structural formula NMR MS 86 [00361]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46 (3H, d, J = 6.3 Hz), 2.05 (1H, m), 2.17 (1H, m), 2.84 (1H, dd, J = 16.9, 4.3 Hz), 3.14 (1H, dd, J = 16.7, 5.4 Hz), 4.07 (1H, m), 4.1![text missing or illegible when filed]()
-4.19 (3H, m), 4.34 (1H, m), 4.60 (1H, m), 5.98 (1H, s), 6.80 (1H, d, J = 8.6 Hz), 6.99 (1H, d, J = 8.5 Hz), 7.![text missing or illegible when filed]()
4 (1H, s), 7.08 (1H, dd, J = ![text missing or illegible when filed]()
.7, 2.4 Hz). ESI- MS m/z: 346 [M + H]+ 87 [00362]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46 (3H, d, J = 6.3 Hz), 2.06 (1H, m, J = ![text missing or illegible when filed]()
.9 Hz), 2.18 (1H, m), 2.84 (1H, dd, J = 16.9, 4.3 Hz), 3.14 (1H, dd, J = 16.8, 5.4 Hz), 4.07 (1H, m), 4.13-4.19 (3H, m), 4.34 (1H, m), 4.60 (1H, m), 5.98 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.9 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 8.7, 2.4 Hz). ESI- MS m/z: 348 [M + H]+ 88 [00363]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46 (3H, d, J = 6.3 Hz), 2.05 (1H, m), 2.17 (1H, m), 2.65 (1H, dd, J = 16.6, 4.1 Hz), 3.15 (1H, dd, J = 16.9, 5.4 Hz), 4.13 (1H, m), 4.13-4.19 (3H, m), 4.34 (1H, m), 4.61 (1H, m), 5.96 (1H, s), 6.76 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = ![text missing or illegible when filed]()
.4 Hz), 7.18 (1H, s), 7.22 (1H, dd, J = 8.8, 2.2 Hz). ESI- MS m/z: 392, 394 [M + H]+ 89 [00364]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46 (3H, d, J = 6.3 Hz), 2.06 (1H, m), 2.17 (1H, m), 2.85 (1H, dd, J = 16.9, 4.0 Hz), 3.15 (1H, dd, J = 17.0, 5.4 Hz), 4.06 (1H, m), 4.13-4.19 (3H, m), 4.34 (1H, m), 4.60 (1H, m), 5.96 (1H, s), 6.76 (1H, d, J = 6.6 Hz), 6.98 (1H, d, J = 7.8 Hz), 7.1![text missing or illegible when filed]()
(1H, s), 7.21 (1H, d, J = 8.6 Hz). ESI- MS m/z: 392, 394 [M + H]+ 90 [00365]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.05 (3H, t, J = 7.5 Hz), 1.75 (1H, m), 1.85 (1H, m), 2.05 (1H, m), 2.18 (1H, m), 2.84 (1H, dd, J = 16.8, 4.2 Hz), 3.14 (1H, dd, J = 16.9, 5.2 Hz), 4.01-4.19 (5H, m), 4.60 (1H, m), 5.99 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.9 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 6.6, 2.3 Hz). ESI- MS m/z: 362 [M + H]+ 91 [00366]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.05 (3H, t, J = 7.5 Hz), 1.73 (1H, m), 1.81 (1H, m), 2.05 (1H, m), 2.18 (1H, m), 2.90 (1H, dd, J = 16.7, 4.5 Hz), 3.17 (1H, dd, J = 16.8, 5.1 Hz), 4.92-4.18 (3H, m), 4.21-4.31 (2H, m), 4.63 (1H, m), 5.99 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI- MS m/z: 353 [M + H]+ 92 (iso- mer A) [00367]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06 (3H, t, J = 7.5 Hz), 1.64- 1.88 (2H, m), 2.05 (1H, m), 2.19 (1H, m), 2.90 (1H, dd, J = 16.7, 5.1![text missing or illegible when filed]()
, 3.17 (1H, dd, J = 16.7, 5.1 Hz), 3.99-4.19 (3H, m), 4.21-4.33 (2H, m), 4.63 (1H, m), 6.0![text missing or illegible when filed]()
(1H, s), 6.93 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI- MS m/z: 353 [M + H]+ 92 (iso- mer B) [00368]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06 (3H, t, J = 7.5 Hz), 1.64- 1.66 (2H, m), 2.05 (1H, m), 2.19 (1H, m), 2.90 (1H, dd, J = 16.7, 5.1 Hz), 3.17 (1H, dd, J = 16.7, 5.1 Hz), 3.99-4.19 (3H, m), 4.21-4.33 (2H, m), 4.53 (1H, m), 5.00 (1H, s), 6.93 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 6.8 Hz). ESI- MS m/z: 353 [M + H]+ 93 [00369]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.05 (3H, t, J = 7.5 Hz), 1.72 (1H, m), 1.63 (1H, m), 2.00 (1H, m), 2.16 (1H, m), 2.96 (1H, dd, J = 16.8, 4.3 Hz), 3.24 (1H, dd, J = 16.7, 6.4 Hz), 4.01-4.28 (8H, m), 4.67 (1H, m), 6.00 (1H, s), 6.98 (1H, d, J = 8.4 Hz), 7.03 (1H, d, J = 8.0 Hz), 7.20 (1H, d, J = 2.1 Hz), 7.29 (1H, d, J = 2.3 Hz), 8.65 (2H, s). ESI- MS m/z: 436 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00012 TABLE 12 Example Structural formula NMR MS 94 [00370]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (3H, t, J = 7.2 Hz), 1.48 (1H, m), 1.64 (1H, m), 1.50 (1H, m), 2.06 (1H, m), 2.16 (1H, m), 2.91 (1H, dd, J = 17.7, 5.2 Hz), 3.17 (1H, dd, J = 17.7, 6.9 Hz), 4.06 (1H, m), 4.12-4.32 (5H, m), 4.63 (1H, m), 5.98 (1H, s), 6.92 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 367 [M + H]+ 95 (isomer A) [00371]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (3H, t, J = 7.2 Hz), 1.48 (1H, m), 1.64 (1H, m), 1.89 (1H, m), 2.06 (1H, m), 2.18 (1H, m), 2.91 (1H, dd, J = 17.7, 5.2 Hz), 3.17 (1H, dd, J = 17.7, 6.9 Hz), 4.06 (1H, m), 4.12-4.32 (5H, m), 4.63 (1H, m), 5.98 (1H, s), 6.92 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz) ESI-MS m/z: 367 [M + H]+ 95 (isomer B) [00372]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (3H, t, J = 7.2 Hz), 1.48 (1H, m), 1.64 (1H, m), 1.80 (1H, m), 2.06 (1H, m), 2.18 (1H, m), 2.91 (1H, dd, J = 17.7, 5.2 Hz), 3.17 (1H, dd, J = 17.7, 6.9 Hz), 4.06 (1H, m), 4.12-4.32 (5H, m), 4.63 (1H, m), 5.98 (1H, s), 6.92 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz) ESI-MS m/z: 367 [M + H]+ 96 [00373]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.12-0.16 (2H, m), 0.53-0.55 (2H, m), 0.84 (1H, m), 1.49 (1H, m), 1.81 (1H, m), 2.10 (1H, m), 2.28 (1H, m), 2.91 (1H, m), 3.17 (1H, m), 4.08 (1H, m), 4.15 (1H, m), 4.23-4.31 (3H, m), 4.63 (1H, m), 5.99 (1H, m), 6.92-6.94 (2H, m), 7.38 (1H, m), 7.42 (1H, m). ESI-MS m/z: 379 [M + H]+ 97 (isomer A) [00374]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.12-0.16 (2H, m), 0.53-0.55 (2H, m), 0.84 (1H, m), 1.49 (1H, m), 1.81 (1H, m), 2.10 (1H, m), 2.28 (1H, m), 2.91 (1H, dd, J = 16.4, 4.5 Hz), 3.17 (1H, dd, J = 16.9, 5.2 Hz), 4.08 (1H, m), 4.16 (1H, m), 4.25-4.31 (3H, m), 4.63 (1H, m), 5.99 (1H, s), 6.92-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 379 [M + H]+ 97 (isomer B) [00375]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.12-0.15 (2H, m), 0.53-0.55 (2H, m), 0.84 (1H, m), 1.49 (1H, m), 1.81 (1H, m), 2.11 (1H, m), 2.28 (1H, m), 2.90 (1H, m), 3.17 (1H, dd, J = 16.8, 4.8 Hz), 4.07 (1H, m), 4.17 (1H, m), 4.23-4.31 (3H, m), 4.63 (1H, m), 5.99 (1H, s), 6.92- 6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.4 Hz). ESI-MS m/z: 379 [M + H]+ 98 [00376]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.27 (2H, m), 2.84 (1H, dd, J = 17.0, 4.1 Hz), 3.14 (1H, dd, J = 17.0, 5.2 Hz), 3.66 (1H, dd, J = 10.3, 5.1 Hz), 3.75 (1H, dd, J = 10.3, 5.1 Hz), 4.07 (1H, m), 4.15-4.19 (3H, m), 4.37 (1H, m), 4.56- 4.64 (3H, m), 6.02 (1H, s), 6.80 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 7.9 Hz), 7.03 (1H, d, J = 2.2 Hz), 7.08 (1H, dd, J = 8.7, 2.4 Hz), 7.34 (5H, m). ESI-MS m/z: 454 [M + H]+ 99 [00377]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.27 (2H, m), 2.90 (1H, dd, J = 16.7, 4.6 Hz), 3.17 (1H, dd, J = 16.8, 5.0 Hz), 3.67 (1H, dd, J = 10.3, 5.0 Hz), 3.75 (1H, dd, J = 10.3, 5.1 Hz), 4.06 (1H, m), 4.17 (1H, m), 4.23-4.31 (2H, m), 4.36 (1H, m), 4.60-4.65 (3H, m), 6.03 (1H, s), 6.90-6.94 (2H, m), 7.30-7.43 (7H, m). ESI-MS m/z: 445 [M + H]+ 100 [00378]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.92 (3H, t, J = 7.4 Hz), 1.56-1.64 (2H, m), 2.15-2.29 (2H, m), 2.90 (1H, dd, J = 16.6, 4.8 Hz), 3.17 (1H, dd, J = 16.7, 5.3 Hz), 3.47 (1H, t, J = 6.6 Hz), 3.62 (1H, m), 3.72 (1H, dd, J = 10.5, 5.1 Hz), 4.04- 4.37 (6H, m), 4.63 (1H, m), 6.02 (1H, s), 6.91-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 397 [M + H]+ [00379]![text missing or illegible when filed]()
TABLE-US-00013 TABLE 13 Example Structural formula NMR MS 101 (isomer A) [00380]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.92 (3H, t, J = 7.3 Hz), 1.58-1.64 (2H, m), 2.14-2.27 (2H, m), 2.90 (1H, dd, J = 16.4, 4.2 Hz), 3.17 (1H, dd, J = 16.4, 4.6 Hz), 3.47 (2H, t, J = 6.6 Hz), 3.62 (1H, m), 3.72 (1H, m), 4.08 (1H, m), 4.17-4.36 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.92-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 397 [M + H]+ 101 (isomer B) [00381]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.92 (3H, t, J = 7.4 Hz), 1.57-1.66 (2H, m), 2.14-2.28 (2H, m), 2.90 (1H, dd, J = 16.9, 4.5 Hz), 3.17 (1H, dd, J = 16.7, 5.0 Hz), 3.47 (2H, t, J = 6.6 Hz), 3.62 (1H, m), 3.72 (1H, m), 4.08 (1H, m), 4.17-4.36 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.92-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.8 Hz). ESI-MS m/z: 397 [M + H]+ 102 [00382]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.23 (2H, m), 0.54-0.58 (2H, m), 1.06 (1H, m), 2.16-2.29 (2H, m), 2.90 (1H, dd, J = 16.6, 4.9 Hz), 3.17 (1H, dd, J = 16.8, 5.1 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.66 (1H, ddd, J = 10.5, 5.1, 1.7 Hz), 3.76 (1H, dd, J = 10.4, 5.2 Hz), 4.05- 4.38 (5H, m), 4.63 (1H, m), 6.02 (1H, s), 6.91-6.94 (2H, m), 7.38 ESI-MS m/z: 409 [M + H]+ (1H, s), 7.42 (1H, dd, J = 8.6, 1.7 Hz). 103 (isomer A) [00383]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.23 (2H, m), 0.54-0.58 (2H, m), 1.06 (1H, m), 2.14-2.27 (2H, m), 2.90 1H, dd, J = 16.7, 4.5 Hz), 3.17 (1H, dd, J = 16.8, 5.3 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.65 (1H, dd, J = 10.4, 5.2 Hz), 3.76 (1H, dd, J = 10.4, 5.2 Hz), 4.06 (1H, m), 4.16-4.40 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = ESI-MS m/z: 409 [M + H]+ 8.5 Hz). 103 (isomer B) [00384]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.24 (2H, m), 0.54-0.58 (2H, m), 1.08 (1H, m0, 2.15-2.30 (2H, m), 2.90 (1H, dd, J = 4.7, 16.7 Hz), 3.17 (1H, dd, J = 16.8, 5.0 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.66 (1H, dd, J = 10.4, 5.2 Hz), 3.76 (1H, dd, J = 10.4, 5.2 Hz), 4.08 (1H, m), 4.17-4.39 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.91-6.94 (2H, m), 7.36 (1H, s), 7.42 (1H, d, J = ESI-MS m/z: 409 [M + H]+ 6.5 Hz). 104 [00385]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.20-2.26 (2H, m), 2.90 (1H, dd, J = 16.7, 4.9 Hz), 3.17 (1H, dd, J = 16.5, 5.0 Hz), 3.69 (1H, m), 3.76 (1H, dd, J = 10.4, 5.1 Hz), 4.09 (1H, m), 4.15-4.31 (3H, m), 4.38 (1H, m), 4.60-4.65 (3H, m), 8.03 (1H, s), 6.91-6.94 (2H, m), 6.98-7.05 (2H, m), 7.09 (1H, d, J = 7.7 Hz), 7.32 (1H, q, J = 6.8 Hz), 7.38 ESI-MS m/z: 463 [M + H]+ (1H, s), 7.42 (1H, dd, J = 8.5, 1.7 Hz). 105 [00386]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.29 (2H, m), 2.85 (1H, dd, J = 16.6, 3.9 Hz), 3.15 (1H, dd, J = 16.8, 5.3 Hz), 3.82-3.90 (2H, m), 4.11 (1H, m), 4.19-4.24 (3H, m), 4.45 (1H, m), 4.61 (1H, m), 4.79 (2H, s), 6.03 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 7.00 (1H, d, J = 8.1 Hz), 7.04 (1H, m), 7.06 (1H, dd, J = 8.8, 2.3 Hz), 7.59- 7.65 (2H, m), 7.88 (1H, m). ESI-MS m/z: 523 [M + H]+ 106 [00387]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.23 (2H, m), 0.53-0.58 (2H, m), 1.07 (1H, m), 2.14-2.30 (2H, m), 2.84 (1H, dd, J = 15.9, 4.2 Hz), 3.14 (1H, dd, J = 16.9, 5.3 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.65 (1H, m), 3.76 (1H, m), 4.09 (1H, m), 4.18-4.22 (3H, m), 4.36 (1H, m), 4.60 (1H, m), 6.02 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.99 ESI-MS m/z: 416 [M + H]+ (1H, d, J = 8.3 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 8.7, 2.4 Hz). 107 [00388]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.6 Hz), 0.56 (2H, d, J = 7.9 Hz), 1.07 (1H, m), 2.14-2.30 (2H, m), 2.95 (1H, m), 3.25 (1H, dd, J = 16.2, 5.3 Hz), 3.36-3.39 (2H, m), 3.66 (1H, m), 3.76 (1H, m), 4.03-4.30 (4H, m), 4.39 (1H, m), 4.67 (1H, m), 6.03 (1H, s), 7.02 (2H, d, J = 8.4 Hz), 7.31 (1H, s), 7.39 (1H, dd, J = 8.6, 2.0 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.93 (1H, dd, J = 8.1, 2.2 Hz), 8.90 (1H, d, J = 1.9 Hz). ESI-MS m/z: 486 [M + H]+ [00389]![text missing or illegible when filed]()
TABLE-US-00014 TABLE 14 Example Structural formula NMR MS 108 [00390]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.22 (2H, m), 0.56-0.67 (2H, m), 1.06 (1H, m), 2.13-2.29 (2H, m), 2.85 (1H, dd, J = 4.1, 16.6 Hz), 3.04 (2H, dt, J = 17.4, 4.4 Hz), 3.15 (1H, dd, J = 16.7, 5.4 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.65 (1H, dd, J = 10.3, 6.3 Hz), 3.75 (1H, dd, J = 10.4, 6.2 Hz), 4.08 (1H, m), 4.14-4.22 (3H, m), 4.36 (1H, m), 4.51 (1H, m), 5.72-6.02 (2H, m), 6.84 (1H, d, J = 8.3 Hz), ESI-MS m/z: 448 [M + H]+ 6.99 (1H, s), 7.00-7.01 (2H, m). 109 (isomer A) [00391]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.5 Hz), 0.56 (2H, d, J = 7.9 Hz), 1.06 (1H, m), 2.13- 2.29 (2H, m), 2.88 (1H, m), 3.04 (2H, dt, J = 17.3, 4.2 Hz), 3.16 (1H, dd, J = 16.9, 5.2 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.65 (1H, m), 3.75 (1H, m), 4.05-4.21 (4H, m), 4.36 (1H, m), 4.61 (1H, m), 5.73-6.02 (2H, m), 6.84 (1H, d, J = 8.2 Hz), 6.94 (1H, s), 7.01 (2H, d, J = 8.3 Hz). ESI-MS m/z: 448 [M + H]+ 109 (isomer B) [00392]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.22 (2H, d, J = 4.7 Hz), 0.56 (2H, d, J = 8.0 Hz), 1.07 (1H, m), 2.14-2.29 (2H, m), 2.86 (1H, dd, J = 16.8, 3.7 Hz), 3.04 (2H, dt, J = 17.5, 4.3 Hz), 3.16 (1H, dd, J = 16.7, 5.3 Hz), 3.37 (2H, d, J = 7.0 Hz), 3.65 (1H, m), 3.76 (1H, m), 4.07 (1H, m), 4.15-4.21 (3H, m), 4.35 (1H, m), 4.62 (1H, m), 5.73- 6.02 (2H, m), 6.84 (1H, d, J = 8.4 Hz), 6.94 (1H, s), 7.01 (2H, ESI-MS m/z: 448 [M + H]+ d, J = 8.0 Hz). 110 [00393]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.6 Hz), 0.58 (2H, d, J = 7.9 Hz), 1.06 (1H, m), 2.12-2.26 (2H, m), 2.95 (1H, dd, J = 16.5, 4.1 Hz), 5.26 (1H, dd, J = 16.6, 5.3 Hz), 3.36 (2H, d, J = 6.8 Hz), 3.64 (1H, dd, J = 8.4, 9.9 Hz), 3.78 (1H, dd, J = 10.4, 5.2 Hz), 4.02-4.43 (8H, m), 4.86 (1H, m), 8.02 (1H, s), 0.97 (1H, d, J = 5.2 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.18, (1H, m), 7.84-7.77 (4H, m), 8.64 (1H, d, J = 4.2 Hz). ESI-MS m/z: 461 [M + H]+ 111 (isomer A) [00394]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.19-0.22 (2H, m), 0.53-0.57 (2H, m), 1.06 (1H, m), 2.12-2.29 (2H, m), 2.96 (1H, dd, J = 16.6, 4.0 Hz), 3.26 (1H, dd, J = 16.5, 5.3 Hz), 3.36 (2H, d, J = 6.9 Hz), 3.54 (1H, dd, J = 10.4, 5.2 Hz), 3.75 (1H, dd, J = 10.4, 5.2 Hz), 4.07 (1H, m), 4.18 (1H, m), 4.22-4.28 (2H, m), 4.36 (1H, m), 4.09 (1H, m), 6.02 (1H, s), 6.94-7.03 (2H, m), 7.18 (1H, m), 7.04-7.76 (4H, m), 8.04 (1H, m). ESI-MS m/z: 461 [M + H]+ 111 (isomer B) [00395]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.23 (2H, m), 0.53-0.58 (2H, m), 1.06 (1H, m), 2.13-2.28 (2H, m), 2.96 (1H, dd, J = 16.5, 4.4 Hz), 3.26 (1H, dd, J = 16.5, 5.4 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.65 (1H, m), 3.75 (1H, dd, J = 10.4, 5.2 Hz), 4.06 (1H, m), 4.19 (1H, m), 4.25-4.26 (2H, m), 4.35 (1H, m), 4.66 (1H, m), 6.02 (1H, s), 6.96-7.03 (2H, m), 7.16 (1H, m), 7.64-7.76 (4H, m), 8.64 (1H, m). ESI-MS m/z: 461 [M + H]+ 112 [00396]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.29-0.43 (4H, m), 1.12 (3H, s), 2.13-2.33 (2H, m), 2.91 (1H, dd, J = 16.2, 4.8 Hz), 3.17 (1H, dd, J = 16.8, 5.5 Hz), 3.28-3.35 (2H, m), 3.63 (1H, dd, J = 10.3, 4.8 Hz), 3.75 (1H, dd, J = 10.6, 6.1 Hz), 4.08 (1H, m), 4.16-4.41 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.88-6.96 (2H, m), 7.39 (1H, s), 7.42 (1H, ESI-MS m/z: 423 [M + H]+ dd, J = 8.7, 2.4 Hz). 113 (isomer A) [00397]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.29-0.43 (4H, m), 1.12 (3H, s), 2.13-2.33 (2H, m), 2.91 (1H, dd, J = 16.2, 4.8 Hz), 3.17 (1H, dd, J = 16.8, 5.5 Hz), 3.28-3.35 (2H, m), 3.63 (1H, dd, J = 10.3, 3.8 Hz), 3.75 (1H, dd, J = 10.6, 6.1 Hz), 4.08 (1H, m), 4.16-4.41 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.88-6.95 (2H, m), 7.39 (1H, s), 7.42 (1H, dd, J = 8.7, 2.4 Hz) ESI-MS m/z: 423 [M + H]+ 113 (isomer B) [00398]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.29-0.43 (4H, m), 1.12 (3H, s), 2.13-2.33 (2H, m), 2.91 (1H, dd, J = 16.2, 4.6 Hz), 3.17 (1H, dd, J = 16.8, 5.5 Hz), 3.28-3.35 (2H, m), 3.63 (1H, dd, J = 10.3, 4.8 Hz), 3.75 (1H, dd, J = 10.6, 6.1 Hz), 4.08 (1H, m), 4.16-4.41 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.88-6.95 (2H, m), 7.39 (1H, s), 7.42 (1H, dd, J = 8.7, 2.4 Hz) ESI-MS m/z: 423 [M + H]+ [00399]![text missing or illegible when filed]()
TABLE-US-00015 TABLE 15 Example Structural formula NMR MS 114 [00400]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.27 (2H, m), 2.90 (1H, dd, J = 16.6, 4.8 Hz), 3.17 (1H, dd, J = 16.7, 5.2 Hz), 3.85-3.96 (4H, m), 4.09 (1H, m), 4.20-4.31 (3H, m), 4.37 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.91- 6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 6.5, 1.9 Hz). ESI-MS m/z: 437 [M + H]+ 115 (isomer A) [00401]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.27 (2H, m), 2.90 (1H, m), 3.17 (1H, dd, J = 16.8, 5.4 Hz), 3.84-3.97 (4H, m), 4.10 (1H, m), 4.16-4.31 (3H, m), 4.38 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.91-6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 437 [M + H]+ 115 (isomer B) [00402]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.22-2.27 (2H, m), 2.91 (1H, dd, J = 16.8, 3.9 Hz), 3.17 (1H, dd, J = 16.7, 5.0 Hz), 3.85-3.96 (4H, m), 4.09 (1H, m), 4.19-4.31 (3H, m), 4.37 (1H, m), 4.64 (1H, m), 6.03 (1H, s), 6.91- 6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 437 [M + H]+ 116 [00403]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.31 (2H, m), 2.91 (1H, m), 3.17 (1H, m), 4.06-4.15 (3H, m), 4.21-4.31 (4H, m), 4.41 (1H, m), 4.63 (1H, m), 6.04 (1H, s), 6.91-6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 505 [M + H]+ 117 [00404]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.33 (2H, m), 2.85 (1H, m), 3.15 (1H, dd, J = 16.8, 5.3 Hz), 4.07-4.25 (4H, m), 4.59-4.61 (4H, m), 6.05 (1H, s), 6.81 (2H, d, J = 8.6 Hz), 6.91 (1H, t, J = 6.1 Hz), 6.99 (1H, d, J = 7.6 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 6.8, 2.4 Hz), 7.60 (1H, t, J = 6.3 Hz), 8.13 (1H, d, J = 3.9 Hz). ESI-MS m/z: 441 [M + H]+ 118 [00405]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.27-2.43 (2H, m), 2.91 (1H, dd, J = 16.4, 4.5 Hz), 3.18 (1H, m), 4.11-4.17 (2H, m), 4.24-4.32 (4H, m), 4.55-4.65 (2H, m), 6.06 (1H, s), 6.91-6.94 (4H, m), 7.00 (1H, t, J = 7.4 Hz), 7.31 (2H, t, J = 7.9 Hz), 7.39 (1H, s), 7.42 (1H, d, J = 6.4 Hz). ESI-MS m/z: 431 [M + H]+ 119 [00406]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14 (1H, m), 2.44 (1H, m), 2.90 (1H, dd, J = 16.7, 4.6 Hz), 3.08 (1H, dd, J = 14.1, 8.0 Hz), 3.16 (1H, m), 3.40 (1H, dd, J = 14.1, 5.0 Hz), 4.04 (1H, m), 4.14 (1H, m), 4.22-4.30 (3H, m), 4.62 (1H, m), 6.00 (1H, s), 6.89-6.93 (2H, m), 7.23-7.43 (7H, m). ESI-MS m/z: 447 [M + H]+ 120 [00407]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.28-2.37 (2H, m), 2.85 (1H, dd, J = 16.7, 3.9 Hz), 3.15 (1H, dd, J = 16.8, 5.2 Hz), 4.09-4.33 (6H, m), 4.56-4.62 (2H, m), 6.05 (1H, s), 6.80-6.85 (3H, m), 7.01 (1H, d, J = 8.0 Hz), 7.04 (1H, s), 7.09 (1H, dd, J = 8.6, 2.3 Hz), 8.48 (2H, d, J = 4.8 Hz). ESI-MS m/z: 441 [M + H]+ 121 [00408]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.02 (1H, m), 2.26 (1H, m), 2.34 (3H, s), 2.69 (1H, dd, J = 13.2, 6.6 Hz), 2.74 (1H, dd, J = 13.3, 5.7 Hz), 2.84 (1H, dd, J = 16.8, 4.0 Hz), 3.14 (1H, dd, J = 16.9, 5.2 Hz), 4.29 (1H, m), 4.60 (1H, m), 5.99 (1H, s), 6.80 (1H, d, J = 6.6 Hz), 6.97 (1H, d, J = 7.9 Hz), 7.03 (1H, s), 7.08 (1H, dd, J = 8.7, 2.3 Hz), 7.30-7.34 (5H, m). ESI-MS m/z: 467 [M + H]+ [00409]![text missing or illegible when filed]()
TABLE-US-00016 TABLE 16 Example Structural formula NMR MS 122 [00410]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13 (1H, m), 2.28 (1H, m), 2.50-2.60 (5H, m), 2.76 (1H, dd, J = 13.5, 6.2 Hz), 2.84 (1H, dd, J = 18.9, 4.2 Hz), 3.15 (1H, m), 3.72 (4H, t, J = 4.6 Hz), 4.04-4.19 (4H, m), 4.34 (1H, m), 4.60 (1H, m), 6.01 (1H, s), 6.91 (1H, d, J = 6.7 Hz), 6.99 (1H, d, J = 8.0 Hz), 7.04 (1H, s), 7.08 (1H, ESI-MS m/z: 433 [M + H]+ dd, J = 8.7, 2.4 Hz). 123 [00411]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.22 (3H, dt, J = 7.0, 1.0 Hz), 2.12-2.28 (2H, m), 2.95 (1H, dd, J = 16.7, 4.2 Hz), 3.26 (1H, dd, J = 16.8, 5.2 Hz), 3.55-3.66 (3H, m), 3.71 (1H, dd, J = 10.4, 5.3 Hz), 4.06 (1H, m), 4.17 (1H, m), 4.26 (2H, s), 4.33 (1H, m), 4.66 (1H, m), 6.02 (1H, s), 6.97 (1H, d, J = 6.2 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.18 (1H, m), 7.64- 7.76 (4H, m), 8.64 (1H, d, J = 4.3 Hz). ESI-MS m/z: 435 [M + H]+ 124 (isomer A) [00412]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.22 (3H, t, J = 7.0 Hz), 2.12-2.25 (2H, m), 2.95 (1H, dd, J = 16.4, 3.8 Hz), 3.26 (1H, dd, J = 16.7, 4.9 Hz), 3.55-3.65 (3H, m), 3.71 (1H, dd, J = 10.5, 5.3 Hz), 4.07 (1H, m), 4.17 (1H, m), 4.26 (2H, s), 4.34 (1H, m), 4.66 (1H, m), 6.02 (1H, s), 6.96- 7.03 (2H, m), 7.18 (1H, t, J = 6.0 Hz), 7.65 (1H, d, J = 7.8 Hz), 7.70-7.76 (3H, m), 8.64 (1H, d, J = 4.5 Hz). ESI-MS m/z: 435 [M + H]+ 124 (isomer B) [00413]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.22 (3H, t, J =7.0 Hz), 2.13-2.26 (2H, m), 2.96 (1H, dd, J = 16.8, 3.9 Hz), 3.26 (1H, dd, J = 16.6, 5.4 Hz), 3.55-3.65 (3H, m), 3.71 (1H, dd, J = 10.4, 5.2 Hz), 4.06 (1H, m), 4.15-4.36 (4H, m), 4.66 (1H, m), 6.02 (1H, s), 6.96-7.03 (2H, m), 7.18 (1H, m), 7.65 (1H, d, J = 7.9 Hz), 7.70-7.76 (3H, m), 8.64 (1H, d, J = 4.0 Hz). ESI-MS m/z: 435 [M + H]+ 125 [00414]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.22 (3H, dt, J = 7.0, 1.0 Hz), 2.13-2.28 (2H, m), 2.98 (1H, dd, J = 16.7, 4.1 Hz), 3.25 (1H, dd, J = 16.7, 6.3 Hz), 3.55-3.65 (3H, m), 3.72 (1H, dd, J = 10.1, 4.9 Hz), 4.08 (1H, m), 4.15-4.38 (4H, m), 4.66 (1H, m), 6.03 (1H, s), 7.02 (2H, d, J = 8.4 Hz), 7.31 (1H, s), 7.39 (1H, dd, J = 8.5, 2.0 Hz), 7.73 (1H, d, J = 6.1 Hz), 7.93 (1H, dd, J = 8.1, 2.2 Hz), 8.89 (1H, d, J = 2.0 Hz). ESI-MS m/z: 480 [M + H]+ 126 [00415]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.24 (2H, m), 2.86 (1H, dd, J = 16.7, 3.9 Hz), 3.04 (2H, dt, J = 17.3, 4.5 Hz), 3.17 (1H, dd, J = 16.8, 5.4 Hz), 3.84-3.95 (4H, m), 4.05-4.23 (4H, m), 4.37 (1H, m), 4.61 (1H, m), 5.73-6.03 (2H, m), 6.84 (1H, d, J = 6.3 Hz), 6.94 (1H, s), 7.01 (2H, d, J = 7.1 Hz). ESI-MS m/z: 476 [M + H]+ 127 (isomer A) [00416]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.26 (2H, m), 2.86 (1H, dd, J = 16.6, 3.8 Hz), 3.04 (2H, dt, J = 17.4, 4.4 Hz), 3.17 (1H, dd, J = 16.8, 5.5 Hz), 3.84-3.97 (4H, m), 4.06-4.22 (4H, m), 4.37 (1H, m), 4.61 (1H, m), 5.73-6.03 (2H, m), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.01 (2H, d, J = 8.6 Hz). ESI-MS m/z: 476 [M + H]+ 127 (isomer B) [00417]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.26 (2H, m), 2.86 (1H, dd, J = 16.7, 4.3 Hz), 3.04 (2H, dt, J = 17.4, 4.5 Hz), 3.17 (1H, dd, J = 16.8, 5.5 Hz), 3.84-3.98 (4H, m), 4.05-4.24 (4H, m), 4.36 (1H, m), 4.61 (1H, m), 5.73-6.03 (2H, m), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.00- 7.03 (2H, m). ESI-MS m/z: 476 [M + H]+ 128 [00418]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.22-2.26 (2H, m), 2.85-2.90 (1H, m), 3.15-3.21 (1H, m), 3.79-3.98 (6H, m), 4.06-4.14 (1H, m), 4.17-4.23 (3H, m), 4.35-4.40 (1H, m), 4.57 (2H, s), 4.60-4.64 (1H, m), 6.03 (1H, s), 6.87 (1H, d, J = 6.3 Hz), 7.00-7.05 (2H, m), 7.12 (1H, dd, J = 8.4, 2.0 Hz). ESI-MS m/z: 524 [M + H]+ [00419]![text missing or illegible when filed]()
TABLE-US-00017 TABLE 17 Example Structural formula NMR MS 129 (isomer A) [00420]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.27 (2H, m), 2.85-2.89 (1H, m), 3.15- 3.21 (1H, m), 3.78-3.97 (6H, m), 4.08-4.12 (1H, m), 4.20 (3H, m), 4.35-4.38 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 6.03 (1H, s), 6.87 (1H, d, J = 8.5 Hz), 7.01 (1H, d, J = 8.2 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 7.4 Hz). ESI-MS m/z: 524 [M + H]+ 129 (isomer B) [00421]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24 (2H, m), 2.85-2.89 (1H, m), 3.15- 3.21 (1H, m), 3.78-3.97 (6H), m), 4.09-4.12 (1H, m), 4.21 (3H, m), 4.35-4.37 (1H, m), 4.57 (2H, s), 4.63 (1H, m), 6.03 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.01 (1H, d, J = 8.2 Hz), 7.06 (1H, s), 7.12 (1H, d, J = 8.0 Hz). ESI-MS m/z: 524 [M + H]+ 130 [00422]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.25 (2H, m), 2.96 (1H, m), 3.26 (1H, dd, J = 5.2, 16.6 Hz), 3.84-3.97 (4H, m), 4.08 (1H, m), 4.20 (1H, m), 4.26 (2H, d, J = 2.5 Hz), 4.36 (1H, m), 4.68 (1H, m), 5.03 (1H, s), 6.97 (1H, d, J = 8.3 Hz), 7.02 (1H, d, J = 8.0 Hz), 7.18 (1H, m), 7.65 (1H, d, J = 7.9 Hz), 7.70-7.76 (3H, m), 8.64 (1H, d, J = 4.3 Hz). ESI-MS m/z: 489 [M + H]+ 131 (isomer A) [00423]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.25 (2H, m), 2.96 (1H, m), 3.26 (1H, dd, J = 10.5, 5.3 Hz), 3.83-3.97 (4H, m), 4.08 (1H, m), 4.18 (1H, m), 4.26 (2H, s), 4.38 (1H, m), 4.66 (1H, m), 6.03 (1H, s), 6.96-7.03 (2H, m), 7.18 (1H, t, J = 5.8 Hz), 7.64-7.76 (4H, m), 8.64 (1H, d, J = 4.5 Hz). ESI-MS m/z: 489 [M + H]+ 131 (isomer B) [00424]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.25 (2H, m), 2.96 (1H, m), 3.26 (1H, dd, J = 16.6, 5.0 Hz), 3.84-3.97 (4H, m), 4.07 (1H, m), 4.20 (1H, m), 4.26 (2H, d, J = 3.0 Hz), 4.36 (1H, m), 4.66 (1H, m), 6.03 (1H, s), 6.96- 7.03 (2H, m), 7.18 (1H, m), 7.64-7.76 (4H, m), 8.64 (1H, d, J = 4.7 Hz). ESI-MS m/z: 489 [M + H]+ 132 [00425]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.27 (2H, m), 2.98 (1H, dd, J = 16.7, 4.6 Hz), 3.25 (1H, dd, J = 16.7, 6.2 Hz), 3.84-3.98 (4H, m), 4.10 (1H, m), 4.18-4.31 (3H, m), 4.37 (1H, m), 4.68 (1H, m), 6.04 (1H, s), 7.02 (2H, d, J = 8.5 Hz), 7.31 (1H, d, J = 2.2 Hz), 7.39 (1H, dd, J = 8.5, 2.3 Hz), 7.73 (1H, dd, J = 8.1, 0.7 Hz), 7.93 (1H, dd, J = 8.1, 2.3 Hz), 8.89 (1H, dd, J = 2.3, 0.7 Hz). ESI-MS m/z: 514 [M + H]+ 133 [00426]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25-2.29 (2H, m), 2.91 (1H, dd, J = 4.8, 16.5 Hz), 3.17 (1H, dd, J = 16.2, 5.1 Hz), 4.11-4.28 (6H, m), 4.45 (1H, m), 4.64 (1H, m), 6.06 (1H, s), 6.90-6.94 (2H, m), 7.39-7.43 (2H, m). ESI-MS m/z: 423 [M + H]+ 134 (isomer A) [00427]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.31 (2H, m), 2.88-2.93 (1H, m), 3.17 (1H, dd, J = 16.7, 5.1 Hz), 4.01-4.30 (6H, m), 4.42-4.47 (1H, m), 4.62-4.64 (1H, m), 6.08 (1H, s), 6.90-6.94 (2H, m), 7.39-7.43 (2H, m). ESI-MS m/z: 423 [M + H]+ 134 (isomer B) [00428]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.30 (2H, m), 2.91 (1H, dd, J = 16.5, 4.5 Hz), 3.17 (1H, dd, J = 16.7, 5.1 Hz), 4.08-4.31 (6H, m), 4.41-4.47 (1H, m), 4.63 (1H, m), 6.06 (1H, s), 6.91-6.94 (2H, m), 7.39-7.43 (2H, m). ESI-MS m/z: 423 [M + H]+ [00429]![text missing or illegible when filed]()
TABLE-US-00018 TABLE 18 Example Structural formula NMR MS 135 [00430]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.26 (2H, m), 2.84-3.28 (4H, m), 4.10-4.25 (6H, m), 4.42-4.45 (1H, m), 4.62 (1H, m), 5.73- 6.05 (2H, m), 6.64 (1H, m), 6.94 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 462 [M + H]+ 136 (isomer A) [00431]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.28-2.30 (2H, m), 2.81-3.20 (4H, m), 4.09-4.26 (6H, m), 4.42-4.49 (1H, m), 4.61-4.63 (1H, m), 5.88 (1H, m), 6.05 (1H, s), 6.84 (1H, m), 6.94 (1H, s), 7.01 (2H, m). ESI-MS m/z: 462 [M + H]+ 136 (isomer B) [00432]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.22-2.29 (2H, m), 2.84-3.20 (4H, m), 4.07-4.27 (6H, m), 4.41-4.45 (1H, m), 4.61-4.63 (1H, m), 5.87 (1H, m), 6.05 (1H, s), 6.85 (1H, m), 6.94 (1H, s), 7.01 (2H, m). ESI-MS m/z: 462 [M + H]+ 137 [00433]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.25 (2H, m), 2.66 (1H, dd, J = 16.9, 3.7 Hz), 3.04 (2H, dt, J = 17.4, 4.4 Hz), 3.17 (1H, dd, J = 16.8, 5.3 Hz), 4.05-4.24 (6H, m), 4.41 (1H, m), 4.61 (1H, m), 5.73-6.04 (2H, m), 6.30 (1H, t, J = 73.5 Hz), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.00- 7.02 (2H, m). ESI-MS m/z: 444 [M + H]+ 138 (isomer A) [00434]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.20 (2H, m), 2.66 (1H, dd, J = 16.8, 4.1 Hz), 3.04 (2H, dt, J = 17.4, 4.5 Hz), 3.17 (1H, dd, J = 16.7, 5.5 Hz), 4.05-4.25 (6H, m), 4.41 (1H, m), 4.62 (1H, m), 5.88 (1H, tt, J = 56.7, 4.5 Hz), 6.04 (1H, s), 6.30 (1H, t, J = 73.4 Hz), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 444 [M + H]+ 138 (isomer B) [00435]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.28 (2H, m), 2.86 (1H, m), 3.04 (2H, dt, J = 17.4, 4.8 Hz), 3.17 (1H, dd, J = 16.6, 5.5 Hz), 4.05-4.25 (6H, m), 4.40 (1H, m), 4.62 (1H, m), 5.88 (1H, tt, J = 56.7, 4.5 Hz), 6.04 (1H, s), 6.30 (1H, t, J = 73.4 Hz), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 444 [M + H]+ 139 [00436]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.26 (2H, m), 2.87 (1H, dd, J = 16.8, 3.9 Hz), 3.18 (1H, dd, J = 16.7, 5.3 Hz), 3.82 (2H, q, J = 8.8 Hz), 4.05-4.14 (3H, m), 4.20- 4.23 (3H, m), 4.41 (1H, m), 4.57-4.63 (3H, m), 6.04 (1H, s), 6.30 (1H, t, J = 73.4 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.00- 7.05 (2H, m), 7.12 (1H, d, J = 8.0 Hz). ESI-MS m/z: 492 [M + H]+ 140 (isomer A) [00437]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.28 (2H, m), 2.87 (1H, dd, J = 16.8, 4.0 Hz), 3.18 (1H, dd, J = 16.7, 5.2 Hz), 3.82 (2H, q, J = 6.7 Hz), 4.05-4.14 (3H, m), 4.19- 4.24 (3H, m), 4.41 (1H, s), 4.57 (2H, s), 4.63 (1H, m), 6.04 (1H, s), 6.30 (1H, t, J = 73.4 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.01 (1H, d, J = 8.3 Hz), 7.05 (1H, s), 7.12 (1H, dd, J = 8.3, 2.0 Hz). ESI-MS m/z: 492 [M + H]+ 140 (isomer B) [00438]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.27 (2H, m), 2.87 (1H, m), 3.18 (1H, dd, J = 16.9, 5.5 Hz), 3.82 (2H, q, J = 6.7 Hz), 4.05-4.14 (3H, m), 4.20-4.24 (3H, m), 4.40 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 6.05 (1H, s), 6.30 (1H, t, J = 73.4 Hz), 6.88 (1H, d, J = 8.2 Hz), 7.01 (1H, d, J = 8.1 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 8.1 Hz). ESI-MS m/z: 492 [M + H]+ [00439]![text missing or illegible when filed]()
TABLE-US-00019 TABLE 19 Example Structural formula NMR MS 141 [00440]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.24 (2H, m), 2.82-2.88 (3H, m), 3.16 (1H, dd, J = 16.7, 5.3 Hz), 4.00-4.24 (8H, m), 4.41 (1H, m), 4.61 (1H, m), 6.00-6.48 (3H, m), 6.82 (1H, d, J = 8.3 Hz), 6.91 (1H, s), 6.97-7.33 (2H, m). ESI-MS m/z: 474 [M + H]+ 142 (isomer A) [00441]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.25 (2H, m), 2.82-2.88 (3H, m), 3.16 (1H, dd, J = 16.7, 5.1 Hz), 4.00- 4.23 (8H, m), 4.41 (1H, m), 4.61 (1H, m), 6.00-6.48 (3H, m), 6.82 (1H, d, J = 8.2 Hz), 6.91 (1H, s), 6.98-7.03 (2H, m). ESI-MS m/z: 474 [M + H]+ 142 (isomer B) [00442]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.27 (2H, m), 2.82-2.88 (3H, m), 3.16 (1H, dd, J = 16.6, 5.3 Hz), 4.00- 4.25 (8H, m), 4.40 (1H, m), 4.61 (1H, m), 6.00-6.48 (3H, m), 6.82 (1H, d, J = 8.3 Hz), 6.91 (1H, s), 6.98-7.03 (2H, m). ESI-MS m/z: 474 [M + H]+ 143 [00443]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03-2.25 (4H, m), 2.91 (1H, m), 3.17 (1H, m), 4.07-4.31 (6H, m), 4.38 (1H, m), 4.63 (1H, m), 6.01 (1H, m), 6.91-6.94 (2H, m), 7.38 (1H, m), 7.42 (1H, m). ESI-MS m/z: 437 [M + H]+ 144 (isomer A) [00444]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.07-2.24 (4H, m), 2.91 (1H, m), 3.17 (1H, dd, J = 16.6, 5.2 Hz), 4.07- 4.31 (6H, m), 4.38 (1H, m), 4.63 (1H, m), 6.01 (1H, s), 6.91- 6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 437 [M + H]+ 144 (isomer B) [00445]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.09-2.24 (4H, m), 2.90 (1H, dd, J = 16.9, 5.0 Hz), 3.17 (1H, dd, J = 5.2, 15.7 Hz), 4.06-4.31 (6H, m), 4.37 (1H, m), 4.63 (1H, s), 6.02 (1H, s), 6.90-6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 437 [M + H]+ 145 [00446]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.04-2.18 (3H, m), 2.23 (1H, m), 2.91 (1H, m), 3.17 (1H, m), 4.02-4.19 (4H, m), 4.23-4.31 (2H, m), 4.38 (1H, m), 4.63 (1H, m), 6.01 (1H, m), 6.22 (1H, m), 6.91-6.94 (2H, m), 7.38 (1H, m), 7.42 (1H, m). ESI-MS m/z: 419 [M + H]+ 146 (isomer A) [00447]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.99-2.16 (3H, m), 2.23 (1H, m), 2.91 (1H, dd, J = 16.7, 4.8 Hz), 3.17 (1H, dd, J = 5.2, 16.8 Hz), 4.02-4.20 (4H, m), 4.23-4.32 (2H, m), 4.38 (1H, m), 4.83 (1H, m), 6.01 (1H, s), 6.22 (1H, t, J = 74.4 Hz), 6.91-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 8.6, 2.0 Hz). ESI-MS m/z: 419 [M + H]+ 146 (isomer B) [00448]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.01-2.17 (3H, m), 2.23 (1H, m), 2.91 (1H, m), 3.17 (1H, dd, J = 16.6, 5.1 Hz), 4.02-4.13 (3H, m), 4.18 (1H, m), 4.23-4.31 (2H, m), 4.37 (1H, m), 4.63 (1H, m), 6.01 (1H, s), 6.22 (1H, t, J = 74.4 Hz), 6.90-6.93 (2H, m), 7.39 (1H, s), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 419 [M + H]+ [00449]![text missing or illegible when filed]()
TABLE-US-00020 TABLE 20 Example Structural formula NMR MS 147 [00450]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00-2.16 (3H, m), 2.22 (1H, m), 2.86 (1H, m), 2.99-3.09 (2H, m), 3.16 (1H, m), 4.02-4.21 (6H, m), 4.37 (1H, m), 4.61 (1H, m), 5.72-6.40 (3H, m), 6.84 (1H, m), 6.94 (1H, m), 7.00- 7.02 (2H, m). ESI-MS m/z: 458 [M + H]+ 148 (isomer A) [00451]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00-2.15 (3H, m), 2.22 (1H, m), 2.86 (1H, m), 3.02 (2H, dt, J = 26.2, 4.4 Hz), 3.16 (1H, dd, J = 16.8, 5.4 Hz), 4.02-4.22 (6H, m), 4.37 (1H, m), 4.61 (1H, m), 5.72-6.40 (3H, m), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.01 (2H, m). ESI-MS m/z: 458 [M + H]+ 148 (isomer B) [00452]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00-2.16 (3H, m), 2.22 (1H, m), 2.86 (1H, m), 3.02 (2H, dt, J = 26.2, 4.2 Hz), 3.17 (1H, m), 4.03- 4.21 (6H, m), 4.36 (1H, m), 4.62 (1H, m), 5.73-6.40 (3H, m), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 458 [M + H]+ 149 [00453]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.02-2.24 (4H, m), 2.87 (1H, m), 3.16 (1H, m), 3.79-3.85 (2H, m), 4.02-4.22 (6H, m), 4.37 (1H, m), 4.57-4.63 (3H, m), 6.00 (1H, m), 6.22 (1H, m), 6.87 (1H, m), 7.00 (1H, m), 7.05 (1H, m), 7.12 (1H, m). ESI-MS m/z: 506 [M + H]+ 150 (isomer A) [00454]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00-2.30 (4H, m), 2.87 (1H, m), 3.18 (1H, dd, J = 16.6, 5.1 Hz), 3.82 (2H, q, J = 8.7 Hz), 4.02- 4.23 (6H, m), 4.38 (1H, m), 4.57 (2H, s), 4.63 (1H, m), 6.00 (1H, s), 6.22 (1H, t, J = 74.4 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 7.8 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 7.8 Hz). ESI-MS m/z: 506 [M + H]+ 150 (isomer B) [00455]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.00-2.25 (4H, m), 2.87 (1H, dd, J = 17.1, 4.3 Hz), 3.18 (1H, dd, J = 16.8, 5.4 Hz), 3.82 (2H, q, J = 8.8 Hz), 4.02-4.23 (6H, m), 4.37 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 6.00 (1H, s), 6.22 (1H, l, J = 74.4 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.01 (1H, d, J = 7.6 Hz), 7.05 (1H, s), 7.12 (1H, dd, J = 8.3, 2.0 Hz). ESI-MS m/z: 506 [M + H]+ 151 [00456]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.27 (2H, m), 2.84 (1H, dd, J = 16.5, 4.0 Hz), 3.05-3.26 (5H, m), 4.04-4.22 (5H, m), 4.28 (1H, m), 4.61 (1H, m), 6.00 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.98- 7.09 (3H, m). ESI-MS m/z: 445 [M + H]+ 152 (isomer A) [00457]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.23 (2H, m), 2.84 (1H, dd, J = 17.0, 4.3 Hz), 3.03-3.08 (2H, m), 3.15 (1H, dd, J = 16.9, 5.4 Hz), 3.26 (2H, q, J = 9.3 Hz), 4.09 (1H, m), 4.16-4.22 (3H, m), 4.28 (1H, m), 4.60 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.2 Hz), 7.04 (1H, s), 7.06 (1H, dd, J = 8.7, 2.3 Hz). ESI-MS m/z: 445 [M + H]+ 152 (isomer B) [00458]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.27 (2H, m), 2.85 (1H, m), 3.03- 3.08 (2H, m), 3.16 (1H, m), 3.26 (2H, q, J = 9.3 Hz), 4.08 (1H, m), 4.18-4.22 (3H, m), 4.29 (1H, m), 4.61 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.8 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 8.6, 2.4 Hz). ESI-MS m/z: 445 [M + H]+ [00459]![text missing or illegible when filed]()
TABLE-US-00021 TABLE 21 Example Structural formula NMR MS 153 (isomer A) [00460]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.10-2.34 (4H, m), 2.76-2.90 (5H, m), 2.93-3.10 (2H, m), 3.14 (1H, dd, J = 16.7, 5.1 Hz), 4.06 (1H, m), 4.15-4.21 (3H, m), 4.31 (1H, m), 4.60 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 8.3 Hz), 7.04 (1H, s), 7.08 (1H, d, J = 9.0 Hz). ESI-MS m/z: 453 [M + H]+ 153 (isomer B) [00461]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.10-2.34 (4H, m), 2.77-2.90 (6H, m), 2.94-3.08 (2H, m), 3.15 (1H, m), 4.08 (1H, m), 4.19 (3H, d, J = 2.4 Hz), 4.29 (1H, m), 4.61 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 7.8 Hz), 7.04 (1H, s), 7.08 (1H, d, J = 9.0 Hz). ESI-MS m/z: 453 [M + H]+ 154 (isomer A) [00462]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.10-2.33 (4H, m), 2.76-2.90 (5H, m), 2.93-3.08 (2H, m), 3.18 (1H, dd, J = 16.5, 5.0 Hz), 3.82 (2H, q, J = 8.7 Hz), 4.08 (1H, m), 4.15-4.20 (3H, m), 4.30 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 6.01 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 8.1 Hz), 7.04 (1H, s), 7.12 (1H, d, J = 8.0 Hz). ESI-MS m/z: 531 [M + H]+ 155 [00463]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.20 (1H, m), 2.38 (1H, m), 2.91 (1H, dd, J = 17.7, 4.4 Hz), 3.12-3.22 (2H, m), 3.30 (1H, dd, J = 15.7, 6.3 Hz), 4.09 (1H, m), 4.07- 4.17 (1H, m), 4.18-4.31 (3H, m), 4.63 (1H, m), 6.04 (1H, s), 6.93 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 439 [M + H]+ 156 (isomer A) [00464]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.20 (1H, m), 2.38 (1H, m), 2.91 (1H, dd, J = 17.7, 4.4 Hz), 3.12-3.22 (2H, m), 3.30 (1H, dd, J = 15.7, 6.3 Hz), 4.09 (1H, m), 4.07- 4.17 (1H, m), 4.18-4.31 (3H, m), 4.63 (1H, m), 6.04 (1H, s), 6.93 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 439 [M + H]+ 156 (isomer B) [00465]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.20 (1H, m), 2.38 (1H, m), 2.91 (1H, dd, J = 17.7, 4.4 Hz), 3.12-3.22 (2H, m), 3.30 (1H, dd, J = 15.7, 6.3 Hz), 4.09 (1H, m), 4.07- 4.17 (1H, m), 4.18-4.31 (3H, m), 4.63 (1H, m), 6.04 (1H, s), 6.93 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 439 [M + H]+ 157 [00466]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.36 (2H, m), 2.84 (1H, dd, J = 16.7, 3.5 Hz), 3.15 (1H, dd, J = 16.9, 5.5 Hz), 4.08-4.19 (3H, m), 4.27 (1H, m), 4.38 (1H, m), 4.61 (1H, m), 5.82-6.10 (2H, m), 6.81 (1H, d, J = 8.7 Hz), 6.98-7.10 (3H, m). ESI-MS m/z: 384 [M + H]+ 158 (isomer A) [00467]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.29-2.36 (2H, m), 2.84 (1H, dd, J = 16.8, 4.0 Hz), 3.15 (1H, dd, J = 16.8, 5.4 Hz), 4.08-4.30 (4H, m), 4.38 (1H, m), 4.61 (1H, m), 5.90 (1H, dt, J = 82.1, 3.4 Hz), 6.08 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.99 (1H, d, J = 8.2 Hz), 7.04 (1H, s), 7.09 (1H, dd, J = 8.7, 2.4 Hz). ESI-MS m/z: 384 [M + H]+ 158 (isomer B) [00468]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.38 (2H, m), 2.85 (1H, dd, J = 16.6, 3.7 Hz), 3.15 (1H, dd, J = 16.5, 5.1 Hz), 4.08-4.38 (4H, m), 4.36 (1H, m), 4.60 (1H, m), 5.83-6.11 (2H, m), 6.81 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.1 Hz), 7.04 (1H, s), 7.09 (1H, dd, J = 8.7, 2.4 Hz). ESI-MS m/z: 384 [M + H]+ [00469]![text missing or illegible when filed]()
TABLE-US-00022 TABLE 22 Example Structural formula NMR MS 159 [00470]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.38 (2H, m), 2.85 (1H, dd, J = 16.7, 3.7 Hz), 3.15 (1H, dd, J = 16.9, 5.4 Hz), 4.08-4.29 (4H, m), 4.37 (1H, m), 4.60 (1H, m), 5.90 (1H, dt, J = 82.3, 3.2 Hz), 6.08 (1H, s), 6.76 (1H, s, J = 8.6 Hz), 6.99 (1H, s, J = 2.8 Hz), 7.19 (1H, s). 7.22 (1H, dd, J = 3.6, 2.4 Hz). ESI-MS m/z: 428, 430 [M + H]+ 160 [00471]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.28-2.38 (2H, m), 2.92 (1H, m), 3.21 (1H, m), 4.32 (1H, m), 4.22-4.42 (4H, m), 4.65 (1H, m), 5.83-6.10 (2H, m), 6.94-6.98 (2H, m), 7.33 (1H, m), 7.39 (1H, m). ESI-MS m/z: 418 [M + H]+ 161 (isomer A) [00472]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.40 (2H, m), 2.92 (1H, dd, J = 16.9, 4.2 Hz), 3.21 (1H, dd, J = 16.9, 5.4 Hz), 4.12 (1H, m), 4.25-4.30 (3H, m), 4.39 (1H, m), 4.65 (1H, m), 5.82- 6.10 (2H, m), 6.94-6.98 (2H, m), 7.33 (1H, s). 7.38 (1H, d, J = 8.6 Hz). ESI-MS m/z: 418 [M + H]+ 161 (isomer B) [00473]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.28-2.35 (2H, m), 2.92 (1H, dd, J = 16.3, 4.1 Hz), 3.21 (1H, dd, J = 18.4, 5.2 Hz), 4.12 (1H, m), 4.25-4.30 (3H, m), 4.35 (1H, m), 4.65 (3H, m), 5.83- 6.11 (2H, m), 6.94-6.98 (2H, m), 7.33 (1H, s), 7.39 (1H, d, J = 8.8 Hz). ESI-MS m/z: 418 [M + H]+ 162 [00474]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.37 (2H, m), 2.87 (1H, m), 3.18 (1H, m), 3.77-3.86 (2H, m), 4.11 (1H, m), 4.20-4.21 (2H, m), 4.28 (1H, m), 4.38 (1H, m), 4.57-4.63 (3H, m), 5.82-6.30 (2H, m), 6.88 (1H, m), 7.01 (1H, m), 7.05 (1H, m), 7.12 (1H, m). ESI-MS m/z: 462 [M + H]+ 163 (isomer A) [00475]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25-2.37 (2H, m), 2.87 (1H, m), 3.18 (1H, dd, J = 16.9, 5.6 Hz), 3.82 (2H, q, J = 8.7 Hz), 4.12 (1H, m), 4.21 (2H, d, J = 2.1 Hz), 4.26 (1H, m), 4.38 (1H, m), 4.67 (2H, s), 4.62 (1H, m), 5.82-6.10 (2H, m), 6.88 (1H, d, J = 8.4 Hz), 7.01 (1H, d, J = 8.1 Hz) 7.05 (1H, s), 7.12 (1H, d, J = 8.7 Hz). ESI-MS m/z: 462 [M + H]+ 163 (isomer B) [00476]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.39 (2H, m), 2.87 (1H, dd, J = 16.5, 4.0 Hz), 3.18 (1H, dd, J = 16.7, 5.4 Hz), 3.82 (2H, q, J = 8.8 Hz), 4.11 (1H, m), 4.20 (2H, d, J = 2.92 Hz), 4.27 (1H, m), 4.37 (1H, m), 4.57 (2H, s), 4.63 (1H, m), 5.82- 6.11 (2H, m), 6.88 (1H, d, J = 8.3 Hz), 7.01 (1H, d, J = 8.0 Hz), 7.05 (1H, s), 7.12 (1H, dd, J = 8.4, 2.0 Hz). ESI-MS m/z: 462 [M + H]+ 164 [00477]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25-2.38 (2H, m), 2.82-2.88 (3H, m), 3.17 (1H, m), 4.00-4.03 (2H, m), 4.07-4.18 (3H, m), 4.27 (1H, m), 4.38 (1H, m), 4.61 (1H, m), 5.82-6.38 (3H, m), 6.82 (1H, m), 6.91 (1H, m), 6.99 (1H, m), 7.03 (1H, m). ESI-MS m/z: 444 [M + H]+ 165 (isomer A) [00478]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.37 (2H, m), 2.82-2.88 (3H, m), 3.17 (1H, dd, J = 16.6, 5.4 Hz), 4.01 (2H, t, J = 7.1 Hz), 4.09-4.16 (3H, m), 4.27 (1H, m), 4.38 (1H, m), 4.62 (1H, m), 5.82-6.38 (3H, m), 6.82 (1H, d, J = 8.3 Hz), 6.91 (1H, s), 6.99 (1H, d, J = 8.4 Hz), 7.03 (1H, d, J = 8.0 Hz). ESI-MS m/z: 444 [M + H]+ [00479]![text missing or illegible when filed]()
TABLE-US-00023 TABLE 23 Example Structural formula NMR MS 165 (isomer B) [00480]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26-2.39 (2H, m), 2.82-2.88 (3H, m), 3.17 (1H, dd, J = 16.7, 5.4 Hz), 4.31 (2H, t, J = 7.1 Hz), 4.07-4.18 (3H, m), 4.28 (1H, m), 4.37 (1H, m), 4.61 (1H, m), 6.82-6.38 (3H, m), 8.82 (1H, d, J = 8.3 Hz), 6.91 (1H, s), 6.99 (1H, dd, 8.4, 2.0 Hz). 7.03 (1H, d, J = 7.9 Hz). ESI-MS m/z: 444 [M + H]+ 166 [00481]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.44-1.54 (6H, m), 2.17 (1H, m), 2.31 (1H, m), 2.84 (1H, dd, J = 16.7, 3.8 Hz), 3.15 (1H, dd, J = 16.5, 5.3 Hz), 4.03-4.13 (2H, m), 4.19 (2H, d, J = 3.0 Hz), 4.24 (1H, dd, J = 12.6, 5.9 Hz), 4.80 (1H, m), 6.03 (1H, s), 6.81 (1H, d, J = 8.8 Hz), 5.99 (1H, d, J = 8.1 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 8.7, 2.4 Hz). ESI-MS m/z: 394 [M + H]+ 167 [00482]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.78 (3H, t, J = 19.1 Hz), 2.24-2.41 (2H, m), 2.85 (1H, m), 3.15 (1H, dd, J = 16.9, 5.3 Hz, 4.09 (1H, m), 4.19 (2H, d, J = 2.6 Hz), 4.23-4.29 (2H, m), 4.60 (1H, m), 8.07 (1H, s), 6.81 (1H, d, J = 6.7 Hz), 6.99 (1H, d, J = 8.0 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 8.6, 2.4 Hz). ESI-MS m/z: 398 [M + H]+ 168 [00483]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.91-0.95 (6H, m), 1.44-1.77 (5H, m), 2.17-2.28 (2H, m), 2.65 (1H, m), 3.14 (1H, dd, J = 16.4, 5.2 Hz), 4.01-4.12 (2H, m), 4.15-4.25 (3H, m), 4.60 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.7 Hz, 6.99 (1H, d, J = 8.0 Hz), 7.04 (1H, s), 7.08 (1H, d, J = 8.8 Hz). ESI-MS m/z: 420 [M + H]+ 169 [00484]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.32-2.50 (2H, m), 2.84 (1H, dd, J = 16.0, 4.6 Hz), 3.15 (1H, dd, J = 17.4, 5.5 Hz), 4.09-4.24 (3H, m), 4.25-4.32 (1H, m), 4.68-4.62 (2H, m), 6.13 (1H, s), 6.81 (1H, d, J = 9.2 Hz), 6.96-7.10 (3H, m). ESI-MS m/z: 402 [M + H]+ 170 (isomer A) [00485]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.29-2.51 (2H, m), 2.83 (1H, dd, J = 16.0, 4.6 Hz), 3.15 (1H, dd, J = 17.4, 5.8 Hz), 4.10-4.24 (3H, m), 4.25-4.32 (1H, m), 4.57-4.61 (2H, m), 6.13 (1H, s), 6.81 (1H, d, J = 9.2 Hz), 6.96-7.12 (3H, m). ESI-MS m/z: 402 [M + H]+ 170 (isomer B) [00486]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.29-2.49 (2H, m), 2.84 (1H, dd, J = 16.0, 4.6 Hz), 3.16 (1H, dd, J = 17.4, 5.8 Hz), 4.10-4.26 (3H, m), 4.27-4.34 (1H, m), 4.57-4.60 (2H, m), 6.13 (1H, s), 6.81 (1H, d, J = 9.2 Hz), 8.95-7.16 (3H, m). ESI-MS m/z: 402 [M + H]+ 171 [00487]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.40-2.45 (2H, m), 2.81 (1H, dd, J = 17.0, 3.9 Hz), 3.16 (1H, dd, J = 16.7, 5.0 Hz), 4.16-4.23 (3H, m), 4.26-4.31 (1H, m), 4.56-4.61 (2H, m), 6.13 (1H, s, 6.77 (1H, d, J = 6.8 Hz), 6.99 (1H, d, J = 6.4 Hz), 7.19- 7.24 (2H, m). ESI-MS m/z: 446, 448 [M + H]+ 172 [00488]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.33-2.46 (2H, m), 2.86 (1H, dd, J = 16.9, 3.4 Hz), 3.04 (2H, dt, J = 17.4, 4.4 Hz), 3.17 (1H, dd, J = 16.8, 5.7 Hz), 4.10-4.19 (3H, m), 4.27 (1H, m), 4.55-4.65 (2H, m), 5.85 (1H, tt, J = 56.7, 4.5 Hz), 6.13 (1H, s), 6.85 (1H, s, J = 8.3 Hz), 6.94 (1H, s), 7.01 (2H, d, J = 8.4 Hz). ESI-MS m/z: 432 [M + H]+ [00489]![text missing or illegible when filed]()
TABLE-US-00024 TABLE 24 Example Structural formula NMR MS 173 (isomer A) [00490]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.34-2.45 (2H, m), 2.86 (1H, m), 3.04 (2H, dt, J = 17.3, 4.5 Hz), 3.18 (1H, dd, J = 16.9, 5.3 Hz), 4.12-4.20 (3H, m), 4.26 (1H, m), 4.58-4.62 (2H, m), 5.88 (1H, m), 6.13 (1H, s), 6.85 (1H, d, J = 8.4 Hz), 6.94 (1H, s), 7.02 (2H, d, J = 6.8 Hz). ESI-MS m/z: 432 [M + H]+ 173 (isomer B) [00491]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.35-2.74 (2H, m), 2.86 (1H, dd, J = 16.9, 3.8 Hz), 3.04 (2H, dt, J = 17.4, 4.5 Hz), 3.17 (1H, dd, J = 16.7, 6.4 Hz), 4.10-4.18 (3H, m), 4.29 (1H, m), 4.53-4.65 (2H, m), 5.88 (1H, tt, J = 56.7, 4.5 Hz), 6.13 (1H, s), 6.85 (1H, d, J = 5.3 Hz), 6.94 (1H, s), 7.01 (2H, dd, J = 8.4, 2.0 Hz). ESI-MS m/z: 432 [M + H]+ 174 [00492]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.35-2.46 (2H, m), 2.98 (1H, dd, J = 16.3, 4.0 Hz), 3.26 (1H, dd, J = 17.1, 5.7 Hz), 4.10-4.19 (1H, m), 4.24-4.31 (3H, m), 4.58-4.61 (1H, m), 4.55-4.66 (1H, m), 6.15 (1H, s), 7.01-7.04 (2H, m), 7.32 (1H, s), 7.39 (1H, dd, J = 8.6, 2.4 Hz), 7.73 (1H, d, J = 6.1 Hz), 7.93 (1H, dd, J = 8.0, 2.1 Hz), 8.69 (1H, d, J = 1.8 Hz). ESI-MS m/z: 470 [M + H]+ 175 [00493]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.33-2.47 (2H, m), 2.59 (3H, s), 2.97 (1H, dd, J = 15.6, 3.0 Hz), 3.25 (1H, dd, J = 16.6, 5.2 Hz), 4.12-4.19 (1H, m), 4.25-4.31 (3H, m), 4.54-4.60 (1H, m), 4.65-4.68 (1H, m), 6.14 (1H, s), 6.98 (1H, d, J = 8.4 Hz), 7.05 (1H, d, J = 7.8 Hz), 7.19 (1H, d, J = 8.1 Hz), 7.33-7.35 (1H, m), 7.71 (1H, dd, J = 8.1, 2.1 Hz), 8.67 (1H, d, J = 1.3 Hz). ESI-MS m/z: 459 [M + H]+ 176 [00494]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.33-2.48 (2H, m), 2.96 (1H, dd, J = 16.3, 3.3 Hz), 3.25 (1H, dd, J = 16.2, 5.4 Hz), 4.05 (3H, s), 4.12-4.19 (1H, m), 4.25-4.30 (3H, m), 4.54-4.61 (1H, m), 4.66-4.68 (1H, m), 6.14 (1H, s), 6.98-7.05 (2H, m), 7.21 (1H, s), 7.26-7.30 )1H, m), 8.66 (2H, d, J = 1.3 Hz). ESI-MS m/z: 476 [M + H]+ 177 [00495]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.42 (6H, s), 2.08 (2H, t, J = 6.5 Hz), 2.84 (1H, dd, J = 17.3, 4.2 Hz), 3.14 (1H, dd, J = 16.5, 5.3 Hz), 4.10 (2H, t, J = 6.5 Hz), 4.19 (2H, d, J = 3.1 Hz), 4.60- 4.61 (1H, m), 5.97 (3H, s), 6.81 (1H, d, J = 6.6 Hz), 6.97- 7.09 (3H, m). ESI-MS m/z: 362 [M + H]+ 178 [00496]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.42 (6H, s), 2.08 (2H, t, J = 6.5 Hz), 2.91 (1H, dd, J = 17.0, 4.8 Hz), 3.17 (1H, dd, J = 17.0, 5.8 Hz), 4.10 (2H, s, J = 5.5 Hz), 4.26-4.32 (2H, m), 4.62-4.65 (1H, m), 5.97 (1H, s), 6.91-6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 353 [M + H]+ 179 [00497]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.42 (6H, d, J = 3.7 Hz), 2.08 (2H, t, J = 6.4 Hz), 2.98 (1H, dd, J = 16.1, 4.0 Hz), 3.26 (1H, dd, J = 16.5, 5.3 Hz), 4.09 (2H, t, J = 6.9 Hz), 4.23-4.31 (2H, m), 4.66-4.67 (1H, m), 5.98 (1H, s), 7.02 (2H, d, J = 6.5 Hz), 7.31 (1H, s), 7.39 (1H, dd, J = 6.5, 2.1 Hz, 7.73 (1H, d, J = 8.1 Hz), 7.93 (1H, dd, J = 8.1, 2.3 Hz), 8.89 (1H, d, J = 1. 6 Hz). ESI-MS m/z: 430 [M + H]+ 180 [00498]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.66-1.75 (1H, m), 1.91-2.04 (1H, m), 2.09-2.27 (4H, m), 2.36 (2H, m), 2.90 (1H, dd, J = 16.1, 5.0 Hz), 3.16 (1H, dd, J =17.0, 5.0 Hz), 4.10 (2H, t, J = 6.3 Hz), 4.21-4.32 (2H, m), 4.63 (1H, m), 6.00 (1H, s), 6.88-6.96 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.4 Hz). ESI-MS m/z: 365 [M + H]+ [00499]![text missing or illegible when filed]()
TABLE-US-00025 TABLE 25 Example Structural formula NMR MS 181 [00500]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.88 (1H, dd, J = 16.2, 4.0 Hz), 3.20 (1H, dd, J = 16.9, 4.3 Hz), 4.15-4.21 (3H, m), 4.57-4.65 (2H, m), 5.98 (1H, s), ![text missing or illegible when filed]()
.18 (1H, dt, J = 12.4, 3.2 Hz), 6.86-6.91 (2H, m), 7.05-7.07 (2H, m), 7.13 (1H, t, J = 7.4 Hz), 7.37-7.44 (5H, m). ESI-MS m/z: 362 [M + H]+ 182 [00501]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.91 (1H, dd, J = 16. ![text missing or illegible when filed]()
, 4.5 Hz), 3.18 (1H, dd, J = 17.1, 4.1 Hz), 4.18 (1H, m), 4.24-4.33 (2H, m), 4.59-4.68 (2H, m), 5.99 (1H, s), 6.20 (1H, dt, J = 12.5, 1.8 Hz), 6.91-6.98 (2H, m), 7.36-7.45 (7H, m). ESI-MS m/z: 409 [M + H]+ 183 [00502]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.86 (1H, dd, J = 16.8, 5.2 Hz), 3.19 (1H, dd, J = 16.8, 5.6 Hz), 3.82 (2H, dd, J = 17.8, 9.7 Hz), 4.16-4.25 (2H, m), 4.36 (1H, dd, J = 10.5, 5.5 Hz), 4.50 (1H, t, J = 9.5 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.50 (1H, m), 6.03 (1H, s), 6.88 (1H, d, J = 8. ![text missing or illegible when filed]()
Hz), 7.00 (1H, d, J = 6.8 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 8.8 Hz). ESI-MS m/z: 466 [M + H]+ 184 (isomer A) [00503]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.86 (1H, dd, J = 16.8, 5.2 Hz), 3.19 (1H, dd, J = 16.8, 5.6 Hz), 3.82 (2H, dd, J = 17.8, 9.7 Hz), 4.16-4.25 (2H, m), 4.36 (1H, dd, J = 10.5, 5.5 Hz), 4.50 (1H, t, J = 9.5 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.50 (1H, m), 6.03 (1H, s), 6.88 (1H, d, J = 8. ![text missing or illegible when filed]()
Hz), 7.00 (1H, d, J = 6.8 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 8.8 Hz). ESI-MS m/z: 466 [M + H]+ 184 (isomer B) [00504]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.86 (1H, dd, J = 16.8, 5.2 Hz), 3.19 (1H, dd, J = 16.8, 5.6 Hz), 3.82 (2H, dd, J = 17.8, 9.7 Hz), 4.16-4.25 (2H, m), 4.36 (1H, dd, J = 10.5, 5.5 Hz), 4.50 (1H, t, J = 9.5 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.50 (1H, m), 6.03 (1H, s), 6.88 (1H, d, J = 8. ![text missing or illegible when filed]()
Hz), 7.00 (1H, d, J = 6.8 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 8.8 Hz). ESI-MS m/z: 466 [M + H]+ 185 [00505]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.15-0.19 (2H, m), 0.50-0.57 (2H, m), 1.02 (1H, m), 2.87 (1H, m), 3.18 (1H, m), 3.36 (2H, dd, J = 6.9, 3.8 Hz), 3.73-3.85 (4H, m), 4.14-4.20 (3H, m), 4.31 (1H, dt, J = 13.6, 4.4 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.41 (1H, m), 5.91 (1H, s), 6. ![text missing or illegible when filed]()
7 (1H, d, J = 8.3 Hz), 7.00-7.14 (2H, m), 7.11 (1H, dd, J = 8.3, 2.1 Hz). ESI-MS m/z: 382 [M + H]+ 186 (isomer A) [00506]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.14-0.23 (2H, m), 0.49-0.57 (2H, m), 1.02 (1H, m), 2.87 (1H, dd, J = 16.8, 4.3 Hz), 3.18 (1H, dd, J = 16.6, 5.3 Hz), 3.36 (2H, d, J = 6.9 Hz), 3.73- 3.85 (4H, m), 4.14-4.21 (3H, m), 4.30 (1H, t, J = 9.2 Hz), 4.56 (2H, s), 4.63 (1H, m), 5.41 (1H, m), 5.90 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00-7.04 (2H, m), 7.11 (1H, dd, J = 8.4, 2.0 Hz). ESI-MS m/z: 382 [M + H]+ 186 (isomer B) [00507]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.19 (2H, s), 0.54 (2H, d, J = 7.8 Hz), 1.03 (1H, m), 2.86 (1H, m), 3.18 (1H, dd, J = 16.6, 5.0 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.74-3.85 (4H, m), 4.16- 4.20 (3H, m), 4.29 (1H, t, J = 9.1 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.40 (1H, m), 5.90 (1H, s), 6.87 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.00 (1H, d, J = 8.2 Hz), 7.04 (1H, s), 7.11 (1H, s). ESI-MS m/z: 382 [M + H]+ 187 [00508]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.84-2.89 (1H, m), 3.15-3.21 (1H, m), 3.20 (1H, d, J = 5.16 Hz), 3.82 (2H, q, J = 8.8 Hz), 3.89-3.99 (4H, m), 4.15-4.21 (3H, m), 4.31 (1H, dt, J = 14.1, 4.3 Hz), 4.57 (1H, s), 4.63 (1H, m), 5.42 (1H, m), 5.92 (1H, s), 6.87 (1H, d, J = 8.4 Hz), 7.00-7.04 (2H, m), 7.11 (1H, d, J = 8.6 Hz). ESI-MS m/z: 510 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00026 TABLE 26 Example Structural formula NMR MS 188 (isomer A) [00509]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.83-2.90 (1H, m), 3.15-3.23 (1H, m), 3.20 (1H, d, J = 5.16 Hz), 3.82 (2H, q, J = 8.8 Hz), 3.89-3.97 (4H, m), 4.16-4.23 (3H, m), 4.30 (1H, dt, J = 14.1, 4.3 Hz), 4.57 (1H, s), 4.65 (1H, m), 5.42 (1H, m), 5.92 (1H, s), 6.87 (1H, d, J = 8.4 Hz), 6.99- 7.05 (2H, m), 7.11 (1H, d, J = 8.6 Hz). ESI-MS m/z: 510 [M + H]+ 188 (isomer B) [00510]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85-2.91 (1H, m), 3.14-3.25 (1H, m), 3.20 (1H, d, J = 5.2 Hz), 3.81 (2h, q, J = 8.8 Hz), 3.89-3.98 (4H, m), 4.16-4.23 (3H, m), 4.30 (1H, dt, J = 4.3, 14.1 Hz), 4.58 (1H, s), 4.65 (1H, m), 5.42 (1H, m), 5.92 (1H, s), 6.86 (1H, d, J = 6.4 Hz), 6.99- 7.06 (2H, m), 7.11 (1H, d, J = 8.6 Hz). ESI-MS m/z: 510 [M + H]+ 189 [00511]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.82-2.86 (3H, m), 3.16 (1H, dd, J = 16.7, 5.3 Hz), 3.89-4.03 (6H, m), 4.16-4.21 (3H, m), 4.32 (1H, dt, J = ![text missing or illegible when filed]()
.3, 4.4 Hz), 4.61 (1H, m), 5.41 (1H, m), 5.92 (1H, s), 6.19 (1H, t, J = 74.8 Hz), 6.81 (1H, d, J = 8.4 Hz), 6.90 (1H, s), 6.97-7.03 (2H, m). ESI-MS m/z: 492 [M + H]+ 190 (isomer A) [00512]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.82-2.88 (3H, m), 3.18 (1H, dd, J = 16.6, 5.4 Hz), 3.89-4.03 (6H, m), 4.16-4.20 (3H, m), 4.33 (1H, t, J = 9.3 Hz), 4.61 (1H, m), 5.42 (1H, m), 5.92 (1H, s), 6.19 (1H, t, J = 74. ![text missing or illegible when filed]()
Hz), 6.81 (1H, d, J = 8.3 Hz), 6.90 (1H, s), 6.97-7.03 (2H, m). ESI-MS m/z: 492 [M + H]+ 190 (isomer B) [00513]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.81-2.88 (3H, m), 3.16 (1H, dd, J = 16.7, 5.5 Hz), 3.90-4.03 (6H, m), 4.18-4.21 (3H, m), 4.31 (1H, t, J = 9.3 Hz), 4.61 (1H, m), 5.41 (1H, m), 5.92 (1H, s), 6.19 (1H, t, J = 74.8 Hz), 6. ![text missing or illegible when filed]()
1 (1H, d, J = 8.3 Hz), 6.90 (1H, s), 6.97-7.02 (2H, m). ESI-MS m/z: 492 [M + H]+ 191 [00514]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.86 (1H, m), 3.15-3.31 (3H, m), 3.91-3.98 (4H, m), 4.20 (3H, d, J = 2.3 Hz), 4.33 (1H, m), 4.63 (1H, m), 5.42 (1H, m), 5.92 (1H, s), 6.85 (1H, d, J = 8.3 Hz), 6.98-7.08 (3H, m). ESI-MS m/z: 480 [M + H]+ 192 (isomer B) [00515]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2. ![text missing or illegible when filed]()
6 (1H, dd, J = 17.2, 3.6 Hz), 3.18 (1H, dd, J = 16.9, 5.1 Hz), 3.26 (2H, q, J = 10.8 Hz), 3.89-3.97 (4H, m), 4.20 (3H, s), 4.33 (1H, t, J = 9.5 Hz), 4.63 (1H, m), 5.42 (1H, m), 5.92 (1H, s), 6. ![text missing or illegible when filed]()
(1H, d, J = 8.4 Hz), 6.97 (1H, s), 7.01 (1H, d, J = 7.3 Hz), 7.05 (1H, d, J = 8.2 Hz). ESI-MS m/z: 480 [M + H]+ 193 [00516]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.59 (3H, s), 2.96 (1H, m), 3.26 (1H, m), 3.88-3.96 (4H, m), 4.17 (1H, m), 4.26-4.30 (3H, m), 4.67 (1H, m), 5.41 (1H, m), 5.92 (1H, s), 6.98-7.03 (2H, m), 7.73-7.76 (2H, m), 6.45 (1H, s), ![text missing or illegible when filed]()
.83 (1H, s). ESI-MS m/z: 490 [M + H]+ 194 (isomer A) [00517]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.58 (3H, s), 2.96 (1H, d, J = 17.0 Hz), 3.26 (1H, dd, J = 16.0, 3.8 Hz), 3.88-3.96 (4H, m), 4.16 (1H, t, J = 8.0 Hz), 4.27-4.34 (3H, m), 4.67 (1H, s), 5.41 (1H, s), 5.92 (1H, s), 6.99 (1H, d, J = 8.1 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.73-7.76 (2H, m), 8.45 (1H, s), 8.83 (1H, s). ESI-MS m/z: 490 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00027 TABLE 27 Example Structural formula NMR MS 194 (isomer B) [00518]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.58 (3H, s), 2.96 (1H, d, J = 17.0 Hz), 3.26 (1H, dd, J = 16.0, 3.8 Hz), 3.88-3.96 (4H, m), 4.16 (1H, t, J = 8.0 Hz), 4.27-4.34 (3H, m), 4.67 (1H, s), 5.41 (1H, s), ![text missing or illegible when filed]()
.2 (1H, s), 6.99 (1H, d, J = 8.1 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.73-7.76 (2H, m), 8.45 (1H, s), ![text missing or illegible when filed]()
3 (1H, s). ESI-MS m/z: 490 [M + H]+ 195 [00519]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.87 (1H, dd, J = 16.9, 3.7 Hz), 3.18 (1H, dd, J = 16.7, 5.2 Hz), 3.82 (2H, q, 8.7 Hz), 4.14- 4.32 (5H, m), 4.38 (1H, dt, J = 4.2, 14.2 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.48 (1H, s), 6.94 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00-7.05 (2H, m), 7.12 (1H, d, J = 8.4 Hz). ESI-MS m/z: 496 [M + H]+ 196 (isomer A) [00520]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.87 (1H, dd, J = 17.0, 3.8 Hz), 3.18 (1H, dd, J = 16.7, 5.4 Hz), 3.82 (2H, q, J = 8.7 Hz), 4.15- 4.32 (5H, m), 4.39 (1H, t, J = 9.4 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.49 (1H, m), 5.95 (1H, s), 6.87 (1H, d, J = ![text missing or illegible when filed]()
.3 Hz), 7.00-7.05 (2H, m), 7.12 (1H, dd, J = 8.3, 1.9 Hz). ESI-MS m/z: 496 [M + H]+ 196 (isomer B) [00521]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.87 (1H, dd, J = 16.6, 4.1 Hz), 3.18 (1H, dd, J = 1 ![text missing or illegible when filed]()
, 5.4 Hz), 3.82 (2H, q, J = 8.7 Hz), 4.14- 4.31 (5H, m), 4.40 (1H, dd, J = 10.0, 9.0 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.49 (1H, m), 5.95 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00-7.05 (2H, m), 7.12 (1H, dd, J = 8.3, 2.0 Hz). ESI-MS m/z: 496 [M + H]+ 197 [00522]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (1H, dd, J = 16.8, 3.6 Hz), 3.04 (2H, dt, J = 17.4, 4.3 Hz), 3.17 (1H, dd, J = 16.7, 5.2 Hz), 4.11-4.32 (5H, m), 4.40 (1H, dt, J = 9.5, 4.1 Hz), 4.62 (1H, m), 5.48 (1H, m), 5.81 (1H, tt, J = 84.9, 4.5 Hz), 5.9 ![text missing or illegible when filed]()
(1H, s), 6.84 (1H, d, J = 8.4 Hz), 6.94 (1H, s), 7.01 (2H, d, J = 7.6 Hz). ESI-MS m/z: 448 [M + H]+ 198 (isomer A) [00523]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (1H, m), 3.04 (2H, dt, J = 17.4, 4.5 Hz), 3.17 (1H, dd, J = 16.7, 5.4 Hz), 4.15-4.31 (5H, m), 4.40 (1H, m), 4.62 (1H, m), 5.49 (1H, m), 5.81 (1H, tt, J = 85.0, 4.5 Hz), 5.95 (1H, s), 6.84 (1H, d, J = 8.3 Hz), 6.91 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 448 [M + H]+ 198 (isomer B) [00524]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (1H, dd, J = 17.1, 4.0 Hz), 3.04 (2H, dt, J = 17.4, 4.5 Hz), 3.17 (1H, dd, J = 16.9, 5.4 Hz), 4.16-4.32 (5H, m), 4.39 (1H, t, J = ![text missing or illegible when filed]()
.4 Hz), 4.62 (1H, m), 5.48 (1H, m), 5.81 (1H, tt, J = 85.1, 4.6 Hz), 5.95 (1H, s), 6.84 (1H, d, J = 8.4 Hz), 6.94 (1H, s), 7.01 (2H, d, J = 7.9 Hz). ESI-MS m/z: 448 [M + H]+ 199 [00525]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.90 (1H, dd, J = 16.6, 4.6 Hz), 3.08-3.24 (5H, m), 4.12 (1H, m), 4.28 (2H, m), 4.36-4.41 (1H, m), 4.64 (1H, m), 5.51 (1H, m), 5.93 (1H, s), 6.91- 6.94 (2H, m), 7.39 (1H, s), 7.43 (1H, d, J = 8.5 Hz). ESI-MS m/z: 439 [M + H]+ 200 (isomer A) [00526]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.90 (1H, m), 3.08-3.24 (5H, m), 4.12 (1H, m), 4.28 (2H, s), 4.39 (1H, t, J = 9.2 Hz), 4.64 (1H, m), 5.51 (1H, m), 5.93 (1H, s), 6.91-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 439 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00028 TABLE 28 Example Structural formula NMR MS 200 (isomer B) [00527]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.90 (1H, dd, J = 17.1, 3.8 Hz), 3.08- 3.24 (5H, m), 4.13 (1H, m), 4.28 (2H, s), 4.39 (1H, t, J = 9.1 Hz), 4.64 (1H, m), 5.51 (1H, m), 5.93 (1H, s), 6.90- 6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.8 Hz). ESI-MS m/z: 439 [M + H]+ 201 [00528]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.53 (2H, m), 1.02 (1H, m), 2.18 (2H, m), 2.90 (1H, dd, J = 16.6, 4.2 Hz), 3.17 (1H, dd, J = 16.6, 5.0 Hz), 3.24-3.27 (2H, m), 3.63 (2H, t, J = 4.8 Hz), 4.01 (1H, t, J = 8.8 Hz), 4.23-4.36 (3H, m), 4.64 (1H, m), 5.45 (1H, m), 5.89 (1H, s), 6.92 (2H, d, J = 8.4 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 409 [M + H]+ 202 (isomer A) [00529]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.52 (2H, m), 1.01 (1H, m), 2.10-2.19 (2H, m), 2.90 (1H, dd, J = 17.2, 4.6 Hz), 3.17 (1H, dd, J = 16.4, 4.9 Hz), 3.26 (2H, dd, J = 6.8, 2.9 Hz), 3.62 (2H, t, J = 4.9 Hz), 4.01 (1H, t, J = 8.0 Hz), 4.24- 4.36 (3H, m), 4.64 (1H, m), 5.45 (1H, m), 5.89 (1H, s), 6.92 (2H, d, J = 8.5 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 409 [M + H]+ 202 (isomer B) [00530]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.52 (2H, m), 1.01 (1H, m), 2.10-2.19 (2H, m), 2.90 (1H, dd, J = 17.2, 4.6 Hz), 3.17 (1H, dd, J = 16.4, 4.9 Hz), 3.26 (2H, dd, J = 6.8, 2.9 Hz), 3.62 (2H, t, J = 4.9 Hz), 4.01 (1H, t, J = 8.0 Hz), 4.24- 4.36 (3H, m), 4.64 (1H, m), 5.45 (1H, m), 5.89 (1H, s), 6.92 (2H, d, J = 8.5 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 409 [M + H]+ 203 [00531]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.52 (2H, m), 1.02 (1H, m), 2.16 (2H, m), 2.94 (1H, dd, J = 16.6, 4.3 Hz), 3.22-3.27 (3H, m), 3.62 (2H, m), 4.01 (1H, m), 4.05 (3H, s), 4.25 (2H, m), 4.33 (1H, m), 4.66 (1H, m), 5.45 (1H, m), 6.90 (1H, s), 6.98 (1H, d, J = 8.6 Hz), 7.03 (1H, d, J = 7.7 Hz), 7.19 (1H, s), 7.28 (1H, m), 8.65 (2H, s). ESI-MS m/z: 492 [M + H]+ 204 (isomer A) [00532]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, m), 0.54 (2H, m), 1.03 (1H, m), 2.17 (2H, m), 2.95 (1H, dd, J = 16.8, 4.0 Hz), 3.23 (1H, d, J = 5.1 Hz), 3.27 (2H, d, J = 6. ![text missing or illegible when filed]()
Hz), 3.63 (2H, dd, J = 4.9, 1.6 Hz), 4.02 (1H, dd, J = 9.9, 1.9 Hz), 4.06 (3H, s), 4.26 (2H, d, J = 2.4 Hz), 4.33 (1H, dd, J = 9.8, 1.4 Hz), 4.67 (1H, m), 5.45 (1H, m), 5.91 (1H, s), 6.98 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.0 Hz), 7.20 (1H, s), 7.28 (1H, m), 8.66 (2H, s). ESI-MS m/z: 492 [M + H]+ 204 (isomer B) [00533]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, m), 0.54 (2H, m), 1.03 (1H, m), 2.17 (2H, m), 2.95 (1H, dd, J = 16.8, 4.0 Hz), 3.23 (1H, d, J = ![text missing or illegible when filed]()
.1 Hz), 3.27 (2H, d, J = 6.5 Hz), 3.63 (2H, dd, J = 4.9, 1.6 Hz), 4.02 (1H, dd, J = 9.9, 1.9 Hz), 4.06 (3H, s), 4.26 (2H, d, J = 2.4 Hz), 4.33 (1H, dd, J = 9.8, 1.4 Hz), 4.67 (1H, m), 5.45 (1H, m), 6.91 (1H, s), 6.98 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.0 Hz), 7.20 (1H, s), 7.28 (1H, m), 8.66 (2H, s). ESI-MS m/z: 492 [M + H]+ 205 [00534]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.19 (2H, m), 2.90 (1H, m), 3.22 (1H, m), 3.80-3.86 (4H, m), 3.93-3.95 (4H, m), 4.22 (2H, s), 4.34 (1H, m), 4.64 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.44 (1H, d, J = 2.2 Hz), 6.89 (1H, d, J = 8.2 Hz), 7.02 (1H, m), 7.35 (1H, d, J = 2.2 Hz), 7.51-7.54 (2H, m). ESI-MS m/z: 492 [M + H]+ 206 (isomer A) [00535]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (2H, m), 2.90 (1H, dd, J = 16.5, 3.9 Hz), 3.21 (1H, dd, J = 16.5, 5.2 Hz), 3.79-3.86 (4H, m), 3.92-3.96 (4H, m), 4.22 (2H, m), 4.34 (1H, t, J = 8.4 Hz), 4.64 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.44 (1H, d, J = 2.2 Hz), 6.89 (1H, d, J = 8.4 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.35 (1H, d, J = 2.2 Hz), 7.51 (1H, s), 7.54 (1H, d, J = 2.0 Hz). ESI-MS m/z: 492 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00029 TABLE 29 Example Structural formula NMR MS 206 (isomer B) [00536]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (2H, m), 2.90 (1H, dd, J = 16.5, 3.0 Hz), 3.21 (1H, dd, J = 16.5, 5.2 Hz), 3.79-3.86 (4H, m), 3.92-3.96 (4H, m), 4.22 (2H, m), 4.34 (1H, t, J = 8.4 Hz), 4.64 (1H, m), 5.43 (1H, m), 5.89 (1H, s), ![text missing or illegible when filed]()
.44 (1H, d, J = 2.2 Hz), 6.89 (1H, d, J = 8.4 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.35 (1H, d, J = 2.2 Hz), 7.51 (1H, s), 7.65 (1H, d, J = 2.0 Hz). ESI-MS m/z: 492 [M + H]+ 207 (isomer A) [00537]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (2H, m), 2.95 (1H, d, J = 17.4 Hz), 3.26 (1H, dd, J = 17.0, 4.2 Hz), 3.80-3.86 (4H, m), 3.96 (1H, t, J = 8.2 Hz), 4.26 (2H, s), 4.33 (1H, t, J = 9.1 Hz), 4.66 (1H, m), 5.45 (1H, m), 5.89 (1H, s), 6.96 (1H, d, J = 8.0 Hz), 7.02 (1H, d, J = 7.6 Hz), 7.18 (1H, t, J = 5.4 Hz), 7.65 (1H, d, J = 7.6 Hz), 7.70-7.75 (3H, m), 8.64 (1H, s). ESI-MS m/z: 489 [M + H]+ 207 (isomer B) [00538]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (2H, m), 2.95 (1H, d, J = 17.4 Hz), 3.26 (1H, dd, J = 17.0, 4.2 Hz), 3.80-3.86 (4H, m), 3.96 (1H, t, J = 8.2 Hz), 4.26 (2H, s), 4.33 (1H, t, J = 9.1 Hz), 4.66 (1H, m), 5.45 (1H, m), 5.89 (1H, s), 6.96 (1H, d, J = 8.0 Hz), 7.02 (1H, d, J = 7.6 Hz), 7.18 (1H, t, J = 5.4 Hz), 7.65 (1H, d, J = 7.6 Hz), 7.70-7.75 (3H, m), 8.64 (1H, s). ESI-MS m/z: 489 [M + H]+ 208 [00539]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.27 (2H, m), 2.90 (1H, dd, J = 4. ![text missing or illegible when filed]()
, 16.7 Hz), 3.17 (1H, dd, J = 16.7, 5.0 Hz), 3.95 (1H, m), 4.15-4.28 (4H, m), 4.40 (1H, m), 4.63 (1H, m), 5.44 (1H, m), 5.95 (1H, s), 6.93 (2H, d, J = ![text missing or illegible when filed]()
.4 Hz), 7.38 (1H, s), 7.42 (1H, dd, J = 8.6, 1.7 Hz). ESI-MS m/z: 423 [M + H]+ 209 (isomer A) [00540]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (2H, m), 2.90 (1H, dd, J = 16.5, 4.4 Hz), 3.17 (1H, dd, J = 16.6, 5.0 Hz), 3.95 (1H, dd, J = 9.9, 7.6 Hz), 4.15-4.25 (3H, s), 4.28 (1H, m), 4.40 (1H, t, J = 8.4 Hz), 4.64 (1H, m), 5.45 (1H, m), 5.92 (1H, s), 6. ![text missing or illegible when filed]()
1 (1H, s), 6.93 (1H, d, J = 8.4 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 423 [M + H]+ 209 (isomer B) [00541]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (2H, m), 2.90 (1H, dd, J = 16.5, 4.4 Hz), 3.17 (1H, dd, J = 16.6, 6.0 Hz), 3.95 (1H, dd, J = 9.9, 7.6 Hz), 4.15-4.25 (3H, s), 4.28 (1H, m), 4.40 (1H, t, J = 8.4 Hz), 4.64 (1H, m), 5.45 (1H, m), 5.92 (1H, s), 6.91 (1H, s), ![text missing or illegible when filed]()
.93 (1H, d, J = 8.4 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 423 [M + H]+ 210 [00542]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (2H, m), 2.85 (1H, dd, J = 16.7, 3.9 Hz), 3.04 (3H, dt, J = 17.4, 4.6 Hz), 3.17 (1H, dd, J = 16. ![text missing or illegible when filed]()
, 5.4 Hz), 3.94 (1H, m), 4.12-4.26 (3H, m), 4.39 (1H, m), 4.62 (1H, m), 5.43 (1H, m), 5.86 (1H, m), 5.92 (1H, s), 6.81 (1H, q, J = 6. ![text missing or illegible when filed]()
Hz), 6.96 (1H, s), 6.97-7.02 (2H, m). ESI-MS m/z: 462 [M + H]+ 211 (isomer A) [00543]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (2H, m), 2.85 (1H, dd, J = 17.1, 3.4 Hz), 3.04 (2H, td, J = 17.4, 4.4 Hz), 3.17 (1H, dd, J = 16.4, 5.0 Hz), 3.94 (1H, t, J = 7.7 Hz), 4.15-4.26 (4H, m), 4.40 (1H, t, J = 9.1 Hz), 4.62 (1H, m), ![text missing or illegible when filed]()
.44 (1H, m), 5.88 (1H, m), 5.92 (1H, s), 6.84 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.01 (2H, d, J = 8.2 Hz). ESI-MS m/z: 462 [M + H]+ 211 (isomer B) [00544]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (2H, m), 2.85 (1H, dd, J = 17.1, 3.4 Hz), 3.04 (2H, td, J = 17.4, 4.4 Hz), 3.17 (1H, dd, J = 16.4, 5.0 Hz), 3.94 (1H, t, J = 7.7 Hz), 4.15-4.26 (4H, m), 4.40 (1H, t, J = 9.1 Hz), 4.62 (1H, m), 5.44 (1H, m), 6.88 (1H, m), 5.95 (1H, s), 6.84 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.01 (2H, d, J = 8.2 Hz). ESI-MS m/z: 462 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00030 TABLE 30 Example Structural formula NMR MS 212 [00545]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (2H, m), 2.90 (1H, m), 3.22 (1H, m), 3.93 (4H, m), 4.15-4.23 (4H, m), 4.38 (1H, m), 4.64 (1H, m), 5.42 (1H, m), 5.91 (1H, s), 6.44 (1H, d, J = 1.9 Hz), 6.89 (1H, d, J = 7.6 Hz), 7.02 (1H, m), 7.35 (1H, d, J = 2.0 Hz), 7.52-7.54 (2H, m). ESI-MS m/z: 478 [M + H]+ 213 (isomer A) [00546]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (2H, m), 2.90 (1H, dd, J = 16.4, 3.6 Hz), 3.22 (1H, dd, J = 16.8, 5.0 Hz), 3.90-3.94 (4H, m), 4.14-4.25 (4H, m), 4.39 (1H, dd, J = 8.3, 1.6 Hz), 4.64 (1H, m), 5.43 (1H, m), 5. ![text missing or illegible when filed]()
1 (1H, s), 6.44 (1H, d, J = 2.2 Hz), 6.89 (1H, d, J = 8.0 Hz), 7.02 (1H, d, J = 8.2 Hz), 7.35 (1H, d, J = 2.2 Hz), 7.51 (1H, s), 7.54 (1H, d, J = 2.1 Hz). ESI-MS m/z: 478 [M + H]+ 213 (isomer B) [00547]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (2H, m), 2.90 (1H, dd, J = 3.6, 16.4 Hz), 3.22 (1H, dd, J = 16.8, 6.0 Hz), 3.90-3.94 (4H, m), 4.14-4.25 (4H, m), 4.39 (1H, dd, J = 8.3, 1.6 Hz), 4.64 (1H, m), 5.43 (1H, m), 5.91 (1H, s), 6.44 (1JH, d, J = 2.2 Hz), 6.89 (1H, d, J = 8.0 Hz), 7.02 (1H, d, J = 8.2 Hz), 7.3 ![text missing or illegible when filed]()
(1H, d, J = 2.2 Hz), 7.51 (1H, s), 7.54 (1H, d, J = 2.1 Hz). ESI-MS m/z: 478 [M + H]+ 214 [00548]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.32 (2H, m), 2.87 (1H, dd, J = ![text missing or illegible when filed]()
, 4.2 Hz), 3.1 ![text missing or illegible when filed]()
(1H, dd, J = 16.8, ![text missing or illegible when filed]()
Hz), 3. ![text missing or illegible when filed]()
(1H, d, J = 8.2 Hz), 3. ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 3.94 (1H, dd, J = 10.8, 7.9 Hz), 4. ![text missing or illegible when filed]()
-4.13 (2H, m), 4.20 (2H, m), 4.3 ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 8.6 Hz), 4.56 (2H, s), 4.63 (1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, t, J = 73.5 Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = 7.8 Hz), 7.04 (1H, s), 7.11 (1H, dd, J = 8.5, 1.6 Hz). ESI-MS m/z: 492 [M + H]+ 215 (isomer A) [00549]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.32 (2H, m), 2.87 (1H, dd, J = ![text missing or illegible when filed]()
, 4.2 Hz), 3.1 ![text missing or illegible when filed]()
(1H, dd, J = 16.8, ![text missing or illegible when filed]()
Hz), 3. ![text missing or illegible when filed]()
(1H, d, J = 8.2 Hz), 3. ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 3.94 (1H, dd, J = 10.8, 7.9 Hz), 4. ![text missing or illegible when filed]()
-4.13 (2H, m), 4.20 (2H, m), 4.3 ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 8.6 Hz), 4.56 (2H, s), 4.63 (1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, t, J = 73.5 Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = 7.8 Hz), 7.04 (1H, s), 7.11 (1H, dd, J = 8.5, 1.6 Hz). ESI-MS m/z: 492 [M + H]+ 215 (isomer B) [00550]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.32 (2H, m), 2.87 (1H, dd, J = ![text missing or illegible when filed]()
, 4.2 Hz), 3.1 ![text missing or illegible when filed]()
(1H, dd, J = 16.8, ![text missing or illegible when filed]()
Hz), 3. ![text missing or illegible when filed]()
(1H, d, J = 8.2 Hz), 3. ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 3.94 (1H, dd, J = 10.8, 7.9 Hz), 4. ![text missing or illegible when filed]()
-4.13 (2H, m), 4.20 (2H, m), 4.3 ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 8.6 Hz), 4.56 (2H, s), 4.63 (1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, t, J = 73.5 Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 7.01 (1H, d, J = 7.8 Hz), 7.04 (1H, s), 7.11 (1H, dd, J = 8.5, 1.6 Hz). ESI-MS m/z: 492 [M + H]+ 216 [00551]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.31 (2H, m), 2.80-2.90 (3H, m), 3.16 (1H, dd, J = 16.8, 5.6 Hz), 3.82-4.14 (5H, m), 4.18 (2H, m), 4.37 (1H, t, J = 9.2 Hz), 4.61 (1H, m), ![text missing or illegible when filed]()
.42 (1H, m), ![text missing or illegible when filed]()
.91 (1H, s), 6.19 (1H, t, J = 72.3 Hz), 6.22 (1H, t, J = 72.3 Hz), 6.81 (1H, d, J = ![text missing or illegible when filed]()
Hz), 6.01 (1H, s), 6.95- 7.05 (2H, m). ESI-MS m/z: 474 [M + H]+ 217 (isomer A) [00552]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.31 (2H, m), 2.80-2.90 (3H, m), 3.16 (1H, dd, J = 16.8, 5.6 Hz), 3.82-4.14 (5H, m), 4.18 (2H, m), 4.37 (1H, t, J = 9.2 Hz), 4.61 (1H, m), ![text missing or illegible when filed]()
.42 (1H, m), ![text missing or illegible when filed]()
.91 (1H, s), 6.19 (1H, t, J = 72.3 Hz), 6.22 (1H, t, J = 72.3 Hz), 6.81 (1H, d, J = ![text missing or illegible when filed]()
Hz), 6.01 (1H, s), 6.95- 7.05 (2H, m). ESI-MS m/z: 474 [M + H]+ 217 (isomer B) [00553]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.31 (2H, m), 2.80-2.90 (3H, m), 3.16 (1H, dd, J = 16.8, 5.6 Hz), 3.82-4.14 (5H, m), 4.18 (2H, m), 4.37 (1H, t, J = 9.2 Hz), 4.61 (1H, m), ![text missing or illegible when filed]()
.42 (1H, m), ![text missing or illegible when filed]()
.91 (1H, s), 6.19 (1H, t, J = 72.3 Hz), 6.22 (1H, t, J = 72.3 Hz), 6.81 (1H, d, J = ![text missing or illegible when filed]()
Hz), 6.01 (1H, s), 6.95- 7.05 (2H, m). ESI-MS m/z: 474 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00031 TABLE 31 Example Structural formula NMR MS 218 [00554]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.11-2.31 (2H, m), 2.85 (1H, dd, J = 17.0, 4.0 Hz), 3.04 (2H, td, J = 17.2, 6.0 Hz), 3.17 (1H, dd, J = 16.8, 5.2 Hz), 3.95 (1H, dd, J = 10. ![text missing or illegible when filed]()
, 8.5 Hz), 4.03-4.14 (2H, m), 4.18 (2H, m), 4.38 (1H, dd, J = 10.2, 8.3 Hz), 4.62 (1H, m), 5.39-5.47 (1H, m), 5.88 (1H, tt, J = 5 ![text missing or illegible when filed]()
, 4.3 Hz), 5.91 (1H, s), 6.22 (1H, t, J = 74.2 Hz), 6.84 (1H, d, J = 8.6 Hz), 6.93 (1H, s), 6.98-7.04 (2H, m). ESI-MS m/z: 444 [M + H]+ 219 (isomer A) [00555]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.11-2.31 (2H, m), 2.86 (1H, dd, J = 17.0, 4.0 Hz), 3.04 (2H, td, J = 17.2, 5.0 Hz), 3.17 (1H, dd, J = 16.8, 5.2 Hz), 3.95 (1H, dd, J = 10.9, 8.5 Hz), 4.03- 4.14 (2H, m), 4.18 (2H, m), 4.38 (1H, dd, J = 10.2, 8.3 Hz), 4.82 (1H, m), 6.39-6.47 (1H, m), 5.88 (1H, ![text missing or illegible when filed]()
, J = 56.8, 4.3 Hz), ![text missing or illegible when filed]()
.91 (1H, s), 6.22 (1H, t, J = 74.2 Hz), 5.84 (1H, d, J = 8.6 Hz), 6.93 (1H, s), 6.98-7.04 (2H, m). ESI-MS m/z: 444 [M + H]+ 219 (isomer B) [00556]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.11-2.31 (2H, m), 2.86 (1H, dd, J = 17.0, 4.0 Hz), 3.04 (2H, td, J = 17.2, 5.0 Hz), 3.17 (1H, dd, J = 16.8, 5.2 Hz), 3.95 (1H, dd, J = 10.9, 8.5 Hz), 4.03- 4.14 (2H, m), 4.18 (2H, m), 4.38 (1H, dd, J = 10.2, 8.3 Hz), 4.82 (1H, m), 6.39-6.47 (1H, m), 5.88 (1H, ![text missing or illegible when filed]()
, J = 56.8, 4.3 Hz), ![text missing or illegible when filed]()
.91 (1H, s), 6.22 (1H, t, J = 74.2 Hz), 5.84 (1H, d, J = 8.6 Hz), 6.93 (1H, s), 6.98-7.04 (2H, m). ESI-MS m/z: 444 [M + H]+ 220 [00557]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.31 (2H, m), 2.88 (1H, dd, J = 17.2, 3.3 Hz), 3.20 (1H, dd, J = 17.1, 4.7 Hz), 3.90-3.98 (4H, m), 4.04-4.13 (2H, m), 4.21 (2H, m), 4.36 (1H, t, J = 9.4 Hz), 4.64 (1H, m), 5.42 (1H, m), 6.91 (1H, s), 6.22 (1H, t, J = 74.5 Hz), 6.87 (1H, d, J = 8.0 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.15 (1H, s), 7.23 (1H, d, J = 8.4 Hz), 7.51 (1H, s), 7.67 (1H, s). ESI-MS m/z: 460 [M + H]+ 221 (isomer A) [00558]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.31 (2H, m), 2.88 (1H, dd, J = 17.2, 3.3 Hz), 3.20 (1H, dd, J = 17.1, 4.7 Hz), 3.90-3.98 (4H, m), 4.04-4.13 (2H, m), 4.21 (2H, m), 4.36 (1H, t, J = 9.4 Hz), 4.64 (1H, m), 5.42 (1H, m), 6.91 (1H, s), 6.22 (1H, t, J = 74.5 Hz), 6.87 (1H, d, J = 8.0 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.15 (1H, s), 7.23 (1H, d, J = 8.4 Hz), 7.51 (1H, s), 7.67 (1H, s). ESI-MS m/z: 460 [M + H]+ 221 (isomer B) [00559]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.31 (2H, m), 2.88 (1H, dd, J = 17.2, 3.3 Hz), 3.20 (1H, dd, J = 17.1, 4.7 Hz), 3.90-3.98 (4H, m), 4.04-4.13 (2H, m), 4.21 (2H, m), 4.36 (1H, t, J = 9.4 Hz), 4.64 (1H, m), 5.42 (1H, m), 6.91 (1H, s), 6.22 (1H, t, J = 74.5 Hz), 6.87 (1H, d, J = 8.0 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.15 (1H, s), 7.23 (1H, d, J = 8.4 Hz), 7.51 (1H, s), 7.67 (1H, s). ESI-MS m/z: 460 [M + H]+ 222 [00560]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.30 (2H, m), 2.97 (1H, dd, J = 17.2, 3.4 Hz), 3.27 (1H, dd, J = 1 ![text missing or illegible when filed]()
.0, 3.4 Hz), 3.93 (1H, dd, J = 9. ![text missing or illegible when filed]()
, 8.2 Hz), 4.68 (1H, m), 6.43 (1H, m), 5.91 (1H, s), 6.22 (1H, t, J = 73.8 Hz), 6.96-7.04 (2H, m), 7.7 ![text missing or illegible when filed]()
-7.82 (2H, m), 8.45 (1H, s), 7047 (1H, s), 8.96 (1H, s) ESI-MS m/z: 458 [M + H]+ 223 (isomer A) [00561]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.30 (2H, m), 2.97 (1H, dd, J = 17.2, 3.4 Hz), 3.27 (1H, dd, J = 1 ![text missing or illegible when filed]()
.0, 3.4 Hz), 3.93 (1H, dd, J = 9. ![text missing or illegible when filed]()
, 8.2 Hz), 4.68 (1H, m), 6.43 (1H, m), 5.91 (1H, s), 6.22 (1H, t, J = 73.8 Hz), 6.96- 7.04 (2H, m), 7.7 ![text missing or illegible when filed]()
-7.82 (2H, m), 8.45 (1H, s), 7047 (1H, s), 8.96 (1H, s) ESI-MS m/z: 458 [M + H]+ 223 (isomer B) [00562]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.30 (2H, m), 2.97 (1H, dd, J = 17.2, 3.4 Hz), 3.27 (1H, dd, J = 1 ![text missing or illegible when filed]()
.0, 3.4 Hz), 3.93 (1H, dd, J = 9. ![text missing or illegible when filed]()
, 8.2 Hz), 4.68 (1H, m), 6.43 (1H, m), 5.91 (1H, s), 6.22 (1H, t, J = 73.8 Hz), 6.96- 7.04 (2H, m), 7.7 ![text missing or illegible when filed]()
-7.82 (2H, m), 8.45 (1H, s), 7047 (1H, s), 8.96 (1H, s) ESI-MS m/z: 458 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00032 TABLE 32 Example Structural formula NMR MS 224 (isomer A) [00563]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17 (2H, m), 2.87 (1H, d, J = 15.7 Hz), 3.18 (1H, dd, J = 16.4, 4.3 Hz), 3.63-3.85 (6H, m), 3.96 (1H, t, J = 8. ![text missing or illegible when filed]()
Hz), 4.20 (2H, s), 4.34 (1H, t, J = 9.0 Hz), 4.56 (2H, s), 4.62 (1H, s), 5.44 (1H, t, J = 7.1 Hz), 5.84 (1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 5.89 (1H, s), 6.87 (1H, d, J = 8.2 Hz), 7.01 (1H, d, J = ![text missing or illegible when filed]()
.2 Hz), 7.04 (1H, s), 7.11 (1H, d, J = 6.2 Hz). ESI-MS m/z: 506 [M + H]+ 224 (isomer B) [00564]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17 (2H, m), 2.87 (1H, d, J = 15.7 Hz), 3.18 (1H, dd, J = 16.4, 4.3 Hz), 3.63-3.85 (6H, m), 3.96 (1H, t, J = 8. ![text missing or illegible when filed]()
Hz), 4.20 (2H, s), 4.34 (1H, t, J = 9.0 Hz), 4.56 (2H, s), 4.62 (1H, s), 5.44 (1H, t, J = 7.1 Hz), 5.84 (1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 5.89 (1H, s), 6.87 (1H, d, J = 8.2 Hz), 7.01 (1H, d, J = ![text missing or illegible when filed]()
.2 Hz), 7.04 (1H, s), 7.11 (1H, d, J = 6.2 Hz). ESI-MS m/z: 506 [M + H]+ 225 [00565]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96 (1H, m), 2.13 (1H, m), 2. ![text missing or illegible when filed]()
4 (1H, dd, J = 3.7, 16.9 Hz), 2.96 (2H, m), 3.14 (1H, m), 3.20 (2H, m), 3.93 (1H, m), 4.19 (2H, d, J = 2.7 Hz), 4.36 (1H, m), 4.60 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.98 (1H, d, J = 7.3 Hz), 7.03 (1H, s), 7.08 (1H, dd, J = 8.7, 2.9 Hz). ESI-MS m/z: 445 [M + H]+ 226 (isomer A) [00566]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91-1.99 (1H, m), 2.08-2.17 (1H, m), 2.76-2.90 (1H, m), 2.93-3.02 (2H, m), 3.11-3.23 (3H, m), 3.93 (1H, t, J = 9.1 Hz), 4.18 (2H, m), 4.36 (1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 4.60 (1H, m), 6.44 (1H, m), 6.89 (1H, s), 6.80 (1H, d, J = 6.8 Hz), 6.99 (1H, d, J = 8.0 Hz), 7.03 (1H, s), 7.08 (1H, d, J = 8.8 Hz). ESI-MS m/z: 445 [M + H]+ 226 (isomer B) [00567]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91-1.99 (1H, m), 2.08-2.17 (1H, m), 2.81-2.86 (1H, m), 2.95-2.98 (2H, m), 3.12-3.21 (3H, m), 3.93 (1H, t, J = 8.8 Hz), 4.18 (2H, s), 4.35 (1H, t, J = 9.2 Hz), 4.61 (1H, m), 5.43 (1H, m), ![text missing or illegible when filed]()
.89 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.98 (1H, d, J = 7.8 Hz), 7.04 (1H, s), 7.08 (1H, d, J = 8.7 Hz). ESI-MS m/z: 445 [M + H]+ 227 [00568]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96 (1H, m), 2.11 (1H, m), 2.25 (3H, s), 2.62 (1H, m), 2.97 (2H, m), 3.12-3.23 (3H, m), 3.93 (1H, m), 4.16 (2H, d, J = 2.7 Hz), 4.35 (1H, m), 4.60 (1H, m), 5.42 (1H, m), 5.89 (1H, s), 6.76 (1H, d, J = 8.3 Hz), 6.85 (1H, s), 6.93 (1H, d, J = 8.2 Hz), 7.03 (1H, d, J = 8.0 Hz). ESI-MS m/z: 425 [M + H]+ 228 (isomer A) [00569]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.90-1.96 (1H, m), 2.05-2.09 (1H, m), 2.26 (3H, s), 2.80-2.94 (1H, m), 2.89-3.02 (2H, m), 3.11-3.23 (3H, m), 3.91 (1H, t, J = 8.9 Hz), 4.16 (2H, m), 4.35 (1H, t, J = 9.1 Hz), 4.60 (1H, m), 5.43 (1H, m), 5.88 (1H, s), 6.77 (1H, d, J = 8.3 Hz), 6.85 (1H, s), 6.93 (1H, d, J = 8.3 Hz), 7.03 (1H, d, J = 8.5 Hz). ESI-MS m/z: 425 [M + H]+ 228 (isomer B) [00570]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.93-2.00 (1H, m), 2.07-2.25 (1H, m), 2.25 (3H, s), 2.78-2.94 (1H, m), 2.90-3.02 (1H, m), 3.12-3.23 (1H, m), 3.93 (1H, t, J = 8.9 Hz), 4.16 (2H, m), 4.34 (1H, t, J = 9.1 Hz), 4.60 (1H, m), 5.42 (1H, m), 5.89 (1H, s), 6.76 (1H, d, J = 8.2 Hz), 6.88 (1H, s), 6.93 (1H, d, J = 8.2 Hz), 7.02 (1H, d, J = 8.3 Hz). ESI-MS m/z: 425 [M + H]+ 229 [00571]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.95 (1H, m), 2.11 (1H, m), 2.88- 3.01 (3H, m), 3.16-3.23 (3H, m), 3.93 (1H, m), 4.25 (2H, d, J = 2.6 Hz), 4.35 (1H, m), 4.65 (1H, m), 5.44 (1H, m), 5.90 (1H, s), 6.93-6.97 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.8 Hz). ESI-MS m/z: 479 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00033 TABLE 33 Example Structural formula NMR MS 230 (isomer A) [00572]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91-1.99 (1H, m), 2.08-2.17 (1H, m), 2.88-3.00 (3H, m), 3.16-3.23 (3H, m), 3.90-3.92 (1H, m), 4.25 (2H, d, J = 2.9 Hz), 4.33-4.37 (1H, m), 4.61- 4.68 (1H, m), 5.44 (1H, m), 5.90 (1H, m), 6.93-7.00 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.7 Hz). ESI-MS m/z: 479 [M + H]+ 230 (isomer B) [00573]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91-1.99 (1H, m), 2.08-2.17 (1H, m), 2.92-3.02 (3H, m), 3.16-3.23 (3H, m), 3.90-3.92 (1H, m), 4.26 (2H, d, J = 2.9 Hz), 4.33-4.37 (1H, m), 4.61-4.68 (1H, m), 5.44 (1H, m), 5.90 (1H, s), 6.93- 7.00 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.7 Hz). ESI-MS m/z: 479 [M + H]+ 231 [00574]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96 (1H, m), 2.13 (1H, m), 2.84- 3.01 (3H, m), 3.15-3.24 (3H, m), 3.81 (2H, q, J = 8.7 Hz), 3.93 (1H, m), 4.20 (2H, d, J = 2.8 Hz), 4.35 (1H, m), 4.56 (2H, s), 4. ![text missing or illegible when filed]()
2 (1H, m), 5.42 (1H, m), ![text missing or illegible when filed]()
.89 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 8.6 Hz), 7.04 (1H, m), 7.11 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 523 [M + H]+ 232 (isomer A) [00575]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.97 (1H, m), 2.12 (1H, m), 2.84- 3.03 (3H, m), 3.15-3.24 (3H, m), 3.81 (2H, q, J = 8.7 Hz), 3.93 (1H, t, J = 8.2 Hz), 4.20 (2H, s), 4.34 (1H, t, J = 9.0 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.87 (1H, d, J = ![text missing or illegible when filed]()
.3 Hz), 7.00 (1H, d, J = 8.0 Hz), 7.04 (1H, s), 7.11 (1H, d, J = 8.2 Hz). ESI-MS m/z: 523 [M + H]+ 232 (isomer B) [00576]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.97 (1H, m), 2.12 (1H, m), 2.84- 3.03 (3H, m), 3.15-3.24 (3H, m), 3.81 (2H, q, J = 6.7 Hz), 3.93 (1H, t, J = ![text missing or illegible when filed]()
8.2 Hz), 4.20 (2H, s), 4.34 (1H, t, J = 9.0 Hz), 4.57 (2H, s), 4.63 (1H, m), 5.43 (1H, m), 5.69 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 8.0 Hz), 7.04 (1H, s), 7.11 (1H, d, J = 8.2 Hz). ESI-MS m/z: 523 [M + H]+ 233 [00577]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80-1.90 (1H, m), 1.98-2.08 (1H, m), 2.67-2.88 (3H, m), 3.12-3.18 (1H, m), 3.58-3.62 (4H, m), 3.89-3.94 (1H, m), 5.35-5.42 (1H, m), 5.88 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.96-7.00 (1H, m), 7.03 (1H, d, J = 1.8 Hz), 7.08 (1H, dd, J = 18.6, 2.6 Hz). ESI-MS m/z: 439 [M + H]+ 234 (isomer A) [00578]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86 (1H, m), 1.99-2.04 (1H, m), 2.69-2.88 (3H, m), 3.15 (1H, dd, J = 18.7, 5.1 Hz), 3.57-3.63 (4H, m), 3.91 (1H, t, J = 9.0 Hz), 4.19 (2H, s), 4.36 (1H, t, J = 9.1 Hz), 4.61 (1H, m), 5.37-5.40 (1H, m), 5.89 (1H, s), 6.80 (1H, d, J = 8.8 Hz), 6.97- 7.09 (3H, m). ESI-MS m/z: 439 [M + H]+ 234 (isomer B) [00579]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.87 (1H, m), 2.02-2.08 (1H, m), 2.75-2.86 (3H, m), 3.15 (1H, dd, J = 17.1, 5.3 Hz), 3.57- 3.64 (4H, m), 3.92 (1H, t, J = 8.8 Hz), 4.18 (2H, s), 4.3 ![text missing or illegible when filed]()
(1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 4.61 (1H, m), 5.35-5.42 (1H, m), 5.89 (1H, s), 6.80 (1H, d, J = 8.8 Hz), 6.96- 7.09 (3H, m). ESI-MS m/z: 439 [M + H]+ 235 [00580]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.85-1.87 (1H, m), 1.98-2.05 (1H, m), 2.73-2.93 (3H, m), 3.18-3.23 (1H, m), 3.55-3.63 (4H, m), 3.89-3.94 (1H, m), 4.25-4.26 (2H, m), 4.33-4.38 (1H, m), 4.64-4.66 (1H ,m), 5.3 ![text missing or illegible when filed]()
-5.41 (1H, m), ![text missing or illegible when filed]()
.89 (1H, s), 6.93-7.00 (2H, m), 7.33-7.39 (2H, m). ESI-MS m/z: 473 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00034 TABLE 34 Example Structural formula NMR MS 236 (isomer A) [00581]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.87 (1H, m), 1.99-2.06 (1H, m), 2.75-2.93 (3H, m), 3.18-3.23 (1H, m), 3.60 (4H, m), 3.91(1H, t, J = 8.9 Hz), 4.26 (2H, s), 4.36 (1H, t, J = 9.0 Hz), 4.65 (1H, m), 5.36-5.46 (1H, m), 5.89 (1H, s), 6.93-6.97 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.8 Hz). ESI-MS m/z: 473 [M + H]+ 236 (isomer B) [00582]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.88 (1H, m), 1.98-2.08 (1H, m), 2.74-2.93 (3H, m), 3.18-3.23 (1H, m), 3.60 (4H, m), 3.92 (1H, t, J = 8.8 Hz), 4.25 (2H, s), 4.35 (1H, t, J = 9.0 Hz), 4.65 (1H, m), 5.35-5.44 (1H, m), 5.89 (1H, s), 6.93-6.95 (2H, m), 7.33 (1H ,s), 7.38 (1H, d, J = 9.2 Hz). ESI-MS m/z: 473 [M + H]+ 237 [00583]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.85-1.87 (1H, m), 2.02-2.05 (1H, m), 2.75-2.87 (5H, m), 3.12-3.19 (1H, m), 3.55-3.61 (3H, m), 3.88-3.94 (1H, m), 4.01 (2H, t, J = 7.2 Hz), 4.11-4.18 (3H, m), 4.31-4.38 (1H, m), 4.60-4.61 (1H, m), 5.36-5.40 (1H, m), 5.89 (1H, s), 6.19 (1H, t, J = 74.7 Hz), 6.81 (1H, dd, J = 8.2, 2.1 Hz), 6.90 (1H, s), 6.97-7.01 (2H, m). ESI-MS m/z: 499 [M + H]+ 238 (isomer A) [00584]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1H-NMR (CDCl3) 1.81-1.86 (1H, m), 1.93-2.13 (1H, m), 2.69-2.94 (5H, m), 3.06-3.13 (2H, m), 3.5 ![text missing or illegible when filed]()
(2H, t, J = 11.9 Hz), 3.76 (1H, t, J = 11.9 Hz), 3.91 (1H, m), 4.01 (2H, t, J = 7.1 Hz), 4.1 ![text missing or illegible when filed]()
(2H, s), 4.35 (1H, m), 4.61 (1H, s), 5.41 (1H, m), 5.89 (1H, s), 6.19 (1H, t, J = 74.8 Hz), 6.81 (1H, d, J = 8.2 Hz), 6.90 (1H, s), 6.97-7.02 (2H, m). ESI-MS m/z: 499 [M + H]+ 238 (isomer B) [00585]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.81-1.86 (1H, m), 2.13-1.93 (1H, m), 2.81-2.93 (5H, m), 3.0 ![text missing or illegible when filed]()
-3.13 (2H, m), 3.59 (2H, t, J = 11.9 Hz), 3.77 (1H, t, J = 11.9 Hz), 3.92 (1H, m), 4.01 (2H, t, J = 7.1 Hz), 4.18 (2H, s), 4.34 (1H, m), 4.61 (1H, s), 5.40 (1H, m), 5.89 (1H, s), 6.19 (1H, t, J = 74.7 Hz), 6.81 (1H, d, 8.6 Hz), 6.90 (1H, s), 6.97- 7.02 (2H, m) ESI-MS m/z: 499 [M + H]+ 239 [00586]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.66-1.67 (1H, m), 2.01-2.06 (1H, m), 2.73-2.92 (5H, m), 3.14-3.19 (1H, m), 3.55-3.63 (4H, m), 3.87-3.99 (1H, m), 4.10 (2H, t, J = 7.3 Hz), 4.18 (2H, s), 4.32-4.38 (1H, m), 4.61-4.62 (1H, m), 5.37-5.39 (1H, m), 5.89 (1H, s), 6.82 (1H, d, J = 8.3 Hz), 6.89 (1H, s), 6.96-7.01 (2H, m). ESI-MS m/z: 517 [M + H]+ 240 (isomer A) [00587]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86-1.87 (1H, m), 2.01-2.04 (1H, m), 2.79-2.03 (5H, m), 3.08-3.13 (1H, m), 3.59 (4H, t, J = 11.5 Hz), 3.91 (1H, t, J = 8.7 Hz), 4.10 (2H, t, J = 9.1 Hz), 4.18 (2H, s), 4.35 (1H, t, J = 9.1 Hz), 4.61 (1H, m), 5.3 ![text missing or illegible when filed]()
(1H, m), 5.89 (1H, s), 6.82 (1H, d, J = 8.1 Hz), 6.89 (1H, s), 6.96-7.01 (2H, m). ESI-MS m/z: 517 [M + H]+ 240 (isomer B) [00588]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86-1.87 (1H, m), 2.01-2.04 (1H, m), 2.70-2.96 (5H, m), 3.08-3.16 (1H, m), 3.5 ![text missing or illegible when filed]()
(4H, t, J = 11.9 Hz), 3.91 (1H, t, J = 8.7 Hz), 4.10 (1H, t, J = 7.26 Hz), 4.18 (2H, s), 4.34 (1H, t, J = ![text missing or illegible when filed]()
.1 Hz), 4.61 (1H, m), 5.37 (1H, m), 5.89 (1H, s), 6.82 (1H, d, J = 8.3 Hz), 6.90 (1H, s), 6.90-7.10 (2H, m). ESI-MS m/z: 517 [M + H]+ 241 (isomer A) [00589]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.98 (1H, m), 2.10 (1H, m), 2.22- 2.32 (2H, m), 2.60-2.76 (4H, m), 2.83-2.94 (3H, m), 3.15-3.30 (3H, m), 3.93 (1H, t, J = ![text missing or illegible when filed]()
.9 Hz), 4.20 (2H, s), 4.36 (1H, t, J = 8.9 Hz), 4.62 (1H, m), 5.40 (1H, m), 5.78 (1H, s), 6.85 (1H, d, J = 8.2 Hz), 6.97- 7.06 (3H, m). ESI-MS m/z: 501 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00035 TABLE 35 Example Structural formula NMR MS 241 (isomer B) [00590]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.99 (1H, m), 2.11 (1H, m), 2.22- 2.33 (2H, m), 2.63 (1H, m), 2.6 ![text missing or illegible when filed]()
-2.77 (3H, m), 2.83- 2.98 (3H, m), 3.15-3.30 (3H, m), 3.94 (1H, t, J = 8.8 Hz), 4.20 (2H, s), 4.35 (1H, t, J = 9.0 Hz), 4. ![text missing or illegible when filed]()
2 (1H, m), 5.39 (1H, m), 5.89 (1H, s), 6.85 (1H, d, J = 8.3 Hz), 6.97-7.06 (3H, m). ESI-MS m/z: 501 [M + H]+ 242 (isomer A) [00591]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.92-2.14 (6H, m), 2.55-2.64 (6H, m), 2.91 (1H, m), 3.20 (1H, m), 3.94 (1H, t, J = ![text missing or illegible when filed]()
.8 Hz), 4.25 (2H, d, J = 2.6 Hz), 4.35 (1H, t, J = 9.1 Hz), 4.65 (1H, m), 5.39 (1H, m), 5.89 (1H, s), 6.93-6.97 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.4 Hz). ESI-MS m/z: 501 [M + H]+ 242 (isomer B) [00592]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.93-2.17 (6H, m), 2.5 ![text missing or illegible when filed]()
-2.61 (6H, m), 2.91 (1H, dd, J = 16.9, 4.1 Hz), 3.21 (1H, dd, J = 17.0, 5.2 Hz), 3.95 (1H, t, J = 8.9 Hz), 4.25 (2H, d, J = 2.6 Hz), 4.34 (1H, t, J = 9.0 Hz), 4.65 (1H, m), 5.38 (1H, m), 5.89 (1H, s), 6.93-7.00 (2H, m), 7.33 (1H, s), 7.3 ![text missing or illegible when filed]()
(1H, d, J = 9.0 Hz). ESI-MS m/z: 501 [M + H]+ 243 [00593]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.07 (1H, m), 2.26 (1H, m), 2.82- 2.94 (3H, m), 3.08-3.20 (3H, m), 3.91 (1H, m), 4.28 (2H, s), 4.38 (1H, m), 4.64 (1H, m), ![text missing or illegible when filed]()
.44 (1H, m), 5.91 (1H, s), 6.93 (2H, d, J = 8.5 Hz), 7.38 (1H, s), 7.42 (1H, m). ESI-MS m/z: 453 [M + H]+ 244 (isomer A) [00594]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.07 (1H, m), 2.25 (1H, m), 2.81- 2.95 (3H, m), 3.07-3.20 (3H, m), 3.91 (1H, dd, J = 9.9, 7.6 Hz), 4.28 (2H, m), 4.38 (1H, t, J = 8.5 hz), 4.64 (1H, m), 5.44 (1H, m), 5.91 (1H, s), 6.90 (1H, s), 6.93 (1H, d,J = 8.4 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 453 [M + H]+ 244 (isomer B) [00595]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.07 (1H, m), 2.25 (1H, m), 2.81- 2.95 (3H, m), 3.07-3.20 (3H, m), 3.91 (1H, dd, J = 9.9, 7.6 Hz), 4.28 (2H, m), 4.38 (1H, t, J = 8.5 hz), 4.64 (1H, m), 5.44 (1H, m), 5.91 (1H, s), 6.90 (1H, s), 6.93 (1H, d, J = 8.4 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 453 [M + H]+ 245 [00596]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69-1.92 (2H, m), 1.92-2.09 (2H, m), 2.89 (1H, dd, J = 17.3, 5.7 Hz), 3.18 (1H, dd, J = 14.3, 5.2 Hz), 3.68 (2H, m), 3.77-3.93 (3H, m), 4.22- 4.29 (2H, m), 4.34 (1H, t, J = 8.7 Hz), 4.64 (1H, m), 5.34 (1H, m), 5.89 (1H, s), 6.88-6.94 (2H, m), 7.3 ![text missing or illegible when filed]()
(1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 451 [M + H]+ 246 (isomer A) [00597]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69-1.92 (2H, m), 1.92-2.09 (2H, m), 2.89 (1H, dd, J = 17.3, 5.7 Hz), 3.18 (1H, dd, J = 14.3, 5.2 Hz), 3.68 (2H, m), 3.77-3.93 (3H, m), 4.22- 4.29 (2H, m), 4.34 (1H, t, J = 8.7 Hz), 4.64 (1H, m), 5.34 (1H, m), 5.89 (1H, s), 6.88-6.94 (2H, m), 7.3 ![text missing or illegible when filed]()
(1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 451 [M + H]+ 246 (isomer B) [00598]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69-1.92 (2H, m), 1.92-2.09 (2H, m), 2.89 (1H, dd, J = 17.3, 5.7 Hz), 3.18 (1H, dd, J = 14.3, 5.2 Hz), 3.68 (2H, m), 3.77-3.93 (3H, m), 4.22- 4.29 (2H, m), 4.34 (1H, t, J = 8.7 Hz), 4.64 (1H, m), 5.34 (1H, m), 5.89 (1H, s), 6.88-6.94 (2H, m), 7.3 ![text missing or illegible when filed]()
(1H, s), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 451 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00036 TABLE 36 Example Structural formula NMR MS 247 (isomer A) [00599]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.81-2.06 (4H, m), 2.89 (1H, dd, J = 17.0, 5.7 Hz), 3.18 (1H, dd, J = 17.3, 5.4 Hz), 3.90 (1H, d, J = 9.9, 7.5 Hz), 3.98-4.09 (2H, m), 4.2 ![text missing or illegible when filed]()
(2H, m), 4.36 (1H, dd, J = 10.3, 7.4 Hz), 4.59-4.68 (1H, m), 5.26-5.37 (1H, m), 5.90 (1H, s), 6.89 (1H, m), 6.93 (1H, d, J = 8.0 Hz), 7.36 (1H, s), 7.42 (1H, dd, J = 6.7, 1.8 Jz). ESI-MS m/z: 437 [M + H]+ 247 (isomer B) [00600]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.81-2.06 (4H, m), 2.89 (1H, dd, J = 17.0, 5.7 Hz), 3.18 (1H, dd, J = 17.3, 5.4 Hz), 3.90 (1H, d, J = 9.9, 7.5 Hz), 3.98-4.09 (2H, m), 4.2 ![text missing or illegible when filed]()
(2H, m), 4.36 (1H, dd, J = 10.3, 7.4 Hz), 4.59-4.68 (1H, m), 5.26-5.37 (1H, m), 5.90 (1H, s), 6.89 (1H, m), 6.93 (1H, d, J = 8.0 Hz), 7.36 (1H, s), 7.42 (1H, dd, J = 6.7, 1.8 Jz). ESI-MS m/z: 437 [M + H]+ 248 (isomer A) [00601]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73-2.10 (4H, m), 2.89 (1H, dd, J = 16.7, 4.3 Hz), 3.17 (1H, dd, J = 17.4, 5. ![text missing or illegible when filed]()
Hz), 3.86-3.99 (3H, m), 4.22-4.32 (2H, m), 4.34 (1H, t, J = 8.7 Hz), 4.68 (1H, m), 5.32 (1H, m), 5.90 (1H, s), 6.21 (1H, t, J = 75.0 Hz), 6.88-6.95 (1H, m), 6.89 (1H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 8.7, 1.8 Hz). ESI-MS m/z: 419 [M + H]+ 248 (isomer B) [00602]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73-2.10 (4H, m), 2.89 (1H, dd, J = 16.7, 4.3 Hz), 3.17 (1H, dd, J = 17.4, 5.8 Hz), 3. ![text missing or illegible when filed]()
-3.99 (3H, m), 4.22-4.32 (2H, m), 4.34 (1H, t, J = 8.7 Hz), 4.68 (1H, m), 5.32 (1H, m), 5.90 (1H, s), 6.21 (1H, t, J = 75.0 Hz), 6.88-6.95 (1H, m), 6.69 (1H, m), 7.38 (1H, s), 7.42 (1H, dd, J = ![text missing or illegible when filed]()
.7, 1.8 Hz) ESI-MS m/z: 419 [M + H]+ 249 [00603]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.94-2.98 (1H, m), 3.23-3.26 (1H, m), 4.09-4.38 (4H, m), 4.72 (1H, m), 5.21 (2H, t, J = ![text missing or illegible when filed]()
.2 Hz), 6.41 (1H, m), 6.97 (1H, m), 7.22-7.42 (2H, m), 7.57-7.77 (2H, m). ESI-MS m/z: 420 [M + H]+ 250 [00604]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69-1.71 (6H, m), 2.80 (1H, s), 2.99-3.03 (1H, m), 3.22-3.27 (1H, m), 4.07 (2H, m), 4.23-4.41 (2H, m), 4.70 (1H, s), 6.43 (1H, s), 6.92-6.99 (1H, m), 7.31-7.40 (3H, m), 7.5 ![text missing or illegible when filed]()
(1H, s). ESI-MS m/z: 448 [M + H]+ 251 [00605]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86 (1H, m), 2.11-2.29 (3H, m), 2.92 (1H, d, J = 16.9 Hz), 3.18 (1H, dd, J = 16.6, 5.2 Hz), 4.15 (1H, t, J = 13.2 Hz), 4.24-4.32 (2H, m), 4.39 (1H, d, J = 14.6 Hz), 4.62-4.69 (2H, m), 6.27 (1H, s), 6.93-6.95 (2H, m), 7.37-7.44 (7H, m). ESI-MS m/z: 415 [M + H]+ 252 [00606]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13-2.26 (2H, m), 2.89-2.96 (1H, m), 3.15-3.20 (1H, m), 4.02-4.06 (1H, m), 4.11-4.18 (1H, m), 4.23-4.28 (3H, m), 4.41-4.47 (1H, m), 4.64- 4.66 (2H, m), 6.30 (1H, s), 6. ![text missing or illegible when filed]()
-7.00 (2H, m), 7.39- 7.44 (2H, m). ESI-MS m/z: 423 [M + H]+ 253 (isomer A) [00607]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.10-2.26 (2H, m), 2.88-2.93 (1H, m), 3.18 (1H, dd, J = 16.5, 5.1 Hz), 4.05 (1H, d, J = 12.4 Hz), 4.13-4.1 ![text missing or illegible when filed]()
(1H, m), 4.23-4.31 (3H, m), 4.41-4.47 (1H, m), 4.64 (2H, m), 6.30 (1H, s), 6.90 (1H, d, J = 7.3 Hz), 6.94 (1H, d, J = 8.5 Hz), 7.40 (1H, s), 7.43 (1H, d, J = 6.6 Hz). ESI-MS m/z: 423 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00037 TABLE 37 Example Structural formula NMR MS 253 (isomer B) [00608]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.09-2.26 (2H, m), 2.68-2.94 (1H, m), 3.17 (1H, dd, J = 16.7, 5.2 Hz), 4.03 (1H, d, J = 11.0 Hz), 4.13-4.19 (1H, m), 4.24-4.32 (3H, m), 4.41-4.48 (1H, m), 4.64 (2H, m), 6.30 (1H, s), 6.92-6.96 (2H, m), 7.3 ![text missing or illegible when filed]()
(1H, s), 7.43 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 423 [M + H]+ 254 [00609]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05-2.07 (2H, m), 2.90 (1H, m), 3.18 (1H, m), 3.92-4.18 (6H, m), 4.24-4.31 (2H, m), 4.41- 4.44 (1H, m), 4.63 (1H, m), 6.27 (1H, s), 6.89-6. ![text missing or illegible when filed]()
(2H, m), 7.38-7.44 (2H, m). ESI-MS m/z: 437 [M + H]+ 255 (isomer A) [00610]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.06-2.07 (2H, m), 2.90 (1H, dd, J = 4.8, 16.9 Hz), 3.1 ![text missing or illegible when filed]()
(1H, dd, J = 16.8, 5.3 Hz), 3.92- 4.17 (6H, m), 4.24-4.31 (2H, m), 4.40-4.46 (1H, m), 4. ![text missing or illegible when filed]()
(1H, m), 6.27 (1H, s), 6.90 (1H, d, J = 7.9 Hz), 6.9 ![text missing or illegible when filed]()
(1H, d, J = 8.4 Hz), 7.39 (1H, s), 7.43 (1H, d, J = 8.5 Hz). ESI-MS m/z: 437 [M + H]+ 256 (isomer A) [00611]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05-2.07 (2H, m), 2.85 (1H, d, J = 17.1 Hz), 3.14 (1H, dd, J = 17.3, 5.0 Hz), 3.89-4.01 (4H, m), 4.09-4.19 (4H, m), 4.41-4.46 (1H, m), 4.61 (1H, m), 6.26 (1H, s), 6. ![text missing or illegible when filed]()
(1H, d, J = 8.7 Hz), 6.99- 7.10 (3H, m). ESI-MS m/z: 446 [M + H]+ 256 (isomer B) [00612]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.06-2.07 (2H, m), 2. ![text missing or illegible when filed]()
-2.87 (1H, m), 3.15 (1H, dd, J = 16.8, 4.7 Hz), 3.86-4.19 ( ![text missing or illegible when filed]()
H, m), 4.38-4.46 (1H, m), 4.61 (1H, m), 6.26 (1H, s), 6.81 (1H, d, J = 8.5 Hz), 6.97-6.99 (1H, m), 7.05 (1H, s), 7.09 (1H, d, J = 8.6 Hz). ESI-MS m/z: 446 [M + H]+ 257 (isomer A) [00613]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.06-2.07 (2H, m), 2.84-2.94 (1H, m), 3.15-3.24 (1H, m), 3.91-4.19 (6H, m), 4.25-4.27 (2H, m), 4.41-4.46 (1H, m), 4.64 (1H, s), 6.27 (1H, s), 6. ![text missing or illegible when filed]()
(2H, d, J = 8.2 Hz), 7.34 (1H, s), 7.39 (1H, d, J = 8.9 Hz). ESI-MS m/z: 480 [M + H]+ 257 (isomer B) [00614]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05-2.07 (2H, m), 2.90-2.95 (1H, m), 3.20 (1H, dd, J = 16.1, 5.2 Hz), 3.91-4.16 (6H, m), 4.26 (2H, m), 4.40-4.46 (1H, m), 4.65 (1H, m), 6.26 (1H, s), 6.94-6.98 (2H, m), 7.33 (1H, s), 7.39 (1H, d, J = 8.2 Hz). ESI-MS m/z: 480 [M + H]+ 258 [00615]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86-1.94 (2H, m), 2.11-2.20 (2H, m), 2.97 (1H, m), 3.26 (1H, dd, J = 16.8, 5.5 Hz), 4.18- 4.30 (7H, m), 4.70 (1H, m), 8.65 (1H, s), 6.98 (1H, d, J = 6.4 Hz), 7.36-7.46 (3H, m), 7.60 (1H, s). ESI-MS m/z: 448 [M + H]+ 259 [00616]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 3.01-3.18 (1H, m), 3.18-3.29 (1H, m), 4.09-4.46 (6H, m), 4.71 (1H, m), 4.97 (2H, m), 6. ![text missing or illegible when filed]()
(1H, s), 6.98 (1H, d, J = 8.8 Hz), 7.33-7.61 (3H, m), 7.62 (1H, s). ESI-MS m/z: 434 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00038 TABLE 38 Example Structural formula NMR MS 260 [00617]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.92-2.96 (1H, m), 3.19-3.26 (1H, m), 4.07-4.35 (6H, m), 4.71 (1H, m), 4.99 (2H, s), 6.96 (1H, m), 7.10 (1H, m), 7.31-7.43 (2H, m), 7.67-7.74 (2H, m), 8.21 (1H, m), 8.98 (1H, m). ESI-MS m/z: 445 [M + H]+ 261 [00618]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.35-2.41 (2H, m), 2.80-2.88 (3H, m), 2.96 (2H, t, J = 5.6 Hz), 3.15 (1H, dd, J = 1 ![text missing or illegible when filed]()
.0, 5.2 Hz), 3.72 (2H, s), 4.14 (2H, t, J = 5.4 Hz), 4.19 (2H, d, J = 2.9 Hz), 4.59-4.67 (1H, m), 6.53 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.99-7.13 (3H, m). ESI-MS m/z: 429 [M + H]+ 262 [00619]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.32-2.45 (2H, m), 2.81-2.97 (6H, m), 3.13 (1H, dd, J = 17.4, 6.8 Hz), 3.73 (2H, s), 4.11- 4.1 ![text missing or illegible when filed]()
(4H, m), 4.65-4.73 (1H, m), 5.54 (1H, s), 6.61 (1H, dd, J = 8.1, 1.1 Hz), 6.95-7.10 (3H, m). ESI-MS m/z: 429 [M + H]+ 263 [00620]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.04-0.10 (2H, m), 0.43-0.49 (2H, m), 0.65-0.76 (1H, m), 1.45 (2H, q, J = 8.0 Hz), 2.64 (2H, t, J = 7.7 Hz), 2.81-2. ![text missing or illegible when filed]()
(3H, m), 3.15 (1H, dd, J = 16.5, 5.1 Hz), 3.66 (2H, s), 4.13 (2H, t, J = 5.5 Hz), 4.17-4.20 (2H, m), 4.59-4.65 (1H, m), 6.50 (1H, s), 6.78-6.84 (1H, m), 6.07-7.14 (3H, m). ESI-MS m/z: 401 [M + H]+ 264 [00621]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.08 (2H, q, J = 5.7 Hz), 0.46 (2H, q, J = 6.6 Hz), 0.66-0.73 (1H, m), 1.42-1.49 (2H, m), 2.64 (2H, t, J = 7.6 Hz), 2.90-2.94 (3H, m), 3.15-3.25 (1H, m), 3.68 (2H, s), 4.13 (2H, t, J = 8.6 Hz), 4.22- 4.28 (2H, m), 4.61-4.67 (1H, m), 6.51 (1H, s), 6.93- 7.02 (2H, m), 7.33-7.41 (2H, m). ESI-MS m/z: 436 [M + H]+ 265 [00622]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.47-1.71 (2H, m), 1.88-1.98 (2H, m), 2.18-2.23 (2H, m), 2.77 (2H, t, J = 5.3 Hz), 2.90-2.96 (1H, m), 3.00-3.03 (2H, m), 3.18-3.23 (1H, m), 3.52 (2H, t, J = 5.3 Hz), 3.76 (2H, s), 3.89-3.96 (1H, m), 4.14 (2H, t, J = 5.6 Hz), 4.21-4.29 (2H, m), 4. ![text missing or illegible when filed]()
(1H, m), 6.51 (1H, s), 6.94-7.00 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 9.7 Hz). ESI-MS m/z: 465 [M + H]+ 266 [00623]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.47-1.7 ![text missing or illegible when filed]()
(2H, m), 1.90-1.95 (2H, m), 2.19-2.21 (2H, m), 2.77 (2H, t, J = 5.4 Hz), 2.86-2.91 (1H, m), 3.01 (2H, t, J = 5.6 Hz), 3.16-3.21 (1H, m), 3.52 (2H, t, J = 5.3 Hz), 3.76 (2H, s), 3. ![text missing or illegible when filed]()
2 (2H, q, J = 8.3 Hz), 3.93 (1H, m), 4.12-4.21 (4H, m), 4.57 (2H, s), 4.63 (1H, m), 6.51 (1H, s), 6.87 (1H, d, J = 8.4 Hz), 7.02- 7.1 ![text missing or illegible when filed]()
(3H, m). ESI-MS m/z: 509 [M + H]+ 267 [00624]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03 (1H, m), 2.87-3.06 (2H, m), 3.11-3.24 (4H, m), 4.03-3.08 (2H, m), 4.21-4.30 (3H, m), 4.66 (1H, m), 6.90-9.85 (1H, m), 7.06-7.09 (1H, m), 7.21 (1H, s), 7.31 (1H, m), 7.44-7.77 (2H, m), 8.18 (1H, m), 9.00 (1H, m). ESI-MS m/z: 526 [M + H]+ 268 [00625]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.92 (3H, m), 3.17 (1H, dd, J = 16.8, 5.0 Hz), 3.67 (4H, m), 4.12 (2H, m), 4.23-4.32 (2H, m), 4.64 (1H, m), 6.4 ![text missing or illegible when filed]()
(1H, s), 6.92-6.97 (2H, m), 7.03 (2H, t, J = 8.1 Hz), 7.31 (2H, t, J = 8.3 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 432 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00039 TABLE 39 Example Structural formula NMR MS 269 [00626]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.![text missing or illegible when filed]()
(4H, m), 2.![text missing or illegible when filed]()
-2.99 (3H, m), 3.18 (1H, dd, J = 16.8, 4.9 Hz), 3.75 (2H, s), 4.14 (2H, t, J = 5.5 Hz), 4.24-4.32 (2H, m), 4.![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
7.00 (4H, m), 7.16 (2H, m), 7.39 (1H, s), 1H, d, J = 8.4 Hz). ESI-MS m/z: 446 [M + H]+ 270 [00627]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.93 (![text missing or illegible when filed]()
, d, J = 6.6 Hz), 1.82 (1H, m), 2.29 (2H, d, J = 7.4 Hz), 2.86-2.96 (3H, m), 3.17 (1H, dc, J = 16.5, 5.2 ![text missing or illegible when filed]()
Hz), 3.63 (2H, s), 4.12 (2H, t, J = 5.6 Hz.), 4.23-4.32 (2H, m), 4.64 (1H, m), 6.51 (1H, s), 6.92-6.96 (2H, m), 7.38-7.43 (2H, m). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 271 [00628]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.45- 1.62 (4H, m), 1.74 (2H, m), 1.93 (2H, m), 2.75 (1H, t, J = 7.5 Hz), 2.89-2.98 (3H, m), 3.17 (1H, dd, J = 16.7, 4.9 Hz), 3.73 (2H, m), 4.13 (2H, t, J = 5.6 Hz), 4.25-4.33 (2H, m), 4.64 (1H, m), 6.51 (1H, s), 6.92-6.95 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 8.4, 1.9 Hz). ESI-MS m/z: 392 [M + H]+ 272 [00629]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.20 (9H, s), 2.75 (2H, t, J = ![text missing or illegible when filed]()
Hz), 2.91 (1H, ddm J = 17.6, 5.7 Hz), 3.03 (2H, t, J = 5.3 Hz), 3.20 (1H, dd, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(2H, t, J = 5.8 Hz), 3.77 (2H, ![text missing or illegible when filed]()
), 4.13 (2H, t, J = 5.5 Hz), 4.20-4.27 (2H, m), ![text missing or illegible when filed]()
(1H, m), 6.50 (1H, s), ![text missing or illegible when filed]()
(1H, t, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 7.01 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.22 (1H, s), 7.29 (1H, s). ESI-MS m/z: 449 [M + H]+ 273 [00630]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 4.3 Hz), 3.05 (2H, t, J = 4.8 Hz), 3.15 (1H, dd, J = ![text missing or illegible when filed]()
, 5.3 Hz), ![text missing or illegible when filed]()
(4H, d, J = 3.1 Hz), 3.92 (3H, s), 4.13-4.22 (4H, m), 4.61 (1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = 7.2 Hz), 7.02-7.04 (2H, m), 7.08 (1H, dd, J = ![text missing or illegible when filed]()
, 2.5 Hz), 7.56 (1H, t, J = 7.8 Hz). ESI-MS m/z: 454 [M + H]+ 274 [00631]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.85 (1H, dd, J = ![text missing or illegible when filed]()
, 4.2 Hz), 3.00 (2H, t, J = 5.5 Hz), 3.07 (2H, m), 3.15 (1H, dd, J = ![text missing or illegible when filed]()
, 5.2 Hz), 3.84 (2H, s), 4.15 (2H, t, J = 5.5 Hz), 4.19 (2H, dd, J = ![text missing or illegible when filed]()
, ![text missing or illegible when filed]()
Hz), 4.51 (2H, t, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, m), 7.01-7.04 (2H, m), ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, ![text missing or illegible when filed]()
Hz), 7.58 (1H, m), ![text missing or illegible when filed]()
(1H, ddd, J = ![text missing or illegible when filed]()
, 2.0, 0.7 Hz). ESI-MS m/z: 454 [M + H]+ 275 [00632]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.79-2.84 (1H, m), 3.10-3.23 (5H, m), ![text missing or illegible when filed]()
(2H, s), 4.15 (2H, d, J = 2.7 Hz), 4.19-4.23 (2H, m), 4.55-4.61 (1H, m), ![text missing or illegible when filed]()
-7.04 (4H, m), 7.10-7.15 (1H, m), 7.27-7.35 (5H, m). ESI-MS m/z: 457 [M + H]+ 276 [00633]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, m), 3.19 (1H, dd, J = 17.3, 5.2 Hz), ![text missing or illegible when filed]()
(4H, m), 4.08-4.13 (2H, m), 4.20 (2H, m), ![text missing or illegible when filed]()
(1H, m), 4.69 (1H, s), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(2H, m), 6.99-7.07 (2H, m), 7.14 (1H, t, J = 7.0 Hz), 7.21-7.35 (5H, m). ESI-MS m/z: 417 [M + H]+ 277 [00634]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 4.0 Hz), 3.19 (1H, dd, J = 17.0, ![text missing or illegible when filed]()
Hz), 3.65 (2H, t, J = ![text missing or illegible when filed]()
Hz), 4.18- 4.20 (4H, m), 4.40 (2H, s), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(2H, m), 7.02-7.07 (2H, m), 7.14 (1H, t, J = ![text missing or illegible when filed]()
Hz), 7.73 (1H, t, J = 7.9 Hz), 7.90 (1H, d, J = ![text missing or illegible when filed]()
Hz), 8.01 (1H, d, J = 7.9 Hz), ![text missing or illegible when filed]()
(1H, s). ESI-MS m/z: 507 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00040 TABLE 40 Example Structural formula NMR MS 278 [00635]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.95 (1H, dd, J = ![text missing or illegible when filed]()
, 5.0 Hz), 3.19 (1H, dd, J = ![text missing or illegible when filed]()
, 5.1 Hz), 3.65 (2H, t, J = ![text missing or illegible when filed]()
Hz), 4.22 (2H, t, J = 5.4 Hz), 4.24-4.33 (2H, m), 4.36 (2H, s), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(![text missing or illegible when filed]()
, m), 7.39-7.44 (2H, m). 279 [00636]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
-3.03 (1H, m), 3.24-3.31 (1H, m), ![text missing or illegible when filed]()
(2H, t, J = ![text missing or illegible when filed]()
Hz), 4.23 (2H, t, J = ![text missing or illegible when filed]()
Hz), 4.27-4.32 (2H, m), 4.36 (2H, s), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
- 7.11 (![text missing or illegible when filed]()
, m), 7.29-![text missing or illegible when filed]()
(3H, m), ![text missing or illegible when filed]()
(1H, td, J = ![text missing or illegible when filed]()
, 1.9 Hz), ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 1.5 Hz), ![text missing or illegible when filed]()
(1H, d, J = 2.0 Hz). 280 [00637]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.86 (1H, dd, J = 16.8, 3.9 Hz), 3.16 (1H, dd, J = ![text missing or illegible when filed]()
, 5.3 Hz), 4.21 (2H, m), ![text missing or illegible when filed]()
(4H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(2H, s), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 7.04-7.10 (3H, m), 7.73 (1H, dd, J = ![text missing or illegible when filed]()
, 2.3 Hz), ![text missing or illegible when filed]()
(1H, d, J = 2.1 Hz). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 281 [00638]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.16 (9H, m), 2.85 (1H, dd, J = 16.5, 4.0 Hz), 2.97 (2H, ![text missing or illegible when filed]()
, J = 5.7, 2.1 Hz), 3.15 (1H, dd, J = ![text missing or illegible when filed]()
, ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(2H, s), 4.10 (2H, t, J = 5.4 Hz), 4.17-4.22 (2H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(3H, m). ESI-MS m/z: 389 [M + H]+ 282 [00639]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.91 (2H, m), 1.05 (2H, m), ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 5.0 Hz), ![text missing or illegible when filed]()
(2H, t, J = ![text missing or illegible when filed]()
Hz), 3.15 (1H, dd, J = ![text missing or illegible when filed]()
, 5.2 Hz), 3.71 (2H, s), 4.05 (2H, t, J = ![text missing or illegible when filed]()
Hz), 4.20-4.31 (2H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(2H, m), 7.04 (2H, t, J = ![text missing or illegible when filed]()
Hz), 7.30 (2H, m), 7.37 (1H, s), 7.40 (1H, d, J = ![text missing or illegible when filed]()
Hz). ESI-MS m/z: 458 [M + H]+ 283 [00640]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, m), 1.15 (2H, m), 1.26 (1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, dt, J = ![text missing or illegible when filed]()
, 5.5 Hz), 3.37 (1H, t, J = 5.2 Hz), 4.04 (2H, m), 4.13 (1H, s), ![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(4H, m). ESI-MS m/z: 441 [M + H]+ 284 [00641]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.77 (2H, m), 0.84 (2H, m), ![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(1H, dd, J = 16.9, 3.9 Hz), 3.12-3.17 (3H, m), 3.88 (2H, s), 4.03 (2H, t, J = 5.4 Hz), 4.19 (2H, m), ![text missing or illegible when filed]()
(1H, m), 6.50 (1H, s), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 6.99-7.09 (3H, m). ESI-MS m/z: 455 [M + H]+ 285 [00642]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.50 (6H, s), 2.82-![text missing or illegible when filed]()
(3H, m), 3.15 (1H, dd, J = 11.4, 5.5 Hz), ![text missing or illegible when filed]()
(2H, s), 4.04 (2H, t, J = 5.5 Hz), 4.19 (2H, m), 4.62 (1H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 7.00-7.09 (3H, m), 7.17 (1H, m), 7.65-![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(1H, dt, J = 4.6, 1.3 Hz). ESI-MS m/z: 452 [M + H]+ 286 [00643]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.88- 1.09 (5H, m), 2.87-2.97 (1H, m), 3.04 (1H, t, J = 5.5 Hz), 3.17 (1H, m), 3.76-3.81 (2H, m), ![text missing or illegible when filed]()
(3H, s), ![text missing or illegible when filed]()
(1H, t, J = ![text missing or illegible when filed]()
Hz), 4.11 (1H, m), 4.21-4.34 (2H, m), 4.63 (1H, m), ![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(2H, t, J = 9.1 Hz), 7.04-7.11 (1H, m), 7.37-7.44 (2H, m), 8.07-8.14 (1H, m). ESI-MS m/z: 471 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00041 TABLE 41 Example Structural formula NMR MS 287 [00644]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
-1.28 (1H, m), 2.24-2.28 (1H, m), ![text missing or illegible when filed]()
-2.91 (1H, m), 3.16- 3.22 (1H, dd, J = 16.7, 5.5 Hz), 4.05-4.31 (4H, m), 4.48-![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
-7.15 (6H, m), 7.32-7.37 (4H, m). ESI-MS m/z: 375 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
[1213] The compound of Example 291 was synthesized from the compound of Example 9 by a method similar to Step 1 in Reference Example 3.
[1214] The compound of Example 292 was synthesized from the compound of Example 9 by a method similar to Step 1 to Step 3 in Reference Example 3.
[1215] The compound of Example 293 was synthesized from the compound of Example 9 by a method similar to Step 1 in Reference Example 3.
[1216] The compound of Example 294 was synthesized from the compound of Example 293 under the scheme depicted in the figure below.
##STR00645##
[1217] The compound of Example 295 was synthesized by a method similar to Example 11.
[1218] The compound of Example 296 was synthesized from the compound synthesized in Step 1 in Example 294 under the scheme depicted in the figure below.
##STR00646##
[1219] The compound of Example 297 was synthesized form the compound synthesized in Step 2 in Example 296 under the scheme depicted in the figure below.
##STR00647##
[1220] The compound of Example 298 was synthesized by methods similar to those described in Example 1 and Example 3.
[1221] The compound of Example 299 was synthesized by a method similar to Example 15.
[1222] The compound of Example 300 was synthesized from the compound synthesized in Example 14 under the scheme depicted in the figure below.
##STR00648##
[1223] The compound of Example 301 was synthesized from the compound synthesized in Example 14 by a method similar to Example 29.
[1224] The compound of Example 302 was synthesized from the compound synthesized in Example 14 by a method similar to Step 2 in Reference Example 3.
[1225] The compound of Example 303 was synthesized by a method similar to Example 16.
[1226] The compound of Example 304 was synthesized by a method similar to Example 16.
[1227] The compound of Example 305 was synthesized by methods similar to those described in Example 18 and Reference Example 43.
[1228] The compound of Example 306 was synthesized by methods similar to those described in Example 18 and Reference Example 65.
[1229] The compound of Reference Example 75 (shown in the figure below.) was synthesized by a method similar to Example 26.
##STR00649##
[1230] The compound of Example 307 was synthesized from the compound synthesized in Reference Example 75 under the scheme depicted in the figure below.
##STR00650##
[1231] The compound of Example 308 was synthesized by a method similar to Example 307.
[1232] The compound of Example 309 was synthesized by a method similar to Example 307.
[1233] The compound of Example 310 was synthesized by a method similar to Example 307.
[1234] The compound of Example 311 was synthesized by a method similar to Example 307.
[1235] The compound of Example 312 was synthesized by methods similar to those described in Example 307 and Example 102.
[1236] The compound of Example 313 was synthesized from the compound synthesized in Reference Example 75 under the scheme depicted in the figure below.
##STR00651##
[1237] The compound of Example 314 was synthesized by a method similar to Example 27.
[1238] The compound of Example 315 was synthesized by a method similar to Example 26.
[1239] The compound of Example 316 was synthesized by a method similar to Example 26.
[1240] The compound of Example 317 was synthesized by a method similar to Example 29.
[1241] The compound of Example 318 was synthesized by a method similar to Example 30.
[1242] The compound of Example 319 was synthesized by methods similar to those described in Example 41, Example 168 and Example 157.
[1243] The compound of Example 320 was synthesized by methods similar to those described in Example 29 and Example 157.
[1244] The compound of Example 321 was synthesized by a method similar to Example 41.
[1245] The compound of Example 322 was synthesized from the compound synthesized in Step 1 in Example 42 under the scheme depicted in the figure below.
##STR00652##
[1246] The compound of Example 323 was synthesized by a method similar to Example 62.
[1247] The compound of Example 324 was synthesized by a method similar to Example 43.
[1248] The compound of Example 325 was synthesized by methods similar to those described in Example 62 and Step 3 in Example 41.
[1249] The compound of Example 326 was synthesized by methods similar to those described in Example 43 and Example 45.
[1250] The compound of Example 327 was synthesized by a method similar to Example 325.
[1251] The compound of Example 328 was synthesized by a method similar to Example 49.
[1252] The compound of Reference Example 76 (3-(2-chlorophenyl)-3-fluoropyrrolidine hydrochloride) was synthesized under the scheme depicted in the figure below.
##STR00653##
[1253] The compound of Example 329 was synthesized from the compound of Reference Example 21 and the compound of Reference Example 76 by a method similar to Step 3 in Example 56.
[1254] The compound of Example 330 was synthesized by a method similar to Example 62.
[1255] The compound of Example 331 was synthesized by a method similar to Example 62.
[1256] The compound of Example 332 was synthesized by methods similar to those described in Reference Example 18, Example 58 and Example 3.
[1257] The compound of Example 333 was synthesized by methods similar to those described in Example 59 and Example 45.
[1258] The compound of Reference Example 77 (shown in the figure below.) was synthesized by a method similar to Reference Example 4.
##STR00654##
[1259] The compound of Example 334 was synthesized from the compound of Reference Example 21 and the compound of Reference Example 77 by a method similar to Step 3 in Example 100.
[1260] The compound of Example 335 was synthesized by methods similar to those described in Example 43 and Example 45.
[1261] The compound of Example 336 was synthesized by a method similar to Example 43.
[1262] The compound of Example 337 was synthesized by a method similar to Example 43.
[1263] Compound of Reference Example 78 ((R)-N-(Chroman-3-yl)-3-phenyl-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-2-carboxamide) was synthesized under the scheme depicted in the figure below.
##STR00655##
[1264] The compound of Example 338 was synthesized from the compound of Reference Example 78 by a method similar to Reference Example 69.
[1265] The compound of Example 339 was synthesized from the compound of Reference Example 78 by a method similar to Step 1 in Reference Example 1.
[1266] The compound of Reference Example 79 (6-phenyl-5, 6-dihydro-8H-imidazo[2,1-c][1,4]oxazine-2-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00656## ##STR00657##
[1267] The compound of Example 340 was synthesized from the compound of Reference Example 79 by a method similar to Step 3 in Example 100.
[1268] The compound of Example 341 was synthesized by a method similar to Example 64 and Reference Example 24.
[1269] The compound of Reference Example 80 (shown in the figure below.) was synthesized by a method similar to Step 1 and Step 4 in Reference Example 3.
##STR00658##
[1270] The compound of Example 342 was synthesized by methods similar to those described in Example 66 and Reference Example 80.
[1271] The compound of Example 343 was synthesized by methods similar to those described in Example 66 and Reference Example 52.
[1272] The compound of Example 344 was synthesized by methods similar to those described in Example 64 and Reference Example 1.
[1273] The compound of Example 345 was synthesized by methods similar to those described in Example 64 and Reference Example 43.
[1274] The compound of Example 346 was synthesized by methods similar to those described in Example 64 and Reference Example 43.
[1275] The compound of Example 347 was synthesized by a method similar to Example 69.
[1276] The compound of Example 348 was synthesized by methods similar to those described in Example 69 and Reference Example 1.
[1277] The compound of Example 349 was synthesized by a method similar to Example 70.
[1278] The compound of Example 350 was synthesized by a method similar to Example 70.
[1279] The compound of Example 351 was synthesized by a method similar to Example 70.
[1280] The compound of Example 352 was synthesized by a method similar to Example 70.
[1281] The compound of Example 353 was synthesized by a method similar to Example 70.
[1282] The compound of Example 354 was synthesized by a method similar to Example 70.
[1283] The compound of Example 355 was synthesized by a method similar to Example 70.
[1284] The compound of Example 356 was synthesized by a method similar to Example 70.
[1285] The compound of Example 357 was synthesized from the compound of Example 71 by a method similar to Step 1 in Reference Example 27.
[1286] The compound of Example 358 was synthesized by methods similar to those described in Example 70 and Reference Example 1.
[1287] The compounds of Example 359 and Example 360 were obtained by separating the compound of Example 70.
[1288] The compound of Example 361 was synthesized from the compound of Example 82 by a method similar to Step 2 to Step 3 in Example 296.
[1289] The compound of Example 362 was synthesized by methods similar to those described in Example 70 and Reference Example 1.
[1290] The compound of Example 363 was synthesized by a method similar to Example 70.
[1291] The compound of Example 364 was synthesized by methods similar to those described in Example 70 and Reference Example 24.
[1292] The compound of Example 365 was synthesized by a method similar to Example 361.
[1293] The compound of Example 366 was synthesized by methods similar to those described in Example 70 and Reference Example 24.
[1294] The compound of Example 367 was synthesized by methods similar to those described in Example 70 and Reference Example 1.
[1295] The compound of Example 368 was synthesized from the compound of Example 82 by methods similar to Step 2 in Example 296 and Step 1 in Example 122.
[1296] The compound of Example 369 was synthesized from the compound of Example 82 by a method similar to Step 2 to Step 3 in Example 296.
[1297] The compound of Example 370 was synthesized from the compound of Example 82 by a method similar to Step 2 to Step 3 in Example 296.
[1298] The compound of Example 371 was synthesized by methods similar to those described in Example 70 and Reference Example 1.
[1299] The compound of Example 372 was synthesized by methods similar to those described in Example 70 and Reference Example 24.
[1300] The compound of Example 373 was synthesized by methods similar to those described in Example 169 and Reference Example 24.
[1301] The compounds of Example 374 were obtained by separating the compound of Example 373.
[1302] The compound of Example 375 was synthesized by a methods similar to those described in Example 169 and Reference Example 73.
[1303] The compound of Example 376 was synthesized by a methods similar to those described in Example 169 and Reference Example 23.
[1304] The compound of Example 377 was synthesized from the compound of Example 171 by a method similar to Step 1 in Reference Example 27.
[1305] The compound of Example 378 was synthesized from the compound of Example 171 by a method similar to Step 1 in Reference Example 27.
[1306] The compound of Example 379 was synthesized from the compound synthesized in step 1 in Example 120 under the scheme depicted in the figure below.
##STR00659##
[1307] The compound of Example 380 was synthesized from the compound of Example 171 by a method similar to Step 1 in Reference Example 27.
[1308] The compound of Example 381 was synthesized from the compound synthesized in Step 1 in Example 117 by a method similar to Example 157.
[1309] The compound of Example 382 was synthesized from the compound of Example 171 by a method similar to Step 1 in Reference Example 27.
[1310] The compound of Example 383 was synthesized by methods similar to those described in Example 177 and Reference Example 28.
[1311] The compound of Example 384 was synthesized by methods similar to those described in Reference Example 34, Example 85 and Reference Example 24.
[1312] The compound of Reference Example 81 (6,6-difluoro5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00660##
[1313] The compound of Example 385 was synthesized from the compound of Reference Example 81 and the compound of Reference Example 1 by a method similar to Step 3 in Example 100.
[1314] The compound of Example 386 was synthesized from the compound synthesized in Step 3 in Example 100 under the scheme depicted in the figure below.
##STR00661##
[1315] The compound of Reference Example 82 (1-cyclopropylpropane-1,3-diol) was synthesized under the scheme depicted in the figure below.
##STR00662##
[1316] The compound of Example 387 was synthesized from the compound of Reference Example 82 by methods similar to those described in Example 159 and Reference Example 1.
[1317] The compound of Example 388 was synthesized by methods similar to those described in Reference Example 82, Example 159 and Reference Example 24.
[1318] The compound of Example 389 was synthesized by a method similar to Example 85.
[1319] The compound of Reference Example 83 (5-((tert-butyldiphenylsilyl)oxy)-1-phenylpent-1-yn-3-ol) was synthesized under the scheme depicted in the figure below.
##STR00663##
[1320] The compound of Example 390 was synthesized from the compound of Reference Example 83 by methods similar to those described in Example 85 and Reference Example 24.
[1321] The compound of Example 391 was synthesized from the compound of Example 171 by methods similar to those described in Example 82 and Example 83.
[1322] The compound of Example 392 was synthesized from the compound of Example 171 by a method similar to Step 2 in Example 117.
[1323] The compound of Example 393 was synthesized by methods similar to those described in Example 85 and Reference Example 24.
[1324] The compound of Example 394 was synthesized by methods similar to those described in Reference Example 83, Example 85 and Reference Example 24.
[1325] The compound of Example 395 was synthesized by methods similar to those described in Reference Example 82, Example 159 and Reference Example 1.
[1326] The compound of Example 396 was synthesized from the compound of Example 171 by a method similar to Step 1 in Reference Example 3.
[1327] The compound of Example 397 was synthesized from the compound of Example 396 by methods similar to those described in Step 1 in Reference Example 45 and Step 2 in Reference Example 44.
[1328] The compound of Reference Example 84 ((R)-6-(3-methoxy-3-ethylbut-1-yn-1-yl)chroman-3-amine) was synthesized from the compound synthesized in Step 1 in Reference Example 2 under the scheme depicted in the figure below.
##STR00664##
[1329] The compound of Example 398 was synthesized by methods similar to those described in Example 169 and Reference Example 84.
[1330] The compound of Example 399 was synthesized by a method similar to Example 391.
[1331] The compound of Example 400 was synthesized from the compound of Example 398 by a method similar to Step 2 in Example 1.
[1332] The compound of Example 401 was synthesized by methods similar to those described in Example 169, Reference Example 45 and Example 122.
[1333] The compound of Example 402 was synthesized by methods similar to those described in Reference Example 83, Example 85 and Reference Example 43.
[1334] The compound of Example 403 was synthesized by methods similar to those described in Example 177 and Reference Example 65.
[1335] The compound of Example 404 was synthesized by methods similar to those described in Reference Example 83, Example 85, Reference Example 3 and Reference Example 1.
[1336] The compound of Example 405 was synthesized from the compound synthesized in Step 6 in Example 159 and the compound of Reference Example 80 by a method similar to Step 8 in Example 70.
[1337] The compound of Reference Example 85 was synthesized by methods similar to those described in Reference Example 83, Example 85 and Reference Example 1.
##STR00665##
[1338] The compounds of Example 406 and Example 407 were obtained by separating the compound of Reference Example 85.
[1339] The compound of Example 408 was synthesized by methods similar to those described in Example 85 and Reference Example 24.
[1340] The compound of Example 409 was synthesized by a method similar to Example 157.
[1341] The compound of Example 410 was synthesized by a method similar to Example 100.
[1342] The compound of Example 411 was synthesized by methods similar to those described in Example 117 and Reference Example 24.
[1343] The compound of Example 412 was synthesized by a method similar to Example 114.
[1344] The compound of Example 413 was synthesized by methods similar to those described in Example 100 and Reference Example 1.
[1345] The compound of Example 414 was synthesized by methods similar to those described in Example 100 and Reference Example 28.
[1346] The compound of Example 415 was synthesized from the compound synthesized in Step 1 in Example 117 by a method similar to Step 1 to Step 2 in Example 122.
[1347] The compound of Reference Example 86 (2,3,5,6,6′,7′-hexahydrospiro [pyran-4,5′-pyrazolo[5,1-b][1,3]oxazine]-2′-carboxylic acid) was synthesized under the scheme below.
##STR00666##
[1348] The compound of Example 416 was synthesized from the compound of Reference Example 86 and the compound of Reference Example 1 by a method similar to Step 8 in Example 70.
[1349] The compound of Example 417 was synthesized from the compound synthesized in Step 1 in Example 386 under the scheme depicted in the figure below.
##STR00667##
[1350] The compound of Example 418 was synthesized from the compound synthesized in Step 3 in Example 100 under the scheme depicted in the figure below.
##STR00668##
[1351] The compound of Reference Example 87 (5-(hydroxymethyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00669##
[1352] The compound of Example 419 was synthesized from the compound of Reference Example 87 by methods similar to Step 3 to Step 4 in Example 100.
[1353] The compound of Example 420 was synthesized from the compound of Reference Example 37 and the compound of Reference Example 1 by a method similar to Example 133.
[1354] The compound of Example 421 was synthesized from the compound of Reference Example 37 and the compound of Reference Example 32 by a method similar to Example 133.
[1355] The compound of Example 422 was synthesized by a method similar to Example 114.
[1356] The compounds of Example 423 and Example 424 were obtained by separating the compound of Example 422.
[1357] The compound of Example 425 was synthesized by methods similar to Example 100, Reference Example 2 and Step 1 in Reference Example 27.
[1358] The compound of Example 426 was synthesized by a method similar to Example 425.
[1359] The compound of Example 427 was synthesized by a method similar to Example 425.
[1360] The compound of Example 428 was synthesized by a method similar to Example 425.
[1361] The compound of Example 429 was synthesized by a method similar to Example 425.
[1362] The compound of Example 430 was synthesized by a method similar to Example 425.
[1363] The compound of Example 431 was synthesized by a method similar to Example 425.
[1364] The compound of Example 432 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 43 by a method similar to Step 5 to Step 6 in Example 85.
[1365] The compound of Example 433 was synthesized from the compound of Reference Example 41 and the compound of Reference Example 43 by a method similar to Step 6 in Example 85.
[1366] The compound of Example 434 was synthesized by methods similar to those described in Reference Example 49, Example 85 and Reference Example 24.
[1367] The compound of Example 435 was synthesized by methods similar to those described in Example 434 and Reference Example 60.
[1368] The compound of Example 436 was synthesized from the compound of Reference Example 36 by methods similar to those described in Reference Example 84 and Step 5 to Step 6 in Example 85.
[1369] The compound of Example 437 was synthesized by methods similar to those described in Example 384 and Reference Example 48.
[1370] The compound of Example 438 was synthesized by methods similar to those described in Example 384 and Reference Example 44.
[1371] The compound of Example 439 was synthesized by methods similar to those described in Example 384, Example 157 and Reference Example 24.
[1372] The compound of Example 440 was synthesized by methods similar to those described in Example 122 and Reference Example 44.
[1373] The compound of Example 441 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 52 by a method similar to Step 5 to Step 6 in Example 85.
[1374] The compound of Example 442 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 1 by a method similar to Step 5 to Step 6 in Example 85.
[1375] The compound of Example 443 was synthesized by a method similar to Example 98.
[1376] The compound of Example 444 was synthesized by a method similar to those described in Example 85 and Example 69.
[1377] The compound of Example 445 was synthesized by methods similar to those described in Example 183 and Reference Example 2.
[1378] The compound of Example 446 was synthesized from the compound synthesized in Reference Example 68 by methods similar to those described in Example 249 and Reference Example 1.
[1379] The compound of Example 447 was synthesized by methods similar to those described in Example 183 and Reference Example 65.
[1380] The compound of Example 448 was synthesized from the compound synthesized in Step 1 in Example 187 by a method similar to Example 225.
[1381] The compound of Reference Example 88 (ethyl 2-(1,1-difluoro2-hydroxyethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylate) was synthesized from the compound synthesized in Step 4 in Reference Example 81 under the scheme depicted in the figure below.
##STR00670##
[1382] The compound of Example 449 was synthesized from the compound of Reference Example 88 by methods similar to those described in Reference Example 33 and Step 6 in Example 85.
[1383] The compound of Example 450 was synthesized from the compound synthesized in Step 1 in Example 187 by methods similar to those described in Step 2 in Example 117 and Step 2 to Step 3 in Example 100.
[1384] The compound of Example 451 was synthesized from the compound synthesized in Step 5 in Reference Example 55 by methods similar to those described in Reference Example 35 and Step 5 to Step 6 in Example 85.
[1385] The compound of Example 452 was synthesized from the compound synthesized in Step 1 in Example 187 by methods similar to those described in Example 225 and Reference Example 24.
[1386] The compound of Example 453 was synthesized from the compound synthesized in Step 1 in Reference Example 187 by methods similar to those described in in Reference Example 35 and Step 5 to Step 6 in Example 85.
[1387] The compound of Example 454 was synthesized from the compound of Reference Example 50 by a method similar to Step 3 in Example 100.
[1388] The compound of Example 455 was synthesized by methods similar to those described in Example 451 and Reference Example 24.
[1389] The compound of Example 456 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 60 by a method similar to Step 3 in Example 100.
[1390] The compound of Example 457 was synthesized by methods similar to those described in Example 243 and Reference Example 56.
[1391] The compound of Example 458 was synthesized from the compound synthesized in Step 1 in Example 187 by methods similar to Step 1 in Example 225, Reference Example 64, Reference Example 43 and Step 3 in Example 100.
[1392] The compound of Example 459 was synthesized by methods similar to those described in Example 187 and Reference Example 48.
[1393] The compound of Example 460 was synthesized by methods similar to those described in Example 203 and Reference Example 59.
[1394] The compound of Example 461 was synthesized by methods similar to those described in Example 203 and Reference Example 56.
[1395] The compound of Example 462 was synthesized by methods similar to those described in Reference Example 38, Reference Example 65 and Step 3 in Example 100.
[1396] The compound of Example 463 was synthesized by methods similar to those described in Example 185 and Reference Example 80.
[1397] The compound of Example 464 was synthesized by methods similar to those described in Reference Example 49, Reference Example 50, Reference Example 24 and Step 3 in Example 100.
[1398] The compound of Example 465 was synthesized by methods similar to those described in Reference Example 49, Example 85 and Reference Example 24.
[1399] The compound of Example 466 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 48 by a method similar to Step 3 in Example 100.
[1400] The compound of Example 467 was synthesized by methods similar to those described in Example 465 and Reference Example 60.
[1401] The compound of Example 468 was synthesized from the compound of Reference Example 50 and the compound of Reference Example 29 by a method similar to Step 3 in Example 100.
[1402] The compound of Example 469 was synthesized from the compound of Reference Example 50 and the compound of Reference Example 1 by a method similar to Step 3 in Example 100.
[1403] The compound of Example 470 was synthesized by methods similar to those described in Reference Example 49, Example 85 and Reference Example 24.
[1404] The compound of Example 471 was synthesized by similar methods described in Reference Example 49, Example 85 and Reference Example 48.
[1405] The compound of Example 472 was synthesized by similar methods described in Reference Example 49, Example 85 and Reference Example 44.
[1406] The compound of Example 473 was synthesized by similar methods described in Reference Example 49, Example 85 and Reference Example 59.
[1407] The compound of Example 474 was synthesized by similar methods described in Reference Example 49, Example 85 and Reference Example 60.
[1408] The compound of Example 475 was synthesized by similar methods described in Reference Example 49, Example 85 and Reference Example 53.
[1409] The compounds of Example 476 and Example 477 were synthesized by similar methods described in Example 241 and Reference Example 43.
[1410] The compound of Example 478 was synthesized by similar methods described in Step 1 in Example 224 and Reference Example 48.
[1411] The compound of Example 479 was synthesized by similar methods described in Step 1 in Example 224 and Reference Example 52.
[1412] The compound of Example 480 was synthesized by similar methods described in Example 251 and Reference Example 1.
[1413] The compound of Example 481 was synthesized by similar methods described in Example 258 and Reference Example 1.
[1414] The compound of Example 482 was synthesized by methods similar to those described in Example 254 and Reference Example 44.
[1415] The compound of Reference Example 89 (4-((tert-butyldiphenylsilyl)oxy)-2-(trifluoromethyl)butan-1-ol) was synthesized under the scheme depicted in the figure below.
##STR00671##
[1416] The compound of Example 483 was synthesized from the compound of Reference Example 89 by methods similar to those described in Step 2 to Step 6 in Example 85 and Reference Example 24.
[1417] The compound of Example 484 was synthesized by a method similar to Example 259.
[1418] The compound of Example 485 was synthesized by a method similar to Example 259.
[1419] The compound of Example 486 was synthesized by methods similar to those described in Example 16 and Reference Example 43.
[1420] The compound of Example 487 was synthesized from the compound of Reference Example 72 by a method similar to Step 1 in Example 266.
[1421] The compound of Example 488 was synthesized from the compound of Reference Example 72 by a method similar to Step 1 in Example 266.
[1422] The compound of Example 489 was synthesized by methods similar to those described in Example 487 and Reference Example 24.
[1423] The compound of Example 490 was synthesized from the compound of Reference Example 72 by a method similar to Step 1 in Example 266.
[1424] The compound of Example 491 was synthesized by methods similar to those described in Example 263 and Reference Example 24.
[1425] The compound of Example 492 was synthesized by methods similar to those described in Example 268 and Reference Example 3.
[1426] The compound of Example 493 was synthesized from the compound of Reference Example 71 by a method similar to Step 1 in Example 266.
[1427] The compound of Example 494 was synthesized from the compound of Reference Example 71 by methods similar to those described in Reference Example 69 and Example 157.
[1428] The compound of Example 495 was synthesized by methods similar to those described in Reference Example 69, Example 157 and Step 2 to Step 3 in Example 261.
[1429] The compound of Example 496 was synthesized by methods similar to those described in Reference Example 69 and Step 2 to Step 3 in Example 261.
[1430] The compound of Example 497 was synthesized by a method similar to Example 268.
[1431] The compound of Example 498 was synthesized by a method similar to Example 268.
[1432] The compound of Example 499 was synthesized by a method similar to Example 269.
[1433] The compound of Example 500 was synthesized by a method similar to Example 283.
[1434] The compound of Example 501 was synthesized by a method similar to Example 283.
[1435] The compound of Example 502 was synthesized by methods similar to those described in Example 283 and Reference Example 24.
[1436] The compound of Example 503 was synthesized by methods similar to those described in Example 283 and Reference Example 24.
[1437] The compound of Example 504 was synthesized from the compound of Reference Example 69 by methods similar to those described in Step 2 to Step 3 in Example 261 and Reference Example 48.
[1438] The compound of Example 505 was synthesized from the compound of Reference Example 69 by methods similar to those described in Step 2 to Step 3 in Example 261 and Reference Example 44.
[1439] The compound of Example 506 was synthesized by methods similar to those described in Example 261 and Reference Example 43.
[1440] The compound of Example 507 was synthesized by methods similar to those described in Example 261 and Reference Example 44.
[1441] The compound of Example 508 was synthesized by a method similar to Example 278.
[1442] The compound of Example 509 was synthesized by methods similar to those described in Example 275 and Reference Example 1.
[1443] The compound of Example 510 was synthesized by a method similar to Example 276.
[1444] The compound of Example 511 was synthesized by a method similar to Example 277.
[1445] The compound of Example 512 was synthesized by methods described in those similar to Example 64 and Reference Example 43.
[1446] The compound of Example 513 was synthesized by a method similar to Example 259.
[1447] The compound of Example 514 was synthesized by a method similar to Example 259.
[1448] The compound of Example 515 was synthesized by methods similar to those described in Example 259 and Reference Example 1.
[1449] The compound of Reference Example 90 (3-(6-ethylpyridin-2-yl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazine-2-carboxylic acid) was synthesized from the compound synthesized in Step 1 in Example 259 under the scheme depicted in the figure below.
##STR00672##
[1450] The compound of Example 516 was synthesized from the compound of Reference Example 90 by a method similar to Step 3 in Example 100.
[1451] The compound of Example 517 was synthesized by a method similar to Example 259.
[1452] The compound of Example 518 was synthesized by a method similar to Example 259.
[1453] The compound of Example 519 was synthesized from the compound of Example 514 under the scheme depicted in the figure below.
##STR00673##
[1454] The compound of Example 520 was synthesized from the compound of Example 519 by a method similar to Example 114.
[1455] The compound of Example 521 was synthesized from the compound of Example 519 under the scheme depicted in the figure below.
##STR00674##
[1456] The compound of Example 522 was synthesized from the compound synthesized in Step 2 in Example 519 under the scheme depicted in the figure below.
##STR00675##
[1457] The compound of Example 523 was synthesized from the compound of Example 519 under the scheme depicted in the figure below.
##STR00676##
[1458] The compound of Reference Example 91 (3-(6-methylpyridin-2-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-2-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00677##
[1459] The compound of Example 524 was synthesized from the compound of Reference Example 91 and the compound of Reference Example 43 by a method similar to Step 3 in Example 100.
[1460] The compound of Example 525 was synthesized by methods similar to those described in Reference Example 91, Reference Example 44 and Step 3 in Example 100.
[1461] The compound of Example 526 was synthesized under the scheme depicted in the figure below.
##STR00678##
[1462] The compound of Example 527 was synthesized from the compound synthesized in Step 2 in Example 519 by a method similar to Step 1 in Reference Example 52.
[1463] The compound of Example 528 was synthesized by methods similar to those described in Steps 1 to 3 in Example 259 and Example 260.
[1464] The compounds of Reference Example 92 ((3S)-3-amino-6-(trifluoromethyl)chroman-4-ol (isomer A and isomer B)) were synthesized under the scheme depicted in the figure below.
##STR00679##
[1465] The compound of Example 529 was synthesized from the compound synthesized in Step 1 in Example 259 and the compound synthesized in Reference Example 92 (isomer A) by methods similar to those described in Step 2 to Step 4 in Example 259.
[1466] The compound of Example 530 was synthesized from the compound synthesized in Step 3 in Example 259 under the scheme depicted in the figure below.
##STR00680##
[1467] The compound of Example 531was synthesized from the compound synthesized in Step 3 in Example 259 under the scheme depicted in the figure below.
##STR00681##
[1468] The compound of Example 532 was synthesized by methods similar to those described in Reference Example 34, Example 85 and Reference Example 24.
[1469] The compound of Example 533 was synthesized by methods similar to those described in Reference Example 34, Example 85 and Reference Example 43.
[1470] The compounds of Reference Example 93 (5-(difluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid (isomerA and isomer B)) were synthesized from the compound synthesized in Step 5 in Example 159 under the scheme depicted in the figure below.
##STR00682##
[1471] The compounds of Example 534 (isomer A and isomer B) were synthesized from the compound of Reference Example 93 (isomer A) and the compound of Reference Example 92 (isomer A) by a method similar to Step 6 in Example 85.
[1472] The compound of Example 535 was synthesized from the compound of Example 534 (isomer A) under the scheme depicted in the figure below.
##STR00683##
[1473] The compound of Example 536 was synthesized from the compound of Example 534 (isomer A) by a method similar to Example 114.
[1474] The compound of Example 537 was synthesized from the compound synthesized in Step 7 in Example 70 by a method similar to Step 3 in Example 100.
[1475] The compound of Reference Example 94 (1-((2,4-dihydroxybutoxy)methyl)cyclopropane-1-carbonitrile) was synthesized under the scheme depicted in the figure below.
##STR00684##
[1476] The compound of Example 538 was synthesized from the compound of Reference Example 94 by a method similar to Example 85.
[1477] The compound of Reference Example 95 (ethyl 6-((benzyloxy)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate) was synthesized under the scheme depicted in the figure below.
##STR00685##
[1478] The compound of Example 539 was synthesized from the compound of Reference Example 95 by methods similar to those described in Example 100 and Reference Example 43.
[1479] The compound of Example 540 was synthesized by methods similar to those described in Reference Example 34, Example 169 and Reference Example 24.
[1480] The compound of Example 541 was synthesized by methods similar to those described in Example 449 and Reference Example 24.
[1481] The compound of Example 542 was synthesized from the compound of Reference Example 37 by a method similar to Step 3 in Example 100.
[1482] The compound of Reference Example 96 (4-((tert-butyldiphenylsilyl)oxy)-2-methylbutan-1-ol) was synthesized under the scheme depicted in the figure below.
##STR00686##
[1483] The compound of Example 543 was synthesized from the compound of Reference Example 96 by methods similar to those described in Example 85 and Reference Example 44.
[1484] The compound of Example 544 was synthesized from the compound of Example 534 under the scheme depicted in the figure below.
##STR00687##
[1485] The compound of Example 545 was synthesized by a method similar to Example 543.
[1486] The compound of Example 546 was synthesized from the compound of Example 534 (isomer A) in a method similar to Step 1 in Reference Example 37.
[1487] The compounds of Example 547 (isomer A and isomer B) were synthesized by separating the compound of Example 540.
[1488] The compound of Reference Example 97 (6-(((2,2,2-trifluoroethyl)amino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylic acid) was synthesized from the compound of Reference Example 95 under the scheme depicted in the figure below.
##STR00688##
[1489] The compound of Example 548 was synthesized from the compound of Reference Example 95 by a method similar to Step 6 in Example 85.
[1490] The compound of Reference Example 98 (6-(trifluoromethyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-3-amine hydrochloride) was synthesized under the scheme depicted in the figure below.
##STR00689##
[1491] The compound of Example 549 was synthesized by methods similar to those described in Example 90 and Reference Example 98.
[1492] The compound of Example 550 was synthesized from the compound synthesized in Step 7 in Example 70 and the compound of Reference Example 98 by a method similar to Step 8 in Example 70.
[1493] The compound of Example 551 was synthesized from the compound of Reference Example 93 (isomer A) by a method similar to Step 6 in Example 85.
[1494] The compounds of Example 552 (isomer A and isomer B) were obtained by separating the compound of Example 532.
[1495] The compound of Example 553 was synthesized by methods similar to those described in Example 538 and Reference Example 43.
[1496] The compounds of Example 554 (isomer A and isomer B) were obtained by separating the compound of Example 553.
[1497] The compound of Reference Example 99 (6-((2,2,2-trifluoroethoxy)methyl)-5,6,7,8-tetrahydropyrazolo[5,1-b][1,3]oxazepine-2-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00690##
[1498] The compound of Example 555 was synthesized from the compound of Reference Example 99 by a method similar to Step 3 in Example 100.
[1499] The compound of Example 556 was synthesized from the compound of Reference Example 99 and from the compound of Reference Example 43 by a method similar to Step 3 in Example 100.
[1500] The compound of Example 557 was synthesized from the compound of Reference Example 99 and from the compound of Reference Example 48 by a method similar to Step 3 in Example 100.
[1501] The compound of Example 558 was synthesized from the compound of Reference Example 33 and the compound of Reference Example 92 (isomer A) by a method similar to Step 8 in Example 70.
[1502] The compound of Example 559 was synthesized from the compound of Reference Example 33 and the compound of Reference Example 92 (isomer B) by a method similar to Step 8 in Example 70.
[1503] The compound of Example 560 was synthesized from the compound of Reference Example 50 and the compound of Reference Example 92 (isomer A) by a method similar to Step 8 in Example 70.
[1504] The compound of Example 561 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 92 (isomer A) by a method similar to Step 7 to Step 8 in Example 70.
[1505] The compounds of Example 562 were obtained by separating the compound synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34, Example 169 and Reference Example 24.
[1506] The compounds of Example 563 (isomer A and isomer B) were obtained by separating the compound of Example 538.
[1507] The compound of Reference Example 100 (2-((tetrahydro-2H-pyran-4-yl)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00691##
[1508] The compound of Example 564 was synthesized from the compound of Reference Example 100 and the compound of Reference Example 48 by a method similar to Step 8 in Example 70.
[1509] The compound of Example 565 was synthesized from the compound of Reference Example 100 and the compound of Reference Example 24 by a method similar to Step 8 in Example 70.
[1510] The compound of Reference Example 101 ((R)-6-iodochroman-3-amine) was synthesized from the compound synthesized in Step 1 in Reference Example 1 under the scheme depicted in the figure below.
##STR00692##
[1511] The compound of Example 566 was synthesized from the compound of Reference Example 93 (isomer A) and the compound of Reference Example 101 by a method similar to Step 8 in Example 70.
[1512] The compound of Example 567 was synthesized by methods similar to those described in Reference Example 34, Example 85 and Reference Example 48.
[1513] The compound of Example 568 was synthesized from the compound of Example 534 (isomer B) by a method similar to Example 535.
[1514] The compound of Example 569 was synthesized from the compound synthesized in Step 3 in Example 187 and the compound of Reference Example 92 (isomer A) by methods similar to those described in Step 8 in Example 70 and Example 535.
[1515] The compound of Example 570 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 92 (isomer A) by methods similar to those described instep 7 to Step 8 in Example 70 and Example 535.
[1516] The compound of Example 571 was synthesized from the compound of Reference Example 33 by a method similar to Step 8 in Example 70.
[1517] The compounds of Example 572 (isomer A and isomer B) were obtained by separating the compound of Example 555.
[1518] The compound of Example 573 was synthesized by a method similar to Example 70.
[1519] The compound of Example 574 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 4 by a method similar to Step 5 to Step 6 in Example 85.
[1520] The compounds of Example 575 (isomer A and isomer B) were obtained by separating the compound of Example 559.
[1521] The compounds of Example 576 (isomer A and isomer B) were obtained by separating the compound of Example 560.
[1522] The compounds of Example 577 (isomer A and isomer B) were obtained by separating the compound of Example 565.
[1523] The compound of Reference Example 102 (2-((cyclopropylmethoxy)methyl)-2,3-dihydroimidazo[2,1-b]oxazole-6-carboxylic acid) was synthesized under the scheme depicted in the figure below.
##STR00693##
[1524] The compound of Example 578 was synthesized from the compound of Reference Example 102 and the compound of Reference Example 1 by a method similar to Step 8 in Example 70.
[1525] The compounds of Example 579 (isomer A and isomer B) were synthesized from the compound of Reference Example 93 (isomer A) and Reference Example 92 (isomer A) by methods similar to those described in Step 8 in Example 70 and Example 114.
[1526] The compound of Reference Example 103 (shown in the figure below.) was synthesized from the compound synthesized in Step 1 in Example 259 by a method similar to Reference Example 91.
##STR00694##
[1527] The compound of Example 580 was synthesized from the compound of Reference Example 103 and the compound of Reference Example 92 (isomer A) by a method similar to Step 3 in Example 100.
[1528] The compound of Example 581 was synthesized from the compound of Reference Example 90 and the compound of Reference Example 92 (isomer A) by a method similar to Step 3 in Example 100.
[1529] The compound of Example 582 was synthesized from the compound synthesized in Step 8 in Example 252 under the scheme depicted in the figure below.
##STR00695##
[1530] The compound of Example 583 was synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34, Example 85 and Reference Example 43.
[1531] The compound of Example 584 was synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34, Example 85 and Reference Example 1.
[1532] The compound of Example 585 was synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34, Example 85 and Reference Example 24.
[1533] The compound of Example 586 was synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34, Example 85 and Reference Example 48.
[1534] The compound of Example 587 was synthesized using the compound of Reference Example 92 (isomer A) by a method similar to one described in Example 199.
[1535] The compound of Example 588 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 92 (isomer A) by a method similar to Step 8 in Example 70.
[1536] The compound of Example 589 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 92 (isomer B) by a method similar to Step 8 in Example 70.
[1537] The compounds of Example 590 (isomer A and isomer B) were obtained by separating the compound of Example 564.
[1538] The compound of Reference Example 104 (shown in the figure below.) was synthesized from the compound synthesized in Step 7 in Example 245 by methods similar to those described in Example 114 and Step 7 in Example 70.
##STR00696##
[1539] The compound of Example 591 was synthesized from the compound of Reference Example 104 and the compound of Reference Example 92 (isomer A) by a method similar to Step 8 in Example 70.
[1540] The compound of Example 592 was synthesized from the compound of Reference Example 104 and the compound of Reference Example 92 (isomer B) by a method similar to Step 8 in Example 70.
[1541] The compound of Example 593 was synthesized from the compound of Reference Example 92 (isomer A) by a method similar to Example 268.
[1542] The compound of Example 594 was synthesized from the compound of Reference Example 92 (isomer A) by methods similar to those described in Example 268 and Example 261.
[1543] The compound of Example 595 was synthesized from the compound synthesized in Step 6 in Example 201 and the compound of Reference Example 92 (isomer A) by a method similar to Step 8 in Example 70.
[1544] The compound of Example 596 was synthesized from the compound synthesized in Step 6 in Example 201 and the compound of Reference Example 92 (isomer B) by a method similar to Step 8 in Example 70.
[1545] The compounds of Example 597 (isomer A and isomer B) were obtained by separating the compound of Example 569.
[1546] The compounds of Example 598 (isomer A and isomer B) were obtained by separating the compound of Example 570.
[1547] The compound of Example 599 was synthesized using the compound of Reference Example 92 (isomer B) by a method similar to Example 90.
[1548] The compounds of Example 600 (isomer A and isomer B) were obtained by separating the compound of Example 588.
[1549] The compounds of Example 601 (isomer A and isomer B) were obtained by separating the compound of Example 557.
[1550] The compounds of Example 602 (isomer A and isomer B) were obtained by separating the compound synthesized from the compound of Reference Example 99 and Reference Example 44 by a method similar to Step 3 in Example 100.
[1551] The compounds of Example 603 (isomer A and isomer B) were obtained by separating the compound of Example 591
[1552] The compound of Reference Example 105 was synthesized from the compound synthesized in Step 2 in Example 245 under the scheme depicted in the figure below.
##STR00697##
[1553] The compound of Reference Example 106 (shown in the figure below) was synthesized from the compound of Reference Example 105 by a method similar to one described in Step 5 to Step 8 in Example 245.
##STR00698##
[1554] The compounds of Example 604 (isomer A and isomer B) were obtained by separating the compound synthesized using the compound of Reference Example 106 and Reference Example 24 by a method similar to Step 8 in Example 70.
[1555] The compound of Example 605 was synthesized from the compound of Reference Example 100 and Reference Example 44 by a method similar to Step 8 in Example 70.
[1556] The compound of Reference Example 107 (shown in the figure below) was synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34 and Step 1 to Step 5 in Example 85.
##STR00699##
[1557] The compound of Example 606 was synthesized from the compound of Reference Example 107 and the compound of Reference Example 44 by a method similar to Step 8 in Example 70.
[1558] The compound of Example 607 was synthesized using the compound of Reference Example 106 and the compound of Reference Example 92 (isomer A) by a method similar to one described in Step 8 in Example 70.
[1559] The compounds of Example 608 (isomer A and isomer B) were obtained by separating the compound of Example 607.
[1560] The compound of Example 609 was synthesized using the compound of Reference Example 106 and the compound of Reference Example 92 (isomer B) by a method similar to Step 8 in Example 70.
[1561] The compounds of Example 610 (isomer A and isomer B) were obtained by separating the compound of Example 609.
[1562] The compound of Reference Example 108 (shown in the figure below) was synthesized by a method similar to the compound of Reference Example 107.
##STR00700##
[1563] The compound of Example 611 was synthesized from the compound of Reference Example 108 and the compound of Reference Example 1 by a method similar to one described in Step 8 in Example 70.
[1564] The compound of Example 612 was synthesized from the compound of Reference Example 108 and the compound of Reference Example 43 by a method similar to one described in Step 8 in Example 70.
[1565] The compound of Example 613 was synthesized from the compound of Reference Example 108 and the compound of Reference Example 92 (isomer A) under the scheme depicted in the figure below.
##STR00701##
[1566] The compound of Example 614 was synthesized from the compound of Reference Example 108 and Reference Example 92 (isomer B) by a method similar to Example 613.
[1567] The compounds of Example 615 (isomer A and isomer B) were obtained by separating the compound of Example 606.
[1568] The compounds of Example 616 (isomer A and isomer B) were obtained by separating the compound of Example 592.
[1569] The compound of Reference Example 109 ((3S)-3-amino-4-fluorochroman-6-carbonitrile) was synthesized under the scheme depicted in the figure below.
##STR00702##
[1570] The compounds of Example 617 (isomer A, isomer B, isomer C and isomer D) were obtained by separating the compound synthesized from the compound of Reference Example 33 and the compound of Reference Example 109 by a method similar to Step 8 in Example 70.
[1571] The compound of Reference Example 110 (6-bromo-2-((cyclopropylmethoxy)methyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole) was synthesized under the scheme depicted in the figure below.
##STR00703##
[1572] The compound of Reference Example 111 (shown in the figure below.) was synthesized from the compound of Reference Example 110 by a method similar to one described in Step 8 to Step 10 in Reference Example 79.
##STR00704##
[1573] The compound of Example 618 was synthesized from the compound of Reference Example 111 and the compound of Reference Example 24 by a method similar to one described in Step 8 in Example 70.
[1574] The compound of Example 619 was synthesized from the compound of Reference Example 111 and the compound of Reference Example 48 by a method similar to one described in Step 8 in Example 70.
[1575] The compound of Reference Example 112 (shown in the figure below.) was synthesized by methods similar to those described in Step 3 to Step 5 in Reference Example 34 and Step 1 to Step 5 in Example 85.
##STR00705##
[1576] The compound of Example 620 was synthesized from the compound of Reference Example 112 (isomers A) and the compound of Reference Example 43 by a method similar to one described in Step 8 in Example 70.
[1577] The compound of Example 621 was synthesized from the compound of Example 588 by a method similar to one described in Example 535.
[1578] The compounds of Example 622 (isomer A and isomer B) were obtained by separating the compound of Example 605.
[1579] The compound of Reference Example 113 (shown in the figure below.) was synthesized by a method similar to one described in Reference Example 100.
##STR00706##
[1580] The compound of Example 623 was synthesized from the compound of Reference Example 113 and the compound of Reference Example 24 in a method similar to one described in Step 8 in Example 70.
[1581] The compound of Reference Example 114 (4-((tert-butyldiphenylsilyl)oxy)-1-(2,2-difluoroethoxy)butan-2-ol) was synthesized under the scheme depicted in the figure below.
##STR00707##
[1582] The compound of Reference Example 115 (shown in the figure below) was synthesized from the compound of Reference Example 114 by methods similar to those described in Step 2 to Step 5 in Example 85.
##STR00708##
[1583] The compound of Example 624 was synthesized from the compound of Reference Example 115 and the compound of Reference Example 92 (isomer B) by methods similar to those described in Step 8 in Example 70 and Step 2 in Example 613.
[1584] The compound of Example 625 was synthesized from the compound of Reference Example 70 and the compound of Reference Example 92 (isomer A) by methods similar to those described in Step 7 to Step 8 in Example 70 and Step 2 in Example 613.
[1585] The compound of Reference Example 116 (shown in the figure below) was synthesized by a method similar to one described in Reference Example 4.
##STR00709##
[1586] The compound of Example 626 was synthesized from the compound synthesized in Step 5 in Example 169 and the compound of Reference Example 116 by a method similar to one described in Step 8 in Example 70.
[1587] The compound of Example 627 was synthesized from the compound of Reference Example 36 and the compound of Reference Example 116 by a method similar to one described in Step 7 to Step 8 in Example 70.
[1588] The compound of Example 628 was synthesized from the compound of Reference Example 104 and the compound of Reference Example 116 in a method similar to one described in Step 8 in Example 70.
[1589] The compound of Example 629 was synthesized from the compound of Reference Example 55 and the compound of Reference Example 116 in a method similar to one described in Step 8 in Example 70.
[1590] The compound of Example 630 was synthesized from the compound of Reference Example 108 and the compound of Reference Example 44 in a method similar to one described in Step 8 in Example 70.
[1591] The compound of Example 631 was synthesized from the compound of Reference Example 112 (isomers A) and the compound of Reference Example 44 in a method similar to one described in Step 8 in Example 70.
[1592] The compound of Example 632 was synthesized from the compound of Reference Example 89 by methods similar to those described in Step 2 to Step 6 Example 85 and Reference Example 44.
[1593] The compound of Example 633 was synthesized from the compound of Reference Example 89 by methods similar to those described in Step 2 to Step 6 Example 85 and Reference Example 48
[1594] The compound of Example 634 was synthesized from the compound of Reference Example 99 and the compound of Reference Example 92 (isomer A) by methods similar to those described in Step 8 in Example 70 and Step 2 in Example 613.
[1595] The compound of Example 635 was synthesized from the compound of Reference Example 115 and Reference Example 44 in a method similar to one described in Step 8 in Example 70.
[1596] The compounds of Example 636 (isomer A and isomer B) were obtained by separating the compound of Example 595.
[1597] The compound of Reference Example 117 (shown in the figure below.) was synthesized using the compound of Reference Example 92 (isomer A) by a method similar to one described in Step 1 to Step 2 in Example 268.
##STR00710##
[1598] The compound of Example 637 was synthesized from the compound of Reference Example 117 by methods similar to those described in Step 1 in Example 261 and Step 2 in Example 613.
[1599] The compound of Example 638 was synthesized from the compound of Reference Example 112 (isomers B) and the compound of Reference Example 44 in a method similar to one described in Step 8 in Example 70.
[1600] The compound of Example 639 was synthesized from the compound synthesized in Step 6 in Example 201 and the compound of Reference Example 116 in a method similar to one described in Step 8 in Example 70.
[1601] The compound of Example 640 was synthesized from the compound of Reference Example 106 and the compound of Reference Example 116 in a method similar to one described in Step 8 in Example 70.
[1602] The compounds of Example 641 (isomer A and isomer B) were obtained by separating the compound of Example 587.
[1603] The compound of Example 642 was synthesized from the compound of Reference Example 117 by methods similar to those described in Reference Example 69 and Step 2 in Example 613.
[1604] The compound of Example 643 was synthesized from the compound of Reference Example 117 by a method similar to Reference Example 637.
[1605] The compound of Reference Example 118 (shown in the figure below.) was synthesized by a method similar to Step 1 in Example 267.
##STR00711##
[1606] The compound of Example 644 was synthesized from the compound of Reference Example 118 and the compound of Reference Example 43 by a method similar to one described in Step 7 to Step 8 in Example 70.
[1607] The compound of Example 645 was synthesized from the compound of Reference Example 118 and the compound of Reference Example 92 (isomer B) by methods similar to those described in Step 2 to Step 3 in Example 100 and Step 2 in Example 613.
[1608] The compound of Reference Example 119 (shown in the figure below.) was synthesized using the compound of Reference Example 92 (isomer B) by methods similar to one described in Step 1 to Step 2 in Example 268.
##STR00712##
[1609] The compound of Example 646 was synthesized from the compound of Reference Example 119 by methods similar to those described in Reference Example 69 and Step 2 in Example 613.
[1610] The compound of Example 647 was synthesized from the compound of Reference Example 119 by methods similar to those described in Step 1 in Example 261 and Step 2 in Example 613.
[1611] The compound of Example 648 was synthesized from the compound synthesized in Step 5 in Example 169 and the compound of Reference Example 109 by a method similar to one described in Step 8 in Example 70.
[1612] The compound of Example 649 was synthesized from the compound of Reference Example 89 by methods similar to those described in Step 2 to Step 6 in Example 85 and Reference Example 109.
[1613] The compound of Example 650 was synthesized from the compound synthesized in Step 6 in Example 201 and the compound of Reference Example 109 by a method similar to Step 8 in Example 70.
[1614] The compound of Reference Example 120 (shown in the figure below.) was synthesized by a method similar to one described in the compound of Reference Example 107.
##STR00713##
[1615] The compound of Example 651 was synthesized from the compound of Reference Example 120 and the compound of Reference Example 44 by a method similar to Step 8 in Example 70.
[1616] The compound of Example 652 was synthesized from the compound of Reference Example 117 by a method similar to Reference Example 69.
[1617] The compound of Example 653 was synthesized by methods similar to those described in Example 268 and Reference Example 43.
[1618] The compound of Example 654 was synthesized from the compound of Example 652 by a method similar to one described in Step 2 in Example 613.
[1619] The compound of Example 655 was synthesized by methods similar to those described in Reference Example 82, Example 159 and Reference Example 44.
[1620] The compound of Reference Example 121 (shown in the figure below.) was synthesized from the compound synthesized in Step 3 in Reference Example 92 by methods similar to those described in Step 1 and Step 3 in Reference Example 1 and Step 2 in Example 613.
##STR00714##
[1621] The compound of Example 656 was synthesized from the compound synthesized in Step 8 in Example 252 and the compound of Reference Example 121 under the scheme depicted in the figure below.
##STR00715##
[1622] The compound of Reference Example 122 (2-((2-(2,2,2-trifluoroethoxy)ethoxy)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-6-carboxylic acid) was synthesized from the compound synthesized in Step 1 in Example 187 under the scheme depicted in the figure below.
##STR00716##
[1623] The compound of Example 657 was synthesized from the compound of Reference Example 122 and the compound of Reference Example 43 by a method similar to Step 3 in Example 100.
[1624] The compound of Example 658 was synthesized from the compound of Reference Example 122 and the compound of Reference Example 1 by a method similar to Step 3 in Example 100.
[1625] The compound of Example 659 was synthesized from the compound of Reference Example 122 and the compound of Reference Example 24 by a method similar to Step 3 in Example 100.
[1626] The compound of Example 660 was synthesized from the compound of Reference Example 122 and the compound of Reference Example 92 (isomer A) by a method similar to Step 3 in Example 100.
[1627] The compound of Example 661 was synthesized from the compound of Reference Example 122 and the compound of Reference Example 44 by a method similar to Step 3 in Example 100.
[1628] The compound of Reference Example 123 (shown in the figure below.) was synthesized from the compound synthesized in Step 1 in Example 100 by a method similar to Reference Example 122.
##STR00717##
[1629] The compound of Example 662 was synthesized from the compound of Reference Example 123 and the compound of Reference Example 1 by a method similar to Step 8 in Example 70.
[1630] The compound of Example 663 was synthesized from the compound of Reference Example 123 and the compound of Reference Example 43 by a method similar to Step 8 in Example 70.
[1631] The compound of Example 664 was synthesized from the compound of Reference Example 123 and the compound of Reference Example 24 by a method similar to Step 8 in Example 70.
[1632] The compound of Example 665 was synthesized from the compound of Reference Example 123 and the compound of Reference Example 92 (isomer B) by methods similar to those described in Step 8 in Example 70 and Step 2 in Example 613.
[1633] The compound of Example 666 was synthesized by methods similar to those described in Example 268 and Reference Example 43.
[1634] The compound of Example 667 was synthesized from the compound of Reference Example 118 and the compound of Reference Example 44 by methods similar to those described in Step 7 to Step 8 in Example 70.
[1635] The compound of Example 668 was synthesized from the compound of Reference Example 120 and the compound of Reference Example 48 by a method similar to Step 8 in Example 70.
[1636] The compound of Example 669 was synthesized by methods similar to those described in Example 268 and Reference Example 43.
[1637] The compound of Example 670 was synthesized from the compound of Reference Example 119 by methods similar to those described in Step 1 in Example 261 and Step 2 in Example 613.
[1638] The compound of Example 671 was synthesized from the compound of Reference Example 119 by methods similar to those described in Reference Example 69 and Step 2 in Example 613.
[1639] The compound of Example 672 was synthesized from the compound of Reference Example 119 by methods similar to those described in Reference Example 69 and Step 2 in Example 613.
[1640] The compound of Example 673 was synthesized from the compound of Reference Example 119 by methods similar to those described in Reference Example 69 and Step 2 in Example 613.
[1641] The compound of Example 674 was synthesized by methods similar to those described in Reference Example 82, Example 159 and Reference Example 48.
[1642] The compound of Example 675 was synthesized from the compound of Reference Example 122 and the compound of Reference Example 92 (isomer B) was synthesized by a method similar to Step 3 in Example 100.
[1643] The compound of Example 676 was synthesized from the compound of Example 660 by a method similar to one described in Step 2 in Example 613.
[1644] The compound of Example 677 was synthesized from the compound of Reference Example 117 by a method similar to Reference Example 69.
[1645] The compound of Example 678 was synthesized from the compound of Reference Example 117 and the compound of Example 119 by methods similar to those described in Reference Example 69 and Step 2 in Example 613.
[1646] The compound of Example 679 was synthesized from the compound synthesized in Step 6 in Example 254 and the compound of Reference Example 92 (isomer B) by methods similar to those described in Step 8 in Example 70 and Step 2 in Example 613.
[1647] The compound of Reference Example 124 (shown in the figure below.) was synthesized from the compound synthesized in Step 8 in Example 252 by a method similar to Reference Example 122.
##STR00718##
[1648] The compound of Example 680 was synthesized from the compound of Reference Example 124 and the compound of Reference Example 43 by a method similar to Step 8 in Example 70.
[1649] The compound of Example 681 was synthesized from the compound of Reference Example 124 and the compound of Reference Example 92 (isomer A) by a method similar to Step 8 in Example 70.
[1650] The compound of Example 682 was synthesized from the compound of Reference Example 124 and the compound of Reference Example 1 by a method similar to Step 8 in Example 70.
[1651] The compound of Example 683 was synthesized from the compound of Reference Example 99 and the compound of Reference Example 92 (isomer A) by methods similar to those described in Step 3 in Example 100 and Step 2 in Example 613.
[1652] In the tables below, on the compounds synthesized in Example 291 to Example 683, chemical structures and instrumental analysis data are shown.
TABLE-US-00042 TABLE 42 Example Structural formula NMR MS 291 [00719]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.94 (1H, m), 2.33 (1H, m), 2.65-2.85 (3H, m), 2.98-3.08 (2H, m), 3.98 (1H, m), 4.07-4.30 (3H, m), 4.55 (1H, m), ![text missing or illegible when filed]()
(1H, dd, J = 1.2, 7.4 Hz), ![text missing or illegible when filed]()
(1H, d, J = 8.0 Hz), 7.07 (1H, d, J = 8.4 Hz), 7.19 (1H, t, J = 7.8 Hz), 7.27-7.42 (6H, m). ESI-MS m/z: 442 [M + H]+ 292 [00720]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.97 (1H, m), 2.34 (1H, m), 2.75-2.86 (2H, m), 2.95-![text missing or illegible when filed]()
(2H, m), 3.27 (1H, m), 4.00 (1H, t, J = 12.4 Hz), 4.14 (1H, m), 4.24-4.31 (2H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, t, J = 55.6 Hz), 7.00 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.10 (1H, d, J = 7.4 Hz), 7.19-7.21 (2H, m), 7.47 (1H, s). ESI-MS m/z: 416 [M + H]+ 293 [00721]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, m), 2.34 (1H, m), 2.82 (3H, m), 3.05 (1H, m), 3.14 (1H, dd, J = 5.8, 16.9 Hz), 3.99 (1H, t, J = 11.6 Hz), 4.15 (2H, m), ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
, 12.5 Hz), 4.66 (1H, m), ![text missing or illegible when filed]()
(1H, dd, J = 1.2, 11.0 Hz), ![text missing or illegible when filed]()
(1H, dd, J = 1.3, 17.4 Hz), 6.79 (2H, m), 7.11 (2H, m), 7.22 (1H, d, J = 7.9 Hz), 7.46 (1H, s). ESI-MS m/z: 392 [M + H]+ 294 [00722]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.96 (1H, m), 2.33 (1H, m), 2.74-3.08 (4H, m), 3.26 (1H, m), 3.96 (1H, m), 4.11-4.31 (3H, m), 4.66 (1H, m), ![text missing or illegible when filed]()
-7.27 (4H, m), 7.47 (1H, m). ESI-MS m/z: 391 [M + H]+ 295 [00723]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.20 (3H, t, J = 7.6 Kz), 1.94 (1H, m), 2.33 (1H, m), 2.55 (2H, q, J = ![text missing or illegible when filed]()
Hz), 2.74-![text missing or illegible when filed]()
(3H, m), 3.05 (1H, m), ![text missing or illegible when filed]()
(1H, m), 3.99 (1H, m), 4.12 (1H, m), 4.19 (1H, m), 4.27 (1H, m), 4.60 (1H, m), 6.79 (1H, d, J = ![text missing or illegible when filed]()
Hz), 6.87 (1H, s), 0.95 (1H, dd, J = 2.1, 8.3 Hz), 7.20 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.45 (1H, s). ESI-MS m/z: 394 [M + H]+ 296 [00724]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.23 (3H, t, J = 7.0 Hz), 1.95 (1H, m), 2.34 (1H, m), 2.79- 2.87 (3H, m), ![text missing or illegible when filed]()
(1H, m), 3.17 (1H, dd, J = 5.7, ![text missing or illegible when filed]()
Hz), 3.53 (2H, q, J = ![text missing or illegible when filed]()
Hz), 3.99 (1H, t, J = ![text missing or illegible when filed]()
Hz), 4.11 (1H, m), 4 20- 4.30 (2H, m), 4.42 (2H, s), 4.65 (1H, m), ![text missing or illegible when filed]()
(1H, d, J = 8.1 Hz), 6.95 (1H, d, J = 6.5 Hz), 7.11 (1H, ![text missing or illegible when filed]()
, J = 7.8 Hz), 7.21 (1H, m), ![text missing or illegible when filed]()
(1H, s). ESI-MS m/z: 424 [M + H]+ 297 [00725]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.95 (1H, m), 2.34 (1H, m), 2.75-2.85 (3H, m), 3.03-3.11 (2H, m), ![text missing or illegible when filed]()
(2H, s), 4.00 (1H, t, J = 10.9 Hz), 4.13-4.30 (3H, m), ![text missing or illegible when filed]()
(1H, m), 6.90 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.01 (1H, d, J = 7.2 Hz), 7.17 (1H, t, J = 7.9 Hz), 7.23 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.48 (1H, s). ESI-MS m/z: 405 [M + H]+ 298 [00726]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.93 (1H, m), 2.32 (1H, m), 2.75-4.71 (11H, m), 5.26 (1H, m), 6.85 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.08 (1H, s), 7.15 (1H, dd, J = 2.3, ![text missing or illegible when filed]()
Hz), 7.22-7.32 (5H, m), 7.48 (1H, s). ESI-MS m/z: 534 [M + H]+ 299 [00727]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.95 (1H, m), 2.34 (1H, m), 2.68 (1H, m), 2.80-2.91 (2H, m), 3.09-3.17 (2H, m), 3.70 (1H, t, J = 11.8 Hz), 3.91 (1H, dd, J = 4.2, 13.0 Hz), 4.08-4.20 (2H, m), 4.54 (1H, m), ![text missing or illegible when filed]()
(2H, m), 7.03 (1H, t, J = 6.1 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.29 (1H, d, J = 8.4 Hz), 7.39-7.50 (5H, m). ESI-MS m/z: 442 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00043 TABLE 43 Example Structural formula NMR MS 300 [00728]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.96 (1H, m), 2.34 (1H, m), 2.78-2.84 (2H, m), 2.90 (1H, dd, J = 4.9, 16.3 Hz), 3.06 (1H, m), 3.17 (1H, m), 4.00 (1H, m), 4.20-4.32 (3H, m), 4.63 (1H, m), ![text missing or illegible when filed]()
(1H, d, J = 8.6 Hz), 7.11 (1H, d, J = 7.7 Hz), 7.38 (1H, s), 7.42 (1H, dd, J = 2.0, 8.8 Hz), 7.47 (1H, s). ESI-MS m/z: 391 [M + H]+ 301 [00729]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.74-1.78 (2H, m), 1.90 (1H, m), 2.32 (1H, m), 2.71-2.82 (2H, m), 2.86 (1H, dd, J = 4.6, 16.5 Hz), 2.99-3.11 (2H, m), 3.16-3.22 (2H, m), 3.46-3.52 (2H, m), 3.76 (1H, m), 4.11- 4.23 (3H, m), 4.59 (1H, m), 4.75 (1H, t, J = 7.0 Hz), ![text missing or illegible when filed]()
(2H, m), 7.06 (1H, d, J = 7.6 Hz), 7.13 (1H, m), 7.40 (1H, d, J = 7.3 Hz). ESI-MS m/z: 424 [M + H]+ 302 [00730]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.91 (1H, m), 2.32 (1H, m), 2.71-2.90 (3H, m), 3.07 (1H, m), 3.18 (1H, m), 3.91 (1H, t, J = 11.6 Hz), 4.15 (1H, m), 4.23 (1H, m), 4.33 (1H, dd, J = 5.4, 12.5 Hz), 4.59 (1H, m), 5.53 (1H, d, J = 12.3 Hz), 5.72 (1H, d, J = 18.4 Hz), 6.86-6.91 (2H, m), 7.05 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.13 (1H, m), 7.30-7.38 (2H, m). ESI-MS m/z: 392 [M + H]+ 303 [00731]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.93-1.94 (4H, m), ![text missing or illegible when filed]()
(3H, m), 3.15 (1H, dd, J = 5.5, ![text missing or illegible when filed]()
Hz), 3.91 (3H, s), 4.04-4.05 (2H, m), 4.11 (1H, m), 4.22 (1H, m), 4.55 (1H, m), 6.72 (1H, dd, J = 0.8, ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(2H, m), 7.04 (1H, d, J = 1.0, 7.4 Hz), 7.12 (1H, m), 7.44 (1H, d, J = 8.0 Hz), 7.55 (1H, dd, J = 0.8, 7.4 Hz), 7.66 (1H, dd, J = 7.4, 8.2 Hz). ESI-MS m/z: 405 [M + H]+ 304 [00732]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(4H, m), 2.79-2.96 (3H, m), 3.13 (1H, dt, J = 5.4, 16.9 Hz), 3.51 (1H, m), 3.87 (1H, m), 4.03-4.22 (2H, m), 4.38 (1H, m), 4.51 (1H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(2H, m), 7.04 (1H, m), 7.09-7.14 (2H, m), 7.36 (1H, t, J = 7.8 Hz), 7.83 (1H, m), 8.22 (1H, dt, J = 1.6, 5.0 Hz). ESI-MS m/z: 472 [M + H]+ 305 [00733]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.94 (4H, m), 2.89-2.93 (3H, m), 3.16 (1H, m), 4.02 (2H, m), 4.16 (1H, m), 4.26 (1H, m), 4.56 (1H, m), 6.93 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.26-7.38 (3H, m), 7.47 (1H, m), 7.78 (1H, t, J = 7.9 Hz), 7.91 (1H, d, J = 8.2 Hz), ![text missing or illegible when filed]()
(1H, d, J = 4.1 Hz). ESI-MS m/z: 443 [M + H]+ 306 [00734]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.93 (3H, m), 2.81-2.92 (5H, m), 3.12 (1H, dd, J = 5.2, 16.7 Hz), 4.01-4.21 (7H, m), 4.54 (1H, m), 6.81 (1H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, s), ![text missing or illegible when filed]()
(1H, d, J = 7.7 Hz), 7.24-7.26 (1H, m), 7.48 (1H, d, J = 7.8 Hz), 7.78 (1H, d, J = 7.7 Hz), 7.92 (1H, d, J = 7.8 Hz), ![text missing or illegible when filed]()
(1H, d, J = 4.8 Hz). ESI-MS m/z: 487 [M + H]+ 307 [00735]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.01-4.64 (22H, m), 6.51-6.61 (2H, m), 7.23-7.35 (5H, m), 7.46-7.51 (2H, m). ESI-MS m/z: 458 [M + H]+ 308 [00736]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.22-1.28 (3H, m), 2.01-4.61 (17H, m), ![text missing or illegible when filed]()
(1H, dd, J = 3.6, 8.3 Hz), 6.48 (1H, t, J = 6.7 Hz), 7.24-7.51 (7H, m). ESI-MS m/z: 416 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00044 TABLE 44 Example Structural formula NMR MS 309 [00737]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.98-4.76 (20H, m), 6.20 (1H, dd, J = 3.7, ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, t, J = ![text missing or illegible when filed]()
Hz), 7.26 (7H, s). ESI-MS m/z: 444 [M + H]+ 310 [00738]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.97-2.04 (6H, m), 2.16-2.39 (3H, m), 2.81- 3.07 (2H, m), 3.21 (1H, m), 3.40- 3.41 (4H, m), 3.69 (1H, m), 3.90 (1H, m), 3.99-4.64 (4H, m), 6.23 (1H, dd, J = 3.9, 8.3 Hz), 6.43 (1H, t, J = 6.7 Hz), 7.22-7.41 (6H, m), 7.49 (1H, d, J = 13.2 Hz). ESI-MS m/z: 442 [M + H]+ 311 [00739]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.26 (6H, d, J = 6.16 Hz), 2.01-4.64 (20H, m), 6.51 (1H, dd, J = 3.5, ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, t, J = ![text missing or illegible when filed]()
Hz), 7.22-7.35 (5H, m), 7.43-7.53 (2H, m). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 312 [00740]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.14-4.62 (28H, m), ![text missing or illegible when filed]()
(1H, t, J = 6.6 Hz), ![text missing or illegible when filed]()
(1H, dd, J = 3.6, 8.5 Hz), ![text missing or illegible when filed]()
(5H, m), 7.41 (1H, m), 7.49 (1H, d, J = 13.4 Hz). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 313 [00741]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.05-5.54 (19H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, m), 7.24-7.33 (5H, m), 7.50 (1H, d, J = 14.4 Hz), 7.58 (1H, m). ESI-MS m/z: 445 [M + H]+ 314 [00742]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.20-2.3 (2H, m), ![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, dd, J = 5.7, 16.5 Hz), 3.46 (1H, m), 4.14 (1H, dd, J = 5.5 ![text missing or illegible when filed]()
Hz), 4.25 (1H, dd, J = ![text missing or illegible when filed]()
Hz), 4.34 (2H, d, J = 8.0 Hz), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(2H, m), 7.06 (1H, d, J = 7.5 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.22 (1H, d, J = 6.5 Hz), 7.44 (1H, d, J = 7.8 Hz), 7.49 (1H, s), 7.61 (1H, d, J = 7.8 Hz), 7.86 (1H, t, J = ![text missing or illegible when filed]()
Hz). ESI-MS m/z: 443 [M + H]+ 315 [00743]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.85-2.34 (6H, m), 2.74-3.14 (2H, m), 3.43 (1H, m), 3.89 (1H, m), 4.13-4.35 (4H, m), 5.37 (0.6H, m), 6.15 (0.4H, m), 7.05-7.22 (2H, m), ![text missing or illegible when filed]()
(5H, m), 7.86 (1H, m). ESI-MS m/z: 441 [M + H]+ 316 [00744]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.17-2.42 (3H, m), 2.94 (1H, m), 3.07-3.18 (1H, m), 3.42 (1H, m), 3.54 (1H, m), 3.63-3.75 (1H, m), 3.82- 3.97 (2H, m), 4.05 (3H, d, J = 4.4 Hz), 4.16 (1H, m), 4.35 (2H, m), 4.59 (1H, m), 7.23-7.35 (5H, m), 7.50 (1H, dd, J = 2.0, 12.3 Hz), 7.64 (1H, d, J = 6.2 Hz), 8.40 (1H, s). ESI-MS m/z: 471 [M + H]+ 317 [00745]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.55-1.74 (3H, m), 1.97-2.12 (3H, m), 2.33 (1H, m), 2.62-2.79 (3H, m), 2.98 (1H, m), 3.41 (1H, m), ![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(6H, m), 4.45 (1H, m), 6.70 (1H, dd, J = 3.1, 8.4 Hz), 7.22-7.34 (5H, m), 7.39-7.46 (2H, m), 7.95 (1H, m). ESI-MS m/z: 431 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00045 TABLE 45 Example Structural formula NMR MS 318 [00746]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.39-2.36 (14H, m), 2.76 (1H, m), 3.03-3.06 (2H, m), 3.49 (1H, m), 3.70 (1H, m), 3.94-4.11 (2H, m), 4.37 (1H, m), 4.77 (0.6H, m), 5.21 (0.4H, m), 7.20-7.31 (5H, m), 7.43 (1H, m). ESI-MS m/z: 414 [M + H]+ 319 [00747]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.94-1.06 ( ![text missing or illegible when filed]()
, m), 1.63-2.18 (6H, m), 2.54-3.20 (5H, m), 3.80 (1H, m), 4.08 (1H, m), 4.24 (1H, m), 4.58- 5.42 (2H, m), ![text missing or illegible when filed]()
(2H, m), 7.05 (1H, d, J = 7.4 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.18 (1H, d, J = 7.6 Hz), 7.43 (1H, m). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 320 [00748]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.33 (3H, s), 1.39 (3H, s), 1.49-1.76 (5H, m), 1.96 (1H, m), 2.07 (1H, m), 2.73 (1H, m), ![text missing or illegible when filed]()
(2H, m), 3.18 (1H, dd, J = 5.5, 16.5 Hz), 3.56 (1H, t, J = 11.1 Hz), 4.06-4.15 (2H, m), 4.24 (1H, d, J = 10.6 Hz), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(2H, m), 7.05 (1H, d, J = 7.4 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.18 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.40 (1H, s). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 321 [00749]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, s), 2.20 (1H, m), 2.76-2.99 (3H, m), 3.18 (1H, dd, J = 5.6, 16.6 Hz), 3.71-3.52 (2H, m), 3.96- 4.15 (6H, m), 4.24 (1H, dd, J = 2.3, 10.7 Hz), 4.62 (1H, m), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 7.4 Hz), 7.12 (1H, t, J = 7.7 Hz), 7.18 (1H, d, J = 7.9 Hz), 7.41 (1H, s). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 322 [00750]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.74 (1H, m), 1.87 (1H, m), 2.73 (1H, m), 2.84 (3H, d, J = 1.7 Hz), 2.88 (1H, m), 2.96 (1H, m), 3.18 (1H, td, J = 5.4, 16.5 Hz), 3.83 (1H, m), 4.01 (1H, dd, J = 5.5, 12.3 Hz), 4.13 (1H, m), 4.22 (1H, m), 4.39 (1H, m), 4.51 (1H, m), ![text missing or illegible when filed]()
(2H, m), 7.04 (1H, t, J = 6.9 Hz), 7.10-7.17 (2H, m), 7.35 (1H, s), 7.55-7.59 (2H, m), 7.65 (1H, m), 7.82-7.85 (2H, m), ESI-MS m/z: 467 [M + H]+ 323 [00751]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.16 (3H, m), 3.07 (2H, t, J = 7.1 Hz), 3.49 (1H, d, J = 15.6 Hz), 3.57 (1H, t, J = 7.2 Hz), 3.76 (2H, ![text missing or illegible when filed]()
, J = 6.8 Hz), 4.06-4.10 (3H, m), 7.05 (1H, m), 7.12 (1H, m), 7.7-7.21 (2H, m), 7.32-7.39 (6H, m), 7.43 (1H, s), 7.64 (1H, d, J = 7.8 Hz), 8.25 (1H, s). 324 [00752]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.97 (2H, t, J = 7.2 Hz), 3.65-3.70 (2H, m), 4.18-4.31 (3H, m), 4.42-4.47 (2H, m ![text missing or illegible when filed]()
), 7.11 (1H, m), 7.40- 7.53 (5H, m), 7.68 (1H, d, J = 7.8 Hz), 7.71 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.95 (1H, t, J = 7.7 Hz) ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 325 [00753]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.16 (3H, m), 2.90 (2H, t, J = 7.3 Hz), 3.51 (1H, m), 3.57-3.68 (4H, m), 4.04-4.13 (4H, m), 6.83 (1H, m), 6.95 (1H, m), 7.07-7.11 (4H, m), 7.26 (1H, m), 7.31-7.35 (2H, m), 7.43 (1H, s). 326 [00754]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.27 (3H, s), 2.97 (2H, t, J = 7.3 Hz), 3.67 (2H, q, J = 7.0 Hz), 3.83 (1H, d, J = 16.1 Hz), 4.03 (1H, d, J = ![text missing or illegible when filed]()
Hz), 4.18 (1H, m), 4.31-4.44 (2H, m), 7.11 (1H, m), 7.42-7.51 (5H, m), 7.67-7.71 (2H, m), 7.95 (1H, t, J = 7.7 Hz) ESI-MS m/z: 498 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00046 TABLE 46 Example Structural formula NMR MS 327 [00755]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.40-1.50 (2H, m), 1.77 (2H, m), 2.06 (1H, m), 2.18 (3H, s), 2.88 (2H, t, J = 7.3 Hz), 3.42-3.68 (6H, m), 3.79 (2H, d, J = 6.5 Hz), 4.08-4.13 (5H, m), 6.74- 6.79 (2H, m), 6.83 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.12 (1H, t, J = 6.2 Hz), 7.21 (1H, t, J = ![text missing or illegible when filed]()
Hz), 7.33-7.40 (5H, m), 7.44 (1H, s). 328 [00756]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.91 (9H, s), 1.23- 1.28 (2H, m), 1.39 (1H, m), 1.48-1.54 (2H, m), 2.57 (1H, dd, J = 5.0, 16.4 Hz), 2.99 (1H, m), 3.18 (1H, m), 3.61 (1H, m), ![text missing or illegible when filed]()
-4.04 (2H, m), 4.11-4.16 (2H, m), 4.24 (1H, d, J = 10.8 Hz), 4.62 (1H, m), 6.85-6.90 (2H, m), 7.05 (1H, d, J = 7.6 Hz), 7.12 (1H, m), 7.17 (1H, m), 7.43 (1H, s). 329 [00757]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.26 (2H, m), 2.16 (1H, m), 2.20 (1H, s), 2.38 (1H, m), 2.85-3.10 (1H, m), 3.48-3.53 (2H, m), 4.07-4.28 (4H, m), 4.394.53 (1H, m), 4.64-4.77 (1H, m), 7.23-7.43 (8H, m), 7.52 (1H, m), 7.70 (1H, dd, J = 2.0, 7.4 Hz). ESI-MS m/z: 439 [M + H]+ 330 [00758]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.18 (3H, s), 3.51-3.61 (2H, m), 4.08-4.23 (4H, m), 4.56-4.60 (2H, m), 5.03 (1H, m), 5.50 (1H, m), 6.98 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.30 (1H, d, J = 7.3 Hz), 7.34-7.41 (5H, m), 4.46 (1H, s), 7.75 (1H, t, J = 7.6 Hz). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 331 [00759]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.19 (3H, s), 3.52-3.62 (2H, m), 4.04-4.16 (5H, m), 7.33-7.42 (7H, m), 7.57 (1H, t, J = 7.8 Hz), 7.71 (1H, d, J = 7.9 Hz), 7.76 (1H, d, J = ![text missing or illegible when filed]()
Hz) ![text missing or illegible when filed]()
(1H, s). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 332 [00760]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.20 (3H, s), 3.06-3.11 (4H, m), 4.44-3.70 (4H, m), 4.07-4.25 (4H, m), 7.32-7.61 (10H, m). ESI-MS m/z: 443 [M + H]+ 333 [00761]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.29 (3H, s), 3.58 (1H, m), ![text missing or illegible when filed]()
(1H, d, J = 16.1 Hz), 3.99-4.14 (2H, m), 4.20 (1H, m), 4.40 (1H, m), 5.70 (1H, dd, J = 6.6, ![text missing or illegible when filed]()
Hz), 7.45 (1H, m), 7.53 (1H, s), 7.51-7.55 (2H, m), 7.59-7.63 (2H, m), 7.67-7.73 (3H, m), 7.96 (1H, t, J = 7.8 Hz). ESI-MS m/z: 516 [M + H]+ 334 [00762]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.17-2.19 (3H, m), 3.01-3.95 (5H, m), 4.08-4.31 (4H, m), 4.67- 5.05 (1H, m), 6.95-7.25 (4H, m), 7.35-7.40 (5H, m), 7.46 (1H, s). 335 [00763]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.19-2.31 2.17-2.19 (3H, m), 3.01-3.95 (5H, m), 4.08-4.31 (4H, m), 4.67-5.05 (1H, m), 6.95-7.25 (4H, m), 7.35-7.40 (5H, m), 7.46 (1H, s). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00047 TABLE 47 Example Structural formula NMR MS 336 [00764]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.17-2.28 (3H, m), ![text missing or illegible when filed]()
(3H, m), 4.11-4.37 (6H, m), 5.68 (1H, d, J = 19.5 Hz), 6.50 (1H, t, J = ![text missing or illegible when filed]()
Hz), 6.80 (1H, d, J = 7.4 Hz), 7.21 (1H, t, J = 7.4 Hz), 7.33-7.46 (3H, m), 7.50 (1H, d, J = 7.2 Hz), 7.68 (1H, t, J = ![text missing or illegible when filed]()
Hz). ESI-MS m/z: 524 [M + H]+ 337 [00765]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.09 (1H, m), 3.82 (1H, td, J = 2.7, 11.7 Hz), 3.96 (1H, t, J = 11.0 Hz), 4.09-4.35 (6H, m), 4.62 (1H, d, J = 10.5 Hz), 4.77 (1H, m), 5.39-5.51 (1H, m), 7.23 (1H, dd, J = 1.0, ![text missing or illegible when filed]()
Hz), 7.35-7.51 (5H, m), 7.56 (1H, s), 7.50 (1H, t, J = 7.6 Hz), 7.73 (1H, s). ESI-MS m/z: 541 [M + H]+ 338 [00766]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(1H, dd, J = 4.9, 16.2 Hz), 3.07 (2H, t, J = 5.3 Hz), 3.13 (1H, dd, J = 5.6, 16.7 Hz), 3.18-3.25 (2H, m), 3.80 (2H, t, J = 5.3 Hz), 3.99 (2H, s), 4.09-4.20 (2H, m), 4.54 (1H, m), 6.85-6.90 (2H, m), 7.04 (1H, d, J = 8.2 Hz), 7.41-7.44 (5H, m). ESI-MS m/z: 457 [M + H]+ 339 [00767]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.84 (1H, m), 3.15 (1H, dd, J = 5.7, ![text missing or illegible when filed]()
Hz), 3.85-3.95 (2H, m), 3.94 (1H, m), 4.04 (1H, m), 4.15-4.17 (2H, m), 4.55 (1H, m), 4.91 (2H, s), 6.87-6.91 (2H, m), 7.05 (1H, d, J = 7.4 Hz), 7.14 (1H, t, J = 7.6 Hz), 7.33 (1H, m), 7.42-7.49 (5H, m). ESI-MS m/z: 471 [M + H]+ 340 [00768]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.24-1.46 (2H, m), 2.81 (1H, m), 3.16 (1H, m), 4.03-4.65 (4H, m), 4.85-5.08 (2H, m), 6.85-6.93 (2H, m), 7.02-7.23 (3H, m), 7.36-7.51 (5H, m), 7.68 (1H, m). 341 [00769]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.91 (1H, dd, J = ![text missing or illegible when filed]()
, 16.6 Hz), ![text missing or illegible when filed]()
(1H, dd, J = ![text missing or illegible when filed]()
Hz), 4.05 (2H, t, J = 5.0 Hz), 4.20-4.31 (4H, m), 4.55 (1H, m), 4.82 (2H, s), 6.93 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.31 (1H, d, J = 8.0 Hz), 7.38 (1H, s), 7.41-7.43 (2H, m), 7.77 (1H, t, J = 7.8 Hz), 8.12 (1H, d, J = 7.7 Hz). ESI-MS m/z: 436 [M + H]+ 342 [00770]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 0.60 (2H, d, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(2H, d, J = 8.4 Hz), 1.81 (1H, m), 2.82 (1H, m), 3.12 (1H, dd, J = 5.6, 16.6 Hz), 4.02 (2H, t, J = 4.9 Hz), 4.10-4.20 (4H, m), 4.54 (1H, m), 4.84 (2H, s), 6.77-6.78 (2H, m), ![text missing or illegible when filed]()
(1H, d, J = ![text missing or illegible when filed]()
Hz), 7.28 (1H, m), 7.54 (1H, d, J = 5.0 Hz), 7.79 (1H, t, J = 7.5 Hz), 8.08 (1H, d, J = 7.7 Hz), ![text missing or illegible when filed]()
(1H, d, J = 4.8 Hz). ESI-MS m/z: 417 [M + H]+ 343 [00771]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.86 (1H, dd, J = 4.8, 16.7 Hz), 3.15 (1H, dd, J = 5.5, 16.5 Hz), 3.28 (2H, q, J = 10.8 Hz), 4.02 (2H, t, J = 5.2 Hz), 4.13-4.23 (4H, m), 4.56 (1H, m), 4.84 (2H, s), ![text missing or illegible when filed]()
(1H, d, J = 8.4 Hz), 6.97 (1H, s), 7.05 (1H, d, J = 7.9 Hz), 7.26 (1H, m), 7.55 (1H, d, J = 8.2 Hz), 7.80 (1H, dt, J = 1.8, 7.8 Hz), ![text missing or illegible when filed]()
(1H, d, J = 7.9 Hz), 8.61 (1H, m). ESI-MS m/z: 459 [M + H]+ 344 [00772]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.90 (1H, dd, J = 3.9, 16.9 Hz), 3.19 (1H, dd, J = 5.3, 16.9 Hz), 4.11 (2H, t, J = 5.2 Hz), 4.23-4.25 (4H, m), 4.63 (1H, m), 4.83 (2H, s), 6.54 (1H, s,), 6.83 (1H, d, J = 8.6 Hz), 7.05-7.11 (2H, m), 7.68-7.69 (2H, m), 14.4 (1H, s). ESI-MS m/z: 400 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00048 TABle 48 Example Structural formula NMR MS 345 [00773]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.92 (1H, d, J = 5.2, 16.6 Hz), ![text missing or illegible when filed]()
(1H, dd, J = 5.3, ![text missing or illegible when filed]()
Hz), 3.92 (3H, s), 4.02 (2H, t, J = 5.0 Hz), 4.18-4.29 (4H, m), 4.61 (1H, m), 4.82 (2H, s), 6.93 (1H, d, J = 8.6 Hz), 7.08 (1H, s), 7.31 (1H, s), 7.37 (1H, d, J = 8.8 Hz), 7.41 (1H, s), 7.48 (1H, d, J = 8.0 Hz). ESI-MS m/z: 448 [M + H]+ 346 [00774]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.89 (1H, m), 3.15 (1H, dt, J = 5.3, 17.4 Hz), ![text missing or illegible when filed]()
(1H, m), 3.97-4.05 (3H, m), ![text missing or illegible when filed]()
(2H, m), 4.40 (1H, m), 4.53 (1H, m), 4.79-4.89 (2H, m), 5.22 (1H, m), 6.94 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.14 (1H, dd, J = 5.0, 7.4 Hz), 7.29-7.39 (3H, m), (3H, m), ![text missing or illegible when filed]()
(1H, m), 8.25 (1H, dd, J = 1.7, 4.9 Hz). ESI-MS m/z: 543 [M + H]+ 347 [00775]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.79-1.85 (2H, m), 2.03-2.08 (2H, m), 2.70 (1H, t, J = ![text missing or illegible when filed]()
Hz), ![text missing or illegible when filed]()
(1H, m), 3.12 (1H, dd, J = 5.3, 16.8 Hz), 4.11-4.21 (4H, m), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(2H, m), ![text missing or illegible when filed]()
(1H, d, J = 7.5 Hz), 7.02 (1H, d, J = 7.6 Hz), 7.12 (1H, t, J = 7.4 Hz), ![text missing or illegible when filed]()
(4H, d, 3.9 Hz), 7.46 (1H, m). ESI-MS m/z: 374 [M + H]+ 348 [00776]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.84-1.87 (2H, m), 1.99-2.09 (2H, m), 2.83 (1H, m), 2.99 (2H, t, J = ![text missing or illegible when filed]()
Hz), 3.13 (1H, m), 3.90 (3H, s), 4.06-4.19 (4H, m), 4.58 (1H, m), 6.60 (1H, d, J = 8.4 Hz), 6.79 (1H, m), 7.01-7.07 (2H, m), 7.30 (1H, d, J = 7.8 Hz), 7.38 (1H, d, J = 7.4 Hz), 7.57 (1H, t, J = 7.8 Hz). ESI-MS m/z: 439 [M + H]+ 349 [00777]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(2H, m), 2.88 (1H, dd, J = 3.7, 16.7 Hz), 3.20 (1H, t, J = 5.3, 16.9 Hz), 4.17-4.24 (4H, m), ![text missing or illegible when filed]()
(1H, m), 5.26 (1H, m), 6.09 (1H, s), 6.87-6.92 (2H, m), 7.06 (2H, t, J = 6.7 Hz), 7.14 (1H, t, J = 7.7 Hz), 7.37-7.43 (5H, m). ESI-MS m/z: 376 [M + H]+ 350 [00778]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.05-2.46 (4H, m), 3.44-4.29 (7H, m), 5.28 (1H, m), 6.09 (1H, s), 7.31-7.53 (9H, m). ESI-MS m/z: 442 [M + H]+ 351 [00779]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.39-2.46 (2H, m), 2.79 (1H, dd, J = ![text missing or illegible when filed]()
Hz), 3.00 (1H, dd, J = ![text missing or illegible when filed]()
Hz), 3.80-3.82 (3H, m), 4.10-4.22 (4H, m), 4.62 (1H, m), 5.26 (1H, m), 6.09 (1H, s), 6.45-6.55 (2H, m), 7.00-7.12 (2H, m), 7.36-7.44 (5H, m). ESI-MS m/z: 406 [M + H]+ 352 [00780]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.40-2.46 (2H, m), 2.87 (1H, dd, J = 3.7, 16.8 Hz), 3.17 (1H, dd, J = 5.7, 17.1 Hz), 4.15-4.26 (4H, m), (4H, s), 4.51 (1H, m), 5.27 (1H, m), 6.09 (1H, s), 6.77 (1H, m), ![text missing or illegible when filed]()
(2H, m), 7.04 (1H, d, J = 8.1 Hz), 7.35-7.44 (5H, m). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 353 [00781]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.41-2.48 (2H, m), 2.87 (1H, m), 3.11 (1H, dd, J = 6.3, 17.8 Hz), 4.10-4.27 (4H, m), ![text missing or illegible when filed]()
(1H, m), 5.27 (1H, m), 6.11 (1H, s), 6.86 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.07 (2H, t, J = 8.0 Hz), 7.19 (1H, d, J = 7.8 Hz), 7.36-7.44 (5H, m). ESI-MS m/z: 454, 456 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00049 TABLE 49 Example Structural formula NMR MS 354 [00782]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.41- 2.45 (2H, m), 2.92 (1H, dd, J = 3.8, 17.0 Hz), 3.17 (1H, dd, J = 5.4, 17.1 Hz), 4.11-4.31 (4H, m), 4.65 (1H, m), 5.27 (1H, m), 6.09 (1H, s), ![text missing or illegible when filed]()
(1H, m), ![text missing or illegible when filed]()
(1H, m), 7.07 (1H, d, J = 7.9 Hz), 7.36-7.52 (5H, m). ESI-MS m/z: 412 [M + H]+ 355 [00783]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: ![text missing or illegible when filed]()
(2H, m), 2.86 (1H, dd, J = 4.1, 16.8 Hz), 3.16 (1H, dd, J = 4.9, 16.5 Hz), 4.18-4.23 (4H, m), 4.62 (1H, m), 5.27 (1H, m), 6.09 (1H, s), 6.81 (1H, d, J = ![text missing or illegible when filed]()
Hz), 7.00-7.10 (3H, m), 7.36-7.44 (5H, m). ESI-MS m/z: 410 [M + H]+ 356 [00784]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.41- 2.46 (2H, m), 2.88 (1H, dd, J = 4.7, 17.1 Hz), 3.10 (1H, dd, J = 5.8, 17.2 Hz), 4.18- 4.23 (4H, m), 4.65 (1H, m), 5.27 (1H, m), 6.10 (1H, s), 6.63-6.70 (2H, m), 7.01 (1H, m), 7.36-7.44 (5H, m). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 357 [00785]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.34- 2.50 (2H, m), ![text missing or illegible when filed]()
(1H, dd, J = 4.2, 16.7 Hz), 3.27 (1H, dd, J = 5.1, 16.4 Hz), 4.11-4.31 (4H, m), ![text missing or illegible when filed]()
(1H, m), 5.56 (1H, m), 5.13 (1H, s), 7.02-7.13 (3H, m), 7.18-7.23 (1H, m), 7.29 (1H, s), 7.36 (1H, m), 7.47 (1H, q, J = 1.6, 6.0 Hz), 8.90 (1H, s), 9.16 (1H, s). ESI-MS m/z: 472 [M + H]+ 358 [00786]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.40- 2.47 (2H, m), 2.86 (1H, dd, J = 3.7, 16.8 Hz), 3.16 (1H, dd, J = 5.2, 16.5 Hz), 4.20- 4.30 (4H, m), 4.59-4.54 (1H, m), 5.29-5.33 (1H, m), 6.11 (1H, s), 6.82 (1H, d, J = 8.7 Hz), 7.76 (1H, d, J = 5.7 Hz), ![text missing or illegible when filed]()
(2H, m). ESI-MS m/z: 411 [M + H]+ 359 [00787]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.34- 2.48 (2H, m), ![text missing or illegible when filed]()
(1H, m), 3.18 (1H, m), 4.14-4.33 (4H, m), 4.55 (1H, m), 5.56 (1H, m), ![text missing or illegible when filed]()
(1H, s), 6.93-6.96 (2H, m), 7.10 (1H, t, J = 9.4 Hz), 7.21 (1H, t, J = 7.4 Hz), 7.34-7.48 (4H, m). ESI-MS m/z: 419 [M + H]+ 360 [00788]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.29- 2.50 (2H, m), 2.88 (1H, m), 3.18 (1H, m), 4.14-4.32 (4H, m), 4.65 (1H, m), 5.56 (1H, m), 6.12 (1H, s), 6.93-6.96 (2H, m), 7.11 (1H, m), 7.21 (1H, m), 7.33-7.49 (4H, m). ESI-MS m/z: 419 [M + H]+ 361 [00789]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.34- 2.48 (2H, m), ![text missing or illegible when filed]()
(1H, dd, J = 4.2, 16.7 Hz), 3.19 (1H, dd, J = 5.4, 16.9 Hz), ![text missing or illegible when filed]()
(3H, s), 4.12-4.27 (4H, m), 4.35 (2H, s), 4.64 (1H, m), 5.55 (1H, d, J = 9.5 Hz), 6.10 (1H, s), ![text missing or illegible when filed]()
(1H, t, J = 7.7 Hz), 7.35 (1H, q, J = 7.0 Hz), 7.47 (1H, t, J = 7.6 Hz). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 362 [00790]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.38 (1H, m), 2.52 (1H, m), 3.16 (1H, dd, J = 5.3, 16.9 Hz), 4.17-4.31 (4H, m), 4.62 (1H, m), 5.34 (1H, dt, J = 2.8, 10.1 Hz), 6.16 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.97-7.10 (3H, m), 7.55 (1H, d, J = 5.0 Hz), 7.73 (1H, s), 8.80 (1H, d, J = 5.0 Hz). ESI-MS m/z: 479 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00050 TABLE 50 Example Structural formula NMR MS 363 [00791]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.31- 2.48 (2H, m), 3.21 (1H, m), 3.41 (1H, m), 4.10-4.37 (4H, m), 4.84 (1H, m), 5.54 (1H, m), 6.12 (1H, s), 7.09 (1H, m), 7.17- 7.22 (2H, m), 7.31-7.48 (4H, m), 7.92 (1H, d, J = 9.2 Hz), 8.12 (1H, d, J = 8.5 Hz), 8.80 (1H, d, J = 4.2 Hz), 7.35 (1H, q, J = 7.0 Hz), 7.47 (1H, t, J = 7.6 Hz). ESI-MS m/z: 445 [M + H]+ 364 [00792]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.38- 2.44 (2H, m), 2.92 (1H, dd, J = 4.8, ![text missing or illegible when filed]()
Hz), 4.17-4.32 (4H, m), 4.65 (1H, m), 5.25 (1H, m), 6.09 (1H, s), 6.93- 6.95 (2H, m), 7.11 (1H, t, J = 8.6 Hz), 7.36-7.44 (4H, m). ESI-MS m/z: 419 [M + H]+ 365 [00793]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 1.18 (3H, t, J = 7.0 Hz), 1.41 (3H, d, J = 6.4 Hz), 2.35-2.49 (2H, m), 2.88 (1H, dd, J = 4.3, 16.9 Hz), 3.19 (1H, dd, J = 5.5, 16.9 Hz), 3.36 (2H, q, J = 6.5 Hz), 4.15-4.27 (4H, m, J = 4.93 Hz), 4.32 (4H, q, J = 6.5 Hz), 4.64 (1H, m), 5.56 (1H, m), 6.12 (1H, s), 6.85 (1H, d, J = 8.4 Hz), 7.00 (1H, s), 7.00-7.13 (3H, m), 7.21 (1H, m), 7.36 (1H, q, J = 7.1 Hz), 7.47 (1H, t, J = 7.0 Hz). ESI-MS m/z: ![text missing or illegible when filed]()
[M + H]+ 366 [00794]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.29 (1H, dt, J = 2.2, 14.5 Hz), 2.86- 2.98 (2H, m), 3.18 (1H, dd, J = ![text missing or illegible when filed]()
Hz), 4.19-4.32 (4H, m), 4.55 (1H, m), 5.60 (1H, d, J = 11.9 Hz), ![text missing or illegible when filed]()
(1H, s), 6.93-6.99 (4H, m), 7.33-7.44 (3H, m). ESI-MS m/z: 437 [M + H]+ 367 [00795]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.24 (1H, m), 2.54 (1H, m), 2.86 (1H, dd, J = 4.2, 16.8 Hz), 3.16 (1H, dd, J = 5.2, ![text missing or illegible when filed]()
Hz), 3.99 (3H, s), 4.08-4.15 (2H, m), 4.18-4.26 (2H, m), ![text missing or illegible when filed]()
(1H, m), 5.47 (1H, d, J = 9.5 Hz), 6.11 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.95 (1H, m), 7.01-7.10 (3H, m), 7.70 (1H, d, J = 7.4 Hz), 8.16 (1H, d, J = 5.0 Hz). ESI-MS m/z: 441 [M + H]+ 368 [00796]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.39- 2.49 (5H, m), ![text missing or illegible when filed]()
(1H, m), 3.16 (1H, m), 3.40 (2H, s), 3.70-3.72 (4H, m), ![text missing or illegible when filed]()
(4H, m), 4.63 (1H, m), 4.63 (1H, m), 5.56 (1H, m), 6.12 (1H, s), 6.83 (1H, d, J = 8.3 Hz), 7.01-7.10 (4H, m), 7.21 (1H, m), 7.36 (1H, m), 7.47 (1H, m). ESI-MS m/z: 493 [M + H]+ 369 [00797]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.35- 2.51 (9H, m), 2.86-2.92 (2H, m), 3.19 (1H, m), 3.49-3.64 (3H, m), 4.11-4.28 (5H, m), 4.63 (1H, m), 5.56 (1H, m), 6.11 (1H, s), ![text missing or illegible when filed]()
(1H, d, J = 8.3 Hz), 7.03 (1H, d, J = 7.9 Hz), 7.08-7.23 (4H, m), 7.36 (1H, m), 7.47 (1H, t, J = 7.4 Hz). ESI-MS m/z: 495 [M + H]+ 370 [00798]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.34- 2.47 (2H, m), 2.86 (1H, m), 2.96 (3H, s), 3.00 (3H, s), 3.19 (1H, m), 4.10-4.26 (6H, m), 4.50 (2H, s), 4.62 (1H, m), ![text missing or illegible when filed]()
(1H, m), 6.11 (1H, s), 6.86 (1H, d, J = 8.2 Hz), 7.03-7.15 (4H, m), 7.21 (1H, t, J = 7.8 Hz), 7.36 (1H, m), 7.47 (1H, t, J = 7.6 Hz). ESI-MS m/z: 509 [M + H]+ 371 [00799]![embedded image]()
1H-NMR (CDCl ![text missing or illegible when filed]()
) δ: 2.35- 2.45 (2H, m), 2.85 (1H, m), 3.16 (1H, dd, J = 4.8, 17.1 Hz), 3.95 (3H, s), 4.20-4.24 (4H, m), 4.62 (1H, m), 5.22 (1H, d, J = 9.8 Hz), 6.07 (1H, s), 5.81 (2H, m), 7.00-7.13 (3H, m), 7.63 (1H, d, J = 8.2 Hz), 8.19 (1H, s). ESI-MS m/z: 441 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00051 TABLE 51 Ex- am- ple Structural formula NMR MS 372 [00800]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.39 (1H, t, J = 6.5 Hz), 2.26 (1H, m), 2.56 (1H, m), 2.92 (1H, dd, J = 4.3, 15.2 Hz), 3.18 (1H, dd, J = 4.7, 16.1 Hz), 4.12 (1H, m), 4.19- 4.33 (3H, m), 4.44 (2H, m), 4.65 (1H, m), 5.49 (1H, d, J = 9.2 Hz), 8.12 (1H, s), 6.91-6.95 (3H, m), 7.39 (1H, s), 7.43 (1H, d, J = 8.8 Hz), 7.58 (1H, d, J = 6.8 Hz), 8.14 (1H, d, J = 4.6 Hz). ESI-MS m/z: 446 [M + H]+ 373 [00801]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41-2.46 (2H, m), 2.91 (1H, dd, J = 4.5, 16.6 Hz), 3.18 (1H, dd, J = 5.3, 16.5 Hz), 4.15 (1H, m), 4.25-4.31 (3H, m), 4.57-4.66 (2H, m), 6.14 (1H, s), 6.90-6.95 (2H, m), 7.26-7.44 (1H, m). ESI-MS m/z: 393 [M + H]+ 374 [00802]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41-2.46 (2H, m), 2.91 (1H, dd, J = 4.5, 16.6 Hz), 3.18 (1H, dd, J = 5.3, 16.5 Hz), 4.15 (1H, m), 4.25-4.31 (3H, m), 4.57-4.66 (2H, m), 6.14 (1H, s), 6.90-6.95 (2H, m), 7.26-7.44 (1H, m). 375 [00803]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.37-2.46 (2H, m), 2.96 (1H, dd, J = 3.9, 16.8 Hz), 3.26 (1H, dd, J = 5.2, 16.8 Hz), 4.15 (1H, m), 4.26-4.30 (3H, m), 4.57 (1H, m), 4.67 (1H, m), 6.14 (1H, s), 6.99 (1H, d, J = 8.4 Hz), 7.05 (1H, d, J = 8.0 Hz), 7.29-7.35 (3H, m), 7.81 (1H, td, J = 2.0, 7.9 Hz), 8.55 (1H, dd, J = 1.4, 4.8 Hz), 8.79 (1H, d, J = 1.8 Hz). ESI-MS m/z: 445 [M + H]+ 376 [00804]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.37-2.46 (2H, m), 2.98 (1H, m), 3.26 (1H, m), 4.14 (1H, m), 4.24-4.31 (3H, m), 4.57 (1H, m), 4.68 (1H, m), 6.14 (1H, s), 6.99 (1H, d, J = 8.5 Hz), 7.03 (1H, d, J = 8.0 Hz), 7.37 (1H, s), 7.45 (3H, d, J = 6.2 Hz), 8.61 (2H, d, J = 6.1 Hz). ESI-MS m/z: 445 [M + H]+ 377 [00805]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41-2.45 (2H, m), 2.92 (1H, m), 3.24 (1H, m), 3.98 (3H, s), 4.11-4.29 (4H, m), 4.57- 4.67 (2H, m), 6.14 (1H, s), 6.93-6.97 (2H, m), 7.08 (1H, d, J = 8.1 Hz), 7.36 (1H, m), 7.56 (1H, dd, J = 1.6, 7.3 Hz), 8.13 (1H, dd, J = 1.7, 4.9 Hz). ESI-MS m/z: 475 [M + H]+ 378 [00806]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.38-2.46 (2H, m), 2.94 (1H, m), 3.25 (1H, dd, J = 5.1, 16.6 Hz), 3.97 (3H, s), 4.15 (1H, m), 4.24-4.30 (3H, m), 4.57 (1H, m), 4.66 (1H, m), 6.14 (1H, s), 6.79 (1H, d, J = 8.6 Hz), 6.96 (1H, d, J = 8.4 Hz), 7.06 (1H, d, J = 7.9 Hz), 7.21 (1H, s), 7.30 (1H, m), 7.72 (1H, dd, J = 2.6, 8.6 Hz), 8.32 (1H, d, J = 2.2 Hz). ESI-MS m/z: 475 [M + H]+ 379 [00807]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.79-2.87 (3H, m), 3.15 (1H, dd, J = 5.6, 16.8 Hz), 4.14 (2H, t, J = 6.3 Hz), 4.19 (2H, d, J = 2.8 Hz), 4.48 (1H, s), 4.61 (1H, m), 4.82 (1H, d, J = 1.7 Hz), 6.10 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.99 (1H, d, J = 6.3 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 2.4, 8.7 Hz). ESI-MS m/z: 346 [M + H]+ 380 [00808]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.37-2.46 (4H, m), 2.94 (1H, m), 3.24 (1H, m), 4.11-4.29 (8H, m), 4.55-4.65 (2H, m), 6.14 (1H, s), 6.95 (1H, d, J = 8.6 Hz), 7.05 (1H, d, J = 7.9 Hz), 7.14 (1H, s), 7.23 (1H, m), 8.47 (2H, s). ESI-MS m/z: 501 [M + H]+ [00809]![text missing or illegible when filed]()
TABLE-US-00052 TABLE 52 Ex- am- ple Structural formula NMR MS 381 [00810]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.31 (2H, m), 2.85 (1H, m), 3.15 (1H, dd, J = 5.3, 16.9 Hz), 4.08- 4.26 (4H, m), 4.42 (1H, m), 4.57-4.63 (2H, m), 4.70 (1H, m), 6.05 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 7.00 (1H, d, J = 7.4 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 2.3, 8.6 Hz). ESI-MS m/z: 386 [M + H]+ 382 [00811]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41 (2H, m), 2.95 (1H, m), 3.26 (1H, dd, J = 5.5, 17.2 Hz), 4.12 (1H, m), 4.27 (3H, m), 4.56 (1H, m), 4.68 (1H, m), 8.13 (1H, s), 6.96-7.03 (2H, m), 7.18 (1H, m), 7.64- 7.75 (4H, m), 8.64 (1H, d, J = 4.4 Hz). ESI-MS m/z: 445 [M + H]+ 383 [00812]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.41 (6H, d, J = 2.9 Hz), 2.07 (2H, t, J = 7.3 Hz), 2.96 (1H, dd, J = 4.4, 16.7 Hz), 3.26 (1H, dd, J = 5.2, 16.8 Hz), 4.08 (2H, t, J = 6.5 Hz), 4.25-4.26 (2H, m), 4.56 (1H, m), 5.97 (1H, s), 6.97 (1H, d, J = 8.2 Hz), 7.02 (1H, d, J = 8.3 Hz, 7.18 (1H, t, J = 6.1 Hz), 7.64- 7.76 (4H, m), 8.64 (1H, d, J = 4.8 Hz). 384 [00813]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.04 (1H, m), 2.16 (1H, m), 2.59 (1H, dd, J = 6.7, 16.1 Hz), 3.05 (1H, d, J = 16.2 Hz), 3.41 (1H, m), 3.89 (1H, m), 4.02 (1H, m), 4.13 (1H, m), 4.21-4.30 (2H, m), 4.35 (1H, m), 4.62 (1H, m), 8.00 (1H, s), 6.86-6.93 (2H, m), 7.02 (1H, s), 7.30 (2H, s), 7.37-7.67 (3H, m). ESI-MS m/z: 433 [M + H]+ 385 [00814]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.53 (3H, d, J = 6.6 Hz), 2.84 (1H, m), 3.15 (1H, dd, J = 5.0, 16.7 Hz), 4.11-4.23 (2H, m), 4.30-4.49 (3H, m), 4.60 (1H, m), 6.09 (1H, s), 6.82 (1H, d, J = 8.7 Hz), 6.98 (1H, m), 7.04 (1H, s), 7.09 (1H, m). ESI-MS m/z: 384 [M + H]+ 386 [00815]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41 (1H, m), 2.55 (1H, m), 2.98 (1H, dd, J = 16.7, 4.4 Hz), 3.17 (1H, br d, J = 16.7 Hz), 4.17-4.34 (4H, m), 4.64 (1H, m), 5.22 (1H, m), 6.12 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.95 (1H, m), 7.39 (1H, m), 7.43 (1H, dd, J = 5.5, 2.2 Hz). ESI-MS m/z: 417 [M + H]+ 387 [00816]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.35 (1H, m), 0.55 (1H, m), 0.62-0.76 (2H, m), 1.12 (1H, m), 2.18-2.32 (2H, m), 2.84 (1H, m), 3.14 (1H, m), 3.50 (1H, m), 4.05 (1H, m), 4.18-4.19 (3H, m), 4.50 (1H, m), 8.00 (1H, s), 6.80 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 7.6 Hz), 7.04 (1H, s), 7.08 (1H, m). ESI-MS m/z: 374 [M + H]+ 388 [00817]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86-2.14 (8H, m), 2.58 (1H, m), 2.90 (1H, m), 3.17 (1H, m), 4.00-4.15 (3H, m), 4.22-4.31 (2H, m), 4.63 (1H, m), 6.00 (1H, s), 6.92-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). 389 [00818]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (3H, t, J = 7.2 Hz), 1.41-168. (3H, m), 1.78 (1H, m), 2.05 (1H, m), 2.17 (1H, m), 2.84 (1H, dd, J = 16.8, 4.1 Hz), 3.14 (1H, dd, J = 16.8, 5.3 Hz), 4.00-4.26 (5H, m),, 4.60 (1H, m), 5.98 (1H, s), 6.80 (1H, d, J = 8.6 Hz), 6.99 (1H, m), 7.03 (1H, m), 7.07 (1H, dd, J = 8.6, 2.2 Hz). ESI-MS m/z: 376 [M + H]+ [00819]![text missing or illegible when filed]()
TABLE-US-00053 TABLE 53 Ex- am- ple Structural formula NMR MS 390 [00820]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.42 (1H, m), 2.53 (1H, m), 2.91 (1H, dd, J = 16.7, 4.7 Hz), 3.14 (1H, dd, J = 16.7, 5.2 Hz), 4.16-4.32 (3H, m), 4.37 (1H, m), 4.64 (1H, m), 5.34 (1H, m), 6.10 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 6.95 (1H, s), 7.27-7.45 (7H, m). ESI-MS m/z: 425 [M + H]+ 391 [00821]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.22 (2H, m) 0.54 (2H, q, J = 5.1 Hz), 1.10 (1H, m), 2.42-2.43 (2H, m), 2.86 (1H, d, J = 17.1 Hz), 3.18 (1H, dd, J = 5.2, 16.8 Hz), 3.31 (2H, d, J = 7.0 Hz), 4.13-4.28 (4H, m), 4.42 (2H, s), 4.59 (2H, m), 6.13 (1H, s), 6.85 (1H, d, J = 8.2 Hz), 7.00-7.06 (2H, m), 7.12 (1H, d, J = 7.8 Hz). ESI-MS m/z: 452 [M + H]+ 392 [00822]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.41-2.44 (2H, m), 2.88 (1H, d, J = 13.5 Hz), 3.20 (1H, dd, J = 5.1, 17.2 Hz), 4.10-4.30 (4H, m), 4.56-4.53 (2H, m), 5.27 (2H, s), 6.13 (16, s), 6.79 (1H, d, J = 8.2 Hz), 6.87-6.90 (2H, m), 7.05 (1H, d, J = 7.7 Hz), 7.18 (1H, s), 7.23 (1H, m), 7.58 (1H, t, J = 6.8 Hz), 8.18 (1H, d, J = 4.4 Hz). ESI-MS m/z: 475 [M + H]+ 393 [00823]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.02 (3H, d, J = 6.8 Hz), 1.05 (3H, d, J = 5.7 Hz), 1.99 (1H, m), 2.01-2.23 (2H, m), 2.90 (1H, dd, J = 16.6, 4.7 Hz), 3.17 (1H, dt, J = 16.7, 5.1 Hz), 3.92 (1H, m), 4.05 (1H, m), 4.11-4.34 (3H, m), 4.63 (1H, m), 5.99 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 367 [M + H]+ 394 [00824]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.41 (3H, m), 1.42 (3H, m), 2.30 (1H, m), 2.46 (1H, m), 2.91 (1H, dd, J = 16.6, 4.6 Hz), 3.17 (1H, dt, J = 16.6, 4.8 Hz), 3.26 (3H, m), 4.17 (1H, m), 4.21-4.35 (3H, m), 4.64 (1H, m), 5.17 (1H, m), 6.07 (1H, s), 6.93 (1H, m), 6.94 (1H, d, J = 8.6 Hz), 7.38 (1H, m), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 421 [M + H]+ 395 [00825]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.17-2.26 (9H, m), 2.84 (1H, br d, J = 16.8 Hz), 3.16 (1H, dd, J = 16.8, 5.2 Hz), 3.42 (2H, m), 3.97 (2H, m), 4.03-4.22 (4H, m), 4.30 (1H, m), 4.60 (1H, m), 5.98 (1H, s), 6.80 (1H, d, J = 8.6 Hz), 6.96 (1H, m), 7.04 (1H, s), 7.08 (1H, dd, J = 8.6, 2.2 Hz). ESI-MS m/z: 432 [M + H]+ 396 [00826]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.36-2.47 (2H, m), 2.86 (1H, m), 3.18 (1H, m), 4.10-4.29 (4H, m), 4.54- 4.64 (2H, m), 5.13 (1H, d, J = 11.0 Hz), 5.60 (1H, d, J = 17.6 Hz), 6.13 (1H, s), 5.62 (1H, dd, J = 10.9, 17.5 Hz), 6.84 (1H, d, J = 8.5 Hz), 7.03 (1H, d, J = 7.9 Hz), 7.10 (1H, s), 7.21 (1H, d, J = 8.4 Hz). ESI-MS m/z: 394 [M + H]+ 397 [00827]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.33-2.45 (2H, m), 2.81- 2.87 (2H, m), 3.15 (1H, dd, J = 5.4, 15.7 Hz), 3.47 (1H, t, J = 5.5 Hz), 3.67 (1H, m), 3.76-3.84 (3H, m), 4.10-4.20 (3H, m), 4.26 (1H, m), 4.54- 4.62 (2H, m), 6.13 (1H, s), 6.81 (1H, d, J = 8.3 Hz), 6.91 (1H, s), 7.00 (2H, dd, J = 8.2, 17.9 Hz). ESI-MS m/z: 494 [M + H]+ 398 [00828]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.52 (6H, s), 2.38-2.46 (2H, m), 2.83 (1H, m), 3.14 (1H, m), 3.41 (3H, s), 4.10-4.29 (4H, m), 4.55-4.63 (2H, m), 6.12 (1H, s), 6.81 (1H, d, J = 8.4 Hz), 6.96 (1H, d, J = 7.7 Hz), 7.17 (1H, s), 7.21 (1H, d, J = 8.5 Hz). [00829]![text missing or illegible when filed]()
TABLE-US-00054 TABLE 54 Ex- am- ple Structural formula NMS MS 399 [00830]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.50 (1H, m), 1.71 (1H, q, J = 10.1 Hz), 1.97 (2H, m), 2.22 (2H, m), 2.40 (2H, m), 2.85 (1H, m), 3.18 (1H, m), 4.01 (1H, m), 4.11-4.28 (6H, m), 4.56-4.62 (2H, m), 5.12 (1H, s), 6.84 (1H, d, J = 8.3 Hz), 7.02 (1H, m), 7.05 (1H, s), 7.10 (1H, d, J = 7.7 Hz). ESI-MS m/z: 452 [M + H]+ 400 [00831]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.20 (6H, s), 1.71-1.75 (2H, m), 2.36-2.46 (2H, m), 2.52-2.56 (2H, m), 2.83 (1H, m), 3.16 (1H, m), 3.22 (3H, s), 4.10- 4.17 (3H, m), 4.28 (1H, m), 4.57-4.61 (2H, m), 6.13 (1H, s), 6.80 (1H, d, J = 8.3 Hz), 6.88 (1H, s), 6.96 (1H, d, J = 9.0 Hz), 7.04 (1H, d, J = 7.9 Hz). ESI-MS m/z: 468 [M + H]+ 401 [00832]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.37-2.43 (2H, m), 2.58- 2.92 (4H, m), 3.13-3.24 (2H, m), 3.54 (4H, t, J = 12.5 Hz), 4.11-4.28 (4H, m), 4.57-4.60 (2H, m), 6.13 (1H, s), 6.81 (1H, m), 6.87 (1H, m), 6.95 (1H, d, J = 7.4 Hz), 7.03 (1H, d, J = 8.2 Hz). ESI-MS m/z: 487 [M + H]+ 402 [00833]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.68 (2H, m), 0.80 (2H, m), 1.25 (1H, m), 2.24 (1H, m), 2.39 (1H, m), 2.92 (1H, br d, J = 16.6 Hz), 3.20 (1H, dd, J = 16.6, 5.3 Hz), 4.12 (1H, m), 4.19-4.26 (3H, m), 4.55 (1H, m), 5.04 (1H, m), 6.05 (1H, s), 6.95 (1H, d, J = 6.6 Hz), 6.97 (1H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.6 Hz). ESI-MS m/z: 432 [M + H]+ 403 [00834]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.42-1.44 (6H, d, J = 2.1 Hz), 2.08 (2H, t, J = 6.5 Hz, 2.82-2.92 (3H, m), 3.16 (1H, dd, J = 5.6, 16.6 Hz), 4.08-4.12 (4H, m), 4.17-4.22 (2H, m), 4.61 (1H, m), 5.97 (1H, s), 6.52 (1H, d, J = 8.3 Hz), 6.90 (1H, s), 6.96- 7.02 (1H, m). ESI-MS m/z: 440 [M + H]+ 404 [00835]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.09-2.44 (4H, m), 2.84 (1H, dd, J = 16.8, 4.2 Hz), 3.15 (1H, dd, J = 16.8, 4.6 Hz), 4.06-4.24 (3H, m), 4.44 (1H, m), 4.61 (1H, m), 4.63 (1H, m), 6.01 (1H, s), 5.12 (1H, tdd, J = 56., 6.5, 2.9 Hz), 5.81 (1H, d, J = 8.7 Hz), 6.99 (1H, m), 7.04 (1H, m), 7.08 (1H, dd, J = 8.7, 2.6 Hz) ESI-MS m/z: 398 [M + H]+ 405 [00836]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.58-0.62 (2H, m), 0.87- 0.91 (2H, m), 1.81 (1H, m), 2.24-2.38 (2H, m), 2.82 (1H, m), 3.15 (1H, m), 4.07-4.20 (3H, m), 4.27 (1H, m), 4.37 (1H, m), 4.60 (1H, m), 5.89 (1H, dt, J = 3.4, 82.0 Hz), 6.08 (1H, s), 6.77- 6.79 (2H, m), 6.85 (1H, dd, J = 2.1, 8.5 Hz), 7.04 (1H, d, J = 8.2 Hz). ESI-MS m/z: 390 [M + H]+ 406 [00837]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.68 (2H, m), 0.79 (2H, m), 1.23 (1H, m), 2.24 (1H, m), 2.38 (1H, m), 2.85 (1H, dd, J = 16.8, 4.2, Hz), 3.15 (1H, dd, J = 16.8, 5.4 Hz), 4.13 (1H, m), 4.19 (1H, m), 4.26 (1H, m), 4.61 (1H, m), 5.04 (1H, m), 5.41 (1H, m), 6.04 (1H, s), 5.81 (1H, d, J = 6.7 Hz), 7.00 (1H, m), 7.04 (1H, m), 7.08 (1H, dd, J = 8.7, 2.5 Hz). ESI-MS m/z: 398 [M + H]+ 407 [00838]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.68 (2H, m), 0.79 (2H, m), 1.23 (1H, m), 2.24 (1H, m), 2.38 (1H, m), 2.85 (1H, dd, J = 16.8, 4.2 Hz), 3.15 (1H, dd, J = 16.8, 5.4 Hz), 4.13 (1H, m), 4.19 (1H, m), 4.26 (1H, m), 4.61 (1H, m), 5.04 (1H, m), 5.41 (1H, m), 6.04 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 7.00 (1H, m), 7.04 (1H, m), 7.08 (1H, dd, J = 8.7, 2.5 Hz). ESI-MS m/z: 398 [M + H]+ [00839]![text missing or illegible when filed]()
TABLE-US-00055 TABLE 55 Ex- am- ple Structural formula NMR MS 408 [00840]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.68 (2H, m), 0.79 (2H, m, 1.23 (1H, m), 2.24 (1H, m), 2.38 (1H, m), 2.85 (1H, dd, J = 16.8, 4.2 Hz), 3.15 (1H, dd, J = 16.8, 5.4 Hz), 4.13 (1H, m), 4.19 (1H, m), 4.26 (1H, m), 4.61 (1H, m), 5.04 (1H, m), 5.41 (1H, m), 6.04 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 7.00 (1H, m), 7.04 (1H, m), 7.05 (1H, dd, J = 8.7, 2.5 Hz). ESI-MS m/z: 398 [M + H]+ 409 [00841]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.25-1.31 (3H, m), 2.23-2.37 (2H, m), 2.84 (1H, m), 3.14 (1H, dd, J = 5.3, 16.8 Hz), 3.75 (1H, m, 3.95-4.13 (2H, m), 4.18-4.29 (4H, m), 4.80 (1H, m), 5.43 (1H, m), 6.05 (1H, d, J = 1.0 Hz), 6.81 (1H, d, J = 8.6 Hz), 6.99 (1H, d, J = 7.4 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 2.4, 8.7 Hz). ESI-MS m/z: 410 [M + H]+ 410 [00842]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.68-1.77 (2H, m), 1.82-1.95 (2H, m), 2.01-2.06 (2H, m), 2.15-2.29 (2H, m), 2.56 (1H, m), 2.90 (1H, m), 3.17 (1H, m), 3.49 (2H, d, J = 6.7 Hz), 3.62 (1H, m), 3.72 (1H, m), 4.07 (1H, m), 4.16-4.35 (4H, m), 4.63 (1H, m), 6.02 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 423 [M + H]+ 411 [00843]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.27-2.36 (2H, m), 2.91 (1H, m), 3.17 (1H, m), 4.13 (1H, m), 4.22-4.31 (3H, m), 4.58-4.64 (4H, m), 6.05 (1H, s), 6.81 (1H, d, J = 8.3 Hz), 6.90-6.94 (3H, m), 7.39 (1H, s), 7.42 (1H, m), 7.61 (1H, m), 8.13 (1H, dd, J = 1.3, 4.9 Hz). ESI-MS m/z: 432 [M + H]+ 412 [00844]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.26 (2H, m), 2.91 (1H, m), 3.17 (1H, m), 3.84-3.93 (2H, m), 4.00-4.13 (3H, m), 4.19-4.31 (3H, m), 4.37 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.91-6.94 (2H, m), 7.39 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 487 [M + H]+ 413 [00845]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.24-1.38 (2H, m), 1.81-1.84 (2H, m), 1.86 (1H, m), 2.17- 2.26 (2H, m), 2.84 (1H, dd, J = 3.9, 16.6 Hz), 3.14 (1H, dd, J = 5.5, 16.9 Hz), 3.35-3.41 (4H, m), 3.63 (1H, dd, J = 4.9,10.3 Hz), 3.72 (1H, dd, J = 4.9, 10.5 Hz), 3.97 (2H, dd, J = 3.7, 11.2 Hz), 4.08 (1H, m), 4.18-4.21 (3H, m), 4.33 (1H, m), 4.60 (1H, m), 6.01 (1H, s), 6.85 (1H, d, J = 8.7 Hz), 6.98 (1H, d, J = 8.3 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 2.4, 8.6 Hz). ESI-MS m/z: 462 [M + H]+ 414 [00846]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.23 (2H, m), 2.85 (1H, dd, J = 9.6, 15.7 Hz), 3.06 (1H, dd, J = 4.5, 15.6 Hz), 3.23 (1H, m), 3.36 (1H, m), 3.67 (1H, m), 3.74-3.78 (3H, m), 3.97 (1H, t, J = 9.8 Hz), 4.11 (1H, m), 4.20-4.26 (2H, m), 4.33-4.38 (3H, m), 4.45 (2H, t, J = 6.0 Hz), 4.35 (2H, t, J = 6.1 Hz), 4.64 (1H, m), 4.78-4.82 (4H, m), 5.70 (1H, s), 6.91 (1H, d, J = 8.5 Hz), 7.16 (1H, t, J = 5.9 Hz), 7.64- 7.77 (4H, m), 8.64 (1H, d, J = 4.7 Hz). ESI-MS m/z: 547 [M + H]+ 415 [00847]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.24 (3H, s), 1.25 (3H, s), 2.14 (1H, m), 2.31-2.34 (3H, m), 2.41-2.56 (3H, m), 2.66 (1H, dd, J = 6.5, 13.3 Hz), 2.84 (1H, dd, J = 4.1, 16.9 Hz), 3.14 (1H, dd, J = 4.3, 16.8 Hz), 3.74 (2H, t, J = 4.8 Hz), 4.08 (1H, m), 4.15-4.19 (3H, m), 4.31 (1H, m), 4.60 (1H, m), 6.00 (1H, s), 6.51 (1H, d, J = 8.7 Hz), 6.99 (1H, m), 7.04 (1H, s), 7.08 (1H, m). ESI-MS m/z: 461 [M + H]+ 416 [00848]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69-1.91 (4H, m), 1.96 (2H, m), 2.86 (1H, dd, J = 16.8, 4.2 Hz), 3.76 (1H, dd, J = 16.8, 5.6 Hz), 3.71-3.81 (3H, m), 3.82-3.97 (3H, m), 4.19 (2H, m), 4.62 (1H, m), 6.11 (1H, s), 6.81 (1H, d, J = 8.1 Hz), 6.99 (1H, m), 7.04 (1H, m), 7.09 (1H, br d, J = 8.1 Hz). ESI-MS m/z: 404 [M + H]+ [00849]![text missing or illegible when filed]()
TABLE-US-00056 TABLE 56 Ex- am- ple Structural formula NMS MS 417 [00850]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (1H, m), 2.43 (1H, m), 2.82 (1H, dd, J = 16.6, 3.6 Hz), 3.10 (1H, dd, J = 16.6, 5.0 Hz), 4.13 (1H, m), 4.12-4.25 (3H, m), 4.38 (2H, m), 4.54 (1H, m), 5.05 (1H, br s), 6.06 (1H, s), 6.86 (1H, d, J = 8.5 Hz), 6.98 (1H, d, J = 7.8 Hz), 7.31 (1H, m), 7.35 (1H, d, J = 8.5 Hz). ESI-MS m/z: 423 [M + H]+ 418 [00851]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.43 (2H, m), 2.41 (2H, m), 2.91 (1H, dd, J = 16.7, 4.6 Hz), 3.17 (1H, dd, J = 16.7, 5.3 Hz), 3.66 (1H, dd, J = 10.7, 5.1 Hz), 3.72-3.79 (3H, m), 4.02-4.34 (5H, m), 4.63 (1H, m), 6.02 (1H, s), 6.91 (1H, m), 6.92 (1H, d, J = 8.7 Hz), 7.38 (1H, m), 7.42 (1H, d, J = 8.7 Hz). ESI-MS m/z: 451 [M + H]+ 419 [00852]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.18 (2H, m), 0.58-0.63 (2H, m), 1.00, (1H, m), 1.40 (3H, m), 2.04 (1H, m), 2.35 (1H, m), 2.91 (1H, m), 3.17 (1H, m), 3.31-3.35 (2H, m), 3.48-3.56 (2H, m), 4.04-4.18 (2H, m), 4.22-4.31 (2H, m), 4.63 (1H, m), 5.99 (1H, s), 6.92-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 423 [M + H]+ 420 [00853]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.28 (2H, m), 2.84 (1H, m), 3.15 (1H, m), 4.09-4.26 (6H, m), 4.44 (1H, m), 4.61 (1H, m), 6.05 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 6.99 (1H, d, J = 6.6 Hz), 7.04 (1H, s), 7.08 (1H, d, J = 8.7 Hz). ESI-MS m/z: 432 [M + H]+ 421 [00854]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.29 (2H, m), 2.96 (1H, m), 3.25 (1H, dd, J = 5.4, 16.7 Hz), 4.11-4.25 (6H, m), 4.44 (1H, m), 4.66 (1H, m), 6.06 (1H, s), 6.99 (1H, d, J = 5.3 Hz), 7.04 (1H, d, J = 7.6 Hz), 7.20 (1H, s), 7.29 (2H, m), 8.65 (2H, s). ESI-MS m/z: 506 [M + H]+ 422 [00855]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.26 (1H, m), 2.30 (1H, m), 2.91 (1H, dd, J = 16.8, 4.6 Hz), 2.08 (1H, dd, J = 14.8, 5.7 Hz), 3.06 (1H, dd, J = 14.8, 6.0 Hz), 3.11-3.30 (3H, m), 4.11 (1H, m), 4.06-4.33 (3H, m), 4.40 (1H, m), 4.54 (1H, m), 5.03 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 7.38 (1H, m), 7.42 (1H, dd, J = 8.5, 2.2 Hz). ESI-MS m/z: 453 [M + H]+ 423 [00856]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.15-2.38 (2H, m), 2.91 (1H, dd, J = 16.8, 4.6 Hz), 2.98 (1H, dd, J = 14.0, 6.0 Hz), 3.06 (1H, dd, J = 14.0, 6.0 Hz), 3.12-3.29 (3H, m), 4.10 (1H, m), 4.16-4.36 (3H, m), 4.39 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 453 [M + H]+ 424 [00857]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.15-2.38 (2H, m), 2.91 (1H, dd, J = 16.8, 4.6 Hz), 2.98 (1H, dd, J = 14.0, 6.0 Hz), 3.06 (1H, dd, J = 14.0, 6.0 Hz), 3.12-3.29 (3H, m), 4.10 (1H, m), 4.16-4.36 (3H, m), 4.39 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 453 [M + H]+ 425 [00858]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.6 Hz), 0.55 (2H, d, J = 8.0 Hz), 1.05 (1H, m), 2.13-2.29 (2H, m), 2.97 (1H, m), 3.26 (1H, dd, J = 5.2, 16.8 Hz), 3.37 (2H, d, J = 6.9 Hz), 3.65 (1H, dd, J = 5.2, 9.0 Hz), 3.75 (1H, dd, J = 5.3, 10.5 Hz), 4.07 (1H, m), 4.18 (1H, m), 4.28 (2H, m), 4.35 (1H, m), 4.67 (1H, m), 6.02 (1H, s), 6.72 (1H, d, J = 7.9 Hz), 7.02 (2H, m), 7.76 (1H, s), 8.45 (1H, d, J = 2.4 Hz), 8.56 (1H, t, J = 3.7 Hz), 8.96 (1H, d, J = 1.2 Hz). ESI-MS m/z: 462 [M + H]+ [00859]![text missing or illegible when filed]()
TABLE-US-00057 TABLE 57 Ex- am- ple Structural formula NMR MS 426 [00860]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, m), 0.55 (2H, d, J = 6.8 Hz), 1.06 (1H, m), 2.18-2.27 (2H, m), 2.89 (1H, m), 3.21 (1H, m), 3.37 (2H, d, J = 6.3 Hz), 3.65 (1H, m), 3.74 (1H, m), 3.93 (3H, s), 4.06 (1H, m), 4.16-4.22 (3H, m), 4.35 (1H, m), 4.64 (1H, m), 6.01 (1H, s), 6.44 (1H, s), 6.89 (1H, d, J = 8.6 Hz), 7.02 (1H, d, J = 6.2 Hz), 7.35 (1H, s), 7.52-7.54 (2H, m). ESI-MS m/z: 464 [M + H]+ 427 [00861]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.7 Hz), 0.55 (2H, d, J = 7.5 Hz), 1.06 (1H, m), 2.21 (2H, m), 2.93 (1H, dd, J = 4.0, 16.5 Hz), 3.24 (1H, dd, J = 4.9, 17.0 Hz), 3.37 (2H, d, J = 7.0 Hz), 3.64 (1H, dd, J = 5.1, 10.0 Hz), 3.75 (1H, dd, J = 4.6, 10.5 Hz), 4.07 (1H, m), 4.17-4.24 (2H, m), 4.35 (1H, m), 4.66 (1H, m), 5.02 (1H, s), 6.94 (1H, d, J = 9.3 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.39 (1H, s), 7.66-7.68 (2H, m), 8.85 (1H, s). ESI-MS m/z: 467 [M + H]+ 428 [00862]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.7 Hz), 0.55 (2H, d, J = 8.1 Hz), 1.05 (1H, m), 2.21 (2H, m), 2.92 (1H, dd, J = 3.9, 17.0 Hz), 3.21 (1H, dd, J = 5.1, 16.7 Hz), 3.37 (2H, d, J = 6.6 Hz), 3.65 (1H, m), 3.75 (1H, dd, J = 4.9, 10.4 Hz), 4.08 (1H, m), 4.19 (1H, m), 4.24 (2H, m), 4.35 (1H, m), 4.65 (1H, m), 6.03 (1H, s), 6.92 (1H, d, J = 8.5 Hz), 7.02 (1H, d, J = 8.1 Hz), 7.26 (1H, s), 7.35 (1H, dd, J = 2.1, 8.4 Hz), 7.96 (1H, s), 8.70 (1H, s). ESI-MS m/z: 467 [M + H]+ 429 [00863]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 5.0 Hz), 0.55 (2H, d, J = 7.9 Hz), 1.06 (1H, m), 2.21 (2H, m), 2.92 (1H, m), 3.22 (1H, m), 3.37 (2H, d, J = 7.0 Hz), 3.64 (1H, dd, J = 5.7, 10.3 Hz), 3.75 (1H, dd, J = 5.2, 10.4 Hz), 4.08 (1H, m), 4.16-4.24 (8H, m), 4.35 (1H, m), 4.65 (1H, m), 6.02 (1H, s), 6.93 (1H, d, J = 8.4 Hz), 7.02 (1H, d, J = 8.6 Hz), 7.49 (1H, s), 7.52 (1H, d, J = 8.5 Hz), 7.72 (1H, s). ESI-MS m/z: 465 [M + H]+ 430 [00864]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 4.6 Hz), 0.55 (2H, d, J = 7.9 Hz), 1.06 (1H, m), 2.12-2.29 (2H, m), 2.90 (1H, dd, J = 3.6, 15.5 Hz), 3.20 (1H, dd, J = 5.3, 16.7 Hz), 3.37 (2H, d, J = 6.8 Hz), 3.65 (1H, dd, J = 5.3, 10.4 Hz), 3.75 (1H, dd, J = 5.2, 10.4 Hz), 4.08 (1H, m), 4.17-4.24 (3H, m), 4.35 (1H, m), 4.54 (1H, m), 4.72 (2H, q, J = 8.4 Hz), 6.02 (1H, s), 6.69 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.0 Hz), 7.17 (1H, s), 7.24 (1H, s), 7.65 (1H, s), 7.78 (1H, s). ESI-MS m/z: 532 [M + H]+ 431 [00865]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.21 (2H, d, J = 3.9 Hz), 0.55 (2H, d, J = 7.2 Hz), 1.06 (1H, m), 2.17-2.28 (2H, m), 2.58 (3H, s), 2.97 (1H, m), 3.26 (1H, dd, J = 5.2, 16.2 Hz), 3.37 (2H, d, J = 6.8 Hz), 3.65 (1H, dd, J = 4.8, 9.9 Hz), 3.75 (1H, dd, J = 5.3, 10.8 Hz), 4.07 (1H, m), 4.17 (1H, m), 4.26 (2H, m), 4.35 (1H, m), 4.67 (1H, m), 6.02 (1H, s), 6.98, 7.03 (2H, m), 7.73 (1H, s), 7.76 (1H, s), 8.45 (1H, s), 8.53 (1H, s). ESI-MS m/z: 475 [M + H]+ 432 [00866]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (2H, m), 2.91 (1H, dd, J = 16.8, 4.2 Hz), 3.20 (1H, dd, J = 16.8, 5.2 Hz), 3.83-4.00 (4H, m), 4.10 (1H, m), 4.17-4.30 (3H, m), 4.37 (1H, m), 4.64 (1H, m), 5.03 (1H, s), 6.95 (1H, d, J = 8.1 Hz), 6.98 (1H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.1 Hz). ESI-MS m/z: 480 [M + H]+ 433 [00867]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46-1.47 (3H, m), 2.06 (1H, m), 2.17 (1H, m), 2.87 (1H, m), 3.17 (1H, m), 3.26 (2H, q, J = 10.8 Hz), 4.07 (1H, m), 4.14-4.22 (3H, m), 4.35 (1H, m), 4.62 (1H, m), 5.99 (1H, s), 6.85 (1H, d, J = 8.4 Hz), 6.97-7.06 (3H, m). ESI-MS m/z: 462 [M + H]+ 434 [00868]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.76 (2H, m), 1.04 (2H, m), 2.24 (2H, m), 2.91 (1H, dd, J = 16.7, 4.8 Hz), 3.12 (1H, dd, J = 16.7, 5.2 Hz), 3.62-3.71 (3H, m), 3.76 (1H, dd, J = 9.8, 4.6 Hz), 4.08 (1H, m), 4.21 (1H, m), 4.28 (2H, m), 4.34 (1H, m), 4.63 (1H, m), 6.01 (1H, s), 6.89-6.96 (2H, m), 7.38 (1H, m), 7.42 (1H, dd, J = 8.5, 2.1 Hz). ESI-MS m/z: 477 [M + H]+ [00869]![text missing or illegible when filed]()
TABLE-US-00058 TABLE 58 Ex- am- ple Structural formula NMR MS 435 [00870]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.75 (2H, m), 1.04 (2H, m), 2.21 (2H, m), 2.97 (1H, dd, J = 16.6, 4.4, Hz), 3.27 (1H, dd, J = 16.6, 5.3 Hz), 3.62-3.69 (3H, m), 3.76 (1H, ddd, J = 10.1, 4.4, 0.5 Hz), 4.07 (1H, m), 4.19 (1H, m), 4.26-4.29 (1H, m), 4.33 (1H, m), 4.67 (1H, m), 5.41 (1H, m), 6.01 (1H, s), 5.97-7.05 (2H, m), 7.76-7.82 (2H, m), 7.01 (1H, m), 6.45 (1H, d, J = 2.5 Hz), 8.58 (1H, dd, J = 2.5, 1.6 Hz), 8.96 (1H, d, J = 1.5 Hz). ESI-MS m/z: 530 [M + H]+ 436 [00871]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24 (2H, m), 2.84 (1H, dt, J = 16.9, 3.3 Hz), 2.96 (1H, m), 3.15 (1H, dd, J = 16.8, 4.9 Hz), 3.78-3.99 (4H, m), 4.10 (1H, m), 4.17-4.26 (3H, m), 4.37 (1H, m), 4.60 (1H, m), 5.03 (1H, s), 6.78 (1H, dd, J = 22.7, 8.2 Hz), 6.97 (1H, t, J = 8.2 Hz), 7.23 (1H, m), 7.23 (1H, ddd, J = 22.7, 8.2, 2.6 Hz). ESI-MS m/z: 436 [M + H]+ 437 [00872]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.50 (1H, m), 1.71 (1H, m), 1.57-1.75 (2H, m), 2.19-2.23 (4H, m), 2.86 (1H, m), 2.99-3.09 (2H, m), 3.16 (1H, m), 3.52 (1H, m), 3.52 (1H, m), 3.95-4.12 (2H, m), 4.17-4.21 (3H, m), 4.31 (1H, m), 4.61 (1H, m), 5.72-6.02 (2H, m), 6.84 (1H, d, J = 8.2 Hz), 8.94 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 448 [M + H]+ 438 [00873]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.50 (1H, m), 1.71 (1H, m), 1.89-1.98 (2H, m), 2.17-2.22 (4H, m), 2.87 (1H, m), 3.18 (1H, m), 3.52 (1H, m), 3.62 (1H, m), 3.82 (2H, q, J = 8.8 Hz), 3.95-4.11 (2H, m), 4.16- 4.23 (3H, m), 4.32 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 6.02 (1H, s), 6.87 (1H, d, J = 8.2 Hz), 7.00 (1H, d, J = 7.2 Hz), 7.04 (1H, s), 7.12 (1H, d, J = 8.5 Hz). ESI-MS m/z: 496 [M + H]+ 439 [00874]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.15-2.27 (2H, m), 2.28-2.58 (4H, m), 2.90 (1H, dd, J = 16.5, 4.6 Hz), 3.16 (1H, dd, J = 16.5, 5.2 Hz), 3.56 (1H, dd, J = 10.4, 4.7 Hz), 3.63 (1H, dd, J = 10.4, 5.2 Hz), 4.08 (1H, m), 4.15-4.41 (5H, m), 4.63 (1H, m), 5.20 (1H, m), 6.03 (1H, s), 6.89-5.96 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.8 Hz). ESI-MS m/z: 427 [M + H]+ 440 [00875]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-19 (2H, m), 2.85-2.91 (3H, m), 3.18 (1H, dd, J = 5.4, 16.7 Hz), 3.68-3.74 (4H, m), 3.82 (2H, q, J = 8.7 Hz), 4.05-4.20 (5H, m), 4.57 (2H, s), 4.62 (1H, m), 6.00 (1H, s), 6.87 (1H, d, J = 8.6 Hz), 7.00 (1H, d, J = 8.2 Hz), 7.05 (1H, s), 7.12 (1H, d, J = 8.4 Hz). ESI-MS m/z: 517 [M + H]+ 441 [00876]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24 (2H, m), 2.87 (1H, dd, J = 4.5, 17.4 Hz), 3.15-3.31 (3H, m), 3.84-3.98 (4H, m), 4.09 (1H, m), 4.16-4.22 (3H, m), 4.37 (1H, m), 4.62 (1H, m), 6.03 (1H, s), 6.86 (1H, d, J = 8.3 Hz), 6.98-7.06 (3H, m). ESI-MS m/z: 494 [M + H]+ 442 [00877]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.20-2.26 (2H, m), 2.84 (1H, dd, J = 4.2, 16.9 Hz), 3.14 (1H, dd, J = 5.4, 16.8 Hz), 3.84-3.98 (4H, m), 4.09 (1H, m), 4.18-4.24 (3H, m), 4.37 (1H, m), 4.60 (1H, m), 6.02 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.8 Hz), 7.04 (1H, d, J = 2.5 Hz), 7.08 (1H, dd, J = 2.6, 8.7 Hz). ESI-MS m/z: 446 [M + H]+ 443 [00878]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.25 (2H, m), 2.87 (1H, m), 3.18 (1H, m), 3.66 (1H, m), 3.74 (1H, m), 4.06 (1H, m), 4.14- 4.22 (3H, m), 4.36 (1H, m), 4.60-4.62 (3H, m), 6.02 (1H, s), 6.86-6.91 (2H, m), 7.01-7.07 (2H, m), 7.13 (1H, t, J = 7.7 Hz), 7.29-7.38 (5H, m). ESI-MS m/z: 420 [M + H]+ [00879]![text missing or illegible when filed]()
TABLE-US-00059 TABLE 59 Ex- am- ple Structural formula NMR MS 444 [00880]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.46 (3H, d, J = 6.2 Hz), 2.04 (1H, m), 2.22 (1H, m), 2.80 (1H, m), 3.09 (1H, m), 4.10-4.25 (4H, m), 4.38 (1H, m), 4.58 (1H, m), 6.77 (1H, d, J = 8.7 Hz), 6.92 (1H, d, J = 7.7 Hz), 7.00 (1H, s), 7.07 (1H, d, J = 8.7 Hz), 7.22 (1H, m), 7.31-7.34 (2H, m), 7.51 (2H, d, J = 7.8 Hz). ESI-MS m/z: 424 [M + H]+ 445 [00881]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.84 (1H, br d, J = 16.9 Hz), 3.16 (1H, dd, J = 18.9, 5.2 Hz), 4.15-4.24 (2H, m), 4.36 (1H, dd, J = 10.7, 5.5 Hz), 4.52 (1H, t, J = 9.5 Hz), 4.80 (1H, m), 5.50 (1H, m), 5.02 (1H, m), 6.75 (1H, d, J = 8.6 Hz), 6.97 (1H, d, J = 8.0 Hz), 7.19 (1H, m), 7.22 (1H, br d, J = 8.8 Hz). ESI-MS m/z: 433 [M + H]+ 446 [00882]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.53 (3H, m), 1.54 (3H, s), 2.09 (3H, s), 2.76 (1H, dd, J = 16.8, 4.0 Hz), 3.07 (1H, dd, J = 16.8, 5.3 Hz), 3.67 (2H, s), 4.11 (2H, m), 4.51 (1H, m), 6.72 (1H, d, J = 8.6 Hz), 6.89-6.97 (2H, m), 7.00 (1H, br d, J = 6.4 Hz). ESI-MS m/z: 362 [M + H]+ 447 [00883]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.84 (1H, dt, J = 16.7, 4.0 Hz), 2.90 (1H, t, J = 7.2 Hz), 3.17 (1H, dd, J = 16.7, 5.4 Hz), 4.11 (2H, t, J = 7.2 Hz), 4.14-4.24 (2H, m), 4.36 (1H, m), 4.51 (1H, m), 4.61 (1H, m), 5.50 (1H, m,), 6.02 (1H, s), 6.83 (1H, br d, J =, 8.3 Hz), 6.90 (1H, br s), 6.98 (1H, dd, J = 8.5, 2.0 Hz), 7.01 (1H, m). ESI-MS m/z: 466 [M + H]+ 448 [00884]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.62 (1H, s), 2.83 (1H, m), 3.06 (1H, m), 3.15 (1H, dd, J = 5.3, 16.8 Hz), 3.25 (3H, s), 4.11-4.18 (3H, m), 4.29 (1H, dt, J = 2.7, 9.1 Hz), 4.61 (1H, m), 5.38 (1H, m), 5.90 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 5.0 Hz), 7.04 (1H, s), 7.08 (1H, dd, J = 2.2, 8.7 Hz). ESI-MS m/z: 431 [M + H]+ 449 [00885]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18-0.22 (2H, m), 0.54 (2H, t, J = 8.9 Hz), 1.02 (1H, m), 2.84 (1H, m), 3.15 (1H, m), 3.32-3.41 (2H, m), 3.77-3.96 (2H, m), 4.19 (2H, s), 4.38 (1H, m), 4.48 (1H, m), 4.61 (1H, m), 5.59 (1H, m), 5.95 (1H, s), 6.81 (1H, d, J = 8.8 Hz), 6.99 (1H, d, J = 4.2 Hz), 7.04 (1H, s), 7.08 (1H, d, J = 8.8 Hz). ESI-MS m/z: 454 [M + H]+ 450 [00886]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.90 (1H, m), 3.16 (1H, dd, J = 5.3, 16.5 Hz), 4.22-4.31 (3H, m), 4.40 (1H, t, J = 9.5 Hz), 4.62-4.73 (3H, m), 5.65 (1H, m), 5.93 (1H, s), 6.75 (1H, dd, J = 4.9, 8.3 Hz), 6.92-6.94 (3H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.5 Hz), 7.60 (1H, t, J = 7.7 Hz), 8.12 (1H, m). ESI-MS m/z: 418 [M + H]+ 451 [00887]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.40 (1H, m), 2.48 (1H, m), 2.83 (1H, d, J = 16.9 Hz), 3.14 (1H, dd, J = 5.1, 16.9 Hz), 3.76 (1H, m), 4.18 (2H, s), 4.26 (1H, m), 4.38 (2H, m), 4.59 (1H, m), 5.15 (1H, m), 5.90 (1H, s), 6.26 (1H, s), 6.79 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 7.0 Hz), 7.03 (1H, s), 7.07 (1H, d, J = 8.8 Hz), 7.42 (1H, s), 7.54 (1H, s). ESI-MS m/z: 414 [M + H]+ 452 [00888]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06 (3H, t, J = 7.1 Hz), 2.80 (2H, q, J = 7.1 Hz), 2.90 (1H, dd, J = 4.4, 16.6 Hz), 3.01 (1H, m), 3.08-3.20 (4H, m), 4.13 (1H, m), 4.23-4.31 (3H, m), 4.64 (1H, m), 5.34 (1H, m), 5.90 (1H, s), 6.92-6.94 (2H, m), 7.36 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 450 [M + H]+ [00889]![text missing or illegible when filed]()
TABLE-US-00060 TABLE 60 Ex- am- ple Structural formula NMR KS 453 [00890]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.82 (1H, dd, J = 3.6, 17.1 Hz), 3.13 (1H, dd, J = 5.2, 16.8 Hz), 4.12-4.18 (3H, m), 4.33 (1H, m), 4.55-4.59 (3H, m), 5.63 (1H, m), 5.89 (1H, m), 6.27 (1H, d, J = 2.0 Hz), 6.80 (1H, d, J = 8.6 Hz), 6.95 (1H, d, J = 7.6 Hz), 7.03 (1H, s), 7.07 (1H, d, J = 8.7 Hz), 7.47 (1H, s), 7.52 (1H, s). ESI-MS m/z: 400 [M + H]+ 454 [00891]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, s), 0.54 (2H, d, J = 7.8 Hz), 1.02 (1H, s), 2.90 (1H, dd, J = 4.4, 16.5 Hz), 3.17 (1H, m), 3.37 (2H, dd, J = 3.2, 6.8 Hz), 3.77-3.79 (2H, m), 4.18 (1H, m), 4.23-4.33 (3H, m), 4.64 (1H, m), 5.41 (1H, m), 5.91 (1H, s), 6.93 (2H, d, J = 8.4 Hz), 7.36 (1H, s), 7.42 (1H, d, J = 8.6 Hz). ESI-MS m/z: 395 [M + H]+ 455 [00892]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.44 (1H, m), 2.52 (1H, m), 2.89 (1H, br d, J = 16.8 Hz), 3.17 (1H, dd, J = 16.7, 5.1 Hz), 3.83 (1H, m), 4.27 (2H, m), 4.33 (1H, m), 4.40 (2H, m), 4.63 (1H, m), 5.21 (1H, m), 5.93 (1H, s), 6.91 (1H, m), 6.92 (1H, d, J = 8.6 Hz), 7.37 (1H, s), 7.42 (1H, d, J = 8.6 Hz), 7.70 (1H, m), 7.74 (1H, s). ESI-MS m/z: 473 [M + H]+ 456 [00893]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.19 (2H, m), 2.97 (1H, dd, J = 4.5, 16.7 Hz), 3.27 (1H, dd, J = 5.6, 17.2 Hz), 3.83 (4H, m), 3.96 (1H, m), 4.28 (2H, s), 4.34 (1H, m), 4.68 (1H, m), 5.44 (1H, m), 5.90 (1H, s), 7.00 (2H, d, J = 7.7 Hz), 7.77 (1H, s), 7.80 (1H, s), 8.45 (1H, d, J = 1.9 Hz), 8.56 (1H, s), 8.96 (1H, s). ESI-MS m/z: 490 [M + H]+ 457 [00894]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05 (1H, m), 2.24 (1H, m), 2.84-2.92 (3H, m), 3.11 (2H, m), 3.22 (1H, dd, J = 4.4, 17.2 Hz), 3.86- 3.93 (4H, m), 4.22 (2H, m), 4.36 (1H, m), 4.64 (1H, m), 5.41 (1H, m), 5.89 (1H, s), 6.44 (1H, d, J = 2.0 Hz),6.89 (1H, d, J = 8.2 Hz), 7.02 (1H, m), 7.35 (1H, d, J = 2.0 Hz), 7.51 (1H, s), 7.54 (1H, s). ESI-MS m/z: 508 [M + H]+ 458 [00895]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.18 (3H, m), 1.20 (3H, m), 2.33 (2H, m), 2.49 (2H, m), 2.73 (2H, m), 2.91 (1H, dd, J = 16.7, 3.9 Hz), 3.21 (1H, dd, J = 16.7, 5.3 Hz), 3.70 (2H, m), 4.11-4.35 (4H, m), 4.66 (1H, m), 5.40 (1H, m), 5.89 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.98 (1H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.5 Hz). ESI-MS m/z: 481 [M + H]+ 459 [00896]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (1H, m), 3.04 (2H, dt, J = 4.5, 17.4 Hz), 3.17 (1H, dd, J = 5.5 16.6 Hz), 3.89-3.98 (4H, m), 4.16-4.21 (3H, m), 4.32 (1H, dt, J = 4.0, 9.3 Hz), 4.62 (1H, m), 5.41 (1H, m), 5.88 (1H, tt, J = 4.5, 56.3 Hz), 5.92 (1H, s), 6.84 (1H, d, J = 8.4 Hz), 6.93 (1H, s), 7.01 (2H, d, J = 8.0 Hz). ESI-MS m/z: 462 [M + H]+ 460 [00897]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.52 (2H, m), 1.02 (1H, m), 2.16 (2H, m), 2.88 (1H, m), 3.20 (1H, dd, J = 5.0, 16.9 Hz), 3.26 (2H, d, J = 6.6 Hz), 3.62 (2H, m), 3.93 (3H, s), 4.00 (1H, m), 4.21 (2H, s), 4.33 (1H, m), 4.64 (1H, m), 5.44 (1H, m), 5.89 (1H, s), 6.87 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.5 Hz), 7.15 (1H, m), 7.22 (1H, d, J = 8.3 Hz), 7.51 (1H, s), 7.67 (1H, s). ESI-MS m/z: 464 [M + H]+ 461 [00898]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.53 (2H, m), 1.02 (1H, m), 2.16 (2H, m), 2.89 (1H, m), 3.19-3.27 (3H, m), 3.62 (2H, m), 3.93 (3H, s), 3.99 (1H, m), 4.22 (2H, m), 4.32 (1H, m), 4.64 (1H, m), 5.44 (1H, m), 5.88 (1H, s), 6.44 (1H, d, J = 2.1 Hz), 6.89 (1H, d, J = 8.2 Hz), 7.02 (1H, d, J = 7.8 Hz), 7.35 (1H, d, J = 2.0 Hz), 7.51- 7.53 (2H, m). ESI-MS m/z: 464 [M + H]+ [00899]![text missing or illegible when filed]()
TABLE-US-00061 TABLE 61 Ex- am- ple Structural formula NMR MS 462 [00900]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.82-2.92 (3H, m), 3.16 (1H, dd, J = 5.0, 16.5 Hz), 4.08-4.24 (7H, m), 4.36 (1H, m), 4.61 (1H, m), 5.46 (1H, m), 5.93 (1H, s), 6.36 (1H, dt, J = 5.6, 109.3 Hz), 6.82 (1H, d, J = 8.3 Hz), 6.90 (1H, s), 6.97-7.03 (2H, m). ESI-MS m/z: 478 [M + H]+ 463 [00901]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.15-0.21 (2H, m), 0.51-0.62 (4H, m), 0.86-0.91 (2H, m), 1.02 (1H, m), 1.81 (1H, m), 2.81 (1H, d, J = 15.6 Hz), 3.14 (1H, m), 3.37 (2H, dd, J = 2.7, 6.9 Hz), 3.73-3.82 (2H, m), 4.14- 4.19 (3H, m), 4.29 (1H, dt, J = 4.0, 9.2 Hz), 4.60 (1H, m), 5.40 (1H, m), 5.90 (1H, m), 6.76-6.78 (2H, m), 6.84 (1H, dd, J = 2.0, 8.4 Hz), 7.02 (1H, m). ESI-MS m/z: 410 [M + H]+ 464 [00902]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.63-1.72 (2H, m), 1.77-1.93 (2H, m), 1.96-2.04 (2H, m), 2.53 (1H, m), 2.90 (1H, m), 3.17 (1H, dd, J = 5.1, 16.7 Hz), 3.47-3.50 (2H, m), 3.74-3.75 (2H, m), 4.17 (1H, m), 4.23- 4.31 (3H, m), 4.64 (1H, m), 5.39 (1H, m), 5.91 (1H, s), 6.91-6.94 (2H, m), 7.36 (1H, s), 7.42 (1H, d, J = 8.5 Hz). ESI-MS m/z: 409 [M + H]+ 465 [00903]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.72 (2H, m), 1.02 (2H, m), 2.17 (2H, m), 2.89 (1H, dd, J = 17.3, 4.5 Hz), 3.17 (1H, dd, J = 17.3, 5.1 Hz), 3.47 (1H, dd, J = 10.8, 6.4 Hz), 3.59 (1H, d, J = 10.6 Hz), 3.58-3.68 (2H, m), 4.01 (1H, dd, J = 9.8, 9.4 Hz), 4.24-4.29 (2H, m), 4.34 (1H, m), 4.65 (1H, m), 5.42 (1H, m), 5.89 (1H, s), 6.86-6.97 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 8.4, 2.0 Hz). ESI-MS m/z: 477 [M + H]+ 466 [00904]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.19 (2H, m), 2.84 (1H, d, J = 15.4 Hz), 3.03 (2H, t, J = 17.3 Hz), 3.16 (1H, dd, J = 4.7, 17.1 Hz), 3.80- 3.86 (4H, m), 3.96 (1H, m), 4.18 (2H, s), 4.35 (1H, m), 4.61 (1H, m), 5.43 (1H, m), 5.73-6.02 (2H, m), 6.83 (1H, dd, J = 1.6, 8.2 Hz), 6.93 (1H, s), 7.00 (2H, d, J = 8.3 Hz). ESI-MS m/z: 476 [M + H]+ 467 [00905]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.71 (2H, m), 1.01 (2H, m), 2.16 (2H, m), 2.97 (1H, dd, J = 16.9, 3.7 Hz), 3.27 (1H, dd, J = 16.9, 5.2 Hz), 3.47 (1H, dd, J = 11.0, 6.2 Hz), 3.55 (1H, dd, J = 11.0, 1.6 Hz), 3.57-3.69 (2H, m), 3.99 (1H, m), 4.24-4.29 (1H, m), 4.32 (1H, m), 4.58 (1H, m), 5.41 (1H, m), 5.59 (1H, s), 6.97-7.05 (2H, m), 7.78-7.82 (2H, m), 7.01 (1H, m), 8.45 (1H, d, J = 2.5 Hz), 8.58 (1H, t, J = 1.8 Hz), 8.96 (1H, d, J = 1.2 Hz). ESI-MS m/z: 530 [M + H]+ 468 [00906]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.15-0.20 (2H, m), 0.50-0.57 (2H, m), 1.02 (1H, m), 2.95 (1H, m), 3.25 (1H, dd, J = 4.7, 16.6 Hz), 3.36 (2H, t, J = 6.6 Hz), 3.75-3.81 (2H, m), 4.05 (3H, s), 4.18 (1H, m), 4.25-4.33 (3H, m), 4.67 (1H, m), 5.41 (1H, m), 5.92 (1H, s), 6.98 (1H, d, J = 6.4 Hz), 7.03 (1H, m), 7.19 (1H, s), 7.29 (1H, m), 8.66 (2H, s). ESI-MS m/z: 478 [M + H]+ 469 [00907]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.15-0.21 (2H, m), 0.51-0.57 (2H, m), 1.02 (1H, m), 2.84 (1H, d, J = 16.6 Hz), 3.15 (1H, dd, J = 5.4, 16.6 Hz), 3.37 (2H, dd, J = 3.2, 6.9 Hz), 3.74-3.82 (2H, m), 4.15-4.19 (3H, m), 4.30 (1H, m), 4.61 (1H, m), 5.41 (1H, m), 5.92 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 7.00-7.09 (3H, m). ESI-MS m/z: 404 [M + H]+ 470 [00908]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.49 (1H, m), 1.69 (1H, m), 1.82-1.89 (2H, m), 2.08-2.19 (4H, m), 2.90 (1H, m), 3.17 (1H, m), 3.50 (2H, t, J = 5.5 Hz), 3.69 (1H, t, J = 7.3 Hz), 4.00 (1H, t, J = 8.4 Hz), 4.27-4.35 (3H, m), 4.54 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.92 (2H, d, J = 8.4 Hz), 7.38-7.43 (2H, m). ESI-MS m/z: 409 [M + H]+ [00909]![text missing or illegible when filed]()
TABLE-US-00062 TABLE 62 Ex- am- ple Structural formula NMR MS 471 [00910]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.51 (1H, m), 1.69 (1H, m), 1.82-1.90 (2H, m), 2.05- 2.21 (4H, m), 2.85 (1H, dd, J = 3.9, 16.4 Hz), 3.06 (2H, dt, J = 4.5, 26.1 Hz), 3.17 (1H, dd, J = 5.4, 16.5 Hz), 3.48-3.50 (2H, m), 3.90 (1H, m), 3.99 (1H, m), 4.19 (2H, s), 4.33 (1H, m), 4.62 (1H, m), 5.41 (1H, m), 5.73-6.02 (2H, m), 5.83 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.00 (2H, d, J = 8.2 Hz). ESI-MS m/z: 448 [M + H]+ 472 [00911]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.49 (1H, m), 1.70 (1H, m), 1.83-1.90 (2H, m), 2.07- 2.19 (4H, m), 2.85 (1H, m), 3.18 (1H, m), 3.49-3.51 (2H, m), 3.81 (2H, q, J = 8.8 Hz), 3.89 (1H, t, J = 7.1 Hz), 3.99 (1H, m), 4.20 (2H, s), 4.32 (1H, dt, J = 4.2, 9.0 Hz), 4.56 (2H, s), 4.63 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.87 (1H, d, J = 8.5 Hz), 7.00 (1H, d, J = 7.7 Hz), 7.04 (1H, s), 7.11 (1H, d, J = 6.2 Hz). ESI-MS m/z: 496 [M + H]+ 473 [00912]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.50 (1H, m), 1.68 (1H, m), 1.80-1.89 (2H, m), 2.04-2.21 (4H, m), 2.58 (1H, dd, J = 3.9, 16.7 Hz), 3.20 (1H, dd, J = 5.3, 16.7 Hz), 3.48-3.51 (2H, m), 3.88-4.01 (5H, m), 4.21 (2H, d, J = 2.8 Hz), 4.32 (1H, m), 4.54 (1H, m), 5.42 (1H, m), 5.89 (1H, s), 6.87 (1H, d, J = 8.4 Hz), 7.04 (1H, d, J = 8.1 Hz), 7.14 (1H, d, J = 1.3 Hz), 7.23 (1H, dd, J = 2.2, 8.4 Hz), 7.51 (1H, s), 7.67 (1H, s). ESI-MS m/z: 464 [M + H]+ 474 [00913]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.51 (1H, m), 1.68 (1H, m), 1.82-1.89 (2H, m), 2.05- 2.21 (4H, m), 2.97 (1H, m), 3.27 (1H, m), 3.48-3.51 (2H, m), 3.89 (1H, m), 3.98 (1H, m), 4.27-4.35 (3H, m), 4.68 (1H, m), 5.42 (1H, m), 5.89 (1H, s), 6.99-7.02 (2H, m), 7.78-7.80 (2H, m), 8.45 (1H, d, J = 2.5 Hz), 8.58 (1H, t, J = 2.0 Hz), 8.96 (1H, d, J = 1.4 Hz). ESI-MS m/z: 462 [M + H]+ 475 [00914]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.51 (1H, m), 1.69 (1H, m), 1.82-1.89 (2H, m), 2.05- 2.18 (4H, m), 2.50-2.59 (3H, m), 2.96 (1H, m), 3.25 (1H, dd, J = 5.3, 16.8 Hz), 3.48-3.50 (2H, m), 3.89 (1H, m), 3.98 (1H, m), 4.20-4.34 (3H, m), 4.67 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.97-7.03 (2H, m), 7.73-7.75 (2H, m), 8.45 (1H, s), 8.83 (1H, s). ESI-MS m/z: 476 [M + H]+ 476 [00915]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.98 (1H, m), 2.10 (1H, m), 2.21-2.32 (2H, m), 2.62 (1H, m), 2.69-2.76 (3H, m), 2.86-2.94 (3H, m), 3.20 (1H, dd, J = 5.1, 16.6 Hz), 3.93 (1H, t, J = 8.8 Hz), 4.26 (2H, s), 4.36 (1H, t, J = 9.0 Hz), 4.65 (1H, m), 5.49 (1H, m), 5.89 (1H, s), 6.93- 7.09 (2H, m), 7.33 (1H, s), 7.35 (1H, d, J = 8.6 Hz). ESI-MS m/z: 487 [M + H]+ 477 [00916]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.99 (1H, m), 2.11 (1H, m), 2.22-2.33 (2H, m), 2.63 (1H, m), 2.69-2.77 (3H, m), 2.86-2.93 (3H, m), 3.21 (1H, dd, J = 5.5, 16.8 Hz), 3.94 (1H, t, J = 9.0 Hz), 4.25 (2H, d, J = 2.6 Hz), 4.35 (1H, t, J = 9.1 Hz), 4.65 (1H, m), 5.39 (1H, m), 5.89 (1H, s), 6.93-6.96 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.6 Hz). ESI-MS m/z: 487 [M + H]+ 478 [00917]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17 (2H, m), 2.85 (1H, dd, J = 3.4, 16.7 Hz), 3.03 (2H, td, J = 4.3, 17.4 Hz), 3.17 (1H, dd, J = 5.2, 16.7 Hz), 3.63-3.75 (4H, m), 3.97 (1H, m), 4.19 (2H, s), 4.34 (1H, m), 4.61 (1H, m), 5.43 (1H, m), 5.70-6.03 (3H, m), 6.83 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.01 (2H, d, J = 8.0 Hz). ESI-MS m/z: 458 [M + H]+ 479 [00918]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (2H, m), 2.86 (1H, m), 3.15-3.30 (3H, m), 3.63- 3.75 (4H, m), 3.97 (1H, m), 4.20 (2H, s), 4.35 (1H, m), 4.62 (1H, m), 5.43 (1H, m), 5.84 (1H, m), 5.90 (1H, s), 6.85 (1H, d, J = 8.4 Hz), 6.97-7.06 (3H, m). ESI-MS m/z: 476 [M + H]+ [00919]![text missing or illegible when filed]()
TABLE-US-00063 TABLE 63 Ex- am- ple Structural formula NMR MS 480 [00920]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.88 (1H, m), 2.03- 2.25 (3H, m), 2.86 (1H, m), 3.16 (1H, m), 4.14 (1H, t, J = 12.3 Hz), 4.20 (2H, d, J = 2.9 Hz), 4.40 (1H, d, J = 14.4 Hz), 4.59- 4.69 (2H, m), 5.26 (1H, s), 6.82 (1H, m), 7.00-7.05 (2H, m), 7.09 (1H, d, J = 5.7 Hz), 7.35-7.41 (6H, m). ESI-MS m/z: 424 [M + H]+ 481 [00921]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.58 (2H, m), 2.06 (2H, m), 2.76-2.81 (1H, m), 3.06-3.13 (1H, m), 4.04 (2H, m), 4.15 (2H, m), 4.26 (2H, m), 4.57 (1H, m), 6.77 (1H, m), 6.92 (1H, d, J = 8.20 Hz), 7.00 (1H, s), 7.07 (1H, d, J = 8.20 Hz), 7.27 (1H, m), 7.13-7.35 (2H, m), 7.44-7.47 (2H, m). ESI-MS m/z: 424 [M + H]+ 482 [00922]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.05-2.07 (2H, m), 2.88 (1H, m), 3.18 (1H, m), 3.83 (2H, q, J = 8.8 Hz), 3.91-4.16 (6H, m), 4.21 (2H, s), 4.43 (1H, m), 4.57 (2H, s), 4.61 (1H, m), 6.26 (1H, s), 6.88 (1H, d, J = 8.9 Hz), 7.01-7.05 (2H, m), 7.12 (1H, d, J = 7.9 Hz). ESI-MS m/z: 524 [M + H]+ 483 [00923]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91 (1H, m), 2.30 (1H, m), 2.82 (1H, m), 2.91 (1H, m), 3.18 (1H, m), 3.80 (1H, m), 4.09 (1H, m), 4.27- 4.29 (2H, m), 4.45 (1H, m), 4.56 (1H, ), 4.64 (1H, ), 6.28 (1H, s), 6.91-7.00 (2H, m), 7.39 (1H, s), 7.43 (1H, m). ESI-MS m/z: 407 [M + H]+ 484 [00924]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.96 (1H, m), 3.22 (1H, m), 3.91 (3H, s), 4.13 (2H, d, J = 4.9 Hz), 4.19 (2H, d, J = 5.0 Hz), 4.28 (2H, s), 4.66 (1H, m), 5.17 (2H, s), 6.60 (1H, d, J = 8.6 Hz), 6.95 (1H, d, J = 8.8 Hz), 7.34 (2H, s), 7.39 (1H, d, J = 8.6 Hz), 7.60 (1H, t, J = 7.9 Hz), 7.91 (1H, d, J = 7.5 Hz). ESI-MS m/z: 475 [M + H]+ 485 [00925]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.94-2.99 (1H, m), 3.20-3.26 (1H, m), 4.13 (2H, m), 4.18 (2H, m), 4.29 (2H, m), 4.64 (1H, m), 5.11 (2H, s), 6.96 (1H, m), 7.15 (1H, m), 7.35-7.41 (3H, m), 7.66 (1H, m), 8.34 (1H, m). ESI-MS m/z: 479 [M + H]+ 486 [00926]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.30-2.55 (2H, m), 2.94-2.95 (1H, m), 3.22-3.28 (1H, m), 4.15- 4.19 (2H, m), 4.30 (2H, m), 4.44-4.46 (2H, m), 4.69 (1H, m), 6.56 (1H, m), 6.97 (1H, d, J = 8.5 Hz), 7.44-7.58 (3H, m), 7.64-7.69 (2H, m). ESI-MS m/z: 434 [M + H]+ 487 [00927]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.88 (1H, m), 3.16- 3.25 (5H, m), 3.95 (2H, s), 4.13-4.16 (2H, m), 4.19-4.21 (2H, m), 4.64 (1H, m), 6.53 (1H, s), 6.87-6.92 (2H, m), 7.06 (2H, d, J = 7.7 Hz), 7.13 (1H, t, J = 7.8 Hz). ESI-MS m/z: 431 [M + H]+ 488 [00928]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.20-2.39 (3H, m), 2.65-2.74 (4H, m), 2.85-2.93 (3H, m), 3.19 (1H, dd, J = 5.1, 16.6 Hz), 3.66 (2H, s), 4.12 (2H, t, J = 5.6 Hz), 4.16-4.24 (2H, m), 4.64 (1H, m), 6.51 (1H, s), 6.87-6.92 (2H, m), 7.04-7.07 (2H, m), 7.13 (1H, t, J = 7.7 Hz). ESI-MS m/z: 403 [M + H]+ [00929]![text missing or illegible when filed]()
TABLE-US-00064 TABLE 64 Ex- am- ple Structural formula NMR MS 489 [00930]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.92 (1H, dd, J = 4.8, 16.5 Hz), 3.15-3.26 (5H, m), 3.96 (2H, s), 4.16 (2H, t, J = 5.5 Hz), 4.24-4.32 (2H, m), 4.64 (1H, m), 6.54 (1H, s), 6.92-6.96 (2H, m), 7.39-7.44 (2H, m) ESI-MS m/z: 456 [M + H]+ 490 [00931]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.15-0.23 (4H, m), 0.38-0.48 (4H, m), 0.63-0.68 (2H, m), 1.28 (1H, m), 2.62 (2H, d, J = 6.6 Hz), 2.59-2.63 (3H, m), 3.18 (1H, m), 3.68 (2H, s), 4.11 (2H, t, J = 5.5 Hz), 4.18-4.22 (2H, m), 4.63 (1H, m), 6.49 (1H, s), 6.86-6.91 (2H, m), 7.04-7.07 (2H, m), 7.12 (1H, t, J = 8.0 Hz). ESI-MS m/z: 407 [M + H]+ 491 [00932]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.06 (2H, q, J = 5.0 Hz), 0.44-0.48 (2H, m), 0.70 (1H, m), 1.45 (2H, q, J = 7.3 Hz), 2.65 (2H, t, J = 7.6 Hz), 2.89-2.94 (3H, m), 3.17 (1H, dd, J = 5.5, 16.8 Hz), 3.68 (2H, s), 4.13 (2H, t, J = 6.6 Hz), 4.22-4.32 (2H, m), 4.64 (1H, m), 8.51 (1H, s), 6.92-6.95 (2H, m), 7.38-7.43 (2H, m). ESI-MS m/z: 392 [M + H]+ 492 [00933]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.91 (1H, m), 3.00 2H, m), 3.19 (1H, m), 3.75 (2H, d, J = 4.9 Hz), 3.87 (2H, d, J = 5.4 Hz), 4.15 (2H, m), 4.23 (2H, m), 4.63 (1H, m), 6.40-6.70 (2H, m), 6.92 (1H, t, J = 7.8 Hz), 7.01 (1H, m), 7.23 (3H, m), 7.41 (1H, t, J = 5.8 Hz), 7.69 (1H, m), 8.58 (1H, m). ESI-MS m/z: 440 [M + H]+ 493 [00934]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (1H, dd, J = 3.9, 16.9 Hz), 3.01-3.03 (4H, m), 3.06-3.18 (1H, m), 3.80 (2H, s), 4.15 (2H, t, J = 5.5 Hz), 4.19 (2H, d, J = 2.8 Hz), 4.61 (1H, m), 6.54 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 7.01-7.10 (3H, m). 494 [00935]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.88 (1H, m), 1.27 (2H, m), 1.99 (1H, m), 2.47 (2H, m), 2.66 (1H, m), 2.85-3.08 (4H, m), 3.16 (1H, m), 3.71 (2H, s), 4.13-4.32 (3H, m), 4.63 (1H, m), 6.52 (1H, d, J = 11.3 Hz), 6.82 (1H, m), 7.05 (2H, m), 7.29 (1H, s). ESI-MS m/z: 437 [M + H]+ 495 [00936]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.69 (2H, m), 0.68 (2H, m), 1.40 (1H, m), 2.86 (1H, dd, J = 4.2, 17.1 Hz), 2.99 (2H, t, J = 13.2 Hz), 3.15 (3H, m), 3.91 (2H, s), 4.14 (2H, t, J = 5.5 Hz), 4.19 (2H, d, J = 3.0 Hz), 4.62 (1H, m), 6.52 (1H, s), 6.81 (1H, d, J = 8.6 Hz), 7.01-7.10 (3H, m). ESI-MS m/z: 437 [M + H]+ 496 [00937]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.58-1.66 (4H, m), 1.76-1.91 (2H, m) 2.05 (2H, m, 2.30 (1H, m), 2.44 (2H, m), 2.88-2.94 (3H, m), 3.17 1H, dd, J = 5.2, 18.7 Hz), 3.65 (2H, s), 4.12 (2H, t, J = 6.5 Hz), 4.22-4.32 (2H, m), 4.64 (1H, m), 6.51 (1H, s), 6.92-6.96 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 2.1, 8.5 Hz). ESI-MS m/z: 406 [M + H]+ 497 [00938]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.91 (1H, dd, J = 4.5, 16.3 Hz), 2.97 (2H, t, J = 6.0 Hz), 3.17 (1H, dd, J = 6.2, 16.7 Hz), 3.72 (2H, s), 3.79 (2H, s), 4.13 (2H, t, J = 6.2 Hz), 4.22-4.32 (2H, m), 4.63 (1H, m), 6.50 (1H, s), 6.92 (1H, d, J = 8.5 Hz), 6.95 (1H, d, J = 7.8 Hz), 7.07 (1H, m), 7.14 (1H, td, J = 1.1, 7.5 Hz), 7.29 (1H, m), 7.37-7.43 (3H, m). ESI-MS m/z: 432 [M + H]+ [00939]![text missing or illegible when filed]()
TABLE-US-00065 TABLE 65 Ex- am- ple Structural formula NMR MS 498 [00940]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.72 (2H, m), 181-1.97 (2H, m), 2.10 (2H, m), 2.53-2.63 (3H, m), 2.86-2.96 (3H, m), 3.17 (1H, dd, J = 5.2, 16.5 Hz), 3.63 (2H, s), 4.11 (2H, t, J = 5.6 Hz), 4.22-4.32 (2H, m), 4.64 (1H, m), 6.50 (1H, s), 5.93 (1H, d, J = 8.5 Hz), 5.95 (1H, s), 7.38 (1H, s), 7.42 (1H, dd, J = 2.0, 8.5 Hz). ESI-MS m/z: 392 [M + H]+ 499 [00941]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.89-2.97 (3H, m), 3.18 (1H, dd, J = 5.2, 16.7 Hz), 3.79 (2H, s), 3.89 (2H, s), 4.14 (2H, t, J = 5.4 Hz), 4.23-4.33 (2H, m), 4.65 (1H, m), 6.50 (1H, s), 8.93 (1H, d, J = 8.5 Hz), 6.97 (1H, d, J = 7.8 Hz), 7.38-7.43 (3H, m), 7.54 (1H, t, J = 7.6 Hz), 7.67 (1H, d, J = 7.8 Hz), 7.75 (1H, d, J = 7.8 Hz). ESI-MS m/z: 482 [M + H]+ 500 [00942]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.14 (4H, m), 2.84 (1H, dd, J = 4.5, 17.0 Hz), 3.14 (1H, dd, J = 5.3, 16.9 Hz), 3.24 (2H, t, J = 5.3 Hz, 3.96 (2H, s), 4.07 (2H, t, J = 5.5 Hz), 4.14-4.21 (2H, m), 4.60 (1H, m), 6.47 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 5.97-7.08 (3H, m), 7.17 (1H, m), 7.25 (1H, s), 7.65 (1H, td, J = 1.8, 7.7 Hz), 8.58 (1H, d, J = 3.9 Hz). ESI-MS m/z: 450 [M + H]+ 501 [00943]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.50 (6H, s), 2.84 (2H, t, J = 5.2 Hz), 2.92 (1H, dd, J = 5.0, 16.7 Hz), 3.17 (1H, dd, J = 5.1, 16.7 Hz), 3.86 (1H, s), 4.04 (2H, t, J = 5.2 Hz), 4.23-4.32 (2H, m), 4.64 (1H, m), 6.51 (1H, s), 6.92- 6.96 (2H, m), 7.17 (1H, q, J = 3.7 Hz), 7.38 (1H, s), 7.42 (1H, d, J = 8.6 Hz), 7.66 (2H, d, J = 3.7 Hz), 8.57 (1H, d, J = 4.6 Hz). ESI-MS m/z: 443 [M + H]+ 502 [00944]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.04 (2H, m), 0.47 (2H, m), 0.73 (1H, m), 1.17 (6H, s), 1.41 (2H, d, J = 6.4 Hz), 2.91 (1H, dd, J = 4.9, 16.4 Hz), 2.98 (2H, t, J = 5.8 Hz), 3.17 (1H, dd, J = 5.2, 16.5 Hz), 3.83 (2H, s), 4.08 (2H, t, J = 5.4 Hz), 4.22-4.33 (2H, m), 4.64 (1H, m), 5.91 (1H, s), 6.92-6.96 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 1.7, 8.5 Hz). ESI-MS m/z: 420 [M + H]+ 503 [00945]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25-2.38 (2H, m), 2.91 (1H, dd, J = 4.9, 16.5 Hz), 3.12-3.20 (3H, m), 3.89 (2H, s), 4.03 (1H, t, J = 5.2 Hz), 4.23-4.31 (3H, m), 4.64 (1H, m), 6.51 (1H, s), 6.92-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, d, J = 8.4 Hz). ESI-MS m/z: 446 [M + H]+ 504 [00946]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.06 (2H, q, J = 5.0 Hz), 0.43-0.48 (2H, m), 0.71 (1H, m), 1.45 (2H, t, J = 7.4 Hz), 2.54 (2H, t, J = 7.6 Hz), 2.84-2.93 (3H, m), 3.06 (2H, dt, J = 4.5, 26.1 Hz), 3.17 (1H, dd, J = 5.5, 16.7 Hz), 3.68 (2H, s), 4.11-4.23 (4H, m), 4.63 (1H, m), 5.88 (1H, m), 6.51 (1H, s), 6.84 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.08-7.05 (2H, m). ESI-MS m/z: 431 [M + H]+ 505 [00947]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.06-0.07 (2H, m), 0.45-0.47 (2H, m), 0.70 (1H, m), 1.45 (2H, q, J = 7.4 Hz), 2.64 (2H, t, J = 7.6 Hz), 2.86- 2.93 (3H, m), 3.18 (1H, m), 3.68 (2H, s), 3.81 (2H, t, J = 8.8 Hz), 4.13 (2H, t, J = 5.6 Hz), 4.20-4.24 (2H, m), 4.57 (2H, s), 4.64 (1H, m), 6.51 (1H, s), 6.87 (1H, d, J = 8.6 Hz), 7.02-7.05 (2H, m), 7.11 (1H, d, J = 8.1 Hz). ESI-MS m/z: 479 [M + H]+ 506 [00948]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.32-2.44 (2H, m), 2.80-2.84 (2H, m), 2.90-2.97 (3H, m), 3.18- 3.22 (1H, m), 3.72 (2H, s), 4.11-4.16 (2H, m), 4.26 (2H, m), 4.66 (1H, m), 6.53 (1H, s), 6.93-7.00 (2H, m), 7.33 (1H, s), 7.39- 7.45 (1H, m). ESI-MS m/z: 463 [M + H]+ [00949]![text missing or illegible when filed]()
TABLE-US-00066 TABLE 66 Ex- am- ple Structural formula NMR MS 507 [00950]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.32-2.45 (2H, m), 2.77-2.90 (3H, m), 2.95 (2H, m), 3.16- 3.21 (1H, m), 3.72 92H, s), 3.78-3.88 (2H, m), 4.10-4.17 (2H, m), 4.21 (2H, m), 4.57 (2H, s), 4.84 (1H, m), 6.53 (1H, s), 8.88 (1H, d, J = 8.3 Hz), 7.00- 7.05 (2H, m), 7.12 (1H, d, J = 8.3 Hz). ESI-MS m/z: 507 [M + H]+ 508 [00951]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.89 (1H, m), 3.21 (1H, m), 3.65 (2H, t, J = 5.5 Hz), 4.21- 4.23 (4H, m), 4.36 (2H, s), 4.65 (1H, m), 6.63 (1H, s), 6.87-6.95 (4H, m), 6.98-7.16 (5H, m). ESI-MS m/z: 393 [M + H]+ 509 [00952]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.77 (1H, m), 3.06-3.23 (5H, m), 3.86 (2H, s), 4.10- 4.24 (4H, m), 4.56 (1H, m), 5.77 (1H, d, J = 8.7 Hz), 6.90 (1H, d, J = 8.6 Hz), 7.00 (1H, m), 7.07 (1H, dd, J = 2.3, 8.5 Hz), 7.30-7.37 (5H, m). ESI-MS m/z: 491 [M + H]+ 510 [00953]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.71 (2H, q, J = 6.1 Hz), 2.88 (1H, m), 297-3.01 (2H, m), 3.20 (1H, dd, J = 5.5, 16.8 Hz), 3.77 (1H, m), 3.99-4.09 (3H, m), 4.21 (2H, d, J = 3.0 Hz), 4.59 (1H, s), 4.64 (1H, m), 4.80 (1H, s), 6.56 (1H, m), 6.87-6.92 (2H, m), 7.06-7.07 (2H, m), 7.12-7.24 (6H, m). ESI-MS m/z: 431 [M + H]+ 511 [00954]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.87 (1H, dd, J = 4.1, 16.5 Hz), 3.19 (1H, dd, J = 5.3, 16.6 Hz), 3.82 (2H, t, J = 5.5 Hz), 4.19- 4.21 (4H, m), 4.50 (2H, s), 4.63 (1H, m), 6.58 (1H, s), 6.87-6.92 (2H, m), 7.04-7.07 (2H, m), 7.14 (1H, m), 7.75- 7.78 (2H, m), 7.93 (1H, m), 8.23 (1H, m) ESI-MS m/z: 507 [M + H]+ 512 [00955]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.37 (3H, s), 2.97 (1H, m), 3.23 (1H, dd, J = 4.9, 16.8 Hz), 4.09-4.18 (2H, m), 4.20-4.21 (2H, m), 4.28 (2H, s), 4.66 (1H, m), 4.82 (2H, s), 6.33 (1H, s), 6.96 (1H, d, J = 8.5 Hz), 7.34 (1H, s), 7.39 (1H, d, J = 8.2 Hz), 7.48 (1H, s), 7.63 (1H, d, J = 7.8 Hz). ESI-MS m/z: 448 [M + H]+ 513 [00956]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.94-2.99 (1H, m), 3.20-3.25 (1H, s), 4.12 (2H, m), 4.18-4.21 (2H, m), 4.29 (2H, m), 4.64- 4.69 (1H, m), 5.12 (2H, s), 6.73-6.77 (1H, m), 6.95-7.00 (1H, m), 7.35-7.43 (3H, m), 7.76-7.82 (1Hm), 8.24-8.29 (1H, m). ESI-MS m/z: 463 [M + H]+ 514 [00957]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.94-2.99 (1H, m), 3.20-3.25 (1H, m), 4.13 (2H, m), 4.18 (2H, m), 4.29 (2H, m), 4.62-4.70 (1H, m), 5.11 (2H, s), 6.95-6.99 (1H, m), 7.14-7.16 (1H, m), 7.35-7.41 (3H, m), 7.64-7.68 (1H, m), 8.32-8.35 (1H, m). ESI-MS m/z: 479 [M + H]+ 515 [00958]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.87-2.90 (1H, m), 3.10-3.19 (1H, m), 4.06-4.28 (8H, m), 4.46-4.51 (1H, m), 5.00 (2H, s), 6.73- 6.82 (1H, m), 7.00-7.11 (3H, m), 7.69- 7.79 (2H, m), 8.30 (1H, m), 8.81 (1H, m). ESI-MS m/z: 411 [M + H]+ [00959]![text missing or illegible when filed]()
TABLE-US-00067 TABLE 67 Ex- am Structural formula NMR MS ple 516 [00960]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.30 (3H, t, J = 7.60 Hz), 2.79 (2H, t, J = 7.60 Hz), 2.92-2.97 (1H, m), 3.15-3.21 (1H, m), 4.13-4.20 (4H, m), 4.23-4.33 (2H, m), 4.64 (1H, m), 5.08 (2H, s), 6.91-6.93 (1H, m), 7.00-7.02 (1H, m), 7.36-7.43 (2H, m), 7.55-7.58 (1H, m), 7.60-7.64 (1H, m), 7.90-7.92 (1H, m). ESI-MS m/z: 430 [M + H]+ 517 [00961]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.91 (1H, dd, J = 3.3, 16.9 Hz), 3.17 (1H, dd, J = 5.3, 17.0 Hz), 4.11-4.28 (8H, m), 4.62 (1H, m), 4.87 (2H, s), 6.91 (1H, d, J = 8.6 Hz), 7.07 (1H, d, J = 7.8 Hz), 7.31 (1H, s), 7.36 (1H, d, J = 8.5 Hz), 7.41 (1H, m), 7.73 (1H, dd, J = 1.7, 8.4 Hz), 7.82 (1H, d, J = 8.4 Hz), 7.86 (1H, s), 8.16 (1H, d, J = 7.5 Hz), 8.91 (1H, m). ESI-MS m/z: 495 [M + H]+ 518 [00962]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.99 (1H, m), 3.23 (1H, dd, J = 5.7, 17.1 Hz), 3.78 (3H, s), 4.10-4.12 (2H, m), 4.22-4.24 (2H, m), 4.26-4.35 (2H, m), 4.71 (1H, m), 4.97 (2H, s), 6.63 (1H, d, J = 2.3 Hz), 6.93 (1H, d, J = 8.4 Hz), 7.31- 7.38 (3H, m), 8.62 (1H, d, J = 7.9 Hz). ESI-MS m/z: 448 [M + H]+ 519 [00963]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.97 (1H, dd, J = 4.0, 16.7 Hz), 3.22 (1H, dd, J = 5.3, 16.9 Hz), 3.46 (1H, m), 4.10-4.15 (2H, m), 4.19-4.21 (2H, m), 4.28 (2H, m), 4.65 (1H, m), 4.75 (2H, s), 5.04 (2H, s), 6.95 (1H, d, J = 8.6 Hz), 7.11 (1H, d, J = 7.7 Hz), 7.34-7.40 (3H, m), 7.72 (1H, t, J = 7.8 Hz), 8.08 (1H, d, J = 7.8 Hz). ESI-MS m/z: 475 [M + H]+ 520 [00964]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.96 (1H, dd, J = 4.2, 16.8 Hz), 3.22 (1H, dd, J = 5.3, 16.7 Hz), 3.94 (2H, m), 4.11-4.14 (2H, m), 4.18-4.21 (2H, m), 4.28 (2H, d, J = 3.2 Hz), 4.65 (1H, m), 4.75 (2H, s), 5.05 (2H, s), 6.95 (1H, d, J = 8.6 Hz), 7.29 (1H, d, J = 7.6 Hz), 7.34 (1H, s), 7.36-7.40 (2H, m), 7.75 (1H, t, J = 7.8 Hz), 8.18 (1H, d, J = 8.0 Hz). ESI-MS m/z: 557 [M + H]+ 521 [00965]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.55 (6H, s), 2.97 (1H, dd, J = 4.3, 16.8 Hz), 3.22 (1H, dd, J = 5.3, 16.8 Hz), 4.13-4.15 (2H, m), 4.18-4.21 (2H, m), 4.29 (2H, m), 4.58 (1H, s), 4.65 (1H, m), 5.05 (2H, s), 6.96 (1H, d, J = 8.5 Hz, 7.22 (1H, s), 7.25 (1H, dd, J = 0.8, 7.8 Hz), 7.35 (1H, s), 7.39 (1H, d, J = 6.9 Hz), 7.74 (1H, t, J = 7.9 Hz), 8.13 (1H, dd, J = 0.8, 7.9 Hz). ESI-MS m/z: 503 [M + H]+ 522 [00966]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.97 (1H, dd, J = 4.5, 17.0 Hz), 3.21 (1H, dd, J = 5.3, 16.8 Hz), 3.46 (2H, s), 4.11-4.28 (7H, m), 4.54-4.68 (3H, m), 5.06 (2H, s), 6.95 (1H, d, J = 8.5 Hz), 7.26-7.28 (1H, m), 7.34 (1H, s), 7.36 (1H, m), 7.50 (1H, d, J = 7.7 Hz), 7.73 (1H, t, J = 7.8 Hz), 6.07 (1H, d, J = 7.9 Hz). ESI-MS m/z: 489 [M + H]+ 523 [00967]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.97 (1H, dd, J = 4.3, 16.8 Hz), 3.23 (1H, dd, J = 5.4, 16.7 Hz), 3.65 (2H, m), 4.11-4.14 (2H, m), 4.18-4.20 (2H, m), 4.29 (2H, d, J = 3.3 Hz), 4.65 (1H, m), 5.07 (2H, s), 6.98 (1H, d, J = 8.6 Hz), 7.15 (1H, d, J = 7.8 Hz), 7.30 (1H, d, J = 9.0 Hz), 7.35 (1H, s), 7.39 (1H, d, J = 8.5 Hz), 7.71 (1H, t, J = 7.8 Hz), 8.31 (1H, d, J = 8.0 Hz). ESI-MS m/z: 527 [M + H]+ 524 [00968]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18 (2H, m), 2.50 (3H, s), 2.93-2.99 (1H, m), 3.19-3.25 (1H, t, J = 7.34 Hz), 3.46 (2H, m), 4.09 (2H, m), 4.21-4.33 (2H, m), 4.62-4.69 ( 1H, m), 6.85 (1H, m), 6.95 (1H, m), 7.23 (1H, m), 7.21-7.38 (2H, m), 7.47 (1H, s), 7.54 (1H, m), 8.32 (1H, m). ESI-MS m/z: 458 [M + H]+ [00969]![text missing or illegible when filed]()
TABLE-US-00068 TABLE 68 Ex- am- ple Structural formula NMR MS 525 [00970]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.20 (2H, m), 289-2.94 (1H, m), 3.15-3.23 (1H, m), 3.44 (2H, m), 3.78-3.86 (2H, m), 4.07-4.11 (2H, m), 4.24 (2H, m), 4.59 (2H, s), 4.60-4.66 (2H, m), 6.83-6.88 (1H, m), 6.96-6.99 (1H, m), 7.04- 7.06 (1H, m), 7.10-7.21 (1H, m), 7.31-7.40 (2H, m), 7.62-7.66 (1H, m), 8.40-8.41 (1H, m), 8.51-8.53 (1H, m). ESI-MS m/z: 488 [M + H]+ 526 [00971]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.96 (1H, d, J = 16.8 Hz), 3.24 (1H, d, J = 16.1 Hz), 3.90 (2H, s), 4.19-4.43 (6H, m), 4.69 (1H, s), 6.96 (1H, d, J = 8.0 Hz), 7.30- 7.62 (6H, m). ESI-MS m/z: 529 [M + H]+ 527 [00972]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.97 (1H, m), 3.23 (1H, m), 4.07-4.37 (6H, m), 4.65 (1H, m), 4.92-5.09 (4H, m), 6.97 (1H, d, J = 8.5 Hz), 7.26-7.41 (4H, m), 7.82 (1H, t, J = 7.6 Hz), 8.31 (1H, m). ESI-MS m/z: 543 [M + H]+ 528 [00973]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.03 (2H, m), 2.87 (1H, d, J = 16.1 Hz), 3.18 (1H, dd, J = 5.8, 16.5 Hz), 4.05 (2H, m), 4.21 (1H, d, J = 5.5 Hz), 4.28 (1H, m), 4.54 (2H, m), 4.68 (3H, m), 6.94 (1H, d, J = 8.5 Hz), 7.14 (1H, m), 7.32 (1H, s), 7.39 (1H, d, J = 8.3 Hz), 7.48 (1H, d, J = 7.9 Hz), 7.71 (1H, td, J = 1.8, 7.8 Hz), 8.19 (1H, d, J = 4.1 Hz), 8.84 (1H, d, J = 7.6 Hz). ESI-MS m/z: 459 [M + H]+ 529 [00974]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.86 (1H, d, J = 4.8 Hz), 3.91 (3H, s), 4.13-4.15 (2H, m), 4.21-4.27 (3H, m), 4.38 (1H, dd, J = 3.8, 11.0 Hz), 4.67 (1H, m), 4.96 (1H, t, J = 8.1 Hz), 5.18 (2H, d, J = 3.0 Hz), 6.61 (1H, d, J = 7.7 Hz), 6.98 (1H, d, J = 8.8 Hz), 7.49 (1H, d, J = 10.6 Hz), 7.66 (1H, d, J = 7.7 Hz), 7.80 (1H, t, J = 7.9 Hz), 7.68 (1H, d, J = 1.6 Hz), 7.87 (1H, d, J = 7.8 Hz). ESI-MS m/z: 491 [M + H]+ 530 [00975]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.92 (1H, m), 3.22 (1H, m), 4.01-4.13 (4H, m), 4.26 (2H, d, J = 12.7 Hz), 4.59-4.65 (2H, m), 4.82 (1H, d, J = 15.4 Hz), 6.02 (1H, s), 6.53 (1H, m), 6.95 (1H, d, J = 8.2 Hz), 7.16 (1H, s), 7.27-7.40 (3H, m), 7.68 (2H, s), 8.45 (1H, s). ESI-MS m/z: 475 [M + H]+ 531 [00976]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.96 (1H, dd, J = 4.1, 16.6 Hz), 3.07 (4H, s), 3.23 (1H, dd, J = 5.4, 16.7 Hz), 3.93-3.96 (2H, m), 4.02-4.05 (2H, m), 4.28 (2H, m), 4.35 (2H, s), 4.67 (1H, m), 6.96 (1H, d, J = 8.6 Hz), 7.06-7.12 (3H, m), 7.35 (1H, s), 7.39 (1H, d, J = 8.6 Hz), 7.53 (1H, td, J = 1.8, 7.6 Hz), 8.52 (1H, m). ESI-MS m/z: 473 [M + H]+ 532 [00977]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.71 (2H, m), 1.11 (2H, m), 2.16-2.35 (2H, m), 2.90 (1H, dd, J = 16.8, 5.0 Hz), 3.17 (1H, dd, J = 16.5, 5.3 Hz), 3.77-3.84 (3H, m), 3.89 (1H, dd, J = 10.5, 5.1 Hz), 4.10 (1H, m), 4.16-4.33 (3H, m), 4.39 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.92 (1H, m), 6.93 (1H, d, J = 8.5 Hz), 7.39 (1H, m), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 427 [M + H]+ 533 [00978]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.11 (2H, m), 2.16-2.40 (2H, m), 2.92 (1H, dd, J = 16.8, 4.4 Hz), 3.19 (1H, dd, J = 16.7, 5.3 Hz), 3.72-3.84 (3H, m), 3.88 (1H, dd, J = 10.5, 5.1 Hz), 4.09 (1H, m), 4.16-4.29 (3H, m), 4.39 (1H, m), 4.55 (1H, m), 6.03 (1H, s), 6.95 (1H, d, J = 8.6 Hz), 6.97 (1H, m), 7.33 (1H, m), 7.38 (1H, d, J = 8.6 Hz). ESI-MS m/z: 470 [M + H]+ [00979]![text missing or illegible when filed]()
TABLE-US-00069 TABLE 69 Ex- am- ple Structural formula NMR MS 534 (iso- mer A) [00980]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.39 (2H, m), 3.18 (1H, s), 4.12 (1H, m), 4.18-4.26 (2H, m), 4.33-4.44 (2H, m), 4.63 (1H, m), 4.91 (1H, d, J = 3.5 Hz), 5.97 (1H, m), 6.10 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.30 (1H, d, J = 8.8 Hz), 7.48 (1H, dd, J = 2.1, 8.6 Hz), 7.58 (1H, d, J = 1.6 Hz). ESI-MS m/z: 434 [M + H]+ 534 (iso- mer B) [00981]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.24-2.39 (2H, m), 3.12 (1H, s), 4.12 (1H, m), 4.23-4.32 (2H, m), 4.34-4.46 (2H, m), 4.50 (1H, dd, J = 2.2, 11.3 Hz), 4.76 (1H, t, J = 3.8 Hz), 5.96 (1H, m), 8.08 (1H, s), 6.97-7.03 (2H, m), 7.49 (1H, dd, J = 2.1, 8.7 Hz), 7.65 (1H, d, J = 1.8 Hz). ESI-MS m/z: 434 [M + H]+ 535 [00982]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.30 (2H, m), 3.42 (3H, m), 4.10 (1H, m), 4.16-4.33 (5H, m), 4.64 (1H, m), 5.92 (1H, td, J = 54.5, 3.4 Hz), 6.09 (1H, s), 6.90 (1H, d, J = 9.0 Hz), 7.12 (1H, m), 7.44 (1H, d, J = 9.0 Hz), 7.45 (1H, s). ESI-MS m/z: 448 [M + H]+ 536 [00983]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.56 (3H, m), 1.68 (3H, m), 2.33 (1H, m), 4.07-4.44 (3H, m), 4.49 (1H, m), 5.95 (1H, dd, J = 49.3, 3.4 Hz), 5.06 (1H, s), 7.04 (1H, m), 7.05 (1H, d, J = 8.6 Hz), 7.52 (1H, cd, J = 8.6, 2.![text missing or illegible when filed]()
Hz), 7.55 (1H, m). ESI-MS m/z: 516 [M + H]+ 537 [00984]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.38-2.50 (2H, m), 4.10-4.29 (2H, m), 4.34-4.37 (2H, m), 4.43-4.47 (2H, m), 4.86 (1H, m), 5.58 (1H, m), 5.86 (1H, s), 6.13 (1H, s), 7.11 (1H, m), 7.20-7.39 (3H, m), 7.47 (1H, m). ESI-MS m/z: 452 [M + H]+ 538 [00985]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (2H, m), 1.32 (2H, m), 2.18-2.36 (2H, m), 2.85 (1H, dd, J = 16.8, 4.3 Hz), 3.14 (1H, dd, J = 16.7, 5.3 Hz), 3.55 (2H, m), 3.76 (1H, ddd, J = 10.5, 4.8, 1.2 Hz), 3.83 (1H, dd, J = 10.5, 5.1 Hz), 4.10 (1H, m), 4.16-4.28 (3H, m), 4.38 (1H, m), 4.61 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.8 Hz), 7.04 (1H, d, J = 2.6 Hz), 7.08 (1H, dd, J = 8.7, 2.5 Hz). ESI-MS m/z: 443 [M + H]+ 539 [00986]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.21 (2H, m), 0.50-0.56 (2H, m), 1.02 (1H, m), 2.60 (1H, m), 2.92 (1H, m), 3.20 (1H, dd, J = 5.4, 16.7 Hz), 3.28 (2H, dd, J = 2.8, 6.8 Hz), 3.51 (2H, dd, J = 2.1, 6.5 Hz), 4.00 (1H, m), 4.15-4.21 (2H, m), 4.24-4.26 (2H, m), 4.34 (1H, dd, J = 3.1, 11.2 Hz), 4.64 (1H, m), 6.02 (1H, s), 6.94-6.97 (2H, m), 7.33 (1H, s), 7.38 (1H, m). ESI-MS m/z: 452 [M + H]+ 540 [00987]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.47 (3H, m), 1.51 (3H, m), 2.17 (1H, m), 2.31 (1H, m), 2.91 (3H, dd, J = 16.7, 4.7 Hz), 3.17 (1H, dd, J = 16.7, 5.3 Hz), 4.08-4.13 (2H, m), 4.21-4.34 (3H, m), 4.63 (1H, m), 6.04 (1H, s), 6.92 (1H, d, J = 8.5 Hz), 6.96 (1H, m), 7.38 (1H, d, J = 2.0 Hz), 7.42 (1H, dd, J = 8.5, 2.0 Hz) ESI-MS m/z: 385 [M + H]+ 541 [00988]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.16-0.22 (2H, m), 0.51-0.58 (2H, m), 1.01 (1H, m), 2.90 (1H, dd, J = 4.7, 16.6 Hz), 3.17 (1H, m), 3.32-3.42 (2H, m), 3.77-3.98 (2H, m), 4.23-4.30 (2H, m), 4.38 (1H, m), 4.49 (1H, dd, J = 6.2, 10.5 Hz), 4.63 (1H, m), 6.59 (1H, m), 5.96 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, s), 7.43 (1H, dd, J = 1.8, 8.5 Hz). ESI-MS m/z: 445 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00070 TABLE 70 Ex- am- ple Structural formula NMR MS 542 [00989]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.27-2.40 (3H, m), 2.59 (1H, m), 2.89 (1H, dd, J = 5.1, 17.2 Hz), 3.39-3.48 (2H, m), 3.96 (1H, m), 4.16-4.30 (5H, m), 4.48 (1H, m), 6.06 (1H, s), 6.73 (1H, m), 6.96-7.05 (3H, m). ESI-MS m/z: 446 [M + H]+ 543 [00990]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.96-1.00 (3H, m), 1.96 (1H, m), 2.19 (1H, m), 2.85-2.96 (2H, m), 3.18 (1H, m), 3.44 (1H, m), 3.83 (2H, dq, J = 1.4, 11.7 Hz), 4.04 (1H, m), 4.17-4.23 (3H, m), 4.29 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 6.22 (1H, s), 6.88 (1H, d, J = 8.3 Hz), 7.01 (1H, m), 7.05 (1H, s), 7.12 (1H, dd, J = 2.1, 8.3 Hz). ESI-MS m/z: 440 [M + H]+ 544 [00991]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06 (3H, d, J = 7.4 Hz), 1.88 (1H, m), 2.06 (1H, m), 2.35 (2H, m), 4.13 (1H, m), 4.23-4.31 (2H, m), 4.33-4.45 (2H, m), 4.52 (1H, dd, J =10.8, 3.0 Hz), 4.64 (1H, m), 5.97 (1H, td, J = 55.1, 3.4 Hz), 6.10 (1H, s), 6.75 (1H, d, J = 9.2 Hz), 6.99 (1H, 8.6 Hz), 7.49 (1H, dd, J = 8.6, 1.8 Hz), 7.79 (1H, d, J = 1.8 Hz). ESI-MS m/z: 452 [M + H]+ 545 [00992]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.58 (2H, t, J = 5.2 Hz), 0.68 (2H, t, J = 5.3 Hz), 1.68 (2H, m), 2.88 (1H, m), 3.18 (1H, dd, J = 5.4, 16.7 Hz), 3.74 (2H, s), 3.82 (2H, q, J = 8.7 Hz), 4.21- 4.24 (4H, m), 4.57 (2H, s), 4.64 (1H, m), 6.24 (1H, s), 6.88 (1H, d, J = 8.3 Hz), 7.00-7.05 (2H, m), 7.12 (1H, dd, J = 2.0, 8.3 Hz). ESI-MS m/z: 452 [M + H]+ 546 [00993]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.39 (2H, m), 4.18 (1H, m), 4.27 (1H, m), 4.31- 4.47 (3H, m), 4.85 (1H, m), 5.39 (1H, d, J = 3.1 Hz), 5.98 (1H, td, J = ![text missing or illegible when filed]()
55.1, 3.5 Hz), 6.11 (1H, s), 7.01 (1H, d, J = 8.8 Hz), 7.04 (1H, m), 7.56 (1H, m), 7.57 (1H, d, J = 8.6 Hz). ESI-MS m/z: 502 [M + H]+ 547 (iso- mer A) [00994]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.47 (3H, m), 1.61 (3H, m), 2.17 (1H, m), 2.31 (1H, m), 2.91 (1H, dd, J = 16.7, 4.7 Hz), 3.17 (1H, dd, J = 16.7, 5.3 Hz), 4.08-4.13 (2H, m), 4.21-4.34 (3H, m), 4.63 (1H, m), 6.04 (1H, s), 6.92 (1H, d, J = 8.5 Hz), 6.96 (1H, m), 7.38 (1H, d, J = 2.0 Hz), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 385 [M + H]+ 547 (iso- mer B) [00995]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.47 (3H, m), 1.61 (3H, m), 2.17 (1H, m), 2.31 (1H, m, 2.91 (1H, dd, J =16.7, 4.7 Hz), 3.17 (1H, dd, J = 18.7, 5.3 Hz), 4.08-4.13 (2H, m), 4.21-4.34 (3H, m), 4.63 (1H, m), 6.04 (1H, s), 6.92 (1H, d, J = 8.5 Hz), 6.96 (1H, m), 7.38 (1H, d, J = 2.0 Hz), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 385 [M + H]+ 548 [00996]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.37 (1H, m), 2.38 (1H, m), 2.80-2.90 (3H, m), 3.11-3.24 (3H, m), 3.93 (1H, m), 4.11-4.24 (4H, m), 4.35 (1H, dd, J = 3.0, 11.1 Hz), 4.60 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.98 (1H, d, J = 8.0 Hz), 7.04 (1H, d, J = 2.4 Hz), 7.06 (1H, dd, J = ESI-MS m/z: 445 [M + H]+ 2.5, 8.7 Hz). 549 [00997]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06 (3H, t, J = 7.5 Hz), 1.67-1.68 (2H, m), 2.07 (1H, m), 2.18 (1H, m), 3.10 (1H, dd, J = 17.6, 4.5 Hz, 3.39 (1H, dd, J = 17.6, 6.5 Hz), 4.02-4.19 (3H, m), 4.22-4.36 (2H, m), 4.75 (1H, m), 6.00 (1H, s), 6.90 (1H, d, J = 7.7 Hz), 7.28 (1H, d, J = 8.5 Hz), 7.48 (1H, d, J = 8.5 Hz). ESI-MS m/z: 397 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00071 TABLE 71 Ex- am- ple Structural formula NMR MS 550 [00998]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.39 (1H, m), 2.48 (1H, m), 3.12 (1H, dd, J = 17.6, 4.8 Hz), 3.40 (1H, dd, J = 17.6, 5.6 Hz), 4.13-4.37 (4H, m), 4.77 (1H, m), 5.57 (1H, dd, J = 9.5, 2.4 Hz), 6.13 (1H, s), 6.94 (1H, d, J = 7.4 Hz), 7.11 (1H, dd, J = 10.2, 8.5 Hz), 7.21 (1H, d, J = 7.4 Hz), 7.29 (1H, d, J = 8.5 Hz), 7.37 (1H, m), 7.44-7.52 (2H, m). ESI-MS m/z: 463 [M + H]+ 551 [00999]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.34 (2H, m), 2.98 (1H, dd, J = 17.7, 4.4 Hz), 3.11 (1H, dd, J = 17.7, 5.3 Hz), 3.83 (3H, s), 4.19-4.32 (3H, m), 4.39 (1H, m), 4.66 (1H, m), 5.97 (1H, td, J = 54.8, 3.4 Hz), 6.09 (1H, s), 7.01 (1H, d, J =8.6 Hz), 8.73 (1H, d, J = 8.8 Hz), 6.92 (1H, d, J = 7.2 Hz), 7.38 (1H, d, J = 6.8 Hz). ESI-MS m/z: 448 [M + H]+ 552 (iso- mer A) [01000]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.71 (2H, m), 1.11 (2H, m), 2.16-2.36 (2H, m), 2.90 (1H, dd, J = 16.8, 5.0 Hz), 3.17 (1H, dd, J = 16.6, 5.3 Hz), 3.77-3.84 (3H, m), 3.89 (1H, dd, J = 10.5, 5.1 Hz), 4.10 (1H, m), 4.16-4.33 (3H, m), 4.39 (1H, m), 4.63 (1H, m), 6.03 (1H, s), 6.92 (1H, m), 6.93 (1H, d, J = 8.5 Hz), 7.39 (1H, m), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 427 [M + H]+ 552 (iso- mer B) [01001]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.71 (2H, m), 1.11 (2H, m), 2.16-2.36 (2H, m), 2.90 (1H, dd, J =16.8, 5.0 Hz), 3.17 (1H, dd, J = 16.6, 5.3 Hz), 3.77-3.84 (3H, m), 3.89 (1H, dd, J = 10.5, 5.1 Hz), 4.10 (1H, m), 4.16-4.33 (3H, m), 4.39 (1H, m), 4.53 (1H, m), 6.03 (1H, s), 6.92 (1H, m), 5.93 (1H, d, J = 8.5 Hz), 7.39 (1H, m), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 427 [M + H]+ 553 [01002]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (2H, m), 1.31 (2H, m), 2.16-2.39 (2H, m), 2.93 (1H, dd, J = 16.8, 4.6 Hz), 3.19 (1H, dd, J = 16.7, 5.4 Hz), 3.64 (2H, m), 3.74 (1H, dd J = 20.4, 6.0 Hz), 3.84 (1H, dd, J = 10.4, 4.8 Hz), 4.11 (1H, m), 4.17-4.29 (3H, m), 4.39 (1H, m), 4.64 (1H, m), 6.02 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.98 (1H, d, J = 7.9 Hz), 7.33 (1H, d, J = 1.4 Hz), 7.38 (1H, dd, J = 8.5, 1.4 Hz). ESI-MS m/z: 477 [M + H]+ 554 (iso- mer A) [01003]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (2H, m), 1.31 (2H, m), 2.16-2.39 (2H, m), 2.93 (1H, dd, J = 16.8, 4.6 Hz), 3.19 (1H, dd, J = 16.7, 5.4 Hz), 3.54 (2H, m), 3.74 (1H, dd J = 20.4, 5.0 Hz), 3.84 (1H, dd, J = 10.4, 4.8 Hz), 4.11 (1H, m), 4.17-4.29 (3H, m), 4.39 (1H, m), 4.64 (1H, m), 6.02 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.98 (1H, d, J = 7.9 Hz), 7.33 (1H, d, J = 1.4 Hz), 7.38 (1H, dd, J = 8.5, 1.4 Hz). ESI-MS m/z: 477 [M + H]+ 554 (iso- mer B) [01004]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (2H, m), 1.31 (2H, m), 2.16-2.39 (2H, m), 2.93 (1H, dd, J =16.8, 4.6 Hz), 3.19 (1H, dd, J = 16.7, 5.4 Hz), 3.54 (2H, m), 3.74 (1H, dd J = 20.4, 5.0 Hz), 3.84 (1H, dd, J = 10.4, 4.8 Hz), 4.11 (1H, m), 4.17-4.29 (3H, m), 4.39 (1H, m), 4.64 (1H, m), 6.02 (1H, s), 8.94 (1H, d, J = 8.5 Hz), 6.98 (1H, d, J = 7.9 Hz), 7.33 (1H, d, J = 1.4 Hz), 7.38 (1H, dd, J = 8.5, 1.4 Hz). ESI-MS m/z: 477 [M + H]+ 555 [01005]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.74 (1H, m), 2.02 (1H, m), 2.39 (1H, m), 2.91 (1H, dd, J = 4.4, 16.4 Hz), 3.17 (1H, dd, J = 5.3, 16.7 Hz), 3.59-3.68 (2H, m), 3.74-3.85 (3H, m), 4.09 (1H, m), 4.23-4.33 (4H, m), 4.64 (1H, m), 6.24 (1H, s), 6.90-6.95 (2H, m), 7.39 (1H, s), 7.43 (1H, dd, J = 2.1, 5.5 Hz). ESI-MS m/z: 451 [M + H]+ 556 [01006]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73 (1H, m), 2.00 (1H, m), 2.37 (1H, m), 2.92 (1H, dd, J = 3.4, 16.2 Hz), 3.20 (1H, dd, J = 5.2, 16.9 Hz), 3.60-3.68 (2H, m), 3.73-3.85 (3H, m), 4.09 (1H, m), 4.22-4.33 (4H, m), 4.65 (1H, m), 6.24 (1H, s), 6.94-6.98 (2H, m), 7.33 (1H, s), 7.38 (1H, d, J = 8.6 Hz). ESI-MS m/z: 493 [M + H]+ [01007]![text missing or illegible when filed]()
TABLE-US-00072 TABLE 72 Ex- am- ple Structural formula NMR MS 557 [01008]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73 (1H, m), 2.02 (1H, m), 2.38 (1H, m), 2.67 (1H, m), 3.05 (1H, m), 3.02-3.08 (2H, m), 3.19 (1H, m), 3.64-3.68 (2H, m), 3.72-3.82 (3H, m), 4.08 (1H, m), 4.19 (2H, s), 4.28-4.33 (2H, m), 4.51 (1H, m), 5.85 (1H, dt, 4.7, 53.7 Hz), 6.23 (1H, s), 6.85 (1H, d, J = 8.4 Hz), 6.93 (1H, s), 7.01 (2H, d, J = 13.1 Hz). ESI-MS m/z: 490 [M + H]+ 558 [01009]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.24 (2H, m), 0.54-0.58 (2H, m), 1.07 (1H, m), 2.0 ![text missing or illegible when filed]()
- 2.27 (2H, m), 3.37 (2H, d, J = 6.9 Hz), 3.53 (1H, m), 3.65 (1H, m), 3.76 (1H, dd, J = 5.2, 10.4 Hz), 3.93-4.23 (3H, m), 4.31-4.39 (2H, m), 4.62 (1H, m), 4.91 (1H, t, J = 4.0 Hz), 6.04 (1H, s), 6.95 ESI-MS m/z: 468 [M + H]+ (1H, d, J = 8.6 Hz), 7.32 (1H, d, J = 8.1 Hz), 7.47 (1H, dd, J = 2.1, 8.6 (Hz, 7.55 (1H, s). 559 [01010]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.19-0.23 (2H, m), 0.54-0.57 (2H, m), 1.06 (1H, m), 1.61 (1H, s), 2.10-2.30 (2H, m), 3.36 (2H, dd, J = 1.6, 6.9 Hz), 3.65 (1H, m), 3.75 (1H, dd, J = 5.1, 10.5 Hz), 4.07 (1H, m), 4.18 (1H, m), 4.28-4.38 (2H, m), 4.44 (1H, m), 4.49 (1H, d, J = (11.4 Hz), 4.76 ESI-MS m/z: 468 [M + H]+ (1H, s), 6.01 (1H, s), 7.01 (2H, d, J = 8.5 Hz), 7.48 (1H, d, J = 7.9 Hz), 7.65 (1H, d, J = 1.9 Hz). 560 [01011]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.20 (2H, m), 0.52-0.57 (2H, m), 1.03 (1H, 3.07 (1H, m), 3.37 (2H, dd, J = 1.3, 6.9 Hz), 3.74- 3.82 (2H, m), 4.14-4.36 (4H, m), 4.64 (1H, m), 4.92 (1H, s), 5.41 (1H, m), 5.92 (1H, d, J = 2.2 Hz), 6.97 (1H, d, J = 8.6 Hz), 7.28 (1H, m), 7.48 (1H, dd, J = 2.1, 8.7 Hz), 7.62 (1H, d, J = 8.4 Hz). ESI-MS m/z: 454 [M + H]+ 561 [01012]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.15-2.25 (2H, m), 3.54 (1H, m), 3.84-3.98 (4H, m), 4.05- 4.23 (3H, m), 4.32-4.40 (2H, m), 4.62 (1H, m), 4.91 (1H, t, J = 4.0 Hz), 6.05 (1H, d, J = 1.0 Hz), 6.97 (1H, d, J = 8.6 Hz), 7.32 (1H, d, J = 8.7 Hz), 7.48 (1H, dd, J = 2.0, 8.7 Hz), 7.53 (1H, s). ESI-MS m/z: 496 [M + H]+ 562 [01013]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.19 (1H, m), 2.36 (1H, m), 2.50 (1H, m), 2.71 (1H, m), 2.91 (1H, dd, J = 16.7, 4.7 Hz), 3.17 (1H, dd, J = 16.8, 5.2 Hz), 4.09-4.33 (4H, m), 4.53 (1H, m), 4.62 (1H, m), 6.03 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 7.38 (1H, d, J = 2.0 Hz), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 407 [M + H]+ 563 (iso- mer A) [01014]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (2H, m), 1.32 (2H, m), 2.18-2.36 (2H, m), 2.85 (1H, dd, J = 16.5, 4.3 Hz), 3.14 (1H, dd, J = 16.7, 5.3 Hz), 3.55 (2H, m), 3.76 (1H, ddd, J = 10.5, 4.8, 1.2 Hz), 3.83 (1H, dd, J = 10.5, 5.1 Hz), 4.10 (1H, m), 4.16- 4.28 (3H, m), 4.38 (1H, m), 4.61 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 5.7 Hz), 6.99 (1H, d, J = 7.8 Hz), 7.04 (1H, d, J = 2.6 Hz), 7.08 (1H, dd, J = 8.7, 2.6 Hz). ESI-MS m/z: 443 [M + H]+ 563 (iso- mer B) [01015]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (2H, m), 1.32 (2H, m), 2.18-2.36 (2H, m), 2.85 (1H, dd, J = 16.5, 4.3 Hz), 3.14 (1H, dd, J = 16.7, 5.3 Hz), 3.65 (2H, m), 3.76 (1H, ddd, J = 10.5, 4.8, 1.2 Hz), 3.83 (1H, dd, J = 10.5, 5.1 Hz), 4.10 (1H, m), 4.16- 4.28 (3H, m), 4.38 (1H, m), 4.61 (1H, m), 6.01 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 6.99 (1H, d, J = 7.8 Hz), 7.04 (1H, d, J = 2.6 Hz), 7.08 (1H, dd, J = 8.7, 2.6 Hz). ESI-MS m/z: 443 [M + H]+ 564 [01016]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.30-1.45 (2H, m), 1.53-1.74 (3H, m), 1.86 (1H, m), 1.97 (1H, m), 2.85 (1H, dd, J = 4.1, 16.9 Hz), 3.04 (2H, dt, J = 4.5, 17.4 Hz), 3.17 (1H, dd, J = 5.5, 16.8 Hz), 3.39-3.44 (2H, m), 3.85 (1H, m), 3.95-4.01 (2H, m), 4.19 (2H, d, J = 2.9 Hz), 4.34 (1H, m), 4.62 (1H, m), 5.38 (1H, m), 5.88 (1H, m), 5.89 (1H, s), 6.83 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.00 (2H, d, J = 8.2 Hz). ESI-MS m/z: 448 [M + H]+ ![text missing or illegible when filed]()
indicates data missing or illegible when filed
TABLE-US-00073 TABLE 73 Ex- am- ple Structural formula NMR MS 565 [01017]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.31-1.45 (2H, m), 1.63-1.74 (3H, m), 1.87 (1H, m), 1.99 (1H, m), 2.90 (1H, m), 3.17 (1H, dd, J = 5.2, 16.6 Hz), 3.38-3.45 (2H, m), 3.85 (1H, m), 3.95-4.01 (2H, m), 4.26-4.28 (2H, m), 4.34 (1H, m), 4.63 (1H, m), 5.39 (1H, m), 5.89 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 2.0, 8.5 Hz). ESI-MS m/z: 409 [M + H]+ 566 [01018]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25-2.40 (2H, m), 2.83 (1H, m), 3.14 (1H, dd, J = 5.3, 16.8 Hz), 4.08-4.22 (3H, m), 4.27 (1H, m), 4.38 (1H, m), 4.60 (1H, m), 5.96 (1H, m), 6.08 (1H, s), 6.85 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 7.9 Hz), 7.37 (1H, s), 7.40 (1H, dd, J = 2.1, 8.6 Hz). ESI-MS m/z: 476 [M + H]+ 567 [01019]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.70 (2H, m), 1.10 (2H, m), 2.14-2.33 (2H, m), 2.68 (1H, dd, J = 17.4, 4.4 Hz), 3.04 (2H, td, 17.4, 4.5 Hz), 3.16 (1H, dd, J = 16.7, 5.5 Hz), 3.75-3.85 (3H, m), 3.88 (1H, dd, J = 10.6, 5.1 Hz), 4.08 (1H, m), 4.14-4.27 (3H, m), 4.39 (1H, m), 4.81 (1H, m), 5.88 (1H, tt, J = 56.4, 4.5 Hz), 8.02 (1H, s), 6.83 (1H, d, J = 8.3 Hz), 6.94 (1H, d, J = 2.0 Hz), 7.00 (1H, dd, J = 8.3, 2.0 Hz), 7.03 (1H, m). ESI-MS m/z: 466 [M + H]+ 568 [01020]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.36 (2H, m), 3.49 (3H, m), 4.18 (1H, m), 4.24-4.46 (5H, m), 4.67 (1H, m), 5.98 (1H, td, J = ![text missing or illegible when filed]()
54.3, 3.5 Hz), 6.10 (1H, s), 6.97 (1H, d, J = 8.3 Hz), 7.21 (1H, d, J = 8.5 Hz), 7.51 (1H, d, J = 8.3 Hz), 7.52 (1H, m). ESI-MS m/z: 448 [M + H]+ 569 [01021]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 3.49 (3H, d, J = 1.1 Hz), 3.91-4.00 (4H, m), 4.21-4.29 (3H, m), 4.34-4.40 (2H, m), 4.70 (1H, m), 5.44 (1H, m), 5.94 (1H, s), 6.97 (1H, d, J = 9.0 Hz), 7.20 (1H, d, J = 8.6 Hz), 7.50-7.51 (2H, m). ESI-MS m/z: 496 [M + H]+ 570 [01022]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.29 (2H, m), 3.49 (3H, s), 3.85-3.99 (4H, m), 4.14 (1H, m), 4.24-4.32 (3H, m), 4.34 (1H, d, J = 3.6 Hz), 4.39 (1H, m), 4.70 (1H, m), 6.05 (1H, s), 6.97 (1H, d, J = 9.2 Hz), 7.21 (1H, d, J = 8.4 Hz), 7.50-7.51 (2H, m). ESI-MS m/z: 510 [M + H]+ 571 [01023]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.22 (2H, m), 0.55 (2H, m), 1.06 (1H, m), 1.45 (1H, m), 2.09-2.33 (2H, m), 3.35-3.39 (2H, m), 3.66 (1H, m), 3.76 (1H, m), 3.96-4.31 (3.5H, m), 4.31-4.46 (2H, m), 4.60 (0.5H, m), 4.67 (0.5H, m), 4.84 (0.5H, m), 6.99 (0.5H, s), 6.04 ESI-MS m/z: 434 [M + H]+ (0.5H, s), 6.78-6.89 (1H, m), 7.03 (1H, m), 7.14-7.22 (1H, m), 7.24- 7.37 (1H, m). 572 (iso- mer A) [01024]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73 (1H, m), 2.01 (1H, m), 2.38 (1H, m), 2.91 (1H, dd, J = 5.0, 17.0 Hz), 3.17 (1H, dd, J = 4.9, 16.8 Hz), 3.59-3.67 (2H, m), 3.74-3.85 (3H, m), 4.09 (1H, M), 4.24-4.34 (4H, m), 4.83 (1H, m), 6.24 (1H, s), 6.91-7.00 (2H, m), 7.39 (1H, s), 7.43 (1H, dd, J = 2.0, 8.5 ESI-MS m/z: 451 [M + H]+ Hz). 572 (iso- mer B) [01025]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.74 (1H, m), 2.01 (1H, m), 2.38 (1H, m), 2.90 (1H, dd, J = 4.8, 16.5 Hz), 3.17 (1H, dd, J = 5.2, 16.7 Hz), 3.60-3.68 (2H, m), 3.75-3.85 (3H, m), 4.09 (1H, m), 4.23-4.33 (4H, m), 4.63 (1H, m), 8.24 (1H, s), 5.90-5.94 (2H, m), 7.39 ESI-MS m/z: 451 [M + H]+ (1H, s), 7.43 (1H, dd, J = 2.0, 8.6 Hz). ![text missing or illegible when filed]()
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TABLE-US-00074 TABLE 74 Exam- ple Structural formula NMR MS 573 [01026]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.44 (2H, m), 4.11-4.67 (5H, m), 4.53 (0.5H, m), 4.65 (0.5H, m), 4.75 (0.5H, m), ![text missing or illegible when filed]()
4.92 (0.5H, m), 5.56 (1H, m), 5.06-6.14 (1H, m), 6.92-7.01 (1H, m), 7.04-7.15 (2H, m), 7.16-7.22 (1H, m), 7.37 (1H, m), 7.42-7.54 (2H, m), 7.70 (1H, m). ESI-MS m/z: 435 [M + H]+ 574 [01027]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.25 (2H, m), 2.78-2.94 (1H, m), 2.95-3.17 (1H, m), 3.84-3.99 (4H, m), 4.02-4.40 (5H, m), 4.51-4.74 (1H, m), 6.04 (1H, s), 6.82 (1H, m), 6.95-7.03 (2H, m), 7.09 (1H, m). ESI-MS m/z: 446 [M + H]+ 575 (iso- mer A) [01028]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.24 (2H, m), 0.54-0.59 (2H, m), 1.07 (1H, m), 2.11-2.30 (2H, m), 3.25 (1H, s), 3.38 (2H, d, J = 6.9 Hz), 3.65 (1H, dd, J = 5.2, 10.4 Hz), 3.76 (1H, dd, J = 5.2, 10.4 Hz), 4.04-4.26 (3H, m), 4.33- 4.40 (2H, m), 4.64 (1H, m), 4.91 (1H, s), 6.04 (1H, s), 6.97 (1H, d, J = ESI-MS m/z: 468 [M + H]+ 8.6 Hz), 7.29 (1H, m), 7.48 (1H, dd, J = 2.1, 8.6 Hz), 7.59 (1H, s). 575 (iso- mer B) [01029]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20-0.24 (2H, m), 0.53-0.59 (2H, m), 1.07 (1H, m), 2.15-2.29 (2H, m), 3.23 (1H, s), 3.38 (2H, d, J = 6.9 Hz), 3.68 (1H, dd, J = 5.2, 10.5 Hz), 3.76 (1H, dd, J = 5.1, 10.6 Hz), 4.04 (1H, m), 4.18-4.23 (2H, m), 4.33-4.39 (2H, m), 4.64 (1H, ESI-MS m/z: 468 [M + H]+ m), 4.92 (1H, s), 8.64 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.29 (1H, m), 7.48 (1H, dd, J = 2.1, 8.6 Hz), 7.60 (1H, s). 576 (iso- mer A) [01030]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.21 (2H, m), 0.52-0.57 (2H, m), 1.03 (1H, m), 2.95 (1H, s), 3.37 (2H, d, J = 6.9 Hz), 3.76-3.83 (2H, m), 4.17-4.23 (2H, m), 4.29-4.36 (2H, m), 4.65 (1H, m), 4.93 (1H, s), 5.42 (1H, m), 5.92 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.25 (1H, m), 7.48 (1H, dd, J = 2.2, 8.6 Hz), 7.65 (1H, d, J = 2.0 Hz). ESI-MS m/z: 454 [M + H]+ 576 (iso- mer B) [01031]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.21 (2H, m), 0.52-0.57 (2H, m), 1.03 (1H, m), 3.03 (1H, s), 3.38 (2H, d, J = 6.9 Hz), 3.79 (2H, dd, J = 1.5, 4.7 Hz), 4.17- 4.36 (4H, m), 4.64 (1H, m), 4.92 (1H, t, J = 4.0 Hz), 5.41 (1H, m), 5.92 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.28 (1H, m), 7.48 (1H, dd, J =2.0, 8.8 Hz), 7.62 (1H, d, J = 1.6 Hz). ESI-MS m/z: 454 [M + H]+ 577 (iso- mer A) [01032]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.31-1.45 (2H, m), 1.62-1.74 (3H, m), 1.87 (1H, m), 1.98 (1H, m), 2.90 (1H, dd, J = 4.7, 16.7 Hz), 3.17 (1H, dd, J = 5.1, 16.8 Hz), 3.41 (2H, dt, J = 2.2, 11.8 Hz), 3.85 (1H, dd, J = 7.9, 9.8 Hz), 3.95- 4.01 (2H, m), 4.26-4.37 (3H, m), 4.84 (1H, m), 5.39 (1H, m), 5.89 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, d, J = ESI-MS m/z: 409 [M + H]+ 1.8 Hz), 7.42 (1H, dd, J = 2.1, 8.5 Hz). 577 (iso- mer B) [01033]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.31-1.46 (2H, m), 1.63-1.75 (3H, m), 1.87 (1H, m), 1.99 (1H, m), 2.90 (1H, dd, J = 4.5, 16.9 Hz), 3.17 (1H, dd, J = 5.4, 18.9 Hz), 3.42 (1H, dt, J = 2.2, 11.8 Hz), 3.85 (1H, dd, J = 8.0, 9.8 Hz), 3.96- 4.01 (2H, m), 4.26-4.36 (3H, m), 4.64 (1H, m), 5.38 (1H, m), 5.89 (1H, s), 6.90-6.94 (2H, m), 7.38 (1H, d, J = 1.8 ESI-MS m/z: 409 [M + H]+ Hz), 7.42 (1H, dd, J = 2.0, 8.5 Hz). 578 [01034]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.14-0.19 (2H, m), 0.49-0.56 (2H, m), 1.00 (1H, m), 2.82 (1H, d, J = 4.6, 16.7 Hz), 3.12 (1H, m), 3.33-3.38 (2H, m), 3.76-3.78 (2H, m), 4.11-4.15 (2H, m), 4.18-4.25 (2H, m), 4.57 (1H, m), 5.35 (1H, m), 6.78 (1H, d, J = 8.7 Hz), 7.02-7.08 (3H, m), 7.27 (1H, s). ESI-MS m/z: 404 [M + H]+ ![text missing or illegible when filed]()
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TABLE-US-00075 TABLE 75 Ex- am- ple Structural formula NMR MS 579 (iso- mer A) [01035]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.39 (2H, m), 4.06-4.15 (1H, m), 4.20 (1H, m), 4.33-4.40 (2H, m), 4.42 (1H, m), 4.78 (1H, m), 5.61 (1H, dd, J = 64.9, 2.0 Hz), 6.00 (1H, m), 6.13 (1H, s), 7.02 (1H, d, J = 8.6 Hz), 7.17 (1H, d, J = 6.8 Hz), 7.58 (1H, d, J = 8.6 Hz), 7.63 (1H, m). ESI-MS m/z: 436 [M + H]+ 579 (iso- mer B) [01036]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.44 (2H, m), 4.11 (1H, m), 4.24 (1H, m), 4.33- 4.48 (3H, m), 4.70 (1H, m), 5.42 (1H, dd, J = 54.9, 2.0 Hz), 5.95 (1H, m), 6.08 (1H, s), 6.93 (1H, d, J = 8.8 Hz), 7.08 (1H, d, J = 8.6 Hz), 7.58 (1H, d, J = 8.6 Hz), 7.65 (1H, m). ESI-MS m/z: 436 [M + H]+ 580 [01037]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.53 (3H, s), 3.31 (1H, s), 4.07-4.35 (6H, m), 4.67 (1H, m), 4.94 (1H, d, J = 3.6 Hz), 5.03 (2H, s), 6.95 (1H, d, J = 8.6 Hz), 7.01 (1H, d, J = 7.6 Hz), 7.47 (1H, dd, J = 2.1, 5.7 Hz), 7.80 (1H, t, J = 7.8 Hz), 7.63 (1H, d, J = 1.8 Hz), 7.77 (1H, d, J = 7.9 Hz), 8.05 (1H, d, J = 8.0 Hz). ESI-MS m/z: 475 [M + H]+ 581 [01038]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.30 (3H, t, J = 7.6 Hz), 2.80 (2H, ![text missing or illegible when filed]()
, J = 7.6 Hz), 3.01 (1H, s), 4.12-4.37 (6H, m), 4.67 (1H, m), 4.95 (1H, m), 5.09 (2H, d, J = 3.3 Hz), 6.99 (2H, m), 7.48 (1H, dd, J = 2.3, 8.7 Hz), 7.61 (1H, t, J = 7.8 Hz), 7.65 (1H, m), 7.80 (1H, d, J = 8.4 Hz), 7.91 (1H, d, J = 7.7 Hz). ESI-MS m/z: 489 [M + H]+ 582 [01039]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.98 (3H, dt, J = 3.6, 11.4 Hz), 1.26-1.61 (2H, m), 1.80 (1H, m), 1.91 (1H, m), 2.22 (1H, d, J = 4.7 Hz), 2.92 (1H, m), 3.20 (1H, m), 3.71 (1H, dd, J = 4.8, 12.2 Hz), 4.02 (1H, d, J = 12.3 Hz), 4.15 (1H, m), 4.25 (2H, s), 4.33 (1H, m), 4.65 (1H, m, J = 4.0 Hz), 5.26 (1H, s), 6.94-7.00 (2H, m), 7.33 (1H, s), 7.39 (1H, d, J = ESI-MS m/z: 426 [M + H]+ 6.5 Hz). 583 [01040]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.41-1.61 (3H, m), 1.88 (2H, m), 2.08 (1H, m), 2.19 (1H, m), 2.92 (1H, dd, J = 16.7, 4.4 Hz), 3.20 (1H, dd, J = 16.7, 4.9 Hz), 3.41 (2H, m), 3.95 (1H, m), 4.04 (3H, m), 4.14-4.29 (3H, m), 4.64 (1H, m), 5.99 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.97 (1H, m), 7.33 (1H, m), 7.37 (1H, d, J = 8.5 Hz) ESI-MS m/z: 452 [M + H]+ 584 [01041]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.41-1.64 (3H, m), 1.88 (2H, m), 2.06 (1H, m), 2.20 (1H, m), 2.84 (1H, dd, J = 16.3, 4.4 Hz), 3.15 (1H, dd, J = 16.3, 4.9 Hz), 3.41 (2H, m), 3.94 (1H, m), 4.04 (3H, m), 4.14-4.25 (3H, m), 4.59 (1H, m), 5.96 (1H, s), 6.80 (1H, d, J = 8.7 Hz), 6.99 (1H, m), 7.04 (1H, d, J = 2.1 Hz), 7.08 (1H, d, J = 8.7 Hz). ESI-MS m/z: 418 [M + H]+ 585 [01042]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.44-1.63 (3H, m), 1.88 (2H, m), 2.07 (1H, m), 2.20 (1H, m), 2.90 (1H, dd, J = 16.7 4.7 Hz), 3.17 (1H, dd, J = 16.7, 4.6 Hz), 3.41 (2H, m), 3.96 (1H, m), 4.05 (3H, m), 4.14-4.34 (3H, m), 4.64 (1H, m), 6.00 (1H, s), 6.93 (1H, d, J = 8.5 Hz), 6.94 (1H, m), 7.38 (1H, d, J = 2.0 Hz), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 409 [M + H]+ 586 [01043]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.45-1.63 (3H, m), 1.89 (2H, m), 2.07 (1H, m), 2.19 (1H, m), 2.90 (1H, dd, J = 16.7, 4.2 Hz), 3.04 (2H, td, J = 17.4, 4.4 Hz), 3.16 (1H, dd, J = 16.7, 4.8 Hz), 3.42 (2H, m), 3.94 (1H, m), 4.04 (3H, m), 4.13-4.24 (3H, m), 4.61 (1H, m), 5.88 (1H, tt, J = 53.3, 4.5 Hz), 5.99 (1H, s), 8.63 (1H, d, J = 8.3 Hz), 6.95 (1H, d, J = 1.8 Hz), 7.00 (1H, dd, J = 8.3, 1.8 ESI-MS m/z: 448 [M + H]+ Hz), 7.03 (1H, m). ![text missing or illegible when filed]()
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TABLE-US-00076 TABLE 76 Exam- ple Structural formula NMR MS 587 [01044]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.99 (1H, m), 3.09-3.15 (2H, m), 3.21 (H, q, J = 9.7 Hz), 4.11 (1H, m), 4.20 (1H, m), 4.33-4.41 (2H, m), 4.64 (1H, m), 4.92 (1H, s), 5.61 (1H, m), 5.94 (1H, d, J = 1.9 Hz), 6.97 (1H, d, J = 5.6 Hz), 7.29 (1H, m), 7.49 (1H, dd, J = 2.2, 8.7 Hz), 7.63 (1H, dd, J = ESI-MS m/z: 498 [M + H]+ 1.8, 6.5 Hz). 588 [01045]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.22, (2H, m), 3.01 (1H, m), 3.81-3.87 (4H, m), 3.97 (1H, m), 4.20 (1H, t, J = 9.8 Hz), 4.35 (2H, dd, J = 3.6, 10.8 Hz), 4.64 (1H, m), 4.92 (1H, m), 5.45 (1H, m), 5.91 (1H, s), 6.97 (1H, d, J = 8.7 Hz), 7.29 (1H, m), 7.48 (1H, dd, J = 2.1, 8.6 Hz), 7.52 (1H, s). ESI-MS m/z: 496 [M + H]+ 589 [01046]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.15-2.23 (2H, m), 3.49 (1H, m), 3.79-3.86 (4H, m), 3.96 (1H, m), 4.26-4.37 (2H, m), 4.47-4.51 (2H, m), 4.75 (1H, m), 5.43 (1H, m), 5.89 (1H, s), 6.99-7.02 (2H, m), 7.48 (1H, dd, J = 2.1, 8.6 Hz), 7.64 (1H, s). ESI-MS m/z: 496 [M + H]+ 590 (iso- mer A) [01047]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.3 ![text missing or illegible when filed]()
-1.45 (2H, m), 1.63-1.74 (3H, m), 1.56 (1H, m), 1.96 (1H, m), 2.85 (1H, dd, J = 4.1, 16.7 Hz), 3.04 (2H, dt, J = 4.8, 17.4 Hz), 3.17 (1H, dd, J = 6.5, 15.6 Hz), 3.41 (2H, dt, J = 2.2, 11.8 Hz), 3.84 (1H, dd, J = 7.9, 9.7 Hz), 3.96-4.00 (2H, m), 4.19 (2H, d, J = 2.9 Hz), 4.34 (1H, dd, J = 6.2, 9.7 Hz), 4.62 (1H, m), 5.3 ![text missing or illegible when filed]()
(1H, m), 5.85 ![text missing or illegible when filed]()
H, m), 5.89 ESI-MS m/z: 448 [M + H]+ (1H, s), 6.63 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.01 (2H, d, J = 8.1 Hz). 590 (iso- mer B) [01048]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.31-1.46 (2H, m), 1.63-1.74 ( ![text missing or illegible when filed]()
H, m), 1.86 (1H, m), 1.99 (1H, m), 2.85 (1H, dd, J = 4.0, 16.7 Hz), 3.04 (2H, dt, J = 4.5, 17.4 Hz), 3.17 (1H, dd, J = 5.3, 16.8 Hz), 3.40 (2H, dt, J = 2.1, 17.7 Hz), 3.![text missing or illegible when filed]()
5 (1H, dd, J = 8.0, 9.7 Hz), 3.95- 4.00 (2H, m), 4.19 (2H, d, J = 2.8 Hz), 4.33 (1H, dd, J = 8.2, 9.7 Hz), 4.62 (1H, m), 5.37 (1H, m), 5.87 (1H, m), ESI-MS m/z: 496 [M + H]+ 5.89 (1H, s), 6.83 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.00 (2H, d, J = 8.4 Hz). 591 [01049]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.84 (2H, m), 1.99 (2H, m), 3.28 (1H, m), 3.69 (2H, m), 3.77-4.01 (3H, m), 4.17-4.36 (3H, m), 4.61 (1H, m), 4.91 (1H, t, J = 4.2 Hz), 5.32 (1H, m), 6.89 (1H, m), 6.94 (1H, d, J = 8.6 Hz), 7.29 (1H, d, J = 8.3 Hz), 7.47 (1H, dd, J = 8.7, 1.9 Hz), 7.51 (1H, m). ESI-MS m/z: 510 [M + H]+ 592 [01050]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.81 (2H, m), 1.99 (2H, m), 3.53 (1H, m), 3.68 (2H, m), 3.77-3.93 (3H, m), 4.26-4.37 (3H, m), 4.44 (1H, m), 4.49 (1H, m), 4.75 1H, t, J = 3.9 Hz), 5.32 (1H, m), 5.87 (1H, s), 7.00 (1H, d, J = 8.7 Hz), 7.01 (1H, m), 7.48 (1H, dd, J = 8.7, 1.9 Hz), 7.54 (1H, d, J = 2.0 Hz). ESI-MS m/z: 510 [M + H]+ 593 [01051]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.05-0.08 (2H, m), 0.45-0.48 (2H, m), 0.71 (1H, m), 1.46-1.51 (2H, m), 2.64-2.68 (2H, m), 2.86 (1H, d, J = 4.8 Hz), 2.93-2.94 (2H, m), 3.69 (2H, d, J = 4.2 Hz), 4.15-4.25 (3H, m), 4.35 (1H, m), 4.67 (1H, m), 4.93 (1H, m), 6.53 (1H, s), ESI-MS m/z: 451 [M + H]+ 6.97 (1H, m), 7.28 (1H, m, 7.49 (1H, m), 7.63 (1H, m). 594 [01052]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.36-2.42 (2H, m), 2.79-2.86 (3H, m), 2.96-2.99 (2H, m), 3.74 (2H, s), 4.17-4.24 (3H, m), 4.36 (1H, dd, J = 3.8, 11.5 Hz), 4.67 (1H, m), 4.94 (1H, t, J = 3.9 Hz), 6.56 (1H, s), 6.98 (1H, m), 7.30 (1H, m), 7.50 (1H), 7.64 (1H, m). ESI-MS m/z: 478 [M + H]+ ![text missing or illegible when filed]()
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TABLE-US-00077 TABLE 77 Example Structural formula NMR MS 595 [01053]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.21 (2H, m), 0.51-0.56 (2H, m), 1.03 (1H, m), 2.10-2.23 (2H, m), 3.10 (1H, m), 3.27 (2H, d, J = 6.9 Hz), 3.63 (2H, t, J = 6.1 Hz), 3.99 (1H, m), 4.20 (1H, dd, J = 9.1, 10.6 Hz), 4.31-4.36 (2H, m), 4.64 (1H, m), 4.92 (1H, s), 5.46 (1H, m), 5.90 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.29 (1H, s), 7.48 (1H, dd, J = 2.1, 8.7 ESI-MS m/z: 468 [M + H]+ Hz), 7.62 (1H, s) 596 [01054]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.15-0.20 (2H, m), 0.48-0.55 (2H, m), 1.02 (1H, m), 2.09-2.22 (2H, m), 3.21-3.33 (3H, m), 3.62 (2H, q, J = 5.5 Hz), 4.00 (1H, m), 4.26-4.35 (2H, m), 4.44 (1H, m), 4.50 (1H, dd, J = 1.8, 11.4 Hz), 4.75 (1H, s), 5.45 (1H, m), 5.88 (1H, s), 6.98-7.01 (2H, m), 7.48 (1H, m), 7.64 (1H, s). ESI-MS m/z: 468 [M + H]+ 597 (isomer A) [01055]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 3.49 (3H, s), 3.94 (2H, q, J = 8.5 Hz), 3.99 (2H, d, J = 4.2 Hz), 4.23-4.29 (3H, m), 4.34- 4.39 (2H, m), 4.70 (1H, m), 5.44 (1H, m), 5.94 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.20 (1H, d, J = 8.2 Hz), 7.49- 7.52 (2H, m). ESI-MS m/z: 496 [M + H]+ 597 (isomer B) [01056]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 3.49 (3H, s), 3.94 (2H, q, J = 8.5 Hz), 3.99 (2H, d, J = 4.2 Hz), 4.21-4.29 (3H, m), 4.32- 4.41 (2H, m), 4.69 (1H, m), 5.44 (1H, m), 5.94 (1H, s), 6.97 (1H, d, J = 9.0 Hz), 7.20 (1H, d, J = 8.4 Hz), 7.49- 7.51 (2H, m). ESI-MS m/z: 496 [M + H]+ 598 (isomer A) [01057]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.29 (2H, m), 3.49 (3H, s), 3.86-4.00 (4H, m), 4.14 (1H, m), 4.25-4.32 (3H, m), 4.34 (1H, d, J = 3.6 Hz), 4.39 (1H, m), 4.70 (1H, m), 6.05 (1H, s), 6.97 (1H, d, J = 9.2 Hz), 7.21 (1H, d, J = 8.8 Hz), 7.49- 7.51 (2H, m). ESI-MS m/z: 610 [M + H]+ 598 (isomer B) [01058]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.23-2.29 (2H, m), 3.49 (3H, s), 3.86-3.98 (4H, m), 4.15 (1H, m), 4.24-4.32 (3H, m), 4.34 (1H, d, J = 3.6 Hz), 4.39 (1H, m), 4.70 (1H, m), 6.05 (1H, s), 6.97 (1H, d, J = 9.3 Hz), 7.21 (1H, d, J = 8.6 Hz), 7.50- 7.51 (2H, m). ESI-MS m/z: 610 [M + H]+ 599 [01059]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.06 (3H, t, J = 7.5 Hz), 1.72 (1H, m), 1.81 (1H, m), 2.01 (1H, m), 2.13 (1H, m), 3.84 (1H, m), 4.00 (1H, m), 4.04-4.25 (3H, m), 4.35 (1H, dd, J = 10.7, 3.5 Hz), 4.62 (1H, m), 4.90 (1H, t, J = 3.9 Hz), 6.02 (1H, s), 6.92 (1H, d, J = 8.6 Hz), 7.34 (1H, d, J = 8.1 Hz), 7.47 (1H, dd, J = 8.7, 2.1 Hz), 7.51 (1H, d, J = 2.1 Hz). ESI-MS m/z: 412 [M + H]+ 600 (isomer A) [01060]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.25 (2H, m), 2.92 (1H, m), 3.79-3.87 (4H, m), 3.98 (1H, t, J = 8.9 Hz), 4.21 (1H, dd, J = 8.8, 10.8 Hz), 4.33-4.39 (2H, m), 4.65 (1H, m), 4.93 (1H, s), 5.46 (1H, m), 5.91 (1H, s), 6.97 (1H, d, J = 8.5 Hz), 7.27 (1H, m), 7.48 (1H, dd, J = 2.1, 8.7 Hz), 7.64 (1H, s). ESI-MS m/z: 496 [M + H]+ 600 (isomer B) [01061]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.26 (2H, m), 2.97 (1H, m), 3.81-3.87 (4H, m), 3.99 (1H, dd, J = 7.8, 10.1 Hz), 4.20 (1H, dd, J = 9.0, 10.8 Hz), 4.33-4.37 (2H, m), 4.64 (1H, m), 4.92 (1H, s), 5.45 (1H, m), 5.81 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.28 (1H, m), 7.48 (1H, dd, J = 2.1, 8.7 Hz), 7.62 (1H, d, J = 1.7 Hz). ESI-MS m/z: 496 [M + H]+
TABLE-US-00078 TABLE 78 Example Structural formula NMR MS 601 (isomer A) [01062]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73 (1H, m), 1.99 (1H, m), 2.38 (1H, m), 2.86 (1H, dd, J = 4.4, 16.9 Hz), 3.04 (2H, dt, J = 4.5, 17.4 Hz), 3.17 (1H, dd, J = 5.4, 16.8 Hz), 3.59-3.67 (2H, m), 3.74-3.85 (3H, m), 4.08 (1H, m), 4.18-4.19 (2H, m), 4.28-4.34 (2H, m), 4.61 (1H, m), 5.81 (1H, tt, J = 4.5, 85.1 Hz), 6.23 (1H, s), 6.85 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.01 (2H, dd, J = 2.2, 8.4 Hz). ESI-MS m/z: 490 [M + H]+ 601 (isomer B) [01063]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73 (1H, m), 2.00 (1H, m), 2.38 (1H, m), 2.86 (1H, dd, J = 4.4, 16.7 Hz), 2.99-3.09 (2H, m, J = 7.9 Hz), 3.17 (1H, dd, J = 5.4, 16.8 Hz), 3.58-3.67 (2H, m), 3.73-3.85 (3H, m), 4.09 (1H, m), 4.18-4.19 (2H, m), 4.28-4.34 (2H, m), 4.61 (1H, m), 5.88 (1H, tt, J = 4.5, 56.8 Hz), 6.23 (1H, s), 6.85 (1H, d, J = 8.3 Hz), 6.94 (1H, s), 7.00-7.04 (2H, m). ESI-MS m/z: 490 [M + H]+ 602 (isomer A) [01064]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.73 (1H, m), 2.00 (1H, m), 2.38 (1H, m), 2.87 (1H, dd, J = 4.3, 16.8 Hz), 3.18 (1H, dd, J = 5.4, 16.6 Hz), 3.59-3.67 (2H, m), 3.75-3.85 (5H, m), 4.08 (1H, m), 4.20 (2H, d, J = 2.9 Hz), 4.27-4.33 (2H, m), 4.57 (2H, s), 4.62 (1H, m), 6.23 (1H, s), 6.88 (1H, d, J = 8.3 Hz), 7.01 (1H, d, J = 8.8 Hz), 7.05 (1H, m), 7.12 (1H, dd, J = 2.1, 8.4 Hz). ESI-MS m/z: 538 [M + H]+ 602 (isomer B) [01065]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.72 (1H, m), 1.99 (1H, m), 2.38 (1H, m), 2.88 (1H, dd, J = 4.1, 16.4 Hz), 3.18 (1H, dd, J = 5.3, 16.8 Hz), 3.58-3.66 (2H, m), 3.73-3.86 (5H, m), 4.09 (1H, m), 4.21 (2H, d, J = 2.8 Hz), 4.27-4.33 (2H, m), 4.57 (2H, s), 4.62 (1H, m), 8.23 (1H, s), 6.88 (1H, d, J = 8.3 Hz), 7.00-7.05 (2H, m), 7.12 (1H, dd, J = 2.0, 8.4 Hz). ESI-MS m/z: 538 [M + H]+ 603 (isomer A) [01066]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.84 (2H, m), 1.99 (2H, m), 3.42 (1H, d, J = 4.9 Hz), 3.69 (2H, m), 3.77-3.87 (3H, m), 4.20 (1H, dd, J = 10.7, 9.2 Hz, 4.27 (1H, dd, J = 10.7, 9.8 Hz), 4.34 (1H, dd, J = 10.6, 3.0 Hz), 4.61 (1H, m), 4.91 (1H, t, J = 4.2 Hz), 5.32 (1H, m), 6.89 (1H, s), 6.94 (1H, d, J = 8.6 Hz), 7.29 (1H, d, J = 8.3 Hz), 7.47 (1H, dd, J = 6.7, 1.9 Hz), 7.61 (1H, d, J = 1.9 Hz). ESI-MS m/z: 510 [M + H]+ 603 (isomer B) [01067]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.84 (2H, m), 1.99 (2H, m), 3.42 (1H, d, J = 4.9 Hz), 3.69 (2H, m), 3.77-3.87 (3H, m), 4.17- 4.28 (2H, m), 4.34 (1H, dd, J = 10.8, 3.0 Hz), 4.61 (1H, m), 4.91 (1H, t, J = 4.2 Hz), 5.32 (1H, m), 5.89 (1H, s), 8.94 (1H, d, J = 8.6 Hz), 7.29 (1H, d, J = 8.3 Hz), 7.47 (1H, dd, J = 8.7, 1.9 Hz), 7.51 (1H, d, J = 1.9 Hz). ESI-MS m/z: 510 [M + H]+ 604 (isomer A) [01068]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.79 (2H, m), 1.99 (2H, m), 2.89 (1H, dd, J = 16.8, 4.5 Hz), 3.17 (1H, dd, J = 16.9, 5.1 Hz), 3.52- 3.73 (4H, m), 3.89 (1H, dd, J = 9.8, 7.7 Hz), 4.23-4.30 (2H, m), 4.33 (1H, dd, J = 9.8, 8.3 Hz), 4.64 (1H, m), 5.38 (1H, m), 5.85 (1H, tt, J = 55.4, 4.0 Hz), 5.89 (1H, s), 6.92 (1H, d, J = 7.7 Hz), 6.93 (1H, d, J = 8.5 Hz), 7.38 (1H, d, J = 2.1 Hz), 7.42 (1H, dd, J = 8.5, 2.1 Hz). ESI-MS m/z: 433 [M + H]+ 604 (isomer B) [01069]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.79 (2H, m), 1.99 (2H, m), 2.89 (1H, dd, J = 16.8, 4.5 Hz), 3.17 (1H, dd, J = 16.9, 5.1 Hz), 3.52- 3.73 (4H, m), 3.89 (1H, dd, J = 9.8, 7.7 Hz), 4.23-4.30 (2H, m), 4.33 (1H, dd, J = 9.8, 8.3 Hz), 4.64 (1H, m), 5.38 (1H, m), 5.85 (1H, tt, J = 55.4, 4.0 Hz), 5.89 (1H, s), 6.92 (1H, d, J = 7.7 Hz), 6.93 (1H, d, J = 8.5 Hz), 7.38 (1H, d, J = 2.1 Hz), 7.42 (1H, dd, J = 8.5, 2.1 Hz). ESI-MS m/z: 433 [M + H]+ 605 [01070]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.33-1.43 (2H, m), 1.62-1.75 (3H, m), 1.86 (1H, m), 1.98 (1H, m), 2.86 (1H, dd, J = 4.0, 16.7 Hz), 3.16 (1H, dd, J = 5.6, 16.6 Hz), 3.41 (2H, t, J = 11.2 Hz,), 3.78- 3.87 (3H, m), 3.97-4.01 (2H, m), 4.20 (2H, d, J = 2.9 Hz), 4.33 (1H, m), 4.56 (2H, s), 4.63 (1H, m), 5.38 (1H, m), 5.89 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 7.5 Hz), 7.04 (1H, s), 7.11 (1H, dd, J = 2.0, 8.4 Hz). ESI-MS m/z: 496 [M + H]+
TABLE-US-00079 TABLE 79 Example Structural formula NMR MS 606 [01071]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.44-1.66 (3H, m), 1.82-1.97 (2H, m), 2.07 (1H, m), 2.19 (1H, m), 2.87 (1H, dd, J = 16.7, 4.2 Hz), 3.17 (1H, dd, J = 16.7, 5.4 Hz), 3.35-3.45 (2H, m), 3.79 (1H, d, J = 8.7 Hz), 3.85 (1H, d, J = 8.7 Hz), 3.94 (1H, m), 3.99- 4.06 (3H, m), 4.14-4.24 (3H, m), 4.57 (2H, s), 4.62 (1H, s), 5.98 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.05 (1H, d, J = 1.6 Hz), 7.12 (1H, dd, J = 8.3, 1.8 Hz). ESI-MS m/z: 496 [M + H]+ 607 [01072]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80 (2H, m), 2.00 (2H, m), 3.55- 3.72 (4H, m), 3.76 (1H, m), 3.83-3.96 (1H, m), 4.07- 4.24 (2H, m), 4.34 (1H, dd, J = 10.7, 3.6 Hz), 4.63 (1H, m), 4.92 (1H, m), 5.33 (1H, m), 5.86 (1H, tt, J = 55.6, 4.0), 5.86 (1H, s), 6.95 (1H, d, J = 8.6 Hz), 7.28 (1H, m), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.60 (0.5H, d, J = 1.8 Hz), 7.63 (0.5H, d, J = 1.8 Hz). ESI-MS m/z: 492 [M + H]+ 608 (isomer A) [01073]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80 (2H, m), 2.00 (2H, m), 3.36 (1H, br s), 3.55-3.72 (4H, m), 3.84 (1H, dd, J = 9.9, 7.7 Hz), 4.15-4.39 (3H, m), 4.62 (1H, m), 4.92 (1H, m), 5.33 (1H, m), 5.86 (1H, tt, J = 55.6, 4.0), 5.89 (1H, s), 6.96 (1H, d, J = 8.6 Hz), 7.28 (1H, d, J = 8.1 Hz), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.63 (1H, d, J = 1.8 Hz). ESI-MS m/z: 492 [M + H]+ 608 (isomer B) [01074]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80 (2H, m), 2.00 (2H, m), 3.44 (1H, br s), 3.55-3.72 (4H, m), 3.84 (1H, dd, J = 9.9, 7.7 Hz), 4.15-4.39 (3H, m), 4.62 (1H, m), 4.92 (1H, m), 5.33 (1H, m), 5.86 (1H, tt, J = 55.6, 4.0), 5.89 (1H, s), 6.96 (1H, d, J = 8.6 Hz), 7.28 (1H, d, J = 8.1 Hz), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.63 (1H, d, J = 1.8 Hz). ESI-MS m/z: 492 [M + H]+ 609 [01075]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.57-1.80 (2H, m), 1.90 (2H, m), 3.46-3.65 (4H, m), 3.74-3.85 (2H, m), 4.20-4.30 (2H, m), 4.38 (1H, m), 4.67 (1H, m), 4.92 (1H, m), 5.25 (1H, m), 5.78 (1H, m), 5.80 (1H, s), 6.93 (1H, d, J = 8.6 Hz), 6.96 (1H, m), 7.40 (1H, dd, J = 8.6, 1.8 Hz), 7.58 (1H, m). ESI-MS m/z: 492 [M + H]+ 610 (isomer A) [01076]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80 (2H, m), 2.00 (2H, m), 3.55- 3.72 (4H, m), 3.84 (1H, br s), 3.84 (1H, dd, J = 9.9, 7.7 Hz), 4.20 (1H, dd, J = 10.8, 9.1 Hz), 4.29 (1H, dd, J = 8.7, 8.3 Hz), 4.34 (1H, dd, J = 10.7, 3.6 Hz), 4.62 (1H, m), 4.92 (1H, m), 5.33 (1H, m), 5.86 (1H, tt, J = 55.6, 4.0), 5.89 (1H, s), 6.96 (1H, d, J = 8.6 Hz), 7.28 (1H, d, J = 8.1 Hz), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.63 (1H, d, J = 1.8 Hz). ESI-MS m/z: 492 [M + H]+ 610 (isomer B) [01077]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.80 (2H, m), 2.00 (2H, m), 3.55- 3.72 (4H, m), 3.84 (1H, dd, J = 9.9, 7.7 Hz), 4.06 (1H, br s), 4.20 (1H, dd, J = 10.8, 9.1 Hz), 4.29 (1H, dd, J = 8.7, 8.3 Hz), 4.34 (1H, dd, J = 10.7, 3.6 Hz), 4.62 (1H, m), 4.92 (1H, m), 5.33 (1H, m), 5.86 (1H, tt, J = 55.6, 4.0), 6.89 (1H, s), 6.96 (1H, d, J = 8.6 Hz), 7.28 (1H, d, J = 6.1 Hz), 7.46 (1H, dd, J = 6.6, 1.8 Hz), 7.63 (1H, d, J = 1.8 Hz). ESI-MS m/z: 492 [M + H]+ 611 [01078]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.66 (1H, m), 1.90-2.29 (3H, m), 2.56 (1H, m), 2.84 (1H, dd, J = 16.9, 4.2 Hz), 3.14 (1H, dd, J = 16.8, 5.3 Hz), 3.60-3.99 (4H, m), 4.00-4.23 (5H, m), 4.60 (1H, m), 5.97-6.01 (1H, m), 6.94 (1H, d, J = 8.5 Hz), 7.00 (1H, d, J = 8.7 Hz), 7.03 (1H, d, J = 2.5 Hz), 7.07 (1H, dd, J = 8.5, 2.5 Hz). ESI-MS m/z: 404 [M + H]+ 612 [01079]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.66 (1H, m), 1.90-2.29 (3H, m), 2.55 (1H, m), 2.91 (1H, dd, J = 16.8, 4.4 Hz), 3.19 (1H, dd, J = 16.8, 5.2 Hz), 3.60-3.99 (4H, m), 4.00-4.29 (5H, m), 4.64 (1H, m), 5.98-6.02 (1H, m), 6.94 (1H, d, J = 8.5 Hz), 6.98 (1H, d, J = 7.8 Hz), 7.33 (1H, d, J = 1.8 Hz), 7.38 (1H, dd, J = 8.5, 1.8 Hz). ESI-MS m/z: 438 [M + H]+
TABLE-US-00080 TABLE 80 Example Structural formula NMR MS 613 [01080]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.6 (1H, m), 1.87-2.33 (3H, m), 2.56 (1H, m), 3.58-4.20 (8H, m), 4.21-4.50 (2H, m), 4.65- 4.87 (1H, m), 5.33-5.62 (1H, m), 5.96-6.07 (1H, m), 6.95 (0.5H, m), 7.00-7.10 (1H, m), 7.18 (0.5H, m), 7.55- 7.68 (1H, m). ESI-MS m/z: 456 [M + H]+ 614 [01081]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.6 (1H, m), 1.870-2.33 (3H, m), 2.56 (1H, m), 3.58-4.20 (8H, m), 4.21-4.50 (2H, m), 4.65- 4.87 (1H, m), 5.33-4.62 (1H, m), 5.96-6.07 (1H, m), 6.93 (0.5H, m), 6.99-7.09 (1H, m), 7.18 (0.5H, m), 7.56- 7.68 (1H, m). ESI-MS m/z: 456 [M + H]+ 615 (isomer A) [01082]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.44-1.66 (3H, m), 1.82-1.97 (2H, m), 2.07 (1H, m), 2.19 (1H, m), 2.87 (1H, dd, J = 16.7, 4.2 Hz), 3.17 (1H, dd, J = 16.7, 6.4 Hz), 3.36-3.46 (2H, m), 3.79 (1H, d, J = 8.7 Hz), 3.85 (1H, d, J = 8.7 Hz), 3.94 (1H, m), 3.99- 4.08 (3H, m), 4.14-4.24 (3H, m), 4.57 (2H, s), 4.62 (1H, m), 5.98 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.05 (1H, d, J = 1.8 Hz), 7.12 (1H, dd, J = 8.3, 1.8 Hz). ESI-MS m/z: 496 [M + H]+ 615 (isomer B) [01083]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.44-1.66 (3H, m), 1.82-1.97 (2H, m), 2.07 (1H, m), 2.19 (1H, m), 2.87 (1H, dd, J = 16.7, 4.2 Hz), 3.17 (1H, dd, J = 16.7, 5.4 Hz), 3.35-3.45 (2H, m), 3.79 (1H, d, J = 8.7 Hz), 3.85 (1H, d, J = 8.7 Hz), 3.94 (1H, m), 3.99- 4.08 (3H, m), 4.14-4.24 (3H, m), 4.57 (2H, s), 4.62 (1H, m), 5.98 (1H, s), 6.94 (1H, d, J = 8.5 Hz), 6.87 (1H, d, J = 8.3 Hz), 7.05 (1H, d, J = 1.8 Hz), 7.12 (1H, dd, J = 8.3, 1.8 Hz). ESI-MS m/z: 496 [M + H]+ 616 (isomer A) [01084]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.70-1.92 (2H, m), 1.96-2.07 (2H, m), 3.60-3.75 (2H, m), 3.80 (2H, m), 3.88 (1H, m), 4.07 (1H, br s), 4.27-4.34 (2H, m), 4.43-4.54 (2H, m), 4.75 (1H, m), 5.31 (1H, m), 5.87 (1H, s), 6.96 (1H, d, J = 8.6 Hz), 7.03 (1H, d, J = 7.6 Hz), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.64 (1H, d, J = 1.8 Hz). ESI-MS m/z: 510 [M + H]+ 616 (isomer B) [01085]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.70-1.92 (2H, m), 1.96-2.07 (2H, m), 3.60-3.75 (2H, m), 3.80 (2H, m), 3.88 (1H, m), 4.07 (1H, br s), 4.27-4.34 (2H, m), 4.43-4.54 (2H, m), 4.75 (1H, m), 5.31 (1H, m), 5.87 (1H, s), 6.96 (1H, d, J = 8.6 Hz), 7.03 (1H, d, J = 7.6 Hz), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.64 (1H, d, J = 1.8 Hz). ESI-MS m/z: 510 [M + H]+ 617 (isomer A) [01086]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.23 (2H, m), 0.57 (2H, m), 1.07 (1H, m), 2.14-2.37 (2H, m), 3.39 (2H, d, J = 6.9 Hz), 3.68 (1H, dd, J = 10.2, 6.2 Hz), 3.78 (1H, dd, J = 10.2, 5.2 Hz), 4.05- 4.48 (5H, m), 4.62-4.98 (1H, m), 5.48 (1H, dd, J = 54.2, 1.7 Hz), 6.06 (1H, s), 7.02 (1H, d, J = 8.8 Hz), 7.16 (1H, m), 7.60 (1H, dt, J = 8.8, 1.7 Hz), 7.68 (1H, t, J = 1.7 Hz). ESI-MS m/z: 427 [M + H]+ 617 (isomer B) [01087]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.23 (2H, m), 0.57 (2H, m), 1.07 (1H, m), 2.14-2.37 (2H, m), 3.39 (2H, d, J = 6.9 Hz), 3.68 (1H, dd, J = 10.2, 6.2 Hz), 3.78 (1H, dd, J = 10.2, 5.2 Hz), 4.05- 4.48 (5H, m), 4.62-4.98 (1H, m), 5.48 (1H, dd, J = 54.2, 1.7 Hz), 6.06 (1H, s), 7.02 (1H, d, J = 8.8 Hz), 7.16 (1H, m), 7.60 (1H, dt, J = 8.8, 1.7 Hz), 7.68 (1H, t, J = 1.7 Hz). ESI-MS m/z: 427 [M + H]+ 617 (isomer C) [01088]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.23 (2H, m), 0.57 (2H, m), 1.07 (1H, m), 2.14-2.37 (2H, m), 3.39 (2H, d, J = 6.9 Hz), 3.68 (1H, dd, J = 10.2, 5.2 Hz), 3.78 (1H, dd, J = 10.2, 5.2 Hz), 4.05- 4.48 (5H, m), 4.62-4.98 (1H, m), 5.48 (1H, dd, J = 54.2, 1.7 Hz), 6.06 (1H, s), 7.02 (1H, d, J = 8.8 Hz), 7.16 (1H, m), 7.60 (1H, dt, J = 8.8, 1.7 Hz), 7.68 (1H, t, J = 1.7 Hz). ESI-MS m/z: 427 [M + H]+
TABLE-US-00081 TABLE 81 Ex- ample Structural formula NMR MS 617 (isomer D) [01089]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.23 (2H, m), 0.57 (2H, m), 1.07 (1H, m), 2.14-2.37 (2H, m), 3.39 (2H, d, J = 6.9 Hz), 3.68 (1H, dd, J = 10.2, 5.2 Hz), 3.78 (1H, dd, J = 10.2, 5.2 Hz), 4.05- 4.48 (5H, m), 4.62-4.98 (1H, m), 5.48 (1H, dd, J = 54.2, 1.7 Hz), 6.06 (1H, s), 7.02 (1H, d, J = 8.8 Hz), 7.16 (1H, m), 7.60 (1H, dt, J = 8.8, 1.7 Hz), 7.68 (1H, t, J = 1.7 Hz). ESI-MS m/z: 427 [M + H]+ 618 [01090]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.11-0.20 (2H, m), 0.46-0.55 (2H, m), 0.99 (1H, m), 1.60 (3H, s), 2.90 (1H, dd, J = 4.5, 16.8 Hz), 3.17 (1H, dd, J = 2.0, 10.4 Hz), 3.64 (1H, dd, J = 3.9, 6.8 Hz), 3.58 (1H, dd, J = 2.0, 10.4 Hz), 3.64 (1H, dd, J = 3.6, 10.4 Hz), 3.89 (1H, dd, J = 1.9, 9.8 Hz), 4.23-4.35 (3H, m), 4.64 (1H, m), 5.88 (1H, s), 6.93 (2H, d, J = 8.5 Hz), 7.38 (1H, s), 7.42 (1H, dd, J = 2.0, 8.5 Hz). ESI-MS m/z: 409 [M + H]+ 619 [01091]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.11-0.20 (2H, m), 0.46-0.55 (2H, m), 0.99 (1H, m), 1.60 (3H, s), 2.85 (1H, dd, J = 4.2, 16.8 Hz), 3.04 (2H, dt, J = 4.5, 17.4 Hz), 3.17 (1H, dd, J = 5.4, 16.8 Hz), 3.34 (2H, dd, J = 4.8, 6.8 Hz), 3.56-3.65 (2H, m), 3.89 (1H, dd, J = 3.8, 9.8 Hz), 4.19 (2H, s), 4.32 (1H, dd, J = 3.4, 9.8 Hz), 4.62 (1H, m), 5.72-6.03 (2H, m), 6.83 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 7.00 (2H, dd, J = 2.0, 8.2 Hz). ESI-MS m/z: 448 [M + H]+ 620 [01092]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13 (1H, m), 2.32 (1H, m), 2.91 (1H, dd, J = 16.8, 4.4 Hz), 3.19 (1H, dd, J = 16.8, 5.4 Hz), 3.60- 3.91 (7H, m), 4.07 (1H, m), 4.15-4.30 (4H, m), 4.64 (1H, m), 6.04 (1H, s), 6.94 (1H, d, J = 8.6 Hz), 6.98 (1H, d, J = 8.0 Hz), 7.32 (1H, d, J = 1.8 Hz), 7.38 (1H, dd, J = 8.6, 1.8 Hz) ESI-MS m/z: 454 [M + H]+ 621 [01093]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.17-2.28 (2H, m), 3.49 (3H, s), 3.61-3.88 (4H, m), 4.02 (1H, m), 4.25-4.29 (2H, m), 4.34 (1H, d, J = 3.6 Hz), 4.41 (1H, m), 4.69 (1H, m), 5.46 (1H, m), 5.92 (1H, s), 6.97 (1H, d, J = 9.3 Hz), 7.21 (1H, d, J = 8.4 Hz), 7.49-7.51 (2H, m). ESI-MS m/z: 510 [M + H]+ 622 (isomer A) [01094]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.30-1.45 (2H, m), 1.63-1.74 (3H, m), 1.85 (1H, m), 1.98 (1H, m), 2.86 (1H, m), 3.18 (1H, dd, J = 5.5, 16.7 Hz), 3.41 (2H, dt, J = 2.2, 11.8 Hz), 3.78-3.86 (3H, m), 3.95-4.01 (2H, m), 4.20 (2H, d, J = 2.9 Hz), 4.34 (1H, dd, J = 6.2, 9.7 Hz), 4.56 (2H, s), 4.62 (1H, m), 5.38 (1H, m), 5.89 (1H, s), 6.67 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 8.2 Hz), 7.04 (1H, s), 7.11 (1H, dd, J = 2.0, 8.3 Hz). ESI-MS m/z: 496 [M + H]+ 622 (isomer B) [01095]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.31-1.45 (2H, m), 1.63-1.74 (3H, m), 1.86 (1H, m), 1.99 (1H, m), 2.86 (1H, m), 3.18 (1H, dd, J = 5.5, 16.8 Hz), 3.42 (2H, dt, J = 2.2, 11.8 Hz), 3.78-3.87 (3H, m), 3.96-4.01 (2H, m), 4.20 (2H, d, J = 2.9 Hz), 4.34 (1H, dd, J = 8.2, 9.7 Hz), 4.56 (2H, s), 4.62 (1H, m), 5.37 (1H, m), 5.89 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00 (1H, d, J = 7.9 Hz), 7.04 (1H, s), 7.11 (1H, dd, J = 2.0, 8.3 Hz). ESI-MS m/z: 496 [M + H]+ 623 [01096]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.23-1.38 (4H, m), 1.45-1.54 (3H, m), 1.82-1.97 (2H, m), 2.90 (1H, dd, J = 4.5, 17.0 Hz), 3.17 (1H, dd, J = 5.2, 16.6 Hz), 3.37 (2H, t, J = 11.7 Hz), 3.88 (1H, m), 3.96 (2H, dd, J = 4.0, 11.3 Hz), 4.24-4.34 (3H, m), 4.64 (1H, m), 5.27 (1H, m), 5.89 (1H, s), 6.90- 6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, dd, J = 2.0, 8.5 Hz). ESI-MS m/z: 423 [M + H]+ 624 [01097]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.18-2.31 (2H, m), 3.70-3.92 (4H, m), 4.02-4.21 (2H, m), 4.22-4.46 (3H, m), 4.66-4.83 (1H, m), 5.35-5.59 (1H, m), 5.70-6.06 (1H, m), 6.03 (0.5H, s), 6.07 (0.5H, s), 6.93 (0.5H, m), 7.03 (0.5H, m), 7.07 (0.5H, m), 7.18 (0.5H, m), 7.53-7.69 (2H, m). ESI-MS m/z: 480 [M + H]+
TABLE-US-00082 TABLE 82 Example Structural formula NMR MS 625 [01098]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.45-1.57 (1H, m), 1.68-1.75 (2H, m), 1.87-1.99 (2H, m), 2.16-2.25 (2H, m), 2.74-2.81 (2H, m), 2.93-3.07 (2H, m), 3.49-3.55 (2H, m), 3.73-3.79 (2H, m), 3.86-3.98 (1H, m), 4.09-4.15 (1H, m), 4.21 (1H, m), 4.35-4.45 (1H, m), 4.69-4.86 (1H, m), 5.38-5.59 (1H, m), 6.51-6.55 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 463 [M + H]+ 626 [01099]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.35-2.54 (2H, m), 2.92 (1H, dd, J = 16.8, 3.9 Hz), 3.11 (1H, dd, J = 16.8, 5.7 Hz), 4.10- 4.21 (3H, m), 4.27 (1H, m), 4.53-4.69 (2H, m), 6.14 (1H, s), 6.62 (1H, m), 6.95 (1H, q, J = 9.3 Hz), 7.00 (1H, m). ESI-MS m/z: 404 [M + H]+ 627 [01100]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.19-2.29 (2H, m), 2.92 (1H, dd, J = 16.8, 4.1 Hz), 3.11 (1H, dd, J = 16.8, 5.7 Hz), 3.83- 3.99 (4H, m), 4.06-4.25 (4H, m), 4.37 (1H, m), 4.63 (1H, m), 6.04 (1H, s), 6.61 (1H, m), 6.94 (1H, q, J = 9.3 Hz), 7.00 (1H, m). ESI-MS m/z: 448 [M + H]+ 628 [01101]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69-1.94 (2H, m), 1.95-2.11 (2H, m), 2.92 (1H, dd, J = 16.8, 3.6 Hz), 3.10 (1H, dd, J = 16.8, 5.7 Hz), 3.82 (2H, m), 3.69 (2H, m), 3.89 (1H, m), 4.10- 4.21 (2H, m), 4.34 (1H, m), 4.64 (1H, m), 5.33 (1H, m), 5.89 (1H, s), 6.61 (1H, m), 6.94 (1H, q, J = 9.3 Hz), 6.98 (1H, m). ESI-MS m/z: 462 [M + H]+ 629 [01102]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.24 (2H, m), 2.91 (1H, dd, J = 16.8, 3.9 Hz), 3.10 (1H, dd, J = 16.8, 5.6 Hz), 3.78- 3.86 (4H, m), 3.98 (1H, m), 4.10-4.21 (2H, m), 4.36 (1H, m), 4.64 (1H, m), 5.45 (1H, m), 5.91 (1H, s), 6.61 (1H, m), 6.94 (1H, q, J = 9.3 Hz), 6.99 (1H, m). ESI-MS m/z: 448 [M + H]+ 630 [01103]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.69 (1H, m), 1.91-2.31 (3H, m), 2.57 (1H, m), 2.88 (1H, dd, J = 16.7, 4.3 Hz), 3.19 (1H, dd, J = 16.7, 5.4 Hz), 3.60-4.28 (11H, m), 4.55-4.72 (3H, m), 5.98-6.04 (1H, m), 6.88 (1H, m), 7.04 (1H, m), 7.06 (1H, s), 7.13 (1H, m). ESI-MS m/z: 482 [M + H]+ 631 [01104]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16 (1H, m), 2.40 (1H, m), 2.88 (1H, dd, J = 16.7, 4.3 Hz), 3.95 (1H, dd, J = 16.7, 5.4 Hz), 3.46- 3.90 (8H, m), 3.99-4.28 (6H, m), 4.58 (2H, s), 4.63 (1H, m), 6.02 (1H, s), 6.88 (1H, m), 7.04 (1H, m), 7.07 (1H, s), 7.13 (1H, m). ESI-MS m/z: 496 [M + H]+ 632 [01105]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91 (1H, m), 2.30 (1H, m), 2.78- 2.90 (2H, m), 3.19 (1H, dd, J = 5.1, 17.0 Hz), 3.76-3.86 (3H, m), 4.08 (1H, m), 4.20-4.21 (2H, m), 4.45 (1H, m), 4.53-4.57 (3H, m), 4.62 (1H, m), 6.28 (1H, s), 6.88 (1H, d, J = 8.4 Hz), 7.00-7.06 (2H, m), 7.12 (1H, dd, J = 2.1, 8.3 Hz). ESI-MS m/z: 494 [M + H]+ 633 [01106]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91 (1H, m), 2.30 (1H, m), 2.78- 2.88 (2H, m), 3.04 (2H, dt, J = 4.5, 17.5 Hz), 3.17 (1H, dd, J = 5.4, 16.7 Hz), 3.80 (1H, m), 4.10 (1H, m), 4.19 (2H, d, J = 2.8 Hz), 4.46 (1H, m), 4.55 (1H, m), 4.62 (1H, m), 5.88 (1H, m), 6.28 (1H, s), 6.85 (1H, d, J = 8.4 Hz), 6.94 (1H, s), 7.00-7.02 (2H, m). ESI-MS m/z: 446 [M + H]+
TABLE-US-00083 TABLE 83 Example Structural formula NMR MS 634 [01107]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.77 (1H, m), 2.03 (1H, m), 2.37 (1H, m), 3.58-4.85 (11H, m), 5.47 (1H, m), 6.25 (1H, m), 6.91-7.19 (2H, m), 7.57-7.66 (2H, m). ESI-MS m/z: 512 [M + H]+ 635 [01108]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.16-2.27 (2H, m), 2.87 (1H, dd, J = 16.7, 4.3 Hz), 3.18 (1H, dd, J = 16.7, 5.4 Hz), 3.71- 3.88 (6H, m), 4.02-4.25 (4H, m), 4.36 (1H, m), 4.57 (2H, s), 4.62 (1H, m), 5.70-6.06 (1H, m), 6.02 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.01 (1H, m), 7.04 (1H, d, J = 1.8 Hz), 7.12 (1H, dd, J = 8.6, 1.8 Hz). ESI-MS m/z: 506 [M + H]+ 636 (isomer A) [01109]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.21 (2H, m), 0.49-0.56 (2H, m), 1.03 (1H, m), 2.09-2.23 (2H, m), 3.08 (1H, s), 3.23- 3.31 (2H, m), 3.60-3.66 (2H, m), 3.98 (1H, m), 4.21 (1H, dd, J = 8.9, 10.9 Hz), 4.31-4.36 (2H, m), 4.64 (1H, m), 4.92 (1H, d, J = 3.8 Hz), 5.46 (1H, m), 5.90 (1H, s), 6.96 (1H, d, J = 8.6 Hz). 7.28 (1H, s), 7.48 (1H, dd, J = 2.2, 8.6 Hz), 7.63 (1H, s). ESI-MS m/z: 468 [M + H]+ 636 (isomer B) [01110]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18-0.21 (2H, m), 0.52-0.56 (2H, m), 1.03 (1H, m), 2.10-2.24 (2H, m), 3.09 (1H, s), 3.24- 3.31 (2H, m), 3.62-3.65 (2H, m), 4.01 (1H, dd, J = 7.9, 10.0 Hz), 4.20 (1H, dd, J = 9.1, 10.8 Hz), 4.28-4.36 (2H, m), 4.64 (1H, m), 4.92 (1H, d, J = 3.8 Hz), 5.45 (1H, m), 5.90 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.29 (1H, s), 7.48 (1H, dd, J = 2.1, 8.7 Hz), 7.61 (1H, d, J = 1.9 Hz). ESI-MS m/z: 468 [M + H]+ 637 [01111]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.68-1.74 (3H, m), 1.84-1.91 (3H, m), 2.83 (1H, m), 3.10-3.16 (2H, m), 3.38-3.46 (2H, m), 3.90-4.54 (6H, m), 4.68-4.86 (1H, m), 5.38-5.59 (1H, m), 6.56-6.60 (1H, m), 6.96-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 469 [M + H]+ 638 [01112]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.13 (1H, m), 2.34 (1H, m), 2.88 (1H, dd, J = 16.7, 4.3 Hz), 3.95 (1H, dd, J = 16.7, 5.4 Hz), 3.46- 3.90 (8H, m), 3.59-4.28 (6H, m), 4.58 (2H, s), 4.63 (1H, m), 6.05 (1H, s), 6.88 (1H, m), 7.04 (1H, m), 7.07 (1H, s), 7.13 (1H, m). ESI-MS m/z: 498 [M + H]+ 639 [01113]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.18 (2H, m), 0.53 (2H, m), 1.02 (1H, m), 2.06-2.25 (2H, m), 2.92 (1H, dd, J = 16.8, 3.9 Hz), 3.10 (1H, dd, J = 16.8, 5.7 Hz), 3.22-3.31 (2H, m), 3.58- 3.66 (2H, m), 4.02 (1H, m), 4.09-4.21 (2H, m), 4.34 (1H, m), 4.63 (1H, m), 5.45 (1H, m), 5.90 (1H, s), 6.61 (1H, m), 6.94 (1H, q, J = 9.3 Hz), 6.99 (1H, m). ESI-MS m/z: 420 [M + H]+ 640 [01114]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.70-1.89 (2H, m), 1.90-2.06 (2H, m), 2.92 (1H, dd, J = 16.8, 3.6 Hz), 3.10 (1H, dd, J = 16.8, 5.7 Hz), 3.55-3.71 (4H, m), 3.89 (1H, m), 4.09-4.21 (2H, m), 4.33 (1H, m), 4.64 (1H, m), 5.33 (1H, m), 5.68-6.02 (1H, m), 5.89 (1H, s), 6.61 (1H, m), 6.94 (1H, q, J = 9.3 Hz), 6.98 (1H, m). ESI-MS m/z: 444 [M + H]+ 641 (isomer A) [01115]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.95 (1H, s), 3.14 (2H, t, J = 5.4 Hz), 3.21 (2H, q, J = 9.8 Hz), 4.12 (1H, dd, J = 7.1, 10.1 Hz), 4.20 (1H, dd, J = 9.0, 10.8 Hz), 4.33-4.39 (2H, m), 4.64 (1H, m), 4.92 (1H, d, J = 3.8 Hz), 5.51 (1H, m), 5.95 (1H, s), 6.97 (1H, d, J = 8.7 Hz), 7.29 (1H, s), 7.49 (1H, dd, J = 2.1, 8.6 Hz), 7.62 (1H, d, J = 1.8 Hz). ESI-MS m/z: 498 [M + H]+
TABLE-US-00084 TABLE 84 Example Structural formula NMR MS 641 (isomer B) [01116]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.95 (1H, s), 3.13 (2H, dd, J = 1.9, 5.6 Hz), 3.21 (2H, q, J = 9.7 Hz), 4.12 (1H, m, 4.20 (1H, dd, J = 8.9, 10.9 Hz), 4.33-4.41 (2H, m), 4.64 (1H, m), 4.93 (1H, d, J = 3.8 Hz), 5.51 (1H, m), 5.94 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.28 (1H, s), 7.49 (1H, dd, J = 2.2, 8.7 Hz), 7.64 (1H, d, J = 1.9 Hz). ESI-MS m/z: 498 [M + H]+ 642 [01117]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.26-1.84 (5H, m), 2.47 (2H, m), 3.02 (2H, m), 3.36-3.44 (2H, m), 3.76 (2H, m), 3.98 (2H, m), 4.09-4.46 (4H, m), 4.69-4.87 (1H, m), 5.38-5.58 (1H, m), 6.53-6.58 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 483 [M + H]+ 643 [01118]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.89-2.95 (2H, m), 3.65-3.71 (2H, m), 3.84 (1H, m), 4.09-4.44 (5H, m), 4.69-4.82 (4H, m), 5.39-5.59 (1H, m), 6.55-6.59 (1H, m), 6.96-7.23 (2H, m), 7.57-7.66 (2H, m). ESI-MS m/z: 441 [M + H]+ 644 [01119]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.83 (2H, t, J = 5.2 Hz), 2.93 (1H, dd, J = 4.7, 17.4 Hz), 3.03 (2H, m), 3.21 (1H, dd, J = 5.5, 16.8 Hz), 3.78 (2H, s), 3.81-3.90 (4H, m), 4.14 (2H, m), 4.26 (2H, m), 4.66 (1H, m), 6.52 (1H, s), 6.95 (1H, d, J = 8.5 Hz), 7.00 (1H, d, J = 8.5 Hz), 7.33 (1H, s), 7.38 (1H, d, J = 8.6 Hz) ESI-MS m/z: 493 [M + H]+ 645 [01120]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.81-2.88 (2H, m), 2.95-3.09 (2H, m), 3.71-3.91 (6H, m), 4.09-4.49 (4H, m), 4.69-4.87 (1H, m), 5.38-5.59 (1H, m), 6.51-6.56 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 511 [M + H]+ 646 [01121]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.42-2.53 (1H, m), 2.63-2.80 (2H, m), 2.91-3.08 (3H, m), 3.69-3.85 (2H, m), 4.08-4.57 (5H, m), 4.66-4.86 (2H, m), 5.04-5.13 (1H, m), 5.38-5.58 (1H, m), 6.48-6.55 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 455 [M + H]+ 647 [01122]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.31-2.46 (2H, m), 2.79-3.02 (4H, m), 3.70-3.76 (2H, m), 4.09-4.48 (4H, m), 4.69-4.87 (1H, m), 5.38-5.59 (1H, m), 6.53-6.57 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 481 [M + H]+ 648 [01123]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.39-2.54 (2H, m), 4.06-4.28 (2H, m), 4.28-4.46 (2H, m), 4.62 (1H, m), 4.78 (1H, m), 5.50 (1H, dd, J = 54.1, 1.8 Hz), 6.17 (1H, s), 7.02 (1H, d, J = 8.6 Hz), 7.15 (1H, d, J = 8.8 Hz), 7.61 (1H, dt, J = 8.6, 2.0 Hz), 7.68 (1H, t, J = 2.0 Hz). ESI-MS m/z: 411 [M + H]+ 649 [01124]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.91-2.03 (2H, m), 2.36 (1H, m), 2.85 (1H, m), 3.86 (1H, m), 4.07-4.24 (2H, m), 4.39 (1H, m), 4.48-4.64 (1H, m), 4.79 (1H, m), 5.50 (1H, dd, J = 54.0, 1.8 Hz), 6.32 (1H, s), 7.02 (1H, d, J = 8.6 Hz), 7.15 (1H, d, J = 8.8 Hz), 7.61 (1H, dt, J = 8.6, 2.0 Hz), 7.69 (1H, t, J = 2.0 Hz). ESI-MS m/z: 425 [M + H]+
TABLE-US-00085 TABLE 85 Example Structural formula NMR MS 650 [01125]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.23 (2H, m), 0.57 (2H, m), 1.08 (1H, m), 2.14-2.37 (2H, m), 3.39 (2H, d, J = 6.9 Hz), 3.68 (1H, dd, J = 10.2, 5.2 Hz), 3.78 (1H, dd, J = 10.2, 5.2 Hz), 4.05- 4.48 (5H, m), 4.69-4.85 (1H, m), 5.48 (1H, dd, J = 54.0, 2.0 Hz), 6.06 (1H, s), 7.01 (1H, d, J = 8.6 Hz), 7.16 (1H, d, J = 8.9 Hz), 7.60 (1H, dt, J = 8.6, 2.0 Hz), 7.68 (1H, t, J = 2.0 Hz). ESI-MS m/z: 427 [M + H]+ 651 [01126]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86-1.99 (3H, m), 2.03-2.18 (2H, m), 2.70-2.90 (1H, m), 3.15 (1H, m), 3.77-4.24 (11H, m), 4.46- 4.65 (3H, m), 5.80-6.04 (1H, m), 6.86 (1H, dd, J = 8.2, 7.0 Hz), 7.02 (1H, m), 7.04 (1H, br s), 7.12 (1H, m). ESI-MS m/z: 482 [M + H]+ 652 [01127]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.20 (2H, m), 0.55 (2H, m), 1.07 (1H, m), 2.82 (2H, t, J = 5.4 Hz), 2.98-3.06 (3H, m), 3.31 (2H, d, J = 6.9 Hz), 3.66 (2H, t, J = 5.4 Hz), 3.79 (2H, d, J = 3.9 Hz), 4.16-4.24 (3H, m), 4.35 (1H, m), 4.66 (1H, m), 4.93 (1H, t, J = 4.2 Hz), 6.53 (1H, s), 6.97 (1H, d, J = 8.4 Hz), 7.29 (1H, m), 7.48 (1H, m), 7.63 (1H, m). ESI-MS m/z: 481 [M + H]+ 653 [01128]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.29 (2H, m), 1.68 (2H, m), 1.78 (1H, m), 2.40 (2H, d, J = 7.2 Hz), 2.89-2.95 (3H, m), 3.21 (1H, dd, J = 5.3, 16.5 Hz), 3.39 (2H, td, J = 1.9, 11.8 Hz), 3.65 (2H, s), 3.97 (2H, dd, J = 3.5, 12.0 Hz), 4.12 (2H, t, J = 5.4 Hz), 4.22-4.29 (2H, m), 4.66 (1H, m), 6.51 (1H, s), 6.95 (1H, d, J = 8.6 Hz), 7.00 (1H, d, J = 7.9 Hz), 7.33 (1H, s), 7.38 (1H, d, J = 8.7 Hz). ESI-MS m/z: 465 [M + H]+ 654 [01129]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.17-0.23 (2H, m), 0.51-0.58 (2H, m), 1.06 (1H, m), 2.78-2.84 (2H, m), 2.95-3.08 (2H, m), 3.29-3.33 (2H, m), 3.63-3.71 (2H, m), 3.75-3.81 (2H, m), 4.09-4.45 (4H, m), 4.69-4.87 (1H, m), 5.38-5.59 (1H, m), 6.51-6.55 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 483 [M + H]+ 655 [01130]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.24-1.42 (2H, m), 1.49 (1H, m), 1.63 (1H, m), 1.69-1.93 (3H, m), 2.00-2.19 (2H, m), 2.87 (1H, dd, J = 4.0, 16.9 Hz), 3.18 (1H, dd, J = 5.6, 17.0 Hz), 3.39-3.45 (2H, m), 3.82 (2H, q, J = 8.7 Hz), 3.96-3.98 (2H, m), 4.02-4.22 (4H, m), 4.29 (1H, m), 4.55-4.63 (3H, m), 5.99 (1H, s), 6.87 (1H, d, J = 8.3 Hz), 7.00-7.04 (2H, m), 7.11 (1H, dd, J = 1.9, 8.3 Hz). ESI-MS m/z: 510 [M + H]+ 656 [01131]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 0.93-1.01 (3H, m), 1.52-1.63 (2H, m), 1.75-1.99 (2H, m), 2.29 (1H, m), 3.72 (1H, m), 3.99- 4.47 (5H, m), 4.76 (1H, m), 5.43 (0.4H, m), 5.51 (0.6H, d, J = 54.4 Hz), 6.25 (0.4H, s), 6.29 (0.6H, s), 6.91-7.19 (2H, m), 7.52-7.66 (2H, m). ESI-MS m/z: 444 [M + H]+ 657 [01132]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.88 (1H, m), 3.19 (1H, m), 3.70- 3.85 (8H, m), 4.14-4.33 (4H, m), 4.64 (1H, m), 5.40 (1H, m), 5.91 (1H, s), 6.93-6.97 (2H, m), 7.33 (1H, s), 7.38 (1H, m). ESI-MS m/z: 610 [M + H]+ 658 [01133]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.83 (1H, dd, J = 4.2, 16.9 Hz), 3.14 (1H, dd, J = 5.3, 16.5 Hz), 3.71-3.85 (8H, m), 4.14-4.19 (3H, m), 4.30 (1H, dt, J = 2.9, 9.3 Hz), 4.60 (1H, m), 5.41 (1H, m), 5.90 (1H, s), 6.80 (1H, m), 6.99 (1H, m), 7.03 (1H, m), 7.08 (1H, m). ESI-MS m/z: 476 [M + H]+
TABLE-US-00086 TABLE 86 Ex- ample Structural formula NMR MS 659 [01134]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.89 (1H, dd, J = 4.4, 16.9 Hz), 3.17 (1H, dd, J = 5.3, 16.8 Hz), 3.71-3.86 (8H, m), 4.18-4.33 (4H, m), 4.63 (1H, m), 5.41 (1H, m), 5.91 (1H, s), 6.92- 6.94 (2H, m), 7.38 (1H, s), 7.42 (1H, m). ESI-MS m/z: 467 [M + H]+ 660 [01135]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.88 (1H, d, J = 4.9 Hz), 3.74-3.76 (4H, m), 3.80-3.87 (4H, m), 4.17-4.23 (2H, m), 4.30-4.35 (2H, m), 4.65 (1H, m), 4.92 (1H, m), 6.42 (1H, m), 5.92 (1H, s), 6.97 (1H, d, J = 8.7 Hz), 7.24 (1H, m), 7.48 (1H, m), 7.65 (1H, m). ESI-MS m/z: 526 [M + H]+ 661 [01136]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.84 (1H, m), 3.16 (1H, m), 3.71- 3.85 (10H, m), 4.09-4.32 (4H, m), 4.56-4.64 (3H, m), 5.40 (1H, m), 5.90 (1H, s), 6.86 (1H, m), 6.99-7.14 (3H, m). ESI-MS m/z: 554 [M + H]+ 662 [01137]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.27 (2H, m), 2.84 (1H, dd, J = 17.8, 4.6 Hz), 3.14 (1H, dd, J = 17.8, 7.7 Hz), 3.72 (3H, m), 3.79 (3H, m), 3.88 (2H, m), 4.04-4.13 (1H, m), 4.15- 4.26 (3H, m), 4.36 (1H, m), 4.60 (1H, m), 6.02 (1H, s), 6.81 (1H, d, J = 8.7 Hz), 7.00 (1H, d, J = 8.8 Hz), 7.04 (1H, d, J = 2.6 Hz), 7.08 (1H, dd, J = 8.7, 2.6 Hz). ESI-MS m/z: 490 [M + H]+ 663 [01138]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.28 (2H, m), 2.92 (1H, dd, J = 16.6, 4.4 Hz), 3.20 (1H, dd, J = 16.6, 5.3 Hz), 3.72 (3H, m), 3.79 (3H, m), 3.88 (2H, m), 4.04-4.13 (1H, m), 4.15- 4.29 (3H, m), 4.36 (1H, m), 4.63 (1H, m), 6.02 (1H, s), 6.94 (1H, d, J = 8.6 Hz), 6.97 (1H, d, J = 7.8 Hz), 7.33 (1H, d, J = 1.8 Hz), 7.38 (1H, dd, J = 8.6, 1.8 Hz). ESI-MS m/z: 524 [M + H]+ 664 [01139]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.14-2.28 (2H, m), 2.92 (1H, dd, J = 16.6, 5.1 Hz), 3.15 (1H, dd, J = 16.6, 5.4 Hz), 3.72 (3H, m), 3.79 (3H, m), 3.89 (2H, m), 4.04-4.13 (1H, m), 4.15- 4.29 (3H, m), 4.36 (1H, m), 4.63 (1H, m), 6.02 (1H, s), 6.93 (1H, d, J = 8.4 Hz), 6.94 (1H, m), 7.38 (1H, d, J = 2.0 Hz), 7.42 (1H, dd, J = 8.5, 2.0 Hz). ESI-MS m/z: 481 [M + H]+ 665 [01140]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.12-2.32 (2H, m), 3.66-3.97 (9H, m), 4.03-4.21 (2H, m), 4.22-4.27 (3H, m), 4.63-4.87 (1H, m), 5.33-5.61 (1H, m), 6.01 (0.5H, s), 6.06 (0.5H, s), 6.94 (0.5H, m), 6.99-7.10 (1H, m), 7.18 (0.5H, m), 7.54-7.67 (1H, m). ESI-MS m/z: 542 [M + H]+ 666 [01141]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.81 (2H, t, J = 5.3 Hz), 2.93 (1H, dd, J = 4.6, 16.8 Hz), 3.02 (2H, td, J = 2.0, 5.4 Hz), 3.21 (1H, dd, J = 5.4, 16.8 Hz), 3.66-3.77 (6H, m), 4.14 (2H, t, J = 5.5 Hz), 4.21-4.30 (2H, m), 4.65 (1H, m), 5.88 (1H, m), 6.52 (1H, s), 6.95 (1H, d, J = 8.6 Hz), 7.00 (1H, d, J = 7.8 Hz), 7.33 (1H, s), 7.38 (1H, m). ESI-MS m/z: 475 [M + H]+ 667 [01142]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.82-2.91 (3H, m), 3.02 (2H, d, J = 5.6 Hz), 3.18 (1H, dd, J = 5.0, 17.0 Hz), 3.77-3.90 (8H, m), 4.14 (2H, t, J = 5.6 Hz), 4.17-4.24 (2H, m), 4.57 (2H, s), 4.64 (1H, m), 6.52 (1H, s), 8.87 (1H, d, J = 8.3 Hz), 7.05 (2H, s), 7.12 (1H, dd, J = 1.9, 8.4 Hz). ESI-MS m/z: 537 [M + H]+
TABLE-US-00087 TABLE 87 Example Structural formula NMR MS 668 [01143]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.86-2.40 (5H, m), 2.71-2.88 (2H, m), 2.96-3.20 (3H, m), 3.15 (1H, m), 3.76-4.24 (7H, m), 4.43- 4.45 (1H, m), 5.69-6.03 (1H, m), 5.99-6.03 (1H, m), 6.83 (1H, m), 6.93 (1H, br s), 6.97-7.06 (2H, m). ESI-MS m/z: 437 [M + H]+ 669 [01144]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.63 (1H, m), 2.04 (1H, m), 2.46- 2.55 (3H, m), 2.87-2.99 (3H, m), 3.21 (1H, dd, J = 5.5, 16.6 Hz), 3.56 (1H, dd, J = 4.8, 8.7 Hz), 3.69 (2H, t, J = 4.3 Hz), 3.75 (1H, q, J = 8.2 Hz), 3.82-3.90 (2H, m), 4.13 (2H, t, J = 5.5 Hz), 4.22-4.29 (2H, m), 4.66 (1H, m), 6.52 (1H, s), 6.95 (1H, d, J = 8.6 Hz), 7.00 (1H, d, J = 8.0 Hz), 7.33 (1H, s), 7.38 (1H, d, J = 8.5 Hz). ESI-MS m/z: 451 [M + H]+ 670 [01145]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.87-1.99 (1H, m), 2.08-2.19 (1H, m), 2.81-3.07 (2H, m), 3.26 (1H, m), 3.62-4.04 (6H, m), 4.09-4.48 (4H, m), 4.69-4.85 (1H, m), 5.38-5.59 (1H, m), 6.52-6.56 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 455 [M + H]+ 671 [01146]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.15-1.19 (6H, m), 2.75-2.82 (2H, m), 2.96-3.08 (2H, m), 3.54-3.65 (3H, m), 3.74-3.80 (2H, m), 4.09-4.45 (4H, m), 4.69-4.87 (1H, m), 5.38-5.59 (1H, m), 6.50-6.55 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 471 [M + H]+ 672 [01147]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.18-1.30 (2H, m), 1.64 (1H, m), 1.81-1.95 (2H, m), 2.33-2.46 (2H, m), 2.78-3.00 (2H, m), 3.13-3.21 (1H, m), 3.38-3.46 (1H, m), 3.56-3.73 (2H, m), 3.83-3.98 (2H, m), 4.07-4.47 (4H, m), 4.69-4.87 (1H, m), 5.38-5.59 (1H, m), 6.50-6.54 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 483 [M + H]+ 673 [01148]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.63 (1H, m), 2.03 (1H, m), 2.48- 2.57 (3H, m), 2.87-2.99 (2H, m), 3.54-3.91 (6H, m), 4.09- 4.45 (4H, m), 4.68-4.87 (1H, m), 5.38-5.59 (1H, m), 6.51- 6.55 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 469 [M + H]+ 674 [01149]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.24-1.42 (2H, m), 1.49 (1H, m), 1.82 (1H, m), 1.71 (1H, m), 1.76-1.93 (2H, m), 2.00-2.19 (2H, m), 2.86 (1H, m), 3.04 (2H, dt, J = 4.4, 17.4 Hz), 3.16 (1H, dd, J = 5.3, 17.0 Hz), 3.42 (2H, tt, J = 1.8, 11.8 Hz), 3.95-3.99 (2H, m), 4.03-4.21 (4H, m), 4.30 (1H, m), 4.61 (1H, m), 5.88 (1H, tt, J = 4.5, 56.7 Hz), 5.99 (1H, s), 6.84 (1H, d, J = 8.3 Hz), 6.93 (1H, s), 6.99-7.01 (2H, m). ESI-MS m/z: 462 [M + H]+ 675 [01150]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 3.39 (1H, m), 3.71-3.85 (8H, m), 4.18 (1H, m), 4.26-4.32 (1H, m), 4.42 (1H, m), 4.49 (1H, m), 4.74 (1H, m), 5.40 (1H, m), 5.89 (1H, s), 6.99-7.02 (2H, m), 7.48 (1H, m), 7.65 (1H, m). ESI-MS m/z: 526 [M + H]+ 676 [01151]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 3.72-3.91 (8H, m), 4.07-4.44 (4H, m), 4.68-4.84 (1H, m), 5.36-5.58 (2H, m), 5.92 (1H, m), 6.89-7.13 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 528 [M + H]+
TABLE-US-00088 TABLE 88 Example Structural formula NMR MS 677 [01152]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.85 (2H, t, J = 5.2 Hz), 3.02-3.08 (3H, m), 3.78-3.90 (6H, m), 4.16 (2H, m), 4.22 (1H, m), 4.35 (1H, m), 4.66 (1H, m), 4.92 (1H, t, J = 4.2 Hz), 6.54 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.30 (1H, d, J = 8.3 Hz), 7.48 (1H, dd, J = 2.2, 8.6 Hz), 7.62 (1H, s). ESI-MS m/z: 509 [M + H]+ 678 [01153]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.79-2.86 (2H, m), 2.97-3.08 (2H, m), 3.65-3.80 (6H, m), 4.08-4.47 (4H, m), 4.69-4.87 (1H, m), 5.38-5.59 (1H, m), 5.72-6.04 (1H, m), 6.51-6.55 (1H, m), 6.95-7.22 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 493 [M + H]+ 679 [01154]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 2.01-2.15 (2H, m), 3.90-4.21 (7H, m), 4.34-4.54 (2H, m), 4.76 (1H, m), 5.43 (0.4H, m), 5.51 (0.6H, m), 6.26 (0.4H, s), 6.30 (0.6H, s), 6.90-7.18 (2H, m), 7.57-7.65 (2H, m). ESI-MS m/z: 498 [M + H]+ 680 [01155]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96-2.07 (2H, m), 2.92 (1H, dd, J = 16.7, 6.1 Hz), 3.21 (1H, br d, J = 16.7 Hz), 3.73- 4.17 (10H, m), 4.19-4.28 (2H, m), 4.42 (1H, m), 4.65 (1H, m), 6.49 (1H, s), 6.92-7.02 (2H, m), 7.33 (1H, br s), 7.39 (1H, m). ESI-MS m/z: 524 [M + H]+ 681 [01156]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96-2.11 (2H, m), 3.03-3.19 (1H, m), 3.69-3.85 (5H, m), 3.87-4.25 (6H, m), 4.29-4.47 (2H, m), 4.64 (1H, m), 4.92 (1H, m), 6.25-6.26 (1H, m), 6.97 (1H, d, J = 8.6 Hz), 7.25-7.32 (1H, m), 7.48 (1H, dd, J = 8.6, 1.8 Hz), 7.64 (1H, d, J = 1.8 Hz). ESI-MS m/z: 540 [M + H]+ 682 [01157]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.96-2.11 (2H, m), 2.85 (1H, m), 3.15 (1H, m), 3.72-3.83 (5H, m), 3.85-4.23 (7H, m), 4.40 (1H, m), 4.60 (1H, m), 6.24 (1H, s), 6.81 (1H, dd, J = 8.6, 2.0 Hz), 8.99 (1H, m), 7.04 (1H, m), 7.08 (1H, m). ESI-MS m/z: 490 [M + H]+ 683 [01158]![embedded image]()
1H-NMR (CDCl.sub.3) δ: 1.75 (1H, m), 2.02 (1H, m), 2.39 (1H, m), 2.79 (1H, dd, J = 4.7, 18.5 Hz), 3.62-3.67 (2H, m), 3.76-3.86 (3H, m), 4.13 (1H, m), 4.21 (1H, m), 4.33-4.36 (3H, m), 4.65 (1H, m), 4.93 (1H, brs), 6.25 (1H, s), 6.97 (1H, d, J = 8.6 Hz), 7.26-7.31 (1H, m), 7.49 (1H, m), 7.65 (1H, s). ESI-MS m/z: 610 [M + H]+
Test Example 1: Human Nav1.7 Inhibitory Activity Evaluation
[1653] A cell line in which human Nav1.7 and human Navβ1 subunits were stably expressed in HEK293A cells was used. Dulbecco's Modified Eagle Medium (DMEM) supplemeted with 10% fetal bovine serum, 600 μg/ml geneticin, and 2 μg/ml blasticidin S were used as culture medium under the conditions of 37° C. and 5% CO.sub.2 in T175 flasks to carry out culturing. When 60-80% confluence was reached, the cells were detached and a cell suspension of about 0.5-5.0×10.sup.6 cells/mL was prepared. The amount of current through human Nav1.7 was recorded using a fully automatic patch clamp device QPatch16X (Sophion Biosciences) at room temperature. As the extracellular solution, the solution of 145 mM NaCl, 4 mM KCl, 1 mM MgCl.sub.2, 2 mM CaCl.sub.2, 10 mM Glucose, 10 mM 4-(2-hydroxyethyl) -1-piperazine ethanesulfonic acid (HEPES) at pH 7.4 was used. As the intracellular solution, the solution of 135 mM CsF, 1/5 mM glycol ether diaminetetraacetic acid (EGTA)/CsOH, 10 mM HEPES, 10 mM NaCl at pH 7.3 was used. The test compounds were dissolved in dimethyl sulfoxide (DMSO) and diluted with the extracellular solution to attain the DMSO concentration of 0.1% at the time of assay.
[1654] The current response was obtained at a sampling frequency of 25 kHz, and noise was removed with a 3 kHz low-pass filter. The holding potential was −100 mV. Correction of the leakage current was carried out by applying a step pulse of −120 mV before the test pulse. In order to investigate inhibitory action of the test compound, the following test pulse was given: Namely, after depolarizing pulse of −10 mV was applied for 50 milliseconds, it was fixed at −120 mV for 500 milliseconds; a potential at which about 30-40% of the channel was inactivated was maintained for 15 seconds, then fixed again at −120 mV for 100 milliseconds, and finally a −10 mV depolarization pulse was given for 50 milliseconds. Test pulses were given before and after the test compound addition.
[1655] The inhibitory activity of the test compound was determined based on the amount of inward current generated by the second depolarization pulse, and the 50% inhibitory concentration (IC.sub.50) was calculated from the concentration-response curve. IC.sub.50 values are shown in Tables 89 to 98 below.
[1656] Compounds with IC.sub.50 values of less than 1 μM are indicated by the letter “A”, and compounds with IC.sub.50 values less than 10 μM are indicated by the letter “B”.
[1657] Meanwhile, unless otherwise stated, “Example” in the table refers to the compound intended for production in each Example; for example, the evaluation result for Example 1 shows the evaluation result of the compound intended for production in Example 1.
Test Example 2: Human Nav1.5 Inhibitory Activity Evaluation
[1658] A cell line in which human Nav1.5 was stably expressed in HEK293 cells was used. DMEM supplemeted with 15% fetal bovine serum, 500 μg/ml geneticin, 100 units/ml penicillin, 100 μg/ml streptomycin, 20 mM HEPES was used as culture medium under the conditions of 37° C. and 5% CO.sub.2 in T175 flasks to carry out culturing. When 60-80% confluence was reached, a cell suspension of about 0.5-5.0×10.sup.6 cells/mL was prepared. The amount of current through human Nav1.5 was recorded using a fully automatic patch clamp device QPatch16X at room temperature. As the extracellular solution, 145 mM NaCl, 4 mM KCl, 1 mM MgCl.sub.2, 2 mM CaCl.sub.2, 10 mM Glucose, and 10 mM HEPES at pH 7.4 was used. As the intracellular solution, 135 mM CsF, 1/5 mM EGTA/CsOH, 10 mM HEPES, and 10 mM NaCl at pH 7.3 was used. The test compounds were dissolved in DMSO and diluted with the extracellular solution to attend the DMSO concentration of 0.1% at the time of assay.
[1659] The current response was obtained at a sampling frequency of 25 kHz, and noise was removed with a 3 kHz low-pass filter. The holding potential was −80 mV. Correction of the leakage current was carried out by applying a step pulse of −100 mV before the test pulse. In order to investigate human Nav1.5 inhibitory effect of the test compound, test pulses imitating the action potential of cardiomyocytes were continuously given 20 times. The test pulses were given before and after the test compound addition.
[1660] The inhibitory activity of the test compound was determined based on the amount of inward current generated by the 20th depolarization pulse, and the 50% inhibitory concentration (IC.sub.50) was calculated from the concentration-response curve.
[1661] The IC.sub.50 values of inhibitory action of the test compounds are shown in Tables 89 to 98 below.
[1662] Compounds with an IC.sub.50 value of less than 1 μM are indicated by the letter “A”, compounds with an IC.sub.50 value of 1 μM or more and less than 3 μM are indicated by the letter “B” and compounds with an IC.sub.50 value of 3 μM or more is indicated by the letter “C”.
Test Example 3: Effect on Acute Pain
[1663] Six-week old male ICR mice were used for the test. Test compounds were orally administered at 1-10 mg/kg and the mice were habituated to a clear observation cage for 60 minutes. The mice were lightly restrained under no anesthesia and 20 μL of 80 μg/mL (0.8% ethanol-saline) capsaicin solution was injected subcutaneously into the plantar surface of rihgt hind paw of mice. The mice were returned to the observation cage and, from just after that, the duration of pain-related behavior (licking, shaking) occurring in the right hind limb was measured as the reaction time for 5 minutes.
[1664] The inhibition rate of the test compound was determined by the following calculation formula.
Test compound inhibition rate (%)=100×[1−(response time of test compound administered group/response time of vehicle control group)]
[1665] The effect of the test compound on an acute pain is shown in Table 99 below. Compounds with an inhibition rate of 30% or more are indicated by the letter “A”, and compounds with an inhibition rate of 20% or more and less than 30% are indicated by the letter “B” and compounds with an inhibition rate of 10% or more but less than 20% is indicated by the letter “C”.
Test Example 4: Effect on a Neuropathic Pain
[1666] Five-week old male ICR mice were used for the test. The skin and muscles were incised to expose the sixth lumbar vertebra under isoflurane anesthesia, and the right transverse process was removed. The L5 spinal nerve was isolated from the surrounding tissue to cut out, and then the incision site was sutured.
[1667] The 50% pain threshold of the plantar surface was determined by referring to the method of Chaplan SR et al. (J Neurosci Methods 1994, 53: 55-63) using von Frey filaments (0.008 g, 0.02 g, 0.04 g, 0.07 g, 0.16 g, 0.4 g and 0.6 g). First, the mice were placed in a measurement case with a lattice scaffold and habituatedd until the animal settled; 0.07 g of filament was pressed against the plantar surface for about 3 seconds. If withdrawal behavior was observed, the filament with the stimulation intensity one level lower was used to apply stimulation, and conversely, if the withdrawal behavior was not detected, the filament with the stimulation intensity one level higher was used to apply stimulation. By repeating this operation, starting from 2 times before and after the presence or absence of escape behavior changed, the results for a total of 6 times were recorded, to calculate a 50% pain threshold using the following calculation formula.
50% pain threshold (g)=(10.sup.[Xf+κδ]/10000)
[1668] Xf is the value of the stimulus intensity of the filament used in the last stimulation (log value), κ is the value derived from the pattern of presence/absence of withdrawal behavior for 6 times, and δ is the difference in stimulus intensity (log value) between the filaments used (here 0.365).
[1669] Animals that showed as a 50% pain threshold of the affected limb plantar surface of 0.16 g or more before the surgery and 0.08 g or less after 1 week after the surgery were used as allodynia-developed animals for evaluation of the test substance.
[1670] Each of the present inventive compounds, for example, Example 70, isomer A of Example 103, isomer A of Example 134, isomer A of Example 161, Example 288, and Example 290, increased the 50% pain threshold at a dose of 10 mg/kg or less in single oral administration, and showed antiallodynic effect.
TABLE-US-00089 TABLE 89 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 1 B C 2 (isomer A) A B 2 (isomer B) A C 3 A B 4 B C 5 A B 6 B B 7 (isomer A) A B 7 (isomer B) A C 8 A C 9 (isomer A) B C 9 (isomer B) A C 10 B 11 A C 12 A B 13 B 14 B C 15 A 16 A A 17 A B 18 A 19 A A 20 A A 21 A A 22 B C 23 B C 24 A 25 B B 26 B C 27 A A 28 B C 29 B B 30 B C 31 A 32 B B 33 A B 34 B C 35 A B 36 A C 37 B C 38 B C 39 (isomer A) B B 39 (isomer B) B C 40 B C 41 B C 42 B 43 B C 44 B C 45 B 46 B B 47 B C 48 B C 49 B C 50 B 51 A B 52 A B 53 B 54 B 55 A B 56 B 57 A A 58 B C 59 B C 60 B C 61 B C 62 B C 63 B 64 B A 65 A A 66 B A 67 A A 68 B C 69 B 70 A B 71 A A 72 A C 73 B 74 (isomer A) A C 74 (isomer B) A 75 A C
TABLE-US-00090 TABLE 90 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 76 A C 77 A C 78 B C 79 B C 80 A C 81 A C 82 B 83 A B 84 B C 85 A C 86 A C 87 B C 88 A 89 A 91 B C 92 (isomer A) A C 92 (isomer B) A C 93 A 94 A B 95 (isomer A) A C 95 (isomer B) A C 96 A B 97 (isomer A) A 97 (isomer B) A C 99 A 100 B C 101 (isomer A) A C 101 (isomer B) B C 102 A C 103 (isomer A) A C 103 (isomer B) B C 104 A 105 A A 106 A 107 B 108 A B 109 (isomer A) A B 109 (isomer B) B C 110 A C 111 (isomer A) A B 111 (isomer B) A B 112 A C 113 (isomer A) A B 113 (isomer B) A A 114 B C 115 (isomer A) B C 115 (isomer B) B 116 A 117 A A 118 A A 119 A 120 B 121 B 122 B C 123 B C 124 (isomer A) A C 124 (isomer B) B C 125 B C 126 A B 127 (isomer A) A C 127 (isomer B) A C 128 A B 129 (isomer A) A C 129 (isomer B) A B 130 B C 131 (isomer A) A B 131 (isomer B) B C 132 B 133 A B 134 (isomer A) A B 134 (isomer B) B C 135 A B 136 (isomer A) A A 136 (isomer B) A B 137 A C 138 (isomer A) A 138 (isomer B) B 139 A C
TABLE-US-00091 TABLE 91 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 140 (isomer A) A C 140 (isomer B) A B 141 A C 142 (isomer A) A B 142 (isomer B) A C 143 A C 144 (isomer A) A 144 (isomer B) A C 145 A C 146 (isomer A) B 146 (isomer B) A C 147 A C 148 (isomer A) A 148 (isomer B) A C 143 A B 150 (isomer A) A 150 (isomer B) A B 151 A B 152 (isomer A) A C 152 (isomer B) A C 153 (isomer A) A B 153 (isomer B) A 154 (isomer A) B 155 B C 156 (isomer A) A C 156 (isomer B) B 157 B C 158 (isomer A) A C 158 (isomer B) B 159 A C 160 A C 161 (isomer A) A C 161 (isomer B) B 162 A C 163 (isomer A) A B 163 (isomer B) B 164 A C 165 (isomer A) A 165 (isomer B) B 166 A 167 A B 168 B C 169 A B 170 (isomer A) A B 170 (isomer B) A A 171 A B 172 B C 173 (isomer A) A C 173 (isomer B) B 174 A C 175 B C 176 B 177 A B 178 B C 179 B 180 B 181 A C 182 B C 183 B 184 (isomer A) A B 184 (isomer B) B 185 A C 186 (isomer A) B C 186 (isomer B) A B 187 A C 188 (isomer A) A A 188 (isomer B) A C 189 A C 190 (isomer A) A C 190 (isomer B) A 191 A 192 (isomer B) A 193 B 194 (isomer A) B 194 (isomer B) A C 195 A C 196 (isomer A) A B 196 (isomer B) A C 197 A C 198 (isomer A) B
TABLE-US-00092 TABLE 92 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 198 (isomer B) A C 199 B C 200 (isomer A) B C 200 (isomer B) A C 201 A B 202 (isomer A) A C 202 (isomer B) A A 203 A C 204 (isomer A) A C 204 (isomer B) A B 205 B C 206 (isomer A) A 206 (isomer B) A C 207 (isomer B) A B 208 A A 209 (isomer A) B 209 (isomer B) A A 210 A 211 (isomer A) A 211 (isomer B) A A 212 A C 213 (isomer A) A C 213 (isomer B) A C 214 A B 215 (isomer A) A B 215 (isomer B) A B 216 A 217 (isomer A) A B 217 (isomer B) A A 218 A C 219 (isomer A) B C 219 (isomer B) A B 220 B B 221 (isomer A) B C 221 (isomer B) A B 222 A C 223 (isomer A) B 223 (isomer B) A B 224 (isomer A) A C 224 (isomer B) A B 225 A B 226 (isomer A) A C 226 (isomer B) A B 227 A B 228 (isomer A) A C 228 (isomer B) B 229 A B 230 (isomer A) A C 230 (isomer B) B 231 A C 232 (isomer A) A B 232 (isomer B) A C 233 A A 234 (isomer A) A C 234 (isomer B) A A 235 B 236 (isomer A) A B 236 (isomer B) A B 237 A 238 (isomer A) A 238 (isomer B) A 239 A 240 (isomer A) B 240 (isomer B) B 241 (isomer A) A 242 (isomer A) A 242 (isomer B) A 243 A C 244 (isomer A) A B 244 (isomer B) A A 245 A B 246 (isomer A) A B 246 (isomer B) A C 247 (isomer A) A B 247 (isomer B) A B 248 (isomer A) A B 248 (isomer B) B 249 B
TABLE-US-00093 TABLE 93 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 250 B 251 A C 252 A C 253 (isomer A) B 253 (isomer B) B 255 (isomer A) B 256 (isomer A) A C 256 (isomer B) A B 257 (isomer A) A C 257 (isomer B) A C 258 A A 259 A 260 A C 261 A A 262 B C 263 A B 264 A 265 A C 266 A C 267 B A 268 A C 269 A 270 B 271 B 272 B C 273 A C 274 B 275 A B 276 B C 277 B C 278 A B 279 A C 280 B A 281 B C 282 A B 283 A A 284 A A 285 A B 286 B 287 B C
TABLE-US-00094 TABLE 94 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 291 B C 292 A B 293 B 294 B C 295 A C 296 B 297 B 298 A B 299 A 300 B 301 B 302 B 303 A B 304 B C 305 A B 306 A 307 B B 308 B B 309 B 310 B 311 B C 312 B C 313 B C 314 A 315 B 316 B B 317 B C 318 B C 319 B 320 B 321 B C 322 B 323 B 324 B C 325 A C 326 B C 327 B C 328 B B 329 A 330 B 331 B B 332 B C 333 B C 334 B B 335 B 336 B B 337 B C 338 B C 339 B 340 B C 341 A 342 A 343 A B 344 A 345 A B 346 B 347 B 348 A 349 A B 350 B C 351 A C 352 A C 353 B C 354 B 355 A 356 A C 357 A C 358 B C 359 A C 360 A C 361 A C 362 B C 363 B 364 A B 365 B 366 A B 367 A 368 B 369 B 370 B
TABLE-US-00095 TABLE 95 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 371 A 372 A 373 B C 374 A C 375 A C 376 B 377 B 378 B C 379 A 380 B 381 B 382 B C 383 A C 384 A 385 B 386 A C 387 A 388 A 389 A B 390 B 391 A C 392 A B 393 B 394 B 395 A 396 A 397 A 398 B 399 A 400 A C 401 B C 402 A C 403 A 404 A 405 A 406 A 407 A 408 B 409 A 410 A 411 A C 412 A B 413 A 414 B 416 B 417 B 418 B 419 B 420 A 421 A C 422 B C 423 A 424 B 425 A C 426 B C 427 A B 428 A C 429 B C 430 A 431 A 432 A B 433 A 434 A 435 A 436 A 437 A B 438 A 439 B 440 B 441 A 442 A 444 A 445 A C 446 B 447 A C 448 A B 449 A 450 B C
TABLE-US-00096 TABLE 96 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 451 A B 452 B 453 B 454 B C 455 A 456 A B 457 A C 458 A 459 A C 460 A C 461 A B 462 A C 463 A 464 A C 465 A 466 A B 467 A 468 A C 469 A 470 A B 471 A 472 A 473 A 474 A 475 A 476 A 477 A 478 A 479 A 480 B 481 A C 482 A 483 B 484 A 485 A 486 A 487 A B 488 B C 489 B C 490 B C 491 B C 492 B C 493 A B 494 A B 495 A C 496 A B 497 A C 498 A 499 A B 500 B B 501 B 502 B B 503 B 504 A B 505 A 506 A B 507 A C 508 A 509 B 510 B 511 B 512 B 513 A 514 A 515 A 516 B 517 B 518 A B 519 B 520 A 521 A 522 A 523 A 524 B 525 B 526 B 527 A 528 B 529 A 530 B C
TABLE-US-00097 TABLE 97 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 531 B B 532 B C 533 A 534 (isomer A) B 534 (isomer B) B 535 A C 536 B 537 B 538 A C 539 B 540 A B 541 A C 542 B 543 B C 544 B 545 A 546 A 547 (isomer A) B C 547 (isomer B) B 548 B 549 B 550 A 551 B 552 (isomer A) B C 552 (isomer B) B 553 B 554 (isomer A) A C 554 (isomer B) B 555 A 556 A 557 A 558 A 559 B 560 A 561 B 562 B 563 (isomer A) B B 563 (isomer B) A C 564 B 565 A 566 A 567 A 568 A C 569 A 570 A 571 B 572(isomer A) B C 572(isomer B) B C 573 B 574 A 575(isomer A) A B 575(isomer B) B 576(isomer A) A C 576(isomer B) A C 577(isomer A) B 577(isomer B) B 578 B 579(isomer A) A B 579(isomer B) A 580 A 581 A 582 B 583 A 584 A 585 B 586 A 587 B 588 A 589 B 590(isomer A) A 590(isomer B) A 591 A 592 B 593 B B 594 B 595 A 596 A 597(isomer A) A C 597(isomer B) A B 598(isomer A) A
TABLE-US-00098 TABLE 98 Example NaV1.7 IC.sub.50 NaV1.5 IC.sub.50 598 (isomer B) A B 599 A 600 (isomer A) B 600 (isomer B) A B 601 (isomer A) B 601 (isomer B) B C 602 (isomer A) A C 602 (isomer B) A 603 (isomer A) A 603 (isomer B) A C 604 (isomer A) A B 604 (isomer B) B 605 A 606 A 607 A 608 (isomer A) A C 608 (isomer B) A C 609 B 610 (isomer A) A C 610 (isomer B) B 611 A 612 B 613 A 614 A 615 (isomer A) A B 615 (isomer B) A C 616 (isomer A) A B 616 (isomer B) B 617 (isomer A) A C 617 (isomer B) B 617 (isomer C) B C 617 (isomer D) B 618 B 619 B 620 A 621 A 622 (isomer A) A C 622 (isomer B) A C 623 A 624 A 625 A 626 B 627 B 628 A 629 A 630 A 631 A 632 A 633 A 634 A 635 A 636 (isomer A) A 636 (isomer B) A 637 B 638 B 639 A 640 A 641 (isomer A) B 641 (isomer B) B 642 B 643 B 644 A 645 A 646 A 647 A 648 B 649 B 650 A 651 A 652 B 653 B 654 A 655 A 656 B 657 A 658 A 659 B 660 B 661 A 662 A 663 A 664 B 665 A 666 B 667 A 668 B 669 B 670 A 671 A 672 A 673 A 674 B 675 B 676 A 677 B 678 A 679 A 680 B 681 B 682 B 683 B C
TABLE-US-00099 TABLE 99 Example Inhibition rate (%) 37 B 40 B 44 A 48 A 60 B 61 B 70 A 74 (isomer A) A 92 (isomer A) A 92 (isomer B) A 101 (isomer A) C 103 (isomer A) A 115 (isomer A) A 129 (isomer A) A 134 (isomer A) A 144 (isomer B) A 161 (isomer A) A 204 (isomer A) A 213 (isomer B) B 244 (isomer A) B 260 A 288 A 289 C 290 A
INDUSTRIAL APPLICABILITY
[1671] The present inventive heteroaromatic amide derivative represented by the general formula (I) or the general formula (I-E2) or a salt thereof has a strong Nav1.7 inhibitory effect and a lower Nav1.5 inhibitory effect, so that it is useful as an active ingredient of a therapeutic agent and/or prophylactic for various diseases associated with Nav1.7 with less concern about side effects derived from Nav1.5. For example, the present inventive heteroaromatic amide derivative or a salt thereof is useful as an analgesic for various diseases with pain.
