2-amino-benzimidazole derivatives and their use as 5-lipoxygenase and/or prostaglandin E synthase inhibitors

Abstract

The present invention relates to benzimidazole derivatives having the general formula I, wherein n is 0 or 1; X.sup.1 and X.sup.2 are independently, at each occurrence, CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkoxy, —NH.sub.2, —NHR.sup.6, —NR.sup.7R.sup.8 and —NH—(R.sup.9).sub.n—R.sup.10, n being 0 or 1; R.sup.2 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, —NH.sub.2, —NHR.sup.6, —NR.sup.7R.sup.8 and —NH—(R.sup.9).sub.n—R.sup.10; R.sup.3 is selected from the group consisting of hydrogen, hydroxyl, OR.sup.11, —NR.sup.7R.sup.8, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.3 haloalkyl, —C(O)NHR.sup.11, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; and R.sup.4 is selected from the group consisting of —NH.sub.2, —N(R.sup.12)(V).sub.pR.sup.13, —NH(V).sub.p—OR.sup.14, —NHC(O)R.sup.15, and groups of formula 1a shown below, and their use in the treatment of diseases, in particular inflammatory diseases, cancer, stroke and/or Alzheimer's disease. ##STR00001##

Claims

1. A compound having general formula I: ##STR00606## wherein n is 0 or 1; X.sup.1 and X.sup.2 are independently, at each occurrence, CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.1 is —NHR.sup.6; R.sup.2 is selected from the group consisting of C.sub.2-C.sub.6alkyl, —NH.sub.2, —NHR.sup.6, —NR.sup.7R.sup.8 and —NH—(R.sup.9)n, —R.sup.10, n being 0 or 1; R.sup.3 is selected from the group consisting of hydroxyl, OR.sup.11, —NR.sup.7R.sup.8, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10cycloalkyl, C.sub.1-C.sub.3 haloalkyl, —C(O)NHR.sup.11, aryl, heteroaryl, wherein each of said cycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.4 is selected from the group consisting of —N(R.sup.12)(V).sub.pR.sup.13, —NH(V).sub.p—OR.sup.14, and groups of formula Ia shown below, ##STR00607## wherein, p is 0, V is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.6 cycloalkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C.sub.3-C.sub.6 cycloalkyl group; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6 alkoxy; R.sup.6 is selected from the group consisting of heteroaryl and heterocyclyl, wherein each of said heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.7 and R.sup.8 are independently, at each occurrence, heterocyclyl; or R.sup.7 and R.sup.8 are connected to each other to make a four, five or six membered heterocyclyl or heteroaryl group, wherein each of said heterocyclyl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.9 is C.sub.1-C.sub.4 alkylene, wherein said alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl groups; R.sup.10 is selected from the group consisting of hydroxyl, —OR.sup.11, —CN, —C(O)OR.sup.18, —C(O)NH.sub.2, —C(NH)NH.sub.2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.11 is independently, at each occurrence, selected from the group consisting of aryl heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.12 is selected from the group consisting of hydrogen, C.sub.2-C.sub.6 alkyl, C.sub.1-C.sub.4 alkyl-hydroxyl and C.sub.1-C.sub.4 alkyl-alkoxy; R.sup.13 is selected from the group consisting of C.sub.2, C.sub.5-C.sub.6 alkyl, C.sub.3-C.sub.5, C.sub.7-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkyl-hydroxyl, —OH, —C(O)NH.sub.2, —C(O)OR.sup.18, —CN, C.sub.1-C.sub.3 haloalkyl, and groups of formula Ib shown below, ##STR00608## ##STR00609## wherein, n is 0 or 1; A.sup.1 is —O—, —CH.sub.2O—, —OCH.sub.2.sup.−, —S—, —SO.sub.2.sup.−, —SO.sub.2NH—, —C(O)—, —C(O)NH—, —C(O)N(R.sup.7)—, —CH(OH)—, —CH(OR.sup.7)—, —NH—, —N(CH.sub.3)— or —N(CH.sub.2COOR.sup.7)—; A.sup.2 is —O— or NH—; B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.14 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C.sub.1-C.sub.3 haloalkoxy groups; R.sup.16 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl and hydroxyl; R.sup.17 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, —C(O)R.sup.11, —C(O)NHR.sup.11, —OR.sup.11 and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.18 is hydrogen or C.sub.2-C.sub.6 alkyl; R.sup.19 is selected from the group consisting of hydrogen, —OR.sup.22 and —CH.sub.2OR.sup.22; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, —C(O)R.sup.a and C.sub.1-C.sub.6 haloalkoxy; R.sup.211 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of C.sub.1-C.sub.6 haloalkyl, aryl, and heteroaryl, wherein each of said haloalkyl, aryl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OH, —OCH.sub.3, —NR.sup.bH, —C(O)NR.sup.bH, —C(O)H, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.C, —CN, NO.sub.2, —NR.sup.bR.sup.c, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —CO.sub.2Et or heteroaryl; R.sup.b is independently, at each occurrence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10 cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, or —NH.sub.2; R.sup.c is independently, at each occurrence, selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, or —NH.sub.2; or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

2. A compound having general formula II: ##STR00610## wherein n is 0 or 1; X.sup.1 is CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6 alkoxy; R.sup.23 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.24 is selected from the group consisting of C.sub.3-C.sub.10 cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.25 is selected from the group consisting of —(V).sub.pR.sup.26 and —(V).sub.p—OR.sup.14; wherein, p is 0, V is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C.sub.3-C.sub.6 cycloalkyl group; R.sup.14 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C.sub.1-C.sub.3 haloalkoxy groups; R.sup.26 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, —CN and C.sub.1-C.sub.3 haloalkyl, and groups of formula IIa shown below, ##STR00611## wherein, A.sup.2 is —O— or NH—; A.sup.3 is —O—, —CH.sub.2O—, —OCH.sub.2.sup.−, or —NH—; B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.19 is selected from the group consisting of hydrogen, —OR.sup.22 and —CH.sub.2OR.sup.22; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy and C.sub.1-C.sub.6 haloalkoxy; R.sup.21 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of aryl, and heteroaryl, wherein each of said aryl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.c, —CN, NO.sub.2, —NR.sup.bR.sup.c, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —COOH, —CO.sub.2Et and heteroaryl; R.sup.b and R.sup.c are independently, at each occurence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10 cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, —NH.sub.2; or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

3. A compound having general formula III: ##STR00612## wherein n is 0 or 1; X.sup.1 is CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6 alkoxy; R.sup.23 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.27 is selected from the group consisting of hydrogen, —R.sup.6, and —R.sup.9—R.sup.10; wherein, R.sup.6 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.9 is C.sub.1-C.sub.4 alkylene, wherein said alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl groups; R.sup.10 is selected from the group consisting of hydroxyl, —OR.sup.11, —C(O)OR.sup.18, —C(O)NH.sub.2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.11 is independently, at each occurrence selected from the group consisting of aryl, heteroaryl and heterocyclyl group wherein said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.18 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sup.28 is selected from the group consisting of —(V).sub.pR.sup.29 and —(V).sub.p—OR.sup.14; wherein, p is 0, V is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to three C.sub.1-C.sub.6 alkyl or phenyl groups; R14 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C.sub.1-C.sub.3 haloalkoxy groups; R.sup.29 is selected from the group consisting of C.sub.2, C.sub.5-C.sub.6 alkyl and C.sub.1-C.sub.3 haloalkyl, and groups of formula IIIa shown below, ##STR00613## wherein, A.sup.2 is —O— or NH—; A.sup.3 is —O—, —CH.sub.2O—, —OCH.sub.2—, or —NH—; B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.19 is selected from the group consisting of hydrogen, —OR.sup.22 and —CH.sub.2OR.sup.22; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy and C.sub.1-C.sub.6 haloalkoxy; R.sup.21 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of aryl, and heteroaryl, wherein said aryl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OH, —OCH.sub.3, —NR.sup.bH, —C(O)NR.sup.bH, C(O)H, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.c, —CN, NO.sub.2, —NR.sup.bR.sup.b, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —CO.sub.2Et and heteroaryl; R.sup.b is independently, at each occurrence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, —NH.sub.2; R.sup.c is independently, at each occurrence, selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10 cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, —NH.sub.2; or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

4. A compound having general formula I: ##STR00614## wherein n is 0 or 1; X.sup.1 and X.sup.2 are independently, at each occurrence, CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.1 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkoxy, —NHR.sup.6, —NR.sup.7 R.sup.8 and —NH—(R.sup.9).sub.n—R.sup.10, n being 0 or 1; R.sup.2 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, —NH.sub.2, —NHR.sup.6, —NR.sup.7R.sup.8 and —NH—(R.sup.9).sub.n—R.sup.10, n being 0 or 1; R.sup.3 is selected from the group consisting of hydroxyl, OR.sup.11, —NR.sup.7R.sup.8, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10cycloalkyl, C.sub.1-C.sub.3 haloalkyl, —C(O)NHR.sup.11, aryl, heteroaryl, wherein each of said cycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.4 is —N(R.sup.12)(V).sub.pR.sup.13, R.sup.12 is H, V is C.sub.1-alkylene, p is 1, R.sup.13 is ##STR00615## wherein A.sup.1 is —O—, —CH.sub.2O—, —OCH.sub.2.sup.−, —S—, —SO.sub.2.sup.−, —SO.sub.2NH—, —C(O)—, —C(O)NH—, —C(O)N(R.sup.7)—, —CH(OH)—, —CH(OR.sup.7)—, —NH—, —N(CH.sub.3)— or —N(CH.sub.2COOR.sup.7)—; and B is heteroaryl which is optionally substituted with one to four R.sup.a groups; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6 alkoxy; R.sup.6 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10cycloalkyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.7 and R.sup.8 are independently, at each occurrence, heterocyclyl; or R.sup.7 and R.sup.8 are connected to each other to make a four, five or six membered heterocyclyl or heteroaryl group, wherein each of said heterocyclyl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.9 is C.sub.1-C.sub.4 alkylene, wherein said alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl groups; R.sup.10 is selected from the group consisting of hydroxyl, —OR.sup.11, —CN, —C(O)OR.sup.18, —C(O)NH.sub.2, —C(NH)NH.sub.2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.11 is independently, at each occurrence, selected from the group consisting of aryl heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.18 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, —C(O)R.sup.a and C.sub.1-C.sub.6 haloalkoxy; R.sup.21 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OH, —OCH.sub.3, —NR.sup.bH, —C(O)NR.sup.bH, —C(O)H, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.c, —CN, NO.sub.2, —NR.sup.bR.sup.c, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —CO.sub.2Et or heteroaryl; R.sup.b is independently, at each occurrence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10 cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, or —NH.sub.2; R.sup.c is independently, at each occurrence, selected from the group consisting of C.sub.1-C.sub.10alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10cycloalkenyl, C.sub.2-C.sub.10alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —N.sub.2, or —NH.sub.2; or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

5. A method of inhibiting the activity on an enzyme involved in an inflammatory pathway or several inflammatory pathways, using a compound according to claim 1 at a concentration between 0.001-50 μM, wherein the enzyme is selected from arachidonate 5-lipoxygenase, LTA4-synthase, LTA4-hydrolase, LTC4-synthase, glutamyltranspeptidase, cysteinylglycinase, 5-hydroxy-6,8,11,14-eicosatetraenoic acid dehydrogenase, cyclooxygenase-2, and prostaglandin E synthase.

6. A composition comprising a compound or a pharmaceutically acceptable salt thereof, as defined in claim 1, and a pharmaceutically acceptable carrier.

7. A method of treatment of a disease associated with the 5-LOX-pathway and/or the prostaglandin E synthase (PGES) pathway, said disease being selected from inflammatory diseases, cancer and Alzheimer's disease, said method comprising the administration of a suitable amount of a compound as defined in claim 1 to a patient in need thereof, suffering from a disease associated with the 5-LOX-pathway and/or the prostaglandin E synthase (PGES) pathway.

8. The method of treatment according to claim 7, wherein said inflammatory disease is selected from asthma, allergic rhinitis, dermatitis, chronic obstructive pulmonary disease (COPD), inflammation post infection, arthritis, atherosclerosis, an allergy, an autoimmune disease, an inflammatory bowel disease, celiac disease, acne, and pain.

9. The method, according to claim 5, wherein said compound has an IC.sub.50 on arachidonate 5-lipoxygenase of less than 1 μM and/or an EC.sub.50 of less than 10 μM on the production of leukotriene B4 (LTB4) in rat basophilic leucocyte cells (RBL) and/or rat whole blood (RWB), and/or has a 40-70% inhibitory activity, or a >70% inhibitory activity, on the production of prostaglandin E2 in HeLaS3 cells, stimulated with TNF-α, at a concentration of 10 μM of said compound.

10. The method, according to claim 8, wherein the inflammatory disease is hay fever, lupus erythematosus, Crohn's disease, inflammatory pain or neuropathic pain.

11. A compound having general formula II: ##STR00616## wherein n is 0 or 1; X1 is CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6alkoxy; R.sup.23 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.3 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.24 is selected from the group consisting of C.sub.3-C.sub.10 cycloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.25 is selected from the group consisting of —(V).sub.pR.sup.26 and —(V).sub.p—OR .sup.14; wherein, p is 1, V is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C.sub.3-C.sub.6 cycloalkyl group; R.sup.14 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C.sub.1-C.sub.3 haloalkoxy groups; R.sup.26 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl, —CN and C.sub.1-C.sub.3 haloalkyl, and groups of formula IIa shown below, ##STR00617## wherein, A.sup.2 is —O— or NH—; A.sup.3 is —O—, —CH.sub.2O—, —OCH.sub.2.sup.−, or —NH—; B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.19 is selected from the group consisting of hydrogen, —OR.sup.22 and —CH.sub.2OR.sup.22; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy and C.sub.1-C.sub.6 haloalkoxy; R.sup.21 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of aryl, and heteroaryl, wherein each of said aryl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.c, —CN, NO.sub.2, —NR.sup.bR.sup.c, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —COOH, —CO.sub.2Et and heteroaryl; R.sup.b and R.sup.c are independently, at each occurence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10 cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, —NH.sub.2; or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

12. A compound having general formula III: ##STR00618## wherein n is 0 or 1; X.sup.1 is CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6 alkoxy; R.sup.23 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, aryl, heteroaryl and heterocyclyl, wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.27 is selected from the group consisting of hydrogen, —R.sup.6, and —R.sup.9—R.sup.10; wherein, R.sup.6 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl and heterocyclyl, wherein said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.9 is C.sub.1-C.sub.4 alkylene, wherein said alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl groups; R.sup.10 is selected from the group consisting of hydroxyl, —OR.sup.11, —C(O)OR.sup.18, —C(O)NH.sub.2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.11 is independently, at each occurrence selected from the group consisting of aryl, heteroaryl and heterocyclyl group wherein said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.18 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sup.28 is selected from the group consisting of —(V).sub.pR.sup.29 and —(V).sub.p—OR.sup.14; wherein, p is 1, V is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to three C.sub.1-C.sub.6 alkyl or phenyl groups; R.sup.14 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C.sub.1-C.sub.3 haloalkoxy groups; R.sup.29 is selected from the group consisting of C.sub.4-C.sub.6 alkyl and C.sub.1-C.sub.3 haloalkyl, and groups of formula IIIa shown below, ##STR00619## wherein, A.sup.2 is —O— or NH—; A.sup.3 is —O—, —CH.sub.2O—, —OCH.sub.2—, or —NH—; B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.19 is selected from the group consisting of hydrogen, —OR.sup.22 and —CH.sub.2OR.sup.22; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy and C.sub.1-C.sub.6 haloalkoxy; R.sup.21 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of aryl, and heteroaryl, wherein said aryl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OH, —OCH.sub.3, —NR.sup.bH, —C(O)NR.sup.bH, —C(O)H, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.c, —CN, NO.sub.2, —NR.sup.bR.sup.c, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —CO.sub.2Et and heteroaryl; R.sup.b is independently, at each occurrence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —N.sub.2, —NH.sub.2; R.sup.c is independently, at each occurrence, selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6haloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, —NH.sub.2, or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

13. A compound having one of the following formulae: TABLE-US-00008 No. Structure 35 47 50 53 55 57 59 61 70 72 82 84 85 170 171 182 184 192 193 204 208 211 226 227 251 256 257 262 268 269 270 271 273 275 279 281 283 284 289 291 293 294 296 298 300 302 303 305 306 307 309 312 313 315 316 318 320 322 324 325 326 328 329 331 333 335 337 339 341 343 345 347 349 351 353 355 357 358 359 362 364 365 366 368 369 371 372 374 378 379 381 383 384 386 388 390 392 394 396 398 400 401 403 404 406 407 408 409 412 413 414 415 417 418 420 422 423 425 427 429 431 433 435 437 439 441 443 444 447 448 449 450 453 455 457 459 461 464 465 466 467 468 469 471 473 474 475 476 477 478 479 481 482 483 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 or a pharmaceutically acceptable salt thereof.

14. A compound having general formula I: ##STR00845## wherein n is 0 or 1; X.sup.1 and X.sup.2 are independently, at each occurrence, CR.sup.5 or N; Y is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to two C.sub.1-C.sub.3 alkyl groups; R.sup.1 is selected from the group consisting of C.sub.1-C.sub.6 alkoxy, —NHR.sup.6, —NR.sup.7R.sup.8 and —NH—(R.sup.9).sub.n—R.sup.10, n being 0 or 1; R.sup.2 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl, —NH.sub.2, —NHR.sup.6, —NR.sup.7R.sup.8 and —NH—(R.sup.9), —R.sup.10, n being 0 or 1; R.sup.3 is selected from the group consisting of hydroxyl, OR.sup.11, —NR.sup.7R.sup.8, C.sub.1-C.sub.6 alkoxy, C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.5, C.sub.7-C.sub.10cycloalkyl, C.sub.1-C.sub.3 haloalkyl, —C(O)NHR.sup.11, aryl, heteroaryl, wherein each of said cycloalkyl, aryl, and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.4 is selected from the group consisting of —N(R.sup.12)(V).sub.pR.sup.13, —NH(V).sub.p—OR.sup.14, —NHC(O)R.sup.15, and groups of formula Ia shown below, ##STR00846## wherein, p is 0, V is C.sub.1-C.sub.6 alkylene, wherein alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.6 cycloalkyl or phenyl groups, or wherein a carbon atom of said alkylene forms part of a C.sub.3-C.sub.6 cycloalkyl group; R.sup.5 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 haloalkyl and C.sub.1-C.sub.6 alkoxy; R.sup.6 is selected from the group consisting of C.sub.1-C.sub.6 alkyl, C.sub.3-C.sub.10cycloalkyl, C.sub.1-C.sub.6haloalkyl, aryl, heteroaryl and heterocyclyl, wherein each of said alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.7 and R.sup.8 are independently, at each occurrence, heterocyclyl; or R.sup.7 and R.sup.8 are connected to each other to make a four, five or six membered heterocyclyl or heteroaryl group, wherein each of said heterocyclyl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.9 is C.sub.1-C.sub.4 alkylene, wherein said alkylene is optionally substituted with one to three C.sub.1-C.sub.3 alkyl groups; R.sup.10 is selected from the group consisting of hydroxyl, —OR.sup.11, —CN, —C(O)OR.sup.18, —C(O)NH.sub.2, —C(NH)NH.sub.2, aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.11 is independently, at each occurrence, selected from the group consisting of aryl heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.12 is selected from the group consisting of hydrogen, C.sub.2-C.sub.6 alkyl, C.sub.1-C.sub.4 alkyl-hydroxyl and C.sub.1-C.sub.4 alkyl-alkoxy; R.sup.13 is selected from the group consisting of C.sub.2, C.sub.5 C.sub.6 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkyl-hydroxyl, —OH, —C(O)NH.sub.2, —C(O)OR.sup.18, —CN, C.sub.1-C.sub.3 haloalkyl, and groups of formula 1b shown below, ##STR00847## ##STR00848## wherein, n is 0 or 1; A.sup.1 is —O—, —CH.sub.2O—, —OCH.sub.2.sup.−, —S—, —SO.sub.2.sup.−, —SO.sub.2NH—, —C(O)—, —C(O)NH—, —C(O)N(R.sup.7)—, —CH(OH)—, —CH(OR.sup.7)—, —NH—, —N(CH.sub.3)— or —N(CH.sub.2COOR.sup.7)—; A.sup.2 is —O— or NH—; B is selected from the group consisting of aryl, heteroaryl and heterocyclyl wherein each of said aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four R.sup.a groups; R.sup.14 is selected from the group consisting of hydrogen, C.sub.1-C.sub.6 alkyl and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four halogen or C.sub.1-C.sub.3 haloalkoxy groups; R.sup.15 is aryl, wherein aryl is substituted with one to four halogen groups; R.sup.16 selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl and hydroxyl; R.sup.17 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, —C(O)R.sup.11, —C(O)NHR.sup.11, —OR.sup.11 and aryl, wherein each of said alkyl and aryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.18 is hydrogen or C.sub.1-C.sub.6 alkyl; R.sup.19 is selected from the group consisting of hydrogen, —OR.sup.22 and —CH.sub.2OR.sup.22; R.sup.20 is selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, —C(O)R.sup.a and C.sub.1-C.sub.6 haloalkoxy; R.sup.21 is selected from the group consisting of hydrogen, halogen and C.sub.1-C.sub.6 alkyl; R.sup.22 is selected from the group consisting of C.sub.1-C.sub.6 haloalkyl, aryl, and heteroaryl, wherein each of said haloalkyl, aryl and heteroaryl is optionally and independently substituted with one to four R.sup.a groups; R.sup.a is independently, at each occurrence, selected from the group consisting of hydrogen, halogen, C.sub.1-C.sub.3 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.4 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, C.sub.1-C.sub.3 alkylhydroxyl, —CH.sub.2OH, —OCH.sub.3, —NR.sup.bH, —C(O)NR.sup.bH, —C(O)H, —CH.sub.2OR.sup.c, —OCH.sub.2R.sup.c, —OR.sup.c, —CN, NO.sub.2, —NR.sup.bR.sup.c, —C(O)NR.sup.bR.sup.c, —C(NH)NH.sub.2, —C(O)R.sup.c, —C(O)OR.sup.c, sulfonyl, sulfoxide, heterocyclyl, heteroaryl and aryl, wherein each of said alkyl, haloalkyl, haloalkoxy, alkoxy, cycloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.3 haloalkyl, —CN, —C(O)NH.sub.2, —CO.sub.2Et or heteroaryl; R.sup.b is independently, at each occurrence, selected from the group consisting of hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.1 cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, or —NH.sub.2; R.sup.c is independently, at each occurrence, selected from the group consisting of C.sub.1-C.sub.10 alkyl, C.sub.3-C.sub.10 cycloalkyl, C.sub.1-C.sub.6 alkyl-O-alkyl, C.sub.2-C.sub.10 alkenyl, C.sub.1-C.sub.4 alkoxy, C.sub.1-C.sub.3 alkylhydroxyl, C.sub.3-C.sub.10cycloalkenyl, C.sub.2-C.sub.10 alkynyl, C.sub.1-C.sub.6 haloalkyl, aryl, heteroaryl, and heterocyclyl wherein each of said alkyl, cycloalkyl, alkyl-O-alkyl, alkenyl, alkoxy, cycloalkenyl, alkynyl, haloalkyl, aryl, heteroaryl and heterocyclyl is optionally and independently substituted with one to four C.sub.1-C.sub.3 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, C.sub.1-C.sub.6 haloalkyl, C.sub.1-C.sub.6 haloalkoxy, hydroxyl, —C(O)NH.sub.2, —COOH, —COOMe, —COOEt, —CN, —NO.sub.2, or —NH.sub.2; or R.sup.b and R.sup.c are connected to each other to make a four, five or six membered saturated or unsaturated cyclic or heterocyclic ring; or a pharmaceutically acceptable salts thereof.

15. The compound, according to claim 13, one of the following formulae: TABLE-US-00009 No. Structure 53 57 59 61 70 72 84 144 170 171 182 184 192 204 208 211 226 227 251 256 257 268 269 270 271 273 275 281 283 284 289 291 293 294 296 298 300 302 303 305 306 307 309 312 313 315 316 318 320 324 325 326 328 329 331 333 335 337 339 341 343 345 347 349 351 353 357 358 359 362 364 365 366 368 369 371 372 374 378 379 381 383 384 388 390 392 394 396 398 400 401 403 404 406 407 408 409 412 413 414 415 417 418 420 422 423 425 427 429 431 433 435 437 439 443 444 449 450 453 455 457 459 461 465 466 467 468 469 471 473 474 475 476 477 478 479 481 482 483 486 487 489 490 491 492 495 496 499 501 503 505 507 509 512 513 514 525 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 546 547 548 549 550 551 552 553 554 555 556 or a pharmaceutically acceptable salt thereof.

16. The compound, according to claim 13, having the following formula: TABLE-US-00010 NO. Structure 211 or a pharmaceutically acceptable salt thereof.

17. The compound, according to claim 13, having one of the following formulae: TABLE-US-00011 Structure 53 226 or a pharmaceutically acceptable salt thereof.

18. The compound, according to claim 13, having one of the following formulae: TABLE-US-00012 No. Structure  53  55  57  59  70  84 184 192 193 204 208 211 226 227 251 257 262 268 269 270 271 273 275 279 281 283 284 289 291 293 294 296 298 300 302 305 306 313 316 322 324 325 328 329 331 333 335 347 349 353 357 358 359 365 366 368 369 372 374 378 379 383 384 390 392 396 398 400 401 403 406 407 412 413 414 415 420 422 423 425 427 431 435 437 447 448 449 450 453 455 457 461 464 465 466 467 468 469 471 473 474 475 476 477 478 479 481 482 486 487 489 490 491 492 493 494 495 496 499 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 556 or a pharmaceutically acceptable salt thereof.

19. The compound, according to claim 13, having one of the following formulae: TABLE-US-00013 No. Structure 53 184 193 204 211 226 227 251 256 268 269 270 271 275 279 281 284 289 296 306 324 328 341 345 351 358 362 368 369 374 378 381 392 412 413 414 415 431 433 447 448 449 450 461 464 465 466 468 469 471 473 474 475 476 477 479 481 482 486 487 489 490 491 492 493 494 495 496 498 499 501 502 503 504 505 506 508 509 512 513 514 516 517 518 519 525 526 527 528 529 530 531 532 533 534 535 536 537 538 540 541 542 543 544 545 546 547 550 553 554 or a pharmaceutically acceptable salt thereof.

Description

DESCRIPTION OF THE TABLES

(1) Reference is now made to the tables, wherein

(2) Table 1 summarizes 5-LOX IC.sub.50 inhibitory activities (uM) as measured by fluorescence wherein the compound number refers to the compounds listed in Example 7;

(3) Table 2 summarizes 5-LOX IC.sub.50 inhibitory activities (uM) as detected by ELISA wherein the compound number refers to the compounds listed in Example 7;

(4) Table 3 summarizes LTB4 secretion assay (EC.sub.50, uM) in RBL (rat basophilic leukemia) cells wherein the compound number refers to the compounds listed in Example 7;

(5) Table 4 summarizes LTB4 secretion assay (EC.sub.50, uM) in RWB (rat whole blood) wherein the compound number refers to the compounds listed in Example 7;

(6) Table 5 summarizes PGE.sub.2% inhibition at 10 uM as measured by HTRF (Homogeneous Time Resolved Fluorescence) wherein the compound number refers to the compounds listed in Example 7;

(7) Table 6 summarizes COX-2 (Cyclooxygenase 2) % inhibition at 10 uM as measured by EIA (Enzyme Immunoassay) wherein the compound number refers to the compounds listed in Example 7 and Table 7;

(8) Table 7 summarizes compounds 1-556 the synthesis of which is described in Example 7.

EXAMPLES

(9) The invention is now further described by reference to the following examples which are intended to illustrate, not to limit the scope of the invention.

Example 1

Activity of Compounds Against 5-LOX Enzyme

(10) The activity of compounds against 5-LOX were determined by measuring LTB.sub.4 (leukotriene B4) levels and/or by a fluorescence method. Both approaches are outlined in more detail below;

(11) LTB.sub.4 Measurement by ELISA:

(12) Human 5-lipoxygenase (5-LOX) (Cayman, Cat #60402) produced in insect cells was pre-incubated with compounds for 5 min at RT in incubation buffer (50 mM Tris-Cl, pH 7.4, 2 mM CaCl.sub.2, 0.1 mM ATP, 2% DMSO). Compounds were tested in dose reponse from 0.5 nM to 10 uM. The enzymatic reaction was started by adding arachidonic acid to a final concentration of 3 uM. After 5 min of incubation at 25° C., the reaction was stopped by adding H.sub.2O.sub.2 to a final concentration of 1 mM. LTB.sub.4 levels were quantified using a LTB.sub.4 EIA kit (Cayman, Cat #520111) as instructed.

(13) Fluorescence Method:

(14) Besides the above method for quantifying LTB4 levels, a fluorescence assay measuring 5-hydroperoxyeicosatetraenoic acid (5-HPETE) was introduced for high-throughput screening in a 384 well microplate format (Pufahl et al., 2007) Development of a Fluorescence-based enzyme assay of human 5-lipoxygenase. ANALYTICAL BIOCHEMISTRY 364, 204-212). For nonspecific ester cleavage of the acetate groups in H.sub.2DCFDA(2′,7′-dichlorodihydrofluorescein diacetate), the insect cell lysate expressing human 5-LOX (Cayman Cat #60402) was incubated with H.sub.2DCFDA (50 mM Tris-Cl, pH 7.5, 2 mM CaCl2, 20 uM H.sub.2DCFDA, 600 mU 5-LOX per reaction) for 5 minutes. The compound, in a dose response manner(0.5 nM to 10 uM), and enzyme mixture was pre-incubated for 5 minutes, and the enzymatic reaction was initiated by addition of ATP and arachidonic acid to a final concentration of 100 uM and 3 uM, respectively. After 5 minutes of incubation, fluorescence was measured using Spectramax M5 (Molecular Device, Ex/Em=485 nm/530 nm). All steps were carried out at room temperature.

Example 2

LTB4 Secretion Assay in RBL (Rat Basophilic Leukemia Cells)

(15) Rat basophilic leukemia (RBL) cells (ATCC, Cat #CRL-2256) were maintained in EMEM (ATCC, Cat #30-2003) supplemented with 15% FBS. The day before RBL assay, cells were seeded at a concentration of 2×10.sup.4 cells per well in 96-well plates. The media was replaced with 100 ul of EMEM supplemented with 0.5% FBS and compounds in dose response(5 nM to 100 uM) were added. After 15 min of pre-incubation at 37° C., arachidonic acid and calcium ionophore (A23187) were added to give a final concentration of 2.5 uM and 5 uM, respectively. After a further 10 min incubation at 37° C., culture supernatant was transferred and quantification of LTB4 was done with a Leukotriene B4 EIA kit (Cayman, Cat #520111) as instructed.

Example 3

LTB4 Secretion Assay in RWB (Rat Whole Blood)

(16) Rat blood was drawn from caudal vena cava from male Sprague Dawley rat (6-9 weeks old) in vacuette coated with sodium heparin (Greiner bio-one, Cat #455051). The blood was pooled and diluted with RPMI (WelGENE, Cat #LM 011-05) to 1:1. The diluted blood was aliquoted into 96 well plate (200 ul per well) and compounds were added in dose response to a desired concentration ranging from 2.5 nM to 50 uM. After 15 min of pre-incubation at 37° C., calcium ionophore (A23187) was added to the final concentration of 10 uM. After 10 min of further incubation at 37° C., the LTB4 production was stopped by diluting the reaction mixture with ice cold PBS (1:4 dilutions). Cells were removed by centrifugation at 1000×g, 4° C. for 10 min, and the supernatant was transferred and then the quantification of LTB4 was done with Leukotriene B4 EIA kit (Cayman, Cat #520111) as instructed.

Example 4

Inflammation Efficacy in OVA-Induced Airway Inflammation Model in Brown Norway Rats

(17) The objective of this study is to determine the efficacy of compounds in the lungs of ovalbumin (OVA) induced in Brown Norway rats. As with most models of induced allergic asthma, animals are systemically sensitized to specific antigens and then, after a period of time, challenged with the same allergen administered via the airway. Ovalbumin had been used as the standard allergen to sensitize and challenge animals in this study.

(18) Thirty (30) male Brown Norway rats were randomized into 5 groups on the basis of body weight. For sensitization, 1% OVA in PBS solution was mixed with alum solution (with volume ratio of 1:9). All rats in groups 1-5 were sensitized by i.p injection (1 mL/rat) of 1% OVA-alum sensitization solution on day 1, 2 and 3. At day 21, rats in groups 1-5 were challenged with 1% OVA in PBS solution with aerosolizing dosing system for 20 min.

(19) Test compounds were administered by p.o. from days 19-21 of the study as per schedule below:

(20) Group 1: sensitized-vehicle,

(21) Group 2: reference drug dexamethasone, 0.3 mg/kg, p.o., Day 19-21, BID,

(22) Group 3: compound 211, 25 mg/kg, p.o., Day 19-21, BID,

(23) Group 4: compound 211, 50 mg/kg, p.o., Day 19-21, BID,

(24) Group 5: compound 211, 100 mg/kg, p.o., Day 19-21, BID,

(25) On day 22, bronchoalveolar lavage and lung tissues were harvested. Total cell number and differential cell counts in BALF, leukotriene B4 (LTB4) in BALF and lung tissue, histopathology of lung by H&E staining will be evaluated.

(26) Treatment of rats using compound 211 significantly reduced the increase of inflammatory cells including total cell and eosinophils, reduced LTB4 in BALF and Lung, and significantly reduced inflammation cell infiltration. These data indicate that compound 211 shows antiinflammatory activity in OVA-induced asthma.

Example 5

PGE.SUB.2 .Inhibition Assay

(27) Human epitheloid cervix carcinoma HeLa S3 cells (2×10.sup.6cells/ml) were seeded with modified F-12K buffer medium pH 7.4 in tissue culture plate and incubated for overnight at 37° C. and 5% CO.sub.2. Then medium was changed into new medium contained 10 uM testing compounds or 0.1% DMSO and incubated overnight. After incubation, cells were stimulated with 30 nM TNF-α (Tumor necrosis factor-α) for 16 h. For determination of PGE.sub.2, the supernatant was measured by PGE.sub.2 HTRF (Homogeneous Time Resolved Fluorescence) assay kit Inhibition of PGE.sub.2 by compounds is calculated as a percentage of activity in the presence of drug versus the activity in the stimulator TNF-α.

Example 6

COX-2 Inhibition Assay

(28) Human recombinant cyclooxygenase-2 expressed in insect Sf21 cells was used. The testing compounds and reference compound (Rofecoxib) were dissolved in DMSO (Sigma, USA) and tested at 10 uM. Test samples were pre-incubated with 0.11 U enzyme in 100 mM modified Tris-HCl buffer pH 7.7 for 15 minutes at 37° C. The reactions were initiated by addition of 0.3 μM arachidonic acid for another 5-minute incubation period, then terminated by further addition of 1 N HCl. An aliquot was then combined with the EIA kit for spectrophotometric determination of the quantity of PGE.sub.2 formed. Inhibition % was determined by compared with relative amounts of PGE.sub.2 induced by arachidonic acid. The results show that the compounds according to the present, as exemplified by compounds (cpds.) 90 and 95, do not have an inhibitory effect on cyclooxygenase-2 (COX-2), thus lending support to the fact that their inhibitory action on the PGES-pathway occurs at the level of “PGES”.

Example 7

Preparation of Compounds

(29) The synthesis of compounds described herein may be accomplished using means described in the chemical literature, using the methods described herein, or by a combination thereof.

(30) Compounds described herein may be synthesized using standard synthetic techniques known to those of skill in the art or using methods known in the art in combination with methods described herein. In addition, solvents, temperatures and other reaction conditions presented herein may vary according to those of skill in the art. The starting material used for the synthesis of the compounds described herein may be synthesized or can be obtained from commercial sources, such as, but not limited to, Aldrich Chemical Co. (Milwaukee, Wis.), or Sigma Chemical Co. (St. Louis, Mo.). The compounds described herein, and other related compounds having different substituents can be synthesized using techniques and materials described herein as well as those that are known to those of skill in the art. General methods for the preparation of compound as disclosed herein may be derived from known reactions in the field, and the reactions may be modified by the use of appropriate reagents and conditions, as would be recognized by the skilled person, for the introduction of the various moieties found in the formulae as provided herein. As a guide the synthetic method of Schemes may be utilized to prepare a compound described herein.

(31) The compounds (scaffold I, II and III; see Tables 1-7) underwent derivatization according to the methods outlined below (Schemes 1-37), and the synthesized compounds as well as relevant NMR characterization data are shown in Table 7. Resulting derivatives were examined for inhibitory activity (IC.sub.50, EC.sub.50, in vivo) using the assays described above (Examples 1, 2, 3, 4, 5 and 6), and the results are summarized in Tables 1, 2, 3, 4, 5 and 6.

(32) ##STR00012##

(33) General Procedure for the Synthesis of A1

(34) To a stirred solution of 4-fluorobenzonitrile (5.00 g, 41.3 mmol) and 4-trifluoromethoxy-phenol (8.10 g, 45.5 mmol) in DMA (30 mL) was added K.sub.2CO.sub.3 (6.30 g, 45.6 mmol). The resulting mixture was stirred at 120° C. for 16 hours. The mixture was cooled to 50° C. and 100 mL water was added dropwise under good stirring. The mixture was extracted with EtOAc (100 mL×2), the combined organic phase was washed with water (100 mL) and brine (100 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford A1.

(35) General Procedure for the Synthesis of A2

(36) To a stirred solution of A1 (3.00 g, 10.7 mmol) in anhydrous THF (30 mL) at 0° C. was added LiAlH.sub.4 (1.63 g, 43.0 mmol) in portions, the reaction mixture was stirred at 0° C. for 3 hours, the resulting mixture was stirred at 50° C. for another 16 hours. The mixture was quenched with water (1.6 mL) dropwise at 0° C., then followed NaOH (10%, 3.2 mL) dropwise and water (1.6 mL) to the mixture. The mixture was filtered, the filter cake was washed with EtOAc (30 mL) and the filtrate was concentrated under reduced pressure to afford A2.

(37) ##STR00013##

(38) General Procedure for the Synthesis of B1

(39) To a stirred solution of 2-(4-hydroxyphenyl)acetonitrile (10.0 g, 75.2 mmol) in DMA (120 mL) were added 2,5-dichloro pyridine (12.2 g, 82.7 mmol), K.sub.2CO.sub.3 (15.6 g, 113 mmol) and TBAF (589 mg, 2.26 mmol), then the mixture was stirred at 115° C. for 16 hours. The reaction mixture was poured into water (600 mL) with vigorous stirring for 1 hour. The precipitate was collected by filtration, dried in air for 2 hours and purified by Combi Flash (PE:EtOAc=5:1 to 2:1) to afford B1.

(40) General Procedure for the synthesis of B2

(41) To a stirred solution of B1 (500 mg, 2.04 mmol) in MeOH (15 mL) were added Raney-Ni (400 mg) and NH.sub.3.H.sub.2O (0.5 mL, 28%). The reaction solution was stirred at 15° C. under H.sub.2 atmosphere (45 psi) for 6 hours. Then the solution was filtered through a pad of Celite. The filtrate was concentrated and diluted with DCM (30 mL), then dried over anhydrous Na.sub.2SO.sub.4, evaporated to afford B2.

(42) ##STR00014##

(43) General Procedure for the Synthesis of C1

(44) A mixture of 4′-hydroxyacetophenone (5.00 g, 36.7 mmol), 5-chloro-2-fluoropyridine (5.79 g, 44.0 mmol) and K.sub.2CO.sub.3 (10.1 g, 73.4 mmol) in DMF (150 mL) was stirred at 100° C. for 6 hours. After cooling to room temperature, the reaction mixture was diluted with EtOAc (200 mL), then filtered and the filtrate was washed with brine (150 mL×3), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue. The residue was washed with PE/EtOAc=20/1(40 mL) to afford C1.

(45) General Procedure for the Synthesis of C2

(46) A mixture of C2 (4.50 g, 18.2 mmol) and NH.sub.2OH.HCl (1.26 g, 18.2 mmol) in MeOH/pyridine (25 mL/25 mL) was stirred at 8-10° C. for 16 hours. The resulting mixture was concentrated under reduced pressure, acidified with HCl (2 M, 120 mL), extracted with DCM (50 mL×4), the combined organic layer was washed with water (200 mL×3), brine (200 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford C2.

(47) General Procedure for the Synthesis of C3

(48) A mixture of C2 (4.70 g, 17.9 mmol) and Zn powder (11.6 g, 179 mmol) in AcOH (120 mL) was stirred at 65-75° C. for 28 hours. After cooling to room temperature, the reaction mixture was filtered, washed with EtOAc (10 mL×3) and the combined filtrate was concentrated under reduced pressure to afford a residue. The residue was diluted with saturated NaHCO.sub.3 (150 mL), extracted with EtOAc (100 mL×3), the combined organic layer was washed with brine (200 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford C3.

(49) ##STR00015##

(50) General Procedure for the Synthesis of D1

(51) To a stirred mixture of 5-chloro-2-hydroxypyridine (15.0 g, 76.5 mmol) in anhydrous THF (200 mL) were added 4-cyanobenzyl bromide (8.26 g, 63.8 mmol) and Ag.sub.2CO.sub.3 (10.5 g, 38.3 mmol). The resulting mixture was refluxed for 16 hours. The mixture was cooled to room temperature and filtered. The filter cake was washed with THF (100 mL). The combined filtrate was concentrated under reduced pressure to afford a residue, which was purified by combi flash (PE/EtOAc=92/8 to 70/30) to afford D1.

(52) General Procedure for the Synthesis of D2

(53) To a stirred solution of D1 (5.00 g, 2.04 mmol) in MeOH (100 mL) were added Raney-Ni (1.00 g) and NH.sub.3.H.sub.2O (0.5 mL, 28%) under N.sub.2 atmosphere. The suspension was degassed under vacuum and purged with H.sub.2 for three times. The solution was stirred at 12° C. under H.sub.2 (45 psi) atmosphere for 2 hours. The mixture was filtered through a pad of celite, and the pad was washed with MeOH (200 mL). The filtrate was concentrated under reduced pressure to afford D2.

(54) ##STR00016##

(55) General Procedure for the Synthesis of E1

(56) To a stirred solution of cyclopentanecarboxylic acid (5.00 g, 44.2 mmol) in anhydrous DCM (100 mL) was added CDI (8.10 g, 57.5 mmol) in portions at 28° C. The reaction solution was stirred at 28° C. for 0.5 hour. Then DIEA (8.00 g, 61.9 mmol) and N,O-dimethyl hydroxylamine hydrochloride (5.13 g, 61.9 mmol) were added. The reaction solution was stirred at 28° C. for 16 hours. The reaction solution was diluted with saturated NaHCO.sub.3 (50 mL) and separated. The organic layer was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by Combi Flash (PE:EtOAc=5:1 to 2:1) to afford E1.

(57) General Procedure for the Synthesis of E2

(58) To a stirred solution of 4-bromobenzonitrile (1.40 g, 7.69 mmol) in anhydrous THF (15 mL) was added i-PrMgBr (19.2 mL, 19.2 mmol, 1 M in THF) dropwise at −30° C. under N.sub.2 atmosphere. Then the mixture was stirred at −30° C. under N.sub.2 atmosphere for 30 minutes. A solution of E1 (1.00 g, 6.37 mmol) in anhydrous THF (5 mL) was added dropwise at −30° C. The reaction solution was allowed to warm to 30° C. and stirred at 30° C. for 16 hours. The reaction solution was quenched by saturated NH.sub.4Cl solution (15 mL) at 0° C. The organic phase was separated, concentrated under reduced pressure. The residue was purified by Combi Flash (PE:EtOAc=10:1) to afford E2.

(59) General Procedure for the Synthesis of E3

(60) A mixture of E2 (250 mg, 1.26 mmol), BF.sub.3.Et.sub.2O (0.5 mL), ethylene glycol (1 mL) in toluene (50 mL) was refluxed with azeotropic removal of water for 48 hours. The reaction solution was cooled to room temperature and diluted with saturated Na.sub.2CO.sub.3 (30 mL). The organic layer was separated, dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by prep-TLC (PE:EtOAc=5:1) to afford E3.

(61) General Procedure for the Synthesis of E4

(62) To a stirred solution of E3 (100 mg, 0.410 mmol) in MeOH (5 mL) were added Raney-Ni (100 mg) and ammonia water (0.5 mL, 28%). The reaction solution was stirred at 25° C. under H.sub.2 atmosphere (45 psi) for 2 hours. Then the solution was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to afford E4.

(63) ##STR00017##

(64) General Procedure for the Synthesis of F1

(65) To a stirred solution of 4-chloroaniline (634 mg, 4.96 mmol) and pyridine (1.17 g, 14.9 mmol) in DCM (10 mL) was added a solution of 4-cyanobenzenesulfonyl chloride (1.00 g, 4.96 mmol) in DCM (5 mL) under ice bath, then the mixture was stirred under N.sub.2 atmosphere at 25° C. for 12 hours. The mixture was poured into water (30 mL), extracted with DCM (10 mL×3). The combined extracts was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue, which was purified by flash column chromatography (eluent: DCM) to afford F1.

(66) General Procedure for the Synthesis of F2

(67) To a stirred solution of F2 (500 mg, 1.71 mmol) in anhydrous THF (2.5 mL) was added BH.sub.3/Me.sub.2S (1.35 mL, 13.5 mmol, 10M) under ice bath, the mixture was stirred under N.sub.2 atmosphere at 25° C. for 12 hours. MeOH (5 mL) was added dropwise carefully to quench the reaction, then the mixture was diluted with water (50 mL), adjusted pH 8 by saturated Na.sub.2CO.sub.3, extracted with EtOAc (30 mL×3). The combined extract was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue, which was purified by Combi Flash (eluent: PE/EtOAc=1/1 to EtOAc) to afford F2.

(68) ##STR00018##

(69) General Procedure for the Synthesis of G1

(70) To a stirred solution of 4-bromobenzonitrile (1.00 g, 5.50 mmol), LiCl (252 mg, 6.00 mmol) in anhydrous THF (10 mL) was added i-PrMgCl (3 mL, 6.0 mmol, 2 M in THF) dropwise at −15° C. under N.sub.2 atmosphere. Then the mixture was stirred at −15° C. under N.sub.2 atmosphere for 2 hours. Then picolinaldehyde (640 mg, 6.00 mmol) was added dropwise at −15° C. The reaction solution was allowed to warm to 30° C. TLC showed the reaction was complete. The reaction solution was quenched by saturated NH.sub.4Cl solution (10 mL) at 0° C. The organic layer was separated and concentrated under reduced pressure. The residue was purified by Combi Flash (PE:EtOAc=5:1 to 2:1) to afford G1.

(71) General Procedure for the Synthesis of G2

(72) To a stirred solution of G2 (400 mg, 1.90 mmol) in anhydrous THF (6 mL) was added NaH (298 mg, 2.10 mmol, 60% dispersion in mineral oil) at 0° C., then the mixture was stirred at 0° C. for 15 minutes. Afterwards, MeI (298 mg, 2.10 mmol) was added to the mixture at 0° C. The mixture was stirred under N.sub.2 atmosphere at 25° C. for 1 hour. The reaction mixture was poured into water (10 mL), extracted with EtOAc (10 mL×3). The combined organic layer was washed with brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by Combi Flash (PE:EtOAc=5:1 to 1:1) to afford G2.

(73) General Procedure for the Synthesis of G3

(74) To a stirred solution of G2 (1.50 g, 6.70 mmol) in MeOH (40 mL) were added Raney-Ni (2.0 g) and concentrated ammonia water (4 mL, 28%). The reaction solution was stirred at 25° C. under H.sub.2 atmosphere (45 psi) for 3 hours. Then the solution was filtered through a pad of Celite. The filtrate was concentrated under reduced pressure to afford 1.53 g of residue, which was purified by silica gel column chromatography (DCM:MeOH=10:1) to afford G3.

(75) ##STR00019##

(76) General Procedure for the Synthesis of H1

(77) To a stirred solution of 2-amino-1-phenylethanol (5.00 g, 36.4 mmol) and TEA (5.51 g, 54.6 mmol) in DCM (100 mL) was added Boc.sub.2O (9.54 g, 43.7 mmol), then the resulting mixture was stirred at 27-28° C. for 2 hours. The reaction mixture was concentrated under reduced pressure to remove most of DCM. The residue was diluted with EtOAc (100 mL), then washed with 1% HCl solution (50 mL), brine (50 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was washed with PE/EtOAc (50 mL/5 mL) to afford H1.

(78) General Procedure for the Synthesis of H2

(79) To a stirred solution of H1 (4.00 g, 16.9 mmol), 4-chlorophenol (4.33 g, 33.7 mmol) and PPh.sub.3 (6.63 g, 25.3 mmol) in anhydrous THF (150 mL) was added dropwise a solution of DEAD (4.40 g, 25.3 mmol) in THF (50 mL) at 0-5° C. The resulting mixture was stirred at 26-30° C. for 16 hours. The reaction mixture was diluted with EtOAc (500 mL), then washed with brine (300 mL×3), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by flash column chromatography (PE/EtOAc=20/1 to 5/1), diluted with MTBE (100 mL), then washed with 1 μM NaOH solution (50 mL×3), brine (50 mL×3), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford H2.

(80) General Procedure for the Synthesis of H3

(81) A mixture of H2 (2.00 g, 5.75 mmol) in HCl/dioxane (30 mL, 4.0 M) was stirred at 27° C. for 20 minutes. The reaction mixture was concentrated under reduced pressure to afford H3.

(82) ##STR00020##

(83) General Procedure for the Synthesis of I1

(84) To a stirred solution of 1-Boc-pyrrolidine-3-carboxylic acid (5.00 g, 23.3 mmol) and 4-(trifluoromethoxy)aniline (3.91 g, 22.1 mmol) in anhydrous DMF (50 mL) was added DIPEA (9.0 g, 69.8 mmol). Then HATU (13.2 g, 34.7 mmol) was added portionwise at 0° C. The reaction mixture was stirred at 25° C. for 4 hours. The mixture was quenched with water (100 mL), extracted with EtOAc (100 mL×2). The combined organic phase was washed with saturated NaHCO.sub.3 (100 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford I1.

(85) General Procedure for the Synthesis of I2

(86) To a stirred solution of I1 (6.00 g, 16.0 mmol) in DCM (120 mL) was added TFA (40 mL) dropwise at 0° C. After the addition, the mixture was stirred at 25° C. for 12 hours. The mixture was concentrated under reduced pressure and the residue was diluted with 100 mL water. Solid K.sub.2CO.sub.3 was added to adjust pH 10 and extracted with EtOAc (200 mL×2). The combined organic phase was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford I2.

(87) ##STR00021##

(88) General Procedure for the Synthesis of J1

(89) To a stirred solution of tert-butyl-3-hydroxypyrrolidine-1-carboxylate (10.0 g, 53.4 mmol) in THF (50 mL) was dropwise added aqueous NaOH (5.30 g/134 mmol in 5 mL water) under ice bath (below 10° C.), then TosCl (13.2 g, 68.4 mmol) was added by portions below 10° C. Then the mixture was warmed at 30° C. for 12 hours. THF was concentrated under reduced pressure to afford a residue, the residue was diluted with water (100 mL), extracted with EtOAc (50 mL×3). The combined extract was washed with water (50 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a J1.

(90) General Procedure for the Synthesis of J2

(91) A mixture of compound 2 (5.00 g, 14.6 mmol), 4-(trifluoromethoxy)phenol (2.73 g, 15.3 mmol) and Cs.sub.2CO.sub.3 (9.50 g, 29.2 mmol) in DMF (25 mL) was stirred at 80-90° C. for 2 hours. The mixture was diluted with water (150 mL), extracted with EtOAc (50 mL×4). The combined extract was dried over anhydrous Na.sub.2SO.sub.4 and concentrated to afford a crude, which was purified by flash column chromatography (eluent: EtOAc/PE=1/100 to 1/5) to afford J2

(92) General Procedure for the Synthesis of J3

(93) To a stirred solution of J2 (3.80 g, 10.9 mmol) in MeOH (20 mL) was added aq.HCl (5 mL, 12M) at 10° C., the mixture was stirred at 10° C. for 2 hours. The mixture was concentrated under reduced pressure to afford a residue. The residue was diluted with water (50 mL), adjusted pH=9 by aqueous NaOH (2M), extracted with EtOAc (30 mL×3). The combined extract was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford J3.

(94) ##STR00022##

(95) General Procedure for the Synthesis of K1

(96) To a stirred solution of 4-(4-(trifluoromethoxy)phenyl)piperidine (86.0 g, 0.351 mol) in DMSO (1 L) was added K.sub.2CO.sub.3 (121 g, 0.878 mol) and 4-fluorobenzonitrile (63.8 g, 0.527 mol) at 18° C. The reaction mixture was heated to 120° C. for 16 hours under N.sub.2. After cooling to room temperature, the mixture was concentrated to about 400 mL over high vacuum. H.sub.2O (2 L) was poured into the mixture and the resulting precipitate was collected by filtration. The crude product was triturated with H.sub.2O (1.5 L), dried over high vacuum, then triturated with EtOAc/PE (800 mL/4 L), dried over high vacuum to afford K1.

(97) General Procedure for the Synthesis of K2

(98) To a stirred solution of K1 (60.0 g, 0.173 mol) in anhydrous THF (1.0 L) was added LiAlH.sub.4 (32.9 g, 0.865 mol) at 0° C. The reaction mixture was heated to reflux for 3 hours under N.sub.2. After cooling to room temperature, the mixture was quenched carefully with H.sub.2O (33 mL), 10% NaOH solution (33 mL), H.sub.2O (100 mL) in turn. The mixture was filtered, the filter cake was washed with THF (300 mL), and the filtrate was concentrated under high vacuum to afford K2.

(99) ##STR00023##

(100) General Procedure for the Synthesis of L1

(101) To a stirred solution of 4-(trifluoromethoxy)aniline (2.00 g, 17.7 mmol), DIPEA (2.51 g, 19.3 mmol) in DCM (80 mL) was added a solution of chloroacetyl chloride (2.00 g, 17.7 mmol) in DCM (8 mL) dropwise at 0° C. The reaction mixture was stirred at 0° C. for 0.5 hour and poured into water (50 mL). The mixture was separated and the organic layer was washed with water (20 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by recrystallization from PE/EtOAc (1/1) to afford L1.

(102) ##STR00024##

(103) General Procedure for the Synthesis of M1

(104) To a stirred solution of 2-chloro-5-hydroxypyridine (3.00 g, 23.3 mmol) in anhydrous DMA (40 mL) were added 4-fluoro benzaldehyde (2.88 g, 23.3 mmol) and K.sub.2CO.sub.3 (6.40 g, 46.6 mmol). The resulting mixture was heated to 130° C. for 16 hours. Water (30 mL) was poured into the mixture, then extracted with EtOAc (40 mL×3). The combined organic phase was washed with brine (40 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude product. The residue was purified by Combi-flash (PE:EtOAc=20:1 to 15:1) to afford M1.

(105) ##STR00025##

(106) General Procedure for the Synthesis of N1

(107) To a stirred solution of 1-(4-bromophenyl)ethan-1-one (30.0 g, 150 mmol) in DMF (18 mL) was added DMFDMA (43.5 mL, 300 mmol), the resulting mixture was stirred at 110° C. for 4 hours. After cooling to room temperature, MTBE (150 mL) was added to the mixture, then MeNHNH.sub.2 (78.9 g, 600 mmol) was added into above mixture, the resulting mixture was stirred at 25° C. for 17 hours. The mixture was diluted with EtOAc (100 mL), filtered and the filter cake was washed with EtOAc (150 mL). The combined organic layer was washed with water (200 mL×3) and brine (200 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue. The residue was purified by flash column chromatography (eluted: PE/EtOAc=8/1 to 4/1) to afford N1.

(108) General Procedure for the Synthesis of N2

(109) To a stirred solution of N1 (1.20 g, 5.10 mmol) in anhydrous THF (10 mL) was added NaH (240 mg, 6.00 mmol, 60% dispersion in mineral oil), the resulting mixture was stirred at 0° C. for 1 hour, then n-BuLi (2.3 mL, 5.75 mmol, 2.5 M in hexane) was added into above mixture at −70° C. and stirred at −70° C. for 1 hour, freshly distilled DMF (1.85 g, 25.3 mmol) was added into above mixture and stirred at −70° C. for 1 hour, then the reaction mixture was allowed to warm to 0° C. TLC showed the reaction was completed. The reaction was quenched with water (30 mL) at 0° C., extracted with EtOAc (30 mL×3). The combined organic phase washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue. The residue was purified by flash column chromatography (eluted: PE/EtOAc=2/1) to afford N2.

(110) ##STR00026##

(111) General Procedure for the Synthesis of O1

(112) To a stirred solution of 2-bromo-6-hydroxypyridine (100 mg, 0.57 mmol) and 4-formylphenylboronic acid (72 mg, 0.48 mmol) in DME (2 mL) were added Pd(PPh.sub.3).sub.4 (55 mg, 0.05 mmol) and Na.sub.2CO.sub.3 solution (0.63 mL, 2M). The mixture was stirred under N.sub.2 atmosphere maintaining gentle reflux for 16 hours. The mixture was diluted with water (10 mL) extracted with EtOAc (20 mL×3). The combined extracts were washed with brine (20 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a crude, which was purified by combi flash (eluent: EtOAc) to afford O1.

(113) ##STR00027##

(114) General Procedure for the Synthesis of P1

(115) To a stirred solution of 4,4,4-trifluoro-2-butanol (450 mg, 3.51 mmol) in anhydrous THF (10 mL) were added 4-hydroxybenzaldehyde (390 mg, 3.19 mmol), PPh.sub.3 (1.26 g, 4.28 mmol) and DIAD (967 mg, 4.78 mmol). Then the mixture was stirred at 27-30° C. for 16 hours. Then the mixture was diluted with water (50 mL), extracted with EtOAc (30 mL×2). The combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude residue which was purified by Combi Flash (PE/EtOAc=10/1) to afford P1.

(116) ##STR00028##

(117) General Procedure for the Synthesis of O1

(118) To a stirred solution of DL-serine methyl ester hydrochloride (11.1 g, 71.4 mmol), MgSO.sub.4 (8.64 g, 71.4 mmol) in anhydrous THF (350 mL) were added 4-chloro-benzaldehyde (10.0 g, 71.4 mmol) and TEA (14.4 g, 143 mmol), then the mixture was stirred at 25-30° C. for 12 hours. The resulting mixture was filtered, washed with MTBE (100 mL×2). The combined filtrate was concentrated under reduced pressure to afford a crude Q1.

(119) General Procedure for the Synthesis of Q2

(120) To a stirred solution of Q1 (13.8 g, crude) in anhydrous DCM (220 mL) were added BrCCl.sub.3 (16.4 mL, 166 mmol) and DBU (25 mL, 166 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 2 hours and then at 25-30° C. for 10 hours. The mixture was concentrated under reduced pressure to dryness. The residue was dissolved in EtOAc (250 mL), washed with water (140 mL×2), brine (80 mL) in turn, dried over anhydrous Na.sub.2SO.sub.4 and concentrated to afford a residue. The residue was washed with EtOAc (20 mL) to afford Q2.

(121) General Procedure for the Synthesis of Q3

(122) To a stirred solution of Q2 (3.46 g, 14.6 mmol) in anhydrous DCM (65 mL) was added DIBAL-H (16.1 mL, 16.1 mmol, 1M in toluene) at −78° C. under N.sub.2 atmosphere. The resulting mixture was stirred at 0° C. for 4 hours. The reaction was quenched with saturated NH.sub.4Cl (25 mL) at 0° C. Then the mixture was warmed to room temperature, adjusted pH 2 by HCl (1M). The mixture was extracted with DCM (50 mL×3), the combined organic layer was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue. The residue was washed with DCM (15 mL) to afford Q3.

(123) General Procedure for the Synthesis of Q4

(124) A mixture of Q3 (1.49 g, 7.13 mmol) and MnO.sub.2 (6.20 g, 71.3 mmol) in DCM (65 mL) was stirred under N.sub.2 atmosphere at 25-30° C. for 18 hours. The mixture was filtered and the filter cake was washed with DCM (10 mL×2), the filtrate was concentrated under reduced pressure to dryness to afford Q4.

(125) ##STR00029##

(126) General Procedure for the Synthesis of R1

(127) To a stirred solution of 4-fluorobenzoic acid (50.0 g, 357 mmol), 2,2-dimethyl-1,3-dioxane-4,6-dione (61.7 g, 428 mmol) and DMAP (65.5 g, 536 mmol) in DCM (1.5 L) was added DCC (97.5 g, 464 mmol) dropwised at 0° C. and stirred at 0° C. for 30 minutes, then stirred at 25° C. for 17 hours. The mixture was filtered, the filtrate was washed with aqueous HCl (1 M, 800 mL×3), washed with brine (800 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue. The residue was dissolve in EtOH (600 mL) and stirred at 100° C. for 17 hours. The excessive EtOH was removed under reduced pressure to afford a residue, which was purified by flash column chromatography (eluted: PE/EtOAc=20/1) to afford R1.

(128) General Procedure for the Synthesis of R2

(129) A mixture of R1 (7.50 g, 35.7 mmol) and m-cresol (3.86 g, 35.7 mmol) in MsOH (9.5 mL) was stirred at 40° C. for 17 hours. After cooling to room temperature, the reaction mixture was poured into cooling EtOH (−30° C., 60 mL) and stirred at −30° C. for 1 hour. The precipitate was filtered. The solid was dissolved in EtOAc (50 mL) and then washed with saturated NaHCO.sub.3 (50 mL×2), brine (50 mL), dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford R2.

(130) General Procedure for the Synthesis of R3

(131) To a stirred solution of R2 (1.00 g, 3.94 mmol) in CCl.sub.4 (30 mL) were added NBS (842 mg, 4.73 mmol) and BPO (195 mg, 0.806 mmol), the resulting mixture was stirred at reflux for 48 hours. Then the mixture was filtered, the filtrate was concentrated under reduced pressure to afford a residue, which was purified by flash column chromatography (PE/EtOAc=30/1) to afford R3.

(132) General Procedure for the Synthesis of R4

(133) To a stirred solution of R4 (1.00 g, 3.00 mmol) in dioxane (15 mL) was added NMO (882 mg, 7.53 mmol) and the resulting mixture was stirred at reflux for 6 hours. After cooling to room temperature, the mixture was diluted with water (50 mL), extracted with EtOAc (30 mL×3). The combined organic layer was washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue, which was purified flash column chromatography (PE/EtOAc=20/1) to afford R4.

(134) ##STR00030##

(135) General Procedure for the Synthesis of S1

(136) To a stirred solution of 4-fluoro aniline (360 mg, 3.24 mmol), 4-Bromobenzaldehyde (500 mg, 2.70 mmol), XantPhos (60 mg, 0.108 mmol) and Pd.sub.2(dba).sub.3 (25 mg, 0.027 mmol) in anhydrous toluene (15 mL) was added Cs.sub.2CO.sub.3 (1.32 g, 4.05 mmol) under N.sub.2 atmosphere. The reaction mixture was purged under N.sub.2 atmosphere for 3 times, then heated to reflux (oil bath 120° C.) under N.sub.2 atmosphere for 16 hours. 40 mL water was poured into the mixture, then extracted with EtOAc (20 mL×2), the combined organic phase was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to give crude product. The residue was purified by Combi-flash (PE:EtOAc=20:1 to 9:1) to afford S1.

(137) General Procedure for the Synthesis of S2

(138) To a stirred solution of S1 (200 mg, 0.929 mmol) in anhydrous DMA (20 mL) was added NaH (74 mg, 1.86 mmol, 60% dispersion in mineral oil) at 0° C. for 0.5 hour, then ethyl bromoacetate (186 mg, 1.12 mmol) was added, after 1 hour, the resulting mixture was stirred at 60° C. for another 16 hours. The mixture was quenched with water (20 mL), then extracted with EtOAc (30 mL×2). The combined organic phase was washed with brine (20 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford S2.

(139) ##STR00031##

(140) General Procedure for the Synthesis of T1

(141) A mixture of 5-bromopyridine-2, 3-diamine (5.00 g, 26.6 mmol) in formic acid (80 mL) was heated to 110° C. for 16 hours. The reaction solution was concentrated under reduced pressure. The residue was partitioned between 2 N NaOH (200 mL) and DCM (100 mL). The organic phase was separated and the aqueous layer was cooled to 0° C. for 1 hour. The precipitate was collected by filtration, dried over high vacuum to afford T1.

(142) General Procedure for the Synthesis of T2

(143) To a stirred solution of T1 (200 mg, 1.01 mmol) in DMF (4 mL) were added 1-(2-bromoethoxy)-4-(trifluoromethoxy)benzene (432 mg, 1.52 mmol) and Cs.sub.2CO.sub.3 (823 mg, 2.53 mmol) and stirred at 50° C. for 16 hours. The reaction mixture was poured into water (200 mL) and extracted with EtOAc (20 mL×3). The combined organic layer was washed with water (10 mL×3), brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by Combi Flash (PE:EtOAc=1:1) to afford T2.

(144) General Procedure for the Synthesis of T3

(145) To a stirred solution of diisopropylamine (0.125 mL, 0.894 mmol) in anhydrous THF (1.5 mL) was added n-BuLi (0.37 mL, 2.5 M in hexane) dropwise at −78° C. The solution was stirred at −78° C. for 30 minutes. Then a solution of T2 (200 mg, 0.447 mmol) in anhydrous THF (0.5 mL) was added dropwise at −78° C. and the solution was stirred at −78° C. for 0.5 hours. Then a solution of iodine (226 mg, 0.894 mmol) in anhydrous THF (0.5 mL) was added dropwise. The reaction solution was stirred at −78° C. for 1.5 hours and warmed to room temperature. The reaction mixture was quenched by saturated Na.sub.2S.sub.2O.sub.3 (1.5 mL) and diluted with EtOAc (20 mL). The organic layer was washed with brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was recrystallized from PE/EtOAc (3 mL/3 mL) to afford T3.

(146) General Procedure for the Synthesis of T4

(147) A mixture of T3 (70 mg, 0.133 mmol), pyrrolidine (13 μg, 0.159 mmol) and Na.sub.2CO.sub.3 (21 mg, 0.200 mmol) in EtOH (1 mL) was stirred at 80° C. for 16 hours. The reaction mixture was diluted with EtOAc (20 mL), washed with brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by prep-TLC (PE:EtOAc=1:1) to afford T4.

(148) General Procedure for the Synthesis of T5

(149) To a stirred solution of XantPhos (5 mg, 0.00847 mmol), Pd.sub.2(dba).sub.3 (8 mg, 0.00847 mmol) and NaOt-Bu (20 mg, 0.211 mmol) in anhydrous toluene (1 mL) were added T4 (40 mg, 0.0847 mmol) and benzophenone imine (18 mg, 0.101 mmol). The reaction mixture was stirred at 120° C. under N.sub.2 for 1.5 hours. HCl (1 mL, 4 N) was added to the reaction mixture and the mixture was stirred at 16° C. for 5 minutes. The aqueous layer was basified with NaOH (4 mL, 2 N) and extracted with EtOAc (10 mL×2). The combined extract was washed with brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4, evaporated under reduced pressure. The resulting oil was purified by prep-TLC (DCM/MeOH, 15/1) to afford T5.

(150) ##STR00032## ##STR00033##

(151) General Procedure for the Synthesis of U1

(152) A mixture of 4-bromo-2-nitroaniline (10.0 g, 0.046 mol) and NCS (6.15 g, 0.046 mol) in DMF (100 mL) was stirred at 120° C. for 16 hours. The mixture was poured into water (100 mL), the precipitate was filtered, washed with water (50 mL) and dried under reduced pressure to afford U1.

(153) General Procedure for the Synthesis of U2

(154) To a stirred solution of U1 in MeOH (100 mL) were added concentrated HCl (9 mL, 108 mmol, 12M) and iron powder (10.0 g, 179 mmol). The reaction mixture was stirred at 8-16° C. for 16 hours. After reaction was completed, the mixture was filtered. The filtrate was neutralized to pH 8 with NaHCO.sub.3 aqueous solution and filtered. The filtrate was extracted with EtOAc (100 mL×2). The combined extracts were washed with brine (200 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford U2.

(155) General Procedure for the Synthesis of U3

(156) A mixture of U2 (7.2 g, 32.5 mmol) and CDI (6.32 g, 39.0 mmol) in anhydrous THF (100 mL) was refluxed for 16 hours. After cooling to room temperature, the white precipitate was collected by filtration and dried under reduced pressure to afford U3.

(157) General Procedure for the Synthesis of U4

(158) A mixture of U3 (4.90 g, 19.8 mmol) in POCl.sub.3 (30 mL) was refluxed for 16 hours. After the mixture was cooled to room temperature, the mixture was poured into water (100 mL) under stirring. The white precipitate was collected by filtration, washed with water (50 mL) and dried under reduced pressure to afford U4.

(159) General Procedure for the Synthesis of U5

(160) A mixture of U4 (2.10 g, 7.90 mmol) in pyrrolidine (20 mL) was refluxed for 16 hours. The mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (100 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduce pressure to afford crude residue which was purified by flash column chromatography (PE/EtOAc=5/1-2/1) to afford U5.

(161) General Procedure for the Synthesis of U6

(162) To a stirred solution of U5 (850 mg, 2.83 mmol) in anhydrous DMF (10 mL) was added NaH (170 mg, 4.24 mmol, 60% in mineral oil) at 0° C. The mixture was stirred at 0° C. for 30 minutes, added a solution of 1-(2-bromoethoxy)-4-(trifluoromethoxy)benzene (1.61 g, 5.66 mmol) in anhydrous DMF (5 mL) and stirred at 60° C. for 16 hours. The mixture was quenched with water (50 mL), extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduce pressure to afford crude residue which was purified by Combi Flash to afford U6.

(163) General Procedure for the Synthesis of U7

(164) To a stirred solution of U6 (680 mg, 1.35 mmol), benzophenone imine (488 mg, 2.69 mmol), Pd.sub.2(dba).sub.3 (124 mg, 0.135 mmol) and XantPhos (156 mg, 0.270 mmol) in anhydrous toluene (10 mL) was added NaOt-Bu (324 mg, 3.38 mmol) under N.sub.2 atmosphere. The reaction mixture was purged in N.sub.2 atmosphere for three times. The mixture was heated to 80-100° C. for 16 hours. The mixture was concentrated, dissolved in MeOH (2 mL), added HCl (3 M, 2 mL) and stirred at 20-25° C. for 2 hours. Then the mixture was neutralized to pH 8 with NaHCO.sub.3 aqueous solution and extracted with EtOAc (30 mL×2), the combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude residue, which was purified by prep-HPLC (0.05% HCl) to afford U7.

(165) ##STR00034##

(166) General Procedure for the Synthesis of V2

(167) To a stirred solution of compound 2 (538 mg, 2.61 mmol) in DMA (10 mL) was added NaH (125 mg, 3.13 mmol, 60% dispersion in mineral oil) portionwise. The mixture was stirred at 0° C. under N.sub.2 atmosphere for 5 minutes. Then a solution of 1-(2-bromoethoxy)-4-chlorobenzene (908 mg, 3.90 mmol) in DMA (8 mL) was added to the mixture and the solution was stirred at 60° C. under N.sub.2 for 24 hours. The mixture was diluted with water (80 mL) and extracted with EtOAc (40 mL×3), the combined extracts were washed with water (20 mL×2), brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford the crude product, which was recrystallized from EtOAc (5 mL) to afford a mixture of V2 and V2′.

(168) General Procedure for the Synthesis of V3

(169) To a stirred solution of a mixture of V2 and V2′ (100 mg, 0.302 mmol) in MeOH were added Zn powder (98.2 mg, 1.51 mmol) and NH.sub.4Cl (326 mg, 6004 mmol) at 19° C. The mixture was stirred at 45° C. for 16 hours. The reaction solution was diluted with EtOAc (10 mL) and filtered. The filtrate was concentrated under reduced pressure. The resulting oil was purified by prep-TLC (DCM/MeOH, 20/1) to afford V3.

(170) ##STR00035##

(171) General Procedure for the Synthesis of W2

(172) A mixture of compound W1 (300 mg, 0.843 mmol), oxetan-3-amine (74 mg, 1.0 mmol), K.sub.2CO.sub.3 (175 mg, 1.26 mmol) in DMF (3 mL) was stirred at 10° C. for 16 hours. The reaction solution was diluted with water (15 mL) and extracted with EtOAc (20 mL×2). The combined extract was washed with water (10 mL×2), brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford W2.

(173) General Procedure for the Synthesis of W4

(174) To a stirred solution of W2 (500 mg, 1.22 mmol) in MeOH (20 mL) was added Pd/C (50 mg, 5%, 60% wet) in N.sub.2 atmosphere. The suspension was degassed under vacuum and purged with H.sub.2 several times. The mixture was stirred under H.sub.2 atmosphere (1 atm) for 1.5 hours. The reaction mixture was filtered through a pad of Celite. To the filtrate (W3 in MeOH) was added BrCN (261 mg, 2.44 mmol). The reaction solution was stirred at 10° C. for 16 hours. The reaction solution was concentrated under reduced pressure. The residue was diluted with water (30 mL) and EtOAc (30 mL). Then solid Na.sub.2CO.sub.3 was added with stirring until aqueous layer was basified to pH 9. The organic layer was separated and dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford W4.

(175) ##STR00036##

(176) General Procedure for the Synthesis of X1

(177) A mixture of 3-fluoro-4-nitroaniline (1.00 g, 6.40 mmol), (4-(4-chlorophenoxy)phenyl) methanamine (1.79 g, 7.28 mmol), and DIPEA (1.65 g, 12.8 mmol) in ACN (15 mL) was refluxed 16 hours. The mixture was cooled to room temperature and diluted with water (40 mL). The mixture was extracted with EtOAc (40 mL×2). The combined extracts was dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford 3.42 g of crude residue, which was purified by Combi Flash to afford X1.

(178) General Procedure for the Synthesis of X2

(179) To a stirred solution of X1 (1.50 g, 4.06 mmol), di-tert-butyl dicarbonate (1.15 g, 5.27 mmol) in DCM (20 mL) were added DMAP (248 mg, 2.03 mmol) and TEA (413 mg, 4.06 mmol). The mixture was stirred at 20° C. for 16 hours. The mixture was diluted with water (50 mL) and extracted with EtOAc (40 mL×2). The combined extracts were washed with brine (100 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford 3.00 g of crude residue, which was purified by Combi flash (PE/EtOAc=25/1 to 20/1 to 15/1) to afford X2.

(180) General Procedure for the Synthesis of X3

(181) To a stirred solution of X2 (100 mg, 0.213 mmol) in MeOH (5 mL) was added Raney-Ni (20 mg) under Ar. The suspension was degassed under vacuum and purged with H.sub.2 for three times. The solution was stirred at 28° C. under H.sub.2 (50 psi) for 16 hours. The mixture was filtered through a pad of celite, and the pad was washed with MeOH (200 mL). The filtrate was concentrated under reduced pressure to afford X3.

(182) General Procedure for the Synthesis of X4

(183) A mixture of X3 (80 mg, 182 mmol), cyanogen bromide (29 mg, 0.273 mmol) in EtOH (4 mL) was stirred at 25° C. for 16 hours. The mixture was basified to pH 9 with Na.sub.2CO.sub.3 aqueous solution, diluted with water (20 mL) and extracted with EtOAc (20 mL×2). The combined extracts was washed with brine (40 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford X4.

(184) General Procedure for the Synthesis of X5

(185) To a stirred solution of X4 (80 mg, 0.172 mmol) in MeOH (2 mL) was added HCl solution of MeOH (4M, 2 mL). The resulting solution was stirred at 25° C. for 2 hours. The mixture was diluted with water (20 mL), basified to pH 9 with Na.sub.2CO.sub.3 aqueous solution and extracted with EtOAc (20 mL×2). The combined extracts was washed with brine (40 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude residue, which was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O) to afford X5.

(186) ##STR00037##

(187) General Procedure for the Synthesis of Y1

(188) A mixture of 5-bromo-1,3-dihydro-2H-benzo[d]imidazol-2-one (5.00 g, 23.5 mmol) and POCl.sub.3 (80 mL) was refluxed for 16 hours. After cooled to room temperature, the mixture was poured into water (300 mL) and NaOH aqueous solution (5 M, 80 mL) was added. The precipitate was filtered and washed with water. The filtrate was dried over high vacuum to afford Y1.

(189) General Procedure for the Synthesis of Y2

(190) To a stirred solution of Y1 (500 mg, 2.16 mmol) and DIPEA (558 mg, 4.32 mmol) in THF (5 mL) was added SEMCl (540 mg, 3.24 mmol) at 0° C. and the resulting mixture was stirred at 35° C. for 16 hours. The mixture was diluted with water (50 mL), extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduce pressure to afford a residue. The residue was purified by flash column chromatography to afford Y2.

(191) General Procedure for the Synthesis of Y3

(192) A mixture of Y2 (480 mg, 1.33 mmol), 4-methyl-1H-pyrazole (109 mg, 1.33 mmol) and K.sub.2CO.sub.3 (275 mg, 1.99 mmol) in DMF (5 mL) was stirred at 100° C. for 16 hours. The mixture was diluted with water (50 mL), extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduce pressure to afford a residue. The residue was purified by flash column chromatography to afford Y3.

(193) General Procedure for the Synthesis of Y4

(194) A mixture of Y3 (500 mg, 1.23 mmol), 1-(4-fluorophenyl)piperazine (243 mg, 1.35 mmol), NaOt-Bu (236 mg, 2.45 mmol), Pd.sub.2(dba).sub.3 (112 mg, 0.123 mmol) and Xantphos (71 mg, 0.12 mmol) in toluene (5 mL) was stirred at 120° C. for 16 hours. The mixture was diluted with water (50 mL), extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduce pressure to afford a residue. The residue was purified by flash column chromatography to afford Y4.

(195) General Procedure for the Synthesis of Y5

(196) A mixture of Y4 (160 mg, 0.316 mmol) and conc.HCl (2 mL) in MeOH (6 mL) was stirred at 32° C. for 16 hours. The mixture was diluted with water (50 mL), neutralized with NaOH aqueous solution and extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (50 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduce pressure to afford Y5.

(197) ##STR00038##

(198) General Procedure for the Synthesis of Z1

(199) To a stirred solution of dimethyl amine in THF (18 mL, 2 N) was added 2-chloro-5-nitro-1H-benzo[d]imidazole (1.80 g, 9.1 mmol) at 20° C. The reaction solution was stirred at 150° C. in a sealed tube for 3 hours. The reaction solution was poured into water (20 mL) and extracted with EtOAc (10 mL×3). The combined organic layer was washed with brine (10 mL), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford Z1.

(200) ##STR00039##

(201) General Procedure for the Synthesis of AA1

(202) A mixture of 5-nitro-1H-benzo[d]imidazol-2-amine (200 mg, 1.12 mmol), (4-fluoro-phenyl)-acetaldehyde (388 mg, 2.80 mmol) and Ti(Oi-Pr).sub.4 (637 mg, 2.24 mmol) in anhydrous THF (5 mL) was stirred at 60° C. for 30 minutes, then cooled to 20° C. and kept at this temperature for 30 minutes under stirring. Then NaBH.sub.4 (213 mg, 5.60 mmol) was added into the mixture at 0° C. and stirred at 20° C. for 3 hours, then at 60° C. for 16 hours. The mixture was cooled and quenched with aqueous NH.sub.3.H.sub.2O (2M, 10 mL). The precipitate was filtered and washed with THF (20 mL). The filtrate was diluted with water (20 mL) and extracted with EtOAc (20 mL×2). The combined extracts were washed with brine (50 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude product, which was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O) to afford AA1.

(203) ##STR00040##

(204) General Procedure for the Synthesis of AB1

(205) A mixture of 5-nitro-1H-benzo[d]imidazol-2-amine (1.00 g, 5.60 mmol), 4-fluorobenzaldehyde (2.78 g, 22.4 mmol) and Ti(Oi-Pr).sub.4 (3.18 g, 11.2 mmol) in THF (6 mL) was stirred at 60° C. for 30 minutes, the mixture was cooled to 20° C. and kept at this temperature for 30 minutes. Then NaBH.sub.4 (851 mg, 22.4 mmol) was added into the mixture at 0° C. and stirred at 20° C. for 3 hours and at 60° C. for 16 hours. The mixture was cooled to 20° C. and quenched with aqueous NH.sub.3.H.sub.2O (2M, 15 mL). The precipitate was filtered, washed with THF (50 mL). The filtrate was diluted with water (50 mL) and extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (100 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude product, which was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O) to afford AB1.

(206) ##STR00041##

(207) General Procedure for the Synthesis of AC1

(208) To a stirred solution of 1-methyl-6-nitro-1H-benzo[d]imidazol-2-amine (900 mg, 3.63 mmol) and acetophenone (700 mg, 3.64 mmol) in anhydrous toluene (150 mL) was added Ti(Oi-Pr).sub.4 (3.13 g, 10.9 mmol). The resulting mixture was stirred under reflux under N.sub.2 atmosphere for 24 hours. After cooling to room temperature, NaBH.sub.4 (290 mg, 7.26 mmol) was added to the mixture followed by MeOH (5 mL). The resulting mixture was stirred at 12° C. for 2 hours. The mixture was diluted with EtOAc (200 mL), washed with brine (200 mL) and water (200 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude product, which was purified by flash column chromatography (eluted with PE/EtOAc=50/1 to 5/1) to afford AC1.

(209) ##STR00042##

(210) General Procedure for the Synthesis of AD1

(211) A mixture of 5-nitro-1H-benzo[d]imidazol-2-amine (3.00 g, 16.8 mmol) and 4-fluorobenzoyl chloride (8.10 g, 53.6 mmol) in pyridine (30 mL) was stirred at 20° C. for 10 minutes. The mixture was diluted with water (150 mL) and filtered. The filter cake was washed with water (100 mL) and dried over high vacuum to afford a crude residue which was purified by flash column chromatography to afford AD1.

(212) ##STR00043##

(213) General Procedure for the Synthesis of AE1

(214) A mixture of 2-chloro-5-nitro-1H-benzo[d]imidazole (500 mg, 2.53 mmol), 4-phenylbenzylamine (696 mg, 3.80 mmol) in n-BuOH (8 mL) was refluxed for 36 hours. After reaction was complete, the mixture was diluted with water (50 mL) and extracted with EtOAc (50 mL×2). The combined extracts were washed with brine (100 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude residue, which was purified by combi flash (PE/EtOAc=3/1 to 2/1 to 1/1) to afford AE1.

(215) General Procedure for the Synthesis of AE2

(216) To a stirred solution of AE1 (150 mg, 0.436 mmol) in EtOAc/MeOH (8 mL/2 mL) was added Pd/C (30 mg, 10%) under N.sub.2. The suspension was degassed under vacuum and purged with H.sub.2 for three times. The solution was stirred at 22° C. under H.sub.2 balloon for 16 hours. The mixture was filtered through a pad of celite and washed with EtOAc (30 mL). The filtrate was concentrated under reduced pressure to afford crude residue which was purified by washing with EtOAc/MeOH (5 mL/1 mL) to afford AE2.

(217) ##STR00044##

(218) General Procedure for the Synthesis of AF2

(219) A mixture of A1 (200 mg, 0.488 mmol), AcOH (0.3 mL) and 3-oxetanone (42 mg, 0.59 mmol) in absolute EtOH (3 mL) was stirred at 18-22° C. for 16 hours. Then to the reaction mixture was added NaBH.sub.3CN (92 mg, 1.5 mmol), the resulting mixture was stirred at 18-20° C. for 4 hours. The reaction mixture was diluted with EtOAc (50 mL), then washed with water (40 mL) and brine (40 mL×3), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure. The residue was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O as additive) to afford AF2.

(220) General Procedure for the Synthesis of AF3

(221) A mixture of AF2 (100 mg, 0.229 mmol) and formaldehyde (86 mg, 1.15 mmol, 40% aqueous solution in water) in EtOH (5 mL) was added AcOH (adjusted to pH 4 of reaction mixture). The resulting mixture was stirred at 10° C. for 16 hours. NaBH.sub.3CN (72 mg, 1.15 mmol) was added to the mixture and the reaction mixture was stirred at 10° C. for 4 hours. The mixture was diluted with water (20 mL) and extracted with EtOAc (20 mL×2), the combined extracts were washed with brine (40 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a residue, which was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O) to afford AF3.

(222) ##STR00045##

(223) General Procedure for the Synthesis of AG2

(224) To a stirred solution of AG1 (150 mg, 0.583 mmol), 1H-imidazole-5-carbaldehyde (39 mg, 0.416 mmol) in EtOH (3 mL) was added AcOH (adjusted to pH 4 of reaction mixture). The resulting mixture was stirred at 20° C. for 16 hours. Then NaBH.sub.3CN (73 mg, 1.17 mmol) was added and the mixture was stirred at 20° C. for 16 hours. The mixture was neutralized with Na.sub.2CO.sub.3, diluted with water (20 mL) and extracted with EtOAc (20 mL×2). The combined extracts were washed with brine (40 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude residue, which was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O) to afford AG2.

(225) ##STR00046##

(226) General Procedure for the Synthesis of AH2

(227) To a stirred solution of AH1 (200 mg, 0.69 mmol) and ethyl 2-bromoisobutyrate (537 mg, 2.75 mmol) in EtOH (10 mL) was added NaOAc (226 mg, 2.75 mmol). The mixture was refluxed under N.sub.2 for 16 hours. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL×2). The combined extracts were washed with brine (10 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure afford a crude AH2.

(228) General Procedure for the Synthesis of AH3

(229) To a stirred solution of compound AH2 (200 mg, crude) in anhydrous THF (5 mL) was added LiAlH.sub.4 (75 mg, 1.98 mmol) at 0° C. After stirred at 0° C. for 2 hours, the mixture was allowed to stir at 25° C. under N.sub.2 for 16 hours. The mixture was quenched with NaOH aqueous solution (5 M, 0.2 mL) and filtered. The filtrate was diluted with water (10 mL) and extracted with EtOAc (10 mL×2), the combined extracts were washed with brine, dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford crude product, which was purified by prep-TLC (MeOH:DCM=1:10) to afford AH3.

(230) ##STR00047##

(231) General Procedure for the Synthesis of AI2

(232) A mixture of AI1 (1.00 g, 4.05 mmol), 5-fluoro-2-nitroaniline (631 mg, 4.05 mmol) and DIPEA (1.55 g, 12.2 mmol) in ACN (10 mL) was heated to reflux for 12 hours. The mixture was concentrated under reduced pressure to afford a residue, which was purified by silica gel column (eluent: EtOAc/PE=1/10 to DCM to DCM/EtOAc=1/1) to afford AI2.

(233) General Procedure for the Synthesis of AI3

(234) A mixture of compound AI2 (1.30 g, 3.39 mmol) and Pd—C (200 mg, 10%) in MeOH (30 mL) was stirred at 10° C. under H.sub.2 (1 atm) for 2 hours. The mixture was filtered, the filtrate was concentrated under reduced pressure to afford a crude AI3.

(235) General Procedure for the Synthesis of AI4

(236) To a stirred solution of compound AI3 (100 mg, 0.283 mmol) in MeOH (5 mL) was added BrCN (31 mg, in 0.5 mL ACN) with ice bath, the mixture was stirred at 10° C. for 1 hour. The reaction solution was purified by prep-HPLC (0.01% HCl) to afford AI4.

(237) ##STR00048##

(238) General Procedure for the Synthesis of AJ2

(239) To a stirred solution of AJ1 (100 mg, 0.274 mmol) in anhydrous dioxane (3 mL) were added cyclobutanone (23 mg, 0.329 mmol) and TMSCN (38 mg, 0.384 mmol), the resulting mixture was stirred at 50° C. under N.sub.2 atmosphere for 16 hours. The mixture was diluted with water (15 mL) and extracted with EtOAc (15 mL×2), the combined extracts were washed with brine (30 mL×2), dried over anhydrous Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford 90 mg of crude residue, which was purified by prep-HPLC (0.05% HCl) to afford AJ2.

(240) ##STR00049##

(241) General Procedure for the Synthesis of AK2

(242) To a stirred solution of AK1 (100 mg, 0.244 mmol) in anhydrous toluene (5 mL) were added RuPhos (12 mg, 0.0244 mmol), Pd.sub.2(dba).sub.3 (23 mg, 0.0244 mmol), 3-bromo-1-methyl-1H-pyrazole (47 mg, 0.293 mmol) and NaOt-Bu (58 mg, 0.610 mmol). The mixture was stirred at 110° C. under N.sub.2 for 16 hours. The reaction was diluted with brine (5 mL) and filtered. The filtrate was extracted with EtOAc (5 mL×3). The combined extract was washed with brine (5 mL), dried over Na.sub.2SO.sub.4, evaporated under reduced pressure. The resulting oil was purified by prep-HPLC (0.01% NH.sub.3.H.sub.2O as additive) to afford AK2.

(243) Using the above procedures, compounds 1-556 as shown in Table 7 (further below) were synthesized.

(244) TABLE-US-00001 TABLE 1 5-LO activity by fluorescence method # cpds 5-LO (IC.sub.50, uM) 1 +++ 2 +++ 3 +++ 4 +++ 5 +++ 6 +++ 7 +++ 8 +++ 9 +++ 10 +++ 11 +++ 12 +++ 13 ++ 14 +++ 15 +++ 16 +++ 17 ++ 18 ++ 19 +++ 20 +++ 21 +++ 22 + 23 ++ 24 +++ 25 + 26 ++ 27 ++ 28 +++ 29 +++ 30 +++ 31 +++ 32 +++ 33 +++ 34 +++ 35 ++ 36 +++ 37 +++ 38 +++ 39 +++ 40 +++ 41 ++ 42 ++ 43 ++ 44 +++ 45 + 46 + 47 + 48 +++ 49 + 50 ++ 51 +++ 52 +++ 53 +++ 54 +++ 55 ++ 56 +++ 57 +++ 58 +++ 59 +++ 60 +++ 61 +++ 62 +++ 63 +++ 64 +++ 65 +++ 66 +++ 67 +++ 68 +++ 69 ++ 70 +++ 71 +++ 72 + 73 +++ 74 +++ 75 +++ 76 +++ 77 +++ 78 + 79 +++ 80 +++ 81 +++ 82 + 83 ++ 84 +++ 85 ++ 86 +++ 87 +++ 88 +++ 89 +++ 90 +++ 91 +++ 92 +++ 93 +++ 94 +++ 95 +++ 96 +++ 97 +++ 98 +++ 99 +++ 100 +++ 101 +++ 102 +++ 103 +++ 104 +++ 105 +++ 106 +++ 107 +++ 108 +++ 109 +++ 110 +++ 111 +++ 112 +++ 113 +++ 114 +++ 115 +++ 116 +++ 117 +++ 118 +++ 119 +++ 120 +++ 121 +++ 122 +++ 123 +++ 124 +++ 125 +++ 126 +++ 127 +++ 128 +++ 129 +++ 130 +++ 131 +++ 132 +++ 133 +++ 134 +++ 135 +++ 136 +++ 137 +++ 138 +++ 139 +++ 140 +++ 141 +++ 142 +++ 143 +++ 144 +++ 145 +++ 146 +++ 147 +++ 148 +++ 149 +++ 150 +++ 151 +++ 152 +++ 153 +++ 154 +++ 155 +++ 156 +++ 157 +++ 158 +++ 159 +++ 160 +++ 161 +++ 162 +++ 163 +++ 164 +++ 165 +++ 166 +++ 167 +++ 168 +++ 169 +++ 170 +++ 171 +++ 172 +++ 173 +++ 174 ++ 175 +++ 176 +++ 177 +++ 178 +++ 179 +++ 180 +++ 181 +++ 182 +++ 183 +++ 184 +++ 185 +++ 186 +++ 187 +++ 188 +++ 189 +++ 190 +++ 191 +++ 192 +++ 193 + 194 +++ 195 +++ 196 +++ 197 +++ 198 +++ 199 +++ 200 +++ 201 +++ 202 +++ 203 +++ 204 +++ 205 +++ 206 +++ 207 +++ 208 +++ 209 +++ 210 +++ 211 +++ 212 +++ 213 +++ 214 +++ 215 +++ 216 +++ 217 +++ 218 +++ 219 +++ 220 +++ 221 +++ 222 +++ 223 +++ 224 +++ 225 +++ 226 +++ 227 +++ 228 +++ 229 +++ 230 +++ 231 +++ 232 +++ 233 +++ 234 +++ 235 + 236 +++ 237 +++ 238 +++ 239 +++ 240 +++ 241 +++ 242 ++ 243 +++ 244 +++ 245 + 246 +++ 247 +++ 248 +++ 249 +++ 250 +++ 251 +++ 252 +++ 253 +++ 254 +++ 255 +++ 256 +++ 257 +++ 258 +++ 259 +++ 260 +++ 261 +++ 262 + 263 +++ 264 +++ 265 +++ 266 +++ 267 +++ 268 +++ 269 +++ 270 +++ 271 +++ 272 +++ 273 +++ 274 +++ 275 +++ 276 +++ 277 +++ 278 +++ 279 ++ 280 +++ 281 +++ 282 +++ 283 +++ 284 +++ 285 +++ 286 +++ 287 +++ 288 +++ 289 +++ 290 +++ 291 +++ 292 +++ 293 +++ 294 +++ 295 +++ 296 +++ 297 +++ 298 +++ 299 +++ 300 +++ 301 +++ 302 +++ 303 +++ 304 +++ 305 +++ 306 +++ 307 +++ 308 +++ 309 +++ 310 +++ 311 +++ 312 +++ 313 +++ 314 +++ 315 +++ 316 +++ 317 +++ 318 +++ 319 +++ 320 +++ 321 +++ 322 + 323 +++ 324 +++ 325 +++ 326 +++ 327 +++ 328 +++ 329 +++ 330 +++ 331 +++ 332 +++ 333 +++ 334 +++ 335 +++ 336 +++ 337 +++ 338 +++ 339 +++ 340 +++ 341 +++ 342 +++ 343 +++ 344 +++ 345 +++ 346 +++ 347 +++ 348 +++ 349 +++ 350 +++ 351 +++ 352 +++ 353 +++ 354 +++ 355 ++ 356 +++ 357 +++ 358 +++ 359 +++ 360 +++ 361 +++ 362 +++ 363 +++ 364 +++ 365 +++ 366 +++ 367 +++ 368 +++ 369 +++ 370 +++ 371 +++ 372 +++ 373 +++ 374 +++ 375 +++ 376 +++ 377 +++ 378 +++ 379 +++ 380 +++ 381 +++ 382 +++ 383 +++ 384 +++ 385 +++ 386 ++ 387 +++ 388 +++ 389 +++ 390 +++ 391 +++ 392 +++ 393 +++ 394 +++ 395 +++ 396 +++ 397 +++ 398 +++ 399 +++ 400 +++ 401 +++ 402 +++ 403 +++ 404 +++ 405 +++ 406 +++ 407 +++ 408 +++ 409 +++ 410 +++ 411 +++ 412 +++ 413 +++ 414 +++ 415 +++ 416 +++ 417 +++ 418 +++ 419 +++ 420 +++ 421 +++ 422 +++ 423 +++ 424 +++ 425 +++ 426 +++ 427 +++ 428 +++ 429 + 430 +++ 431 +++ 432 +++ 433 +++ 434 +++ 435 +++ 436 +++ 437 +++ 438 +++ 439 +++ 440 +++ 441 + 442 +++ 443 +++ 444 +++ 445 +++ 446 +++ 447 ++ 448 ++ 449 +++ 450 +++ 451 +++ 452 +++ 453 +++ 454 +++ 455 +++ 456 +++ 457 +++ 458 +++ 459 +++ 460 +++ 461 +++ 462 +++ 463 +++ 464 ++ 465 +++ 466 +++ 467 +++ 468 +++ 469 +++ 470 +++ 471 +++ 472 ++ 473 +++ 474 +++ 475 +++ 476 +++ 477 +++ 478 +++ 479 +++ 480 +++ 481 +++ 482 +++ 483 +++ 484 +++ 485 +++ 486 +++ 487 +++ 488 ++ 489 +++ 490 +++ 491 +++ 492 +++ 493 ++ 494 ++ 495 +++ 496 +++ 497 ++ 498 + 499 +++ 500 ++ 501 +++ 502 ++ 503 +++ 504 ++ 505 +++ 506 + 507 +++ 508 ++ 509 +++ 510 + 511 + 512 +++ 513 +++ 514 +++ 515 + 516 + 517 ++ 518 + 519 + 520 + 521 ++ 522 + 523 + 524 + 525 +++ 526 ++ 527 + 528 + 529 +++ 530 +++ 531 +++ 532 +++ 533 +++ 534 +++ 535 +++ 536 +++ 537 +++ 538 +++ 539 +++ 540 +++ 541 +++ 542 +++ 543 +++ 544 +++ 545 ++ 546 +++ 547 +++ 548 +++ 549 +++ 550 +++ 551 +++ 552 +++ 553 +++ 554 +++ 555 +++ 556 +++ Activity range: +++ indicates <1 uM, ++ indicates between 1-10 uM, + indicates >10 uM

(245) TABLE-US-00002 TABLE 2 5-LO activity by ELISA method # cpds 5LO (IC.sub.50, uM) 14 +++ 48 ++ 49 ++ Activity range: +++ indicates <1 uM, ++ indicates between 1-20 uM, + indicates >20 uM

(246) TABLE-US-00003 TABLE 3 LTB4 secretion assay in RBL # cpds RBL (EC.sub.50, uM) 14 +++ 17 +++ 24 +++ 26 + 27 + 28 ++ 29 +++ 30 +++ 31 + 32 +++ 33 +++ 34 ++ 35 + 36 ++ 37 + 38 +++ 39 ++ 40 ++ 41 ++ 42 ++ 43 +++ 44 +++ 45 +++ 46 +++ 47 + 48 +++ 49 +++ 50 ++ 51 +++ 52 +++ 53 +++ 54 +++ 55 +++ 56 +++ 57 +++ 58 +++ 59 +++ 60 +++ 61 ++ 62 +++ 63 ++ 64 + 65 +++ 66 +++ 67 +++ 68 +++ 69 +++ 70 +++ 71 ++ 72 + 73 +++ 74 +++ 75 ++ 76 + 77 ++ 78 ++ 79 +++ 80 +++ 81 +++ 82 ++ 83 + 84 +++ 85 + 86 +++ 87 +++ 88 +++ 89 + 90 +++ 91 +++ 92 +++ 93 +++ 94 +++ 95 +++ 96 +++ 97 +++ 98 +++ 99 +++ 100 +++ 101 +++ 102 +++ 103 +++ 104 +++ 105 +++ 106 +++ 107 +++ 108 + 109 +++ 110 +++ 111 +++ 112 +++ 113 +++ 114 ++ 115 + 116 +++ 117 ++ 118 +++ 119 +++ 120 +++ 121 +++ 122 +++ 123 +++ 124 +++ 125 +++ 126 +++ 127 +++ 128 +++ 129 +++ 130 +++ 131 +++ 132 +++ 133 ++ 134 +++ 135 +++ 136 +++ 137 +++ 138 +++ 139 + 140 +++ 141 + 142 ++ 143 ++ 144 ++ 145 +++ 146 ++ 147 +++ 148 +++ 149 +++ 150 +++ 151 + 152 +++ 153 +++ 154 + 155 +++ 156 ++ 157 + 158 + 159 + 160 +++ 161 +++ 162 +++ 163 + 164 +++ 165 +++ 166 +++ 167 + 168 +++ 169 +++ 170 ++ 171 + 172 +++ 173 + 174 + 175 +++ 176 +++ 177 +++ 178 ++ 179 +++ 180 +++ 181 + 182 ++ 183 + 184 +++ 185 +++ 186 +++ 187 +++ 188 + 189 + 190 +++ 191 +++ 192 +++ 193 +++ 194 +++ 195 +++ 196 +++ 197 +++ 198 ++ 199 +++ 200 +++ 201 + 202 +++ 203 +++ 204 +++ 205 +++ 206 +++ 207 +++ 208 +++ 209 +++ 210 +++ 211 +++ 212 +++ 213 +++ 214 +++ 215 +++ 216 +++ 217 +++ 218 +++ 219 +++ 220 +++ 221 + 222 ++ 223 +++ 224 +++ 225 + 226 +++ 227 +++ 228 + 229 +++ 230 +++ 231 +++ 232 + 233 +++ 234 +++ 235 +++ 236 +++ 237 + 238 +++ 239 +++ 240 +++ 241 +++ 242 +++ 243 +++ 244 +++ 245 +++ 246 +++ 247 +++ 248 +++ 249 +++ 250 +++ 251 +++ 252 +++ 253 +++ 254 +++ 255 +++ 256 ++ 257 +++ 258 +++ 259 +++ 260 +++ 261 +++ 262 +++ 263 ++ 264 +++ 265 +++ 266 ++ 267 +++ 268 +++ 269 +++ 270 +++ 271 +++ 272 +++ 273 +++ 274 +++ 275 +++ 276 +++ 277 +++ 278 +++ 279 +++ 280 +++ 281 +++ 282 +++ 283 +++ 284 +++ 285 +++ 286 +++ 287 +++ 288 +++ 289 +++ 290 +++ 291 +++ 292 +++ 293 +++ 294 +++ 295 +++ 296 +++ 297 +++ 298 +++ 299 +++ 300 +++ 301 +++ 302 +++ 303 + 304 +++ 305 +++ 306 +++ 307 ++ 308 + 309 + 310 + 311 + 312 + 313 +++ 314 ++ 315 ++ 316 +++ 317 + 318 + 319 + 320 + 321 ++ 322 +++ 323 +++ 324 +++ 325 +++ 326 +++ 327 +++ 328 +++ 329 +++ 330 +++ 331 +++ 332 +++ 333 +++ 334 ++ 335 +++ 336 ++ 337 ++ 338 + 339 ++ 340 +++ 341 ++ 342 +++ 343 + 344 + 345 + 346 +++ 347 +++ 348 + 349 +++ 350 +++ 351 ++ 352 +++ 353 +++ 354 + 355 + 356 ++ 357 +++ 358 +++ 359 +++ 360 ++ 361 +++ 362 ++ 363 + 364 + 365 +++ 366 +++ 367 +++ 368 +++ 369 +++ 370 ++ 371 ++ 372 +++ 373 +++ 374 +++ 375 +++ 376 + 377 +++ 378 +++ 379 +++ 380 +++ 381 + 382 +++ 383 +++ 384 +++ 385 ++ 386 + 387 +++ 388 ++ 389 +++ 390 +++ 391 +++ 392 +++ 393 +++ 394 ++ 395 +++ 396 +++ 397 +++ 398 +++ 399 +++ 400 +++ 401 +++ 402 +++ 403 +++ 404 + 405 +++ 406 +++ 407 +++ 408 + 409 + 410 +++ 411 + 412 +++ 413 +++ 414 +++ 415 +++ 416 ++ 417 + 418 + 419 +++ 420 +++ 421 +++ 422 +++ 423 +++ 424 +++ 425 +++ 426 +++ 427 +++ 428 +++ 429 ++ 430 +++ 431 +++ 432 +++ 433 ++ 434 +++ 435 +++ 436 +++ 437 +++ 438 ++ 439 ++ 440 +++ 441 + 442 +++ 443 + 444 ++ 445 +++ 446 +++ 447 +++ 448 +++ 449 +++ 450 +++ 451 +++ 452 +++ 453 +++ 454 ++ 455 +++ 456 + 457 +++ 458 +++ 459 ++ 460 +++ 461 +++ 462 + 463 +++ 464 +++ 465 +++ 466 +++ 467 +++ 468 +++ 469 +++ 470 +++ 471 +++ 472 +++ 473 +++ 474 +++ 475 +++ 476 +++ 477 +++ 478 +++ 479 +++ 480 +++ 481 +++ 482 +++ 483 + 484 + 485 ++ 486 +++ 487 +++ 488 + 489 +++ 490 +++ 491 +++ 492 +++ 493 +++ 494 +++ 495 +++ 496 +++ 497 + 498 + 499 +++ 500 ++ 501 +++ 502 +++ 503 +++ 504 +++ 505 +++ 506 +++ 507 +++ 508 +++ 509 +++ 510 +++ 511 +++ 512 +++ 513 +++ 514 +++ 515 +++ 516 +++ 517 +++ 518 +++ 519 +++ 520 +++ 521 +++ 522 +++ 523 +++ 524 +++ 525 +++ 526 +++ 527 +++ 528 +++ 529 +++ 530 +++ 531 +++ 532 +++ 533 +++ 534 +++ 535 +++ 536 +++ 537 +++ 538 +++ 539 +++ 540 +++ 541 +++ 542 +++ 543 +++ 544 +++ 545 +++ 546 +++ 547 +++ 548 +++ 549 +++ 550 +++ 551 +++ 552 +++ 553 +++ 554 ++ 555 ++ 556 +++ Activity range: +++ indicates <10 uM, ++ indicates between 10-20 uM, + indicates >20 uM

(247) TABLE-US-00004 TABLE 4 LTB4 secretion assay in Rat whole blood (RWB) # cpds RWB (EC.sub.50, uM) 1 + 3 + 4 + 5 ++ 6 + 7 + 8 + 9 ++ 10 ++ 11 +++ 12 +++ 13 + 14 +++ 15 + 16 + 17 + 20 + 21 + 22 + 23 ++ 24 +++ 30 +++ 32 +++ 38 + 43 + 44 + 48 +++ 49 ++ 51 ++ 52 +++ 53 +++ 54 +++ 55 + 56 ++ 57 + 58 + 59 + 62 +++ 65 +++ 66 + 67 + 68 + 70 + 73 ++ 74 ++ 75 + 77 +++ 79 +++ 80 +++ 81 +++ 86 +++ 87 +++ 88 +++ 90 ++ 91 ++ 92 +++ 93 + 94 +++ 97 +++ 98 +++ 99 + 101 +++ 102 +++ 103 +++ 104 + 105 + 106 +++ 107 + 108 + 109 +++ 110 +++ 111 +++ 112 ++ 113 +++ 114 + 116 ++ 118 + 119 +++ 120 +++ 121 + 122 +++ 123 +++ 125 +++ 126 + 127 + 128 + 129 + 130 +++ 132 + 135 ++ 136 +++ 137 +++ 138 +++ 145 +++ 147 +++ 148 + 149 +++ 150 + 152 ++ 154 + 155 +++ 160 + 161 ++ 164 + 165 +++ 166 +++ 172 ++ 175 + 176 +++ 177 +++ 184 +++ 190 + 191 + 193 +++ 195 +++ 196 ++ 197 + 199 +++ 202 + 203 + 204 +++ 211 +++ 219 + 226 +++ 227 +++ 229 +++ 231 +++ 233 +++ 234 +++ 238 +++ 239 +++ 241 + 243 +++ 245 ++ 249 +++ 251 +++ 253 +++ 256 +++ 268 +++ 269 +++ 270 +++ 271 +++ 273 ++ 275 +++ 277 +++ 279 +++ 281 +++ 284 +++ 288 +++ 289 +++ 291 ++ 294 + 296 +++ 298 + 300 ++ 302 ++ 303 + 305 + 306 +++ 307 + 309 + 311 +++ 315 + 324 +++ 328 +++ 336 +++ 337 ++ 341 +++ 343 ++ 344 ++ 345 +++ 350 +++ 351 +++ 357 ++ 358 +++ 360 +++ 362 +++ 364 + 367 +++ 368 +++ 369 +++ 371 ++ 373 +++ 374 +++ 378 +++ 381 +++ 383 + 392 +++ 394 + 409 + 412 +++ 413 +++ 414 +++ 415 +++ 417 + 418 + 430 +++ 431 +++ 433 +++ 447 +++ 448 +++ 449 +++ 450 +++ 459 ++ 461 +++ 464 +++ 465 +++ 466 +++ 468 +++ 469 +++ 470 +++ 471 +++ 473 +++ 474 +++ 475 +++ 476 +++ 477 +++ 479 +++ 481 +++ 482 +++ 486 +++ 487 +++ 489 +++ 490 +++ 491 +++ 492 +++ 493 +++ 494 +++ 495 +++ 496 +++ 497 + 498 +++ 499 +++ 501 +++ 502 +++ 503 +++ 504 +++ 505 +++ 506 +++ 507 ++ 508 +++ 509 +++ 512 +++ 513 +++ 514 +++ 516 +++ 517 +++ 518 +++ 519 +++ 523 ++ 524 ++ 525 +++ 526 +++ 527 +++ 528 +++ 529 +++ 530 +++ 531 +++ 532 +++ 533 +++ 534 +++ 535 +++ 536 +++ 537 +++ 538 +++ 540 +++ 541 +++ 542 +++ 543 +++ 544 +++ 545 +++ 546 +++ 547 +++ 550 +++ 552 ++ 553 +++ 554 +++ 555 ++ Activity range: +++ indicates <10 uM, ++ indicates between 10-20 uM, + indicates >20 uM

(248) TABLE-US-00005 TABLE 5 PGE.sub.2 inhibition assay # cpds Inhibition (%, 10 uM) 44 ++ 53 +++ 54 +++ 86 +++ 90 +++ 91 +++ 95 +++ 99 +++ 103 +++ 195 + 211 ++ 226 +++ Activity range: +++ indicates >70%, ++ indicates between 40-70%, + indicates <40%

(249) TABLE-US-00006 TABLE 6 COX-2 inhibition assay # cpds Inhibition (%, 10 uM) 90 NA 95 NA NA: not active (<1%)

(250) TABLE-US-00007 No. Structure  1 0  2  3  4  5  6  7  8  9  10  11 0  12  13  14  15  16  17  18  19  20  21 0  22  23  24  25  26  27  28  29  30  31 0  32  33  34  35  36  37  38  39  40  41 0  42  43  44  45  46  47  48  49  50  51 00  52 01  53 02  54 03  55 04  56 05  57 06  58 07  59 08  60 09  61 0  62  63  64  65  66  67  68  69  70  71 0  72  73  74  75  76  77  78  79  80  81 0  82  83  84  85  86  87  88  89  90  91 0  92  93  94  95  96  97  98  99 100 101 0 102 103 104 105 106 107 108 109 110 111 0 112 113 114 115 116 117 118 119 120 121 0 122 123 124 125 126 127 128 129 130 131 0 132 133 134 135 136 137 138 139 140 141 0 142 143 144 145 146 147 148 149 150 151 00 152 01 153 02 154 03 155 04 156 05 157 06 158 07 159 08 160 09 161 0 162 163 164 165 166 167 168 169 170 171 0 172 173 174 175 176 177 178 179 180 181 0 182 183 184 185 186 187 188 189 190 191 0 192 193 194 195 196 197 198 199 200 201 0 202 203 204 205 206 207 208 209 210 211 0 212 213 214 215 216 217 218 219 220 221 0 222 223 224 225 226 227 228 229 230 231 0 232 233 234 235 236 237 238 239 240 241 0 242 243 244 245 246 247 248 249 250 251 00 252 01 253 02 254 03 255 04 256 05 257 06 258 07 259 08 260 09 261 0 262 263 264 265 266 267 268 269 270 271 0 272 273 274 275 276 277 278 279 280 281 0 282 283 284 285 286 287 288 289 290 291 0 292 293 294 295 296 297 298 299 300 301 0 302 303 304 305 306 307 308 309 310 311 0 312 313 314 315 316 317 318 319 320 321 0 322 323 324 325 326 327 328 329 330 331 0 332 333 334 335 336 337 338 339 340 341 0 342 343 344 345 346 347 348 349 350 351 00 352 01 353 02 354 03 355 04 356 05 357 06 358 07 359 08 360 09 361 0 362 363 364 365 366 367 368 369 370 371 0 372 373 374 375 376 377 378 379 380 381 0 382 383 384 385 386 387 388 389 390 391 0 392 393 394 395 396 397 398 399 400 401 0 402 403 404 405 406 407 408 409 410 411 0 412 413 414 415 416 417 418 419 420 421 0 422 423 424 425 426 427 428 429 430 431 0 432 433 434 435 436 437 438 439 440 441 0 442 443 444 445 446 447 448 449 450 451 00 452 01 453 02 454 03 455 04 456 05 457 06 458 07 459 08 460 09 461 0 462 463 464 465 466 467 468 469 470 471 0 472 473 474 475 476 477 478 479 480 481 0 482 483 484 485 486 487 488 489 490 491 0 492 493 494 495 496 497 498 499 500 501 0 502 503 504 505 506 507 508 509 510 511 0 512 513 514 515 516 517 518 519 520 521 0 522 523 524 525 526 527 528 529 530 531 0 532 533 534 535 536 537 538 539 540 541 0 542 543 544 545 546 547 548 549 550 551 00 552 01 553 02 554 03 555 04 556 05 No. NMR Characterization  1 Pale violet solid; 1H NMR (400 MHz, Acetone-d6); δ 9.77 (brs, 1H), 8.34-8.36 (m, 2H), 7.85 (s, 1H), 7.52-7.64 (m, 4H), 6.89 (s, 1H), 6.57 (s, 1H), 6.30-6.34 (m, 2H), 4.75 (s, 2H), 4.03 (brs, 2H); LCMS (electrospray) m/z 440 [M + H]+.  2 Green solid; 1H NMR (400 MHz, MeOH-d4); δ 7.22-7.27 (m, 4H), 6.90-6.99 (m, 5H), 6.69 (d, J = 1.6 Hz, 1H), 6.48 (dd, J = 8.0, 1.6 Hz, 1H), 4.43 (s, 2H), 3.43-3.50 (m, 3H), 3.03-3.09 (m, 2H), 2.06- 2.10 (m, 2H), 1.81-1.87 (m, 2H); LCMS (electrospray) m/z 448 [M + H]+.  3 Pale brown solid; 1H NMR (400 MHz, MeOH-d4); δ 7.25 (d, J = 8. , 2H), 7.22 (d, J = 8.4 Hz, 2H), 6.97-6.99 (m, 1H), 6.90-6.92 (m, 3H), 6.69 (m, 1H), 6.57 (d, J = 8.4 Hz, 2H), 6.50-6.52 (m, 1H), 4.58 (s, 2H, NH), 4.40 (s, 2H), 3.64-3.68 (m, 1H), 3.37-3.51 (m, 4H), 2.27- 2.34 (m, 2H); LCMS (electrospray) m/z 434, 436 [M + H]+.  4 1H NMR (400 MHz, Acetone-d6); δ 7.49 (dd, J = 8.4 2.4 Hz, 2H), 7.41 (dd, J = 8.4 2.4 Hz, 2H), 7.33 (t, J = 9.2 Hz, 2H), 7.08 (d, J = 8.0 Hz, 1H), 6.91 (t, J = 9.2 Hz, 2H), 6.60 (d, J = 34.0 Hz, 1H), 6.40 (dd, J = 34.0 8.0 Hz, 1H), 5.08 (d, J = 8.0 Hz, 2H), 4.56 (d, J = 8.8 Hz, 2H); LCMS (electrospray) m/z 378 [M + H]+.  5 Gray solid; 1H NMR (400 MHz, Methanol-d4); δ 7.27 (d, J = 8.8 Hz, 2H), 7.22-7.25 (m, 2H), 6.94-7.00 (m, 3H), 6.89-6.91 (m, 2H), 6.70 (d, J = 2.0 Hz, 1H), 6.52 (dd, J = 8.2, 2.2 Hz, 1H), 4.44 (s, 2H), 3.85 (d, J = 6.0 Hz, 2H), 3.69-3.72 (m, 2H), 3.60-3.62 (m, 1H), 2.68-2.74 (m, 2H), 1.92-1.95 (m, 2H), 1.50-1.54 (m, 2H); LCMS (electrospray) m/z 462 [M + H]+.  6 Pale yellow solid; 1H NMR (400 MHz, MeOH-d4); δ 7.33 (s, 4H), 7.25 (d, J = 8.8 Hz, 2H), 6.95-7.01 (m, 3H), 6.70 (d, J = 2.4 Hz, 1H), 6.54 (dd, J = 8.4, 2.4 Hz, 1H), 4.56 (s, 2H), 4.44 (s, 2H), 3.58-3.59 (m, 1H), 3.48-3.51 (m, 2H), 2.88-2.94 (m, 2H), 1.91-2.05 (m, 2H), 1.28-1.74 (m, 2H); LCMS (electrospray) m/z 461 [M + H]+.  7 1H NMR (400 MHz, DMSO-d6); δ 7.22 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.0 Hz, 1H), 6.65 (brs, 1H, NH), 6.39 (d, J = 1.6 Hz, 1H), 6.18 (dd, J = 8.0 1.6 Hz, 1H), 4.32 (d, J = 2.0 Hz, 2H), 3.67-3.70 (m, 4H), 3.01-3.05 (m, 4H); LCMS (electrospray) m/z 323 [M + H]+.  8 Dark green solid; 1H NMR (400 MHz, Acetone-d6); δ 9.81 (s, 1H, NH), 7.44-7.50 (m, 3H), 7.37 (d, J = 6.8 Hz, 2H), 7.05 (s, 1H, NH), 6.91-7.00 (m, 5H), 6.83 (d, J = 8.4 Hz, 1H), 6.15-6.25 (m, 1H), 4.63 (s, 2H), 2.21 (s, 3H); LCMS (electrospray) m/z 445 [M + H]+.  9 Dark yellow solid; 1H NMR (400 MHz, Acetone-d6); δ 7.60 (d, J = 8.4 Hz, 1H), 7.40-7.43 (m, 2H), 7.02-7.07 (m, 3H), 6.94-6.96 (m, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.58-6.59 (m, 1H), 6.35-6.38 (m, 1H), 4.70 (s, 2H); LCMS (electrospray) m/z 400 [M + H]+.  10 Dark yellow solid; 1H NMR (400 MHz, Acetone-d6); δ 7.53-7.59 (m, 1H), 7.39-7.43 (m, 2H), 7.17 (s, 1H, NH), 7.03-7.07 (m, 2H), 6.90 (d, J = 8.4 Hz, 1H), 6.72-6.81 (m, 2H), 6.58 (d, J = 2.4 Hz, 1H), 6.35 (dd, J = 8.2, 2.4 Hz, 1H), 4.65 (s, 2H); LCMS (electrospray) m/z 383 [M + H]+.  11 Pale brown solid; 1H NMR (400 MHz, MeOH-d4); δ 7.25-7.29 (m, 4H), 7.00-7.08 (m, 2H), 6.80-6.90 (m, 4H), 6.68 (m, 1H), 6.58-6.60 (m, 2H), 3.60 (t, J = 6.0 Hz, 2H), 2.96 (t, J = 6.0 Hz, 2H); LCMS (electrospray) m/z 379, 381 [M + H]+.  12 Yellow solid; 1H NMR (400 MHz, DMSO-d6); δ 8.87 (s, 1H), 8.10 (s, 1H), 7.99-8.00 (m, 1H), 7.62 (s, 1H), 7.20-7.43 (m, 5H), 7.09- 7.12 (m, 1H), 6.96-7.02 (m, 5H), 6.84-6.86 (m, 1H), 4.47 (d, J = 4.4 Hz, 2H), 2.71-2.76 (m, 1H), 0.66-0.70 (m, 2H), 0.47-0.51 (m, 2H); LCMS (electrospray) m/z 514 [M + H]+.  13 Pale yellow solid; 1H NMR (400 MHz, Acetone-d6); δ 8.07 (s, 1H), 7.98 (s, 1H), 7.75 (s, 1H), 7.44-7.48 (m, 2H), 7.33-7.37 (m, 2H), 7.08-7.10 (m, 2H), 6.93-7.01 (m, 4H), 6.60-6.78 (m, 2H), 4.65 (s, 2H), 4.26 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H); LCMS (electrospray) m/z 503 [M + H]+.  14 Pale yellow solid; 1H NMR (400 MHz, MeOH-d4); δ 8.27-8.28 (m, 1H), 7.45-7.48 (m, 1H), 7.40-7.42 (m, 2H), 7.35-7.39 (m, 1H), 7.03-7.04 (m, 1H), 7.01-7.02 (m, 1H), 6.98-7.00 (m, 1H), 6.70 (d, J = 2.0 Hz, 1H), 6.52 (dd, J = 8.4, 2.0 Hz, 1H), 4.65 (s, 2H); LCMS (electrospray) m/z 365 [M + H]+.  15 Pale yellow solid; 1H NMR (400 MHz, MeOH-d4); δ 7.31-7.33 (m, 1H), 7.28-7.29 (m, 1H), 7.12 (d, J = 8.4 Hz, 2H), 7.05-7.09 (m, 1H), 6.99-7.01 (m, 1H), 6.88-6.90 (m, 1H), 6.85-6.86 (m, 1H), 6.83- 6.84 (m, 1H), 6.55-6.57 (m, 1H), 6.50-6.51 (m, 1H), 4.15 (t, J = 7.2 Hz, 2H), 3.02 (t, J = 7.2 Hz, 2H); LCMS (electrospray) m/z 378 [M + H]+.  16 Brown solid; 1H NMR (400 MHz, Acetone-d6); δ 8.27 (s, 1H), 7.90 (s, 1H), 7.46 (d, J = 7.6 Hz, 2H), 7.36 (d, J = 8.0 Hz, 2H), 7.23-7.28 (m, 2H), 7.07-7.14 (m, 3H), 6.97-6.99 (m, 4H), 6.78 (d, J = 8.0 Hz, 1H), 6.57 (brs, 1H), 4.66 (s, 2H);  17 1H NMR (400 MHz, Acetone-d6); δ 9.21 (s, 1H, NH), 8.09 (s, 1H), 7.83 (s, 1H), 7.40 (s, 1H, NH), 7.15-7.24 (m, 4H), 7.05-7.09 (m, 2H), 6.41 (brs, 2H, NH2), 4.52 (t, J = 2.8 Hz, 2H), 4.42 (t, J = 2.8 Hz, 2H), 2.82-2.86 (m, 1H), 0.71-0.74 (m, 2H), 0.51-0.55 (m, 2H); LCMS (electrospray) m/z 502 [M + H]+.  18 1H NMR (400 MHz, Acetone-d6); δ 9.16 (s, 1H, NH), 8.11 (s, 1H), 7.74 (s, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.06-7.16 (m, 4H), 5.55 (brs, 2H, NH2), .4.46 (t, J = 2.8 Hz, 2H), 4.39 (t, J = 2.8 Hz, 2H), 4.32- 4.37 (m, 1H), 1.94-2.20 (m, 4H), 1.60-1.71 (m, 1H), 1.52-1.59 (m, 3H); LCMS (electrospray) m/z 530 [M + H]+.  19 Pale green solid; 1H NMR (400 MHz, Acetone-d6); δ 9.13 (s, 1H, NH), 8.10 (m, 1H); 7.84 (s, 1H, NH), 7.49 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.10-7.15 (m, 3H), 6.96-7.02 (m, 4H), 4.68 (s, 2H), 4.32-4.36 (m, 1H), 1.96-1.99 (m, 2H), 1.68-1.72 (m, 2H), 1.50-1.61 (m, 4H); LCMS (electrospray) m/z 542, 544 [M + H]+.  20 Dark beige solid; 1H NMR (400 MHz, Acetone-d6); δ 7.65 (s, 1H, NH), 7.56 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 6.97-7.02 (m, 4H), 6.88 (d, J = 8.4 Hz, 1H), 6.55 (s, 1H), 6.39 (d, J = 7.6 Hz, 1H), 1.82 (s, 6H); LCMS (electrospray) m/z 393 [M + H]+.  21 1H NMR (400 MHz, DMSO-d6); δ 7.67 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.24 (t, J = 8.4 Hz, 2H), 6.86 (d, J = 8.0 Hz, 1H), 6.29 (s, 1H), 6.27 (d, J = 8.0 Hz, 1H), 6.11 (s, 2H); LCMS (electrospray) m/z 348 [M + H]+.  22 1H NMR (400 MHz, Acetone-d6); δ 8.15 (s, 1H), 8.02 (s, 1H), 7.78 (s, 1H, NH), 7.21 (d, J = 8.8 Hz, 2H), 7.12-7.17 (m, 2H), 7.06 (d, J = 8.8 Hz, 2H), 5.85 (brs, 2H, NH2), 4.74-4.48 (m, 2H), 4.38-4.30 (m, 2H), 4.28-4.35 (m, 2H), 1.32-1.37 (m, 3H); LCMS (electrospray) m/z 491 [M + H]+.  23 Pale green solid; 1H NMR (400 MHz, Acetone-d6); δ 10.00 (s, 1H, NH), 7.81 (s, 1H), 7.47-7.49 (m, 3H), 7.37 (d, J = 8.4 Hz, 2H), 7.14- 7.18 (m, 1H), 7.11 (s, 1H, NH), 7.02-7.06 (m, 1H), 6.94-7.02 (m, 4H), 6.84 (d, J = 6.8 Hz, 1H), 6.76 (d, J = 6.8 Hz, 1H), 6.41 (s, 1H, NH), 4.66 (s, 2H); LCMS (electrospray) m/z 460 [M + H]+.  24 Pale green solid; 1H NMR (400 MHz, Acetone-d6); δ 7.45-7.50 (m, 3H), 7.37 (d, J = 7.2 Hz, 2H), 6.98-7.00 (m, 4H), 6.78 (s, 1H), 6.55 (d, J = 8.4 Hz, 1H), 6.30-6.35 (m, 2H), 4.63 (s, 2H); LCMS (electrospray) m/z 431 [M + H]+.  25 white solid; mp >220° C.; 1H NMR (DMSO-d6, 400 MHz); δ 12.74 (1H, brs), 8.30 (1H, s), 7.74 (1H, d, J = 3.6 Hz), 7.44 (0.6H, d, J = 8.8 Hz), 7.31 (0.4H, d, J = 8.4 Hz), 6.91-7.18 (6H, m), 3.20-3.30 (8H, m), 2.14 (3H, s); LCMS: 99.3%, MS (ESI); m/z 377.0 [M + H]+.  26 brown solid; 1H NMR (DMSO-d6, 400 MHz); δ 12.02 (1H, brs), 8.07- 8.44 (2H, m), 7.28 (2H, t, J = 8.8 Hz), 7.09 (1H, d, J = 8.4 Hz), 6.63 (1H, d, J = 1.6 Hz), 6.57 (1H, dd, J = 8.4, 2.0 Hz); LCMS: 100%, MS (ESI); m/z 271.0 [M + H]+.  27 yellow amorphous; mp >142.9° C., decomposed; 1H NMR (DMSO-d6, 400 MHz); δ 4.06-4.22 (2H, m), 5.62-5.80 (1H, m), 6.57 (1H, dd, J = 8.4, 2.0 Hz), 6.83 (0.3H, s), 6.98 (0.7H, s), 7.13 (1H, d, J = 8.4 Hz), 7.28 (2H, t, J = 8.8 Hz), 7.50-7.62 (1H, m), 8.12-8.24 (2H, m), 12.02 (3H, brs); LCMS: 100%, MS (ESI); m/z 351.0 [M + H]+.  28 gray powder; 1H NMR (DMSO-d6, 400 MHz); δ 4.42 (2H, d, J = 5.6 Hz), 4.43 (2H, brs), 6.19 (1H, d, J = 8.0 Hz), 6.41 (1H, d, J = 1.6 Hz), 6.68-6.86 (2H, m), 7.08-7.20 (2H, m), 7.36-7.47 (2H, m), 10.38 (1H, brs); LCMS: 99.9%, MS (ESI); m/z 256.9 [M + H]+.  29 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 4.07 (2H, s), 4.42 (2H, d, J = 6.0 Hz), 5.08 (1H, brs), 6.29 (1H, d, J = 7.2 Hz), 6.46 (1H, d, J = 1.6 Hz), 6.78-6.93 (3H, m), 7.08-7.17 (2H, m), 7.35-7.45 (2H, m), 7.54 (1H, s), 10.42 (1H, brs), 11.82 (1H, brs); LCMS: 98.4%, MS (ESI); m/z 337.0 [M + H]+.  30 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.95 (1H, brs) 7.50-7.43 (2H, m), 7.28 (1H, dd, J = 8.4, 2.0 Hz), 6.93 (1H, d, J = 8.0 Hz), 6.52 (1H, s), 6.35 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, s); LCMS: 99.0%, MS (ESI); m/z 291.1 [M + H]+.  31 pale powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.14 (1H, brs), 7.49- 7.40 (2H, m), 7.29-7.25 (1H, m), 7.18-7.01 (2H, m), 6.90-6.75 (1H, m), 5.40 (1H, brs), 4.56 (2H, d, J = 4.8 Hz), 3.26 (2H, s, overlapped with water peak, confirmed after adding D2O), 1.19 (6H, s); LCMS: 96.5%, MS (ESI); m/z 363.2 [M + H]+.  32 white powder; hydroscopic; 1H NMR (DMSO-d6, 400 MHz); δ 8.45 (1H, brs), 7.35 (2H, dd, J = 8.0, 6.0 Hz), 7.13 (2H, t, J = 8.8 Hz), 7.01 (1H, d, J = 8.0 Hz), 6.57 (1H, s), 6.43 (1H, d, J = 7.6 Hz), 3.49 (2H, t, J = 7.2 Hz, overlapped with H2O peak), 2.85 (2H, t, J = 7.2 Hz); LCMS: 96.1%, MS (ESI); m/z 271.2 [M + H]+.  33 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.32-7.25 (2H, m), 7.22-7.18 (2H, m), 6.88 (1H, d, J = 8.4 Hz), 6.39 (1H, brs), 6.27 (1H, d, J = 2.0 Hz), 6.14 (1H, dd, J = 8.4, 2.0 Hz), 5.71 (1H, d, J = 6.8 Hz), 4.81 (2H, t, J = 6.0 Hz), 4.50-4.40 (1H, m), 4.38 (2H, t, J = 6.0 Hz), 3.50-3.45 (2H, m), 2.85 (2H, t, J = 7.2 Hz); LCMS: 99.5%, MS (ESI); m/z 327.2 [M + H]+.  34 brown amorphous; mp = 193.3-205° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.17-7.07 (2H, m), 7.06-6.98 (2H, m), 6.92 (1H, d, J = 8.4 Hz), 6.51 (1H, s), 6.33 (1H, dd, J = 8.4, 1.6 Hz), 4.62-4.50 (1H, m), 3.86-3.70 (2H, m), 3.46-3.40 (2H, m), 2.08-1.95 (2H, m), 1.74-1.59 (2H, m); LCMS: 100%, MS (ESI); m/z 327.2 [M + H]+.  35 brown gum; 1H NMR (DMSO-d6, 400 MHz); δ 7.43 (1H, d, J = 8.8 Hz), 7.19-7.09 (2H, m), 7.09-6.96 (3H, m), 6.89 (1H, dd, J = 8.8, 1.6 Hz), 4.72-4.57 (1H, m), 3.75-3.65 (2H, m), 3.67 (3H, s), 3.49-3.40 (2H, m), 2.18-2.05 (2H, m), 1.90-1.77 (2H, m); LCMS: 100%, MS (ESI); m/z 341.2 [M + H]+.  36 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.99 (1H, brs), 7.06-7.16 (2H, m), 6.98-7.05 (2H, m), 6.94 (1H, brs), 6.29 (1H, s), 6.20 (1H, d, J = 8.0 Hz), 5.78 (1H, brs), 4.82 (2H, t, J = 6.0 Hz), 4.54 (1H, brs), 4.43-4.50 (1H, m), 4.33-4.43 (2H, m), 3.79 (2H, d, m), 3.37-3.43 (2H, m), 1.98 (2H, m), 1.63 (2H, m); LCMS: 98.4%, MS (ESI); m/z 383.2 [M + H]+.  37 light green powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.25 (1H, brs), 7.19-7.08 (2H, m), 7.08-6.92 (4H, m), 6.51-6.36 (2H, m), 5.44 (1H, brs), 4.60-4.52 (1H, m), 3.87-3.75 (2H, m), 3.43-3.41 (2H, m, overlapped with H2O peak), 2.10-2.00 (2H, m), 1.78-1.60 (2H, m), 1.35 (6H, s); LCMS: 100%, MS (ESI); m/z 412.1 [M + H]+.  38 brown powder; 1H NMR (DMSO-d6); δ 7.80 (1H, d, J = 8.4 Hz), 7.56 (1H, s), 7.41-7.25 (3H, m), 6.89 (2H, d, J = 8.8 Hz), 4.72 (2H, t, J = 4.8 Hz), 4.37 (2H, t, J = 4.8 Hz), 3.34 (6H, s); LCMS: 99.4%, MS (ESI); m/z 330.9 [M + H]+.  39 brown powder; 1H NMR (DMSO-d6); δ 7.34-7.24 (2H, m), 7.07 (1H, d, J = 8.0 Hz), 6.98-6.89 (2H, m), 6.66 (1H, d, J = 2.0 Hz), 6.41 (1H, dd, J = 8.0, 2.0 Hz), 4.80 (2H, brs), 4.30 (4H, s), 2.81 (6H, s); LCMS: 99.8%, MS (ESI); m/z 330.9 [M + H]+.  40 green powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.39-7.25 (2H, m), 7.13 (1H, d, J = 8.4 Hz), 6.99-6.85 (2H, m), 6.46 (1H, d, J = 2.0 Hz), 6.37 (1H, dd, J = 8.4, 2.0 Hz), 6.08 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.62-4.47 (1H, m), 4.45-4.36 (2H, m), 4.35-4.25 (4H, m), 2.81 (6H, s); LCMS: 99.8%, MS (ESI); m/z 386.9 [M + H]+.  41 brown amorphous; 1H NMR (CDCl3, 400 MHz); δ 7.24-7.18 (2H, m), 7.14 (1H, d, J = 8.8 Hz), 6.80-6.72 (2H, m), 6.66 (1H, d, J = 2.4 Hz), 6.49 (1H, dd, J = 8.4 Hz, 2.0 Hz), 5.02 (2H, t, J = 6.4 Hz), 4.68- 4.57 (1H, m), 4.53 (2H, d, J = 6.0 Hz), 4.42-4.32 (2H, m), 4.30-4.21 (2H, m), 4.06 (1H, brs), 2.98 (6H, s); LCMS: 99.6%, MS (ESI); m/z 387.0 [M + H]+.  42 white solid; mp = 178.2-179.6° C.; 1H NMR (DMSO-d6, 400 MHz); δ 8.95 (2H, brs), 7.44 (1H, d, J = 8.8 Hz), 7.39 (1H, s), 7.35-7.45 (2H, m), 7.10-7.25 (3H, m), 4.37 (2H, t, J = 7.2 Hz), 2.99 (2H, t, J = 7.2 Hz); LCMS: 99.2%, MS (ESI); m/z 271.0 [M + H]+.  43 white powder; mp = 60.8-61.6° C.; 1H NMR (DMSO-d6); δ 7.26 (2H, d, J = 8.4 Hz), 7.14 (1H, d, J = 8.4 Hz), 6.97 (2H, d, J = 9.2 Hz), 6.59 (1H, d, J = 1.6 Hz), 6.41 (1H, dd, J = 8.4, 2.0 Hz), 4.61 (2H, brs), 4.32 (4H, s), 2.85 (6H, s); LCMS: 99.6%, MS (ESI); m/z 380.9 [M + H]+.  44 white powder; mp >133° C.; 1H NMR (DMSO-d6); δ 7.27 (2H, d, J = 8.4 Hz), 7.14-6.94 (3H, m), 6.66 (1H, s), 6.41 (1H, d, J = 8.0 Hz), 4.77 (2H, brs), 4.25-4.35 (4H, m), 2.80 (6H, s); LCMS: 97.9%, MS (ESI); m/z 381.0 [M + H]+.  45 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.23 (1H, s), 7.62 (1H, d, J = 2.0 Hz), 7.47 (1H, d, J = 2.0 Hz), 7.26 (2H, d, J = 8.8 Hz), 7.19 (1H, d, J = 8.4 Hz), 7.00-7.08 (2H, m), 6.97 (1H, dd, J = 8.4, 2.0 Hz), 5.76 (1H, d, J = 2.0 Hz), 4.37 (4H, dd, J = 8.0 Hz, 4.0 Hz), 3.68 (3H, s), 2.84 (6H, s); LCMS: 98.7%, MS (ESI); m/z 460.8 [M + H]+.  46 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.11 (1H, s), 7.56 (1H, d, J = 2.0 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.22-7.33 (3H, m), 6.91- 7.03 (3H, m), 5.70 (1H, d, J = 2.0 Hz), 4.36 (4H, s), 3.72 (3H, s), 2.88 (6H, s); LCMS: 100%, MS (ESI); m/z 461.0 [M + H]+.  47 yellow gum; 1H NMR (CDCl3, 400 MHz); δ 7.10 (1H, s), 6.95-7.07 (5H, m), 6.63 (1H, dd, J = 8.4, 2.0 Hz), 4.18 (2H, t, J = 7.6 Hz), 3.25- 3.40 (4H, m), 3.06 (2H, t, J = 7.6 Hz), 1.14 (6H, t, J = 7.2 Hz); LCMS: 95.7%, MS (ESI); m/z 327.2 [M + H]+.  48 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.26 (2H, d, J = 8.8 Hz), 6.99 (2H, d, J = 8.8 Hz), 6.81 (1H, d, J = 8.4 Hz), 6.48 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 5.98 (2H, brs), 4.55 (2H, brs), 4.22-4.24 (2H, m), 4.18 (2H, t, J = 5.2 Hz); LCMS: 100%, MS (ESI); m/z 353.1 [M + H]+.  49 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.26 (1H, d, J = 8.8 Hz), 6.96 (2H, d, J = 9.2 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.41 (1H, d, J = 1.6 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 6.17 (2H, brs), 4.39 (2H, brs), 4.22-4.29 (2H, m), 4.11-4.22 (2H, m); LCMS: 100%, MS (ESI); m/z 352.9 [M + H]+.  50 yellow gum; 1H NMR (CDCl3, 400 MHz); δ 7.06 (2H, dd, J = 8.4, 4.2 Hz), 7.00 (2H, t, J = 7.2 Hz), 6.95-6.85 (2H, m), 6.49 (1H, dd, J = 8.4, 6.4 Hz), 4.19 (2H, t, J = 7.2 Hz), 3.52 (4H, t, J = 6.8 Hz), 3.00 (2H, t, J = 7.2 Hz), 1.95-2.05 (4H, m); LCMS: 97.4%, MS (ESI); m/z 324.9 [M + H]+.  51 yellow powder; 1H NMR (CDCl3, 400 MHz); δ 7.31 (1H, d, J = 8.0 Hz), 7.13 (2H, d, J = 8.8 Hz), 6.83 (2H, dd, J = 6.8, 2.0 Hz), 6.60 (1H, d, J = 1.6 Hz), 6.57 (1H, d, J = 8.0 Hz), 4.39 (2H, t, J = 6.0 Hz), 4.25 (2H, t, J = 6.8 Hz), 3.59 (4H, t, J = 6.8 Hz), 1.99 (4H, m); LCMS: 98.3%, MS (ESI); m/z 407.1 [M + H]+.  52 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.28 (2H, d, J = 9.2 Hz), 7.08 (2H, d, J = 9.6 Hz), 6.89 (1H, d, J = 8.0 Hz), 6.58 (1H, t, J = 5.6 Hz), 6.35 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, brs), 4.19 (2H, t, J = 5.6 Hz), 3.52-3.68 (2H, m), 3.36 (3H, s); LCMS: 100%, MS (ESI); m/z 366.9 [M + H]+.  53 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.28 (2H, d, J = 8.8 Hz), 7.09 (2H, d, J = 9.2 Hz), 6.79 (1H, d, J = 8.4 Hz), 6.68 (1H, t, J = 5.6 Hz), 6.48 (1H, d, J = 1.6 Hz), 6.24 (1H, dd, J = 8.0, 1.6 Hz), 4.41 (2H, brs), 4.19 (2H, t, J = 5.6 Hz), 3.65-3.70 (2H, m), 3.38 (3H, s); LCMS: 100%, MS (ESI); m/z 367.1 [M + H]+.  54 pale green powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.72 (1H, brs), 7.30 (2H, d, J = 8.4 Hz), 7.06 (2H, d, J = 8.8 Hz), 6.82 (1H, d, J = 8.0 Hz), 6.45 (1H, s), 6.21 (1H, d, J = 8.0 Hz), 5.16 (1H, s), 4.50 (2H, brs), 3.65-3.85 (1H, m), 3.45-3.65 (3H, m), 2.23-2.40 (1H, m), 2.08-2.23 (1H, m); LCMS: 97.3%, MS (ESI); m/z 378.9 [M + H]+.  55 yellow powder: 1H NMR (CDCl3, 400 MHz); δ 7.12 (2H, d, J = 8.4 Hz), 7.00 (1H, d, J = 8.0 Hz), 6.88 (1H, d, J = 2.0 Hz), 6.82 (2H, dd, J = 6.8, 2.4 Hz), 6.50 (1H, dd, J = 8.4, 2.0 Hz), 4.41 (2H, t, J = 6.0 Hz), 4.24 (2H, t, J = 6.4 Hz), 3.63 (4H, t, J = 6.8 Hz), 2.00 (4H, m); LCMS: 98.5%, MS (ESI); m/z 407.2 [M + H]+.  56 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.56 (1H, d, J = 2.8 Hz), 7.36-7.43 (1H, m), 7.30-7.36 (1H, m), 6.91 (1H, d, J = 8.4 Hz), 6.55 (1H, t, J = 5.6 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.4, 2.0 Hz), 4.54 (2H, brs), 4.31 (2H, t, J = 6.0 Hz), 3.44-3.68 (2H, m), 3.36 (3H, s); LCMS: 100%, MS (ESI); m/z 400.9 [M + H]+.  57 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.56 (1H, d, J = 2.0 Hz), 7.39 (1H, d, J = 9.2 Hz), 7.29-7.36 (1H, m), 6.79 (1H, d, J = 8.4 Hz), 6.67 (1H, t, J = 5.6 Hz), 6.49 (1H, d, J = 2.0 Hz), 6.24 (1H, dd, J = 8.0, 1.6 Hz), 4.41 (2H, brs), 4.30 (2H, t, J = 6.0 Hz), 3.67-3.72 (2H, m), 3.38 (3H, s); LCMS: 100%, MS (ESI); m/z 401.0 [M + H]+.  58 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.47 (1H, d, J = 8.4 Hz), 7.41 (1H, d, J = 3.2 Hz), 7.08 (1H, dd, J = 8.8, 2.8 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.57 (1H, t, J = 5.2 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.4, 2.0 Hz), 4.54 (2H, brs), 4.24 (2H, t, J = 5.6 Hz), 3.60- 3.66 (2H, m), 3.36 (3H, s); LCMS: 99.6%, MS (ESI); m/z 400.9 [M + H]+.  59 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.36-7.47 (2H, m) 7.05 (1H, dd, J = 9.2, 2.8 Hz), 6.77 (1H, d, J = 8.0 Hz), 6.66 (1H, t, J = 5.2 Hz), 6.48 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.0, 1.6 Hz), 4.43 (2H, brs), 4.21 (2H, t, J = 6.0 Hz), 3.62-3.69 (2H, m), 3.37 (3H, s); LCMS: 95.5%, MS (ESI); m/z 400.9 [M + H]+.  60 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.51 (1H, d, J = 9.2 Hz), 7.37 (1H, d, J = 2.8 Hz), 7.01 (1H, dd, J = 8.8, 2.8 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.57 (1H, t, J = 5.2 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.0, 1.6 Hz), 4.57 (2H, brs), 4.21 (2H, t, J = 6.0 Hz), 3.58- 3.66 (2H, m), 3.36 (3H, s); LCMS: 99.7%, MS (ESI); m/z 350.9 [M + H]+.  61 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.48 (1H, d, J = 8.8 Hz), 7.39 (1H, d, J = 2.8 Hz), 7.01 (1H, dd, J = 8.8, 3.2 Hz), 6.79 (1H, d, J = 8.0 Hz), 6.69 (1H, t, J = 5.2 Hz), 6.50 (1H, d, J = 2.0 Hz), 6.24 (1H, dd, J = 8.0, 2.0 Hz), 4.46 (2H, brs), 4.21 (2H, t, J = 6.0 Hz), 3.63- 3.68 (2H, m), 3.38 (3H, s); LCMS: 100%, MS (ESI); m/z 350.9 [M + H]+.  62 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.36 (1H, brs), 7.28 (1H, d, J = 8.8 Hz), 7.07 (1H, d, J = 9.2 Hz), 6.78-6.83 (1H, m), 6.40-6.44 (2H, m), 6.18-6.22 (1H, m.), 4.42 (2H, brs), 4.14 (2H, t, J = 5.6 Hz), 3.59-3.61 (2H, m); LCMS: 100%, MS (ESI); m/z 353.1 [M + H]+.  63 dark powder; 1H NMR (DMSO-d6, 400 MHz); δ 12.17 (2H, brs), 8.23 (2H, brs), 7.30 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.06 (2H, d, J = 9.2 Hz), 6.45-6.55 (2H, m), 5.10-5.20 (1H, m), 3.55-3.75 (1H, m), 3.25-3.48 (3H, m), 2.28-2.49 (1H, m), 2.11-2.25 (1H, m); LCMS: 93.4%, MS (ESI); m/z 379.1 [M + H]+.  64 white gum; 1H NMR (DMSO-d6, 400 MHz); δ 10.50 (1H, brs), 7.74 (1H, d, J = 8.8 Hz), 7.32 (2H, d, J = 8.8 Hz), 6.91 (2H, d, J = 8.4 Hz), 6.52 (1H, s), 6.30-6.34 (1H, m), 3.70-3.80 (1H, m), 3.50-3.70 (2H, m), 3.39-3.50 (2H, overlap with water peak), 2.20-2.33 (2H, m); LCMS: 99.7%, MS (ESI); m/z 406.1 [M + H]+.  65 white powder; 1H NMR (DMSO-d6); δ 7.28 (2H, d, J = 8.8 Hz), 6.95- 7.02 (2H, m), 6.92 (1H, d, J = 8.4 Hz), 6.49 (1H, d, J = 2.0 Hz), 6.29 (1H, dd, J = 8.0, 2.0 Hz), 5.51 (1H, brs), 4.67 (2H, brs), 4.27 (2H, t, J = 5.2 Hz), 4.18 (2H, t, J = 5.2 Hz), 1.42 (9H, s); LCMS: 99.8%, MS (ESI); m/z 409.2 [M + H]+.  66 off-white powder; 1H NMR (DMSO-d6); δ 7.27 (2H, d, J = 8.8 Hz), 6.95 (2H, d, J = 8.8 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.50 (1H, d, J = 2.0 Hz), 6.24 (1H, dd, J = 8.0, 2.0 Hz), 5.58 (1H, brs), 4.40 (2H, brs), 4.28 (2H, t, J = 5.2 Hz), 4.16 (2H, t, J = 5.2 Hz), 1.43 (9H, s); LCMS: 99.5%, MS (ESI); m/z 409.3 [M + H]+.  67 off-white powder; 1H NMR (DMSO-d6); δ 10.57 (1H, brs), 7.73 (2H, d, J = 9.2 Hz), 7.34 (2H, d, J = 8.8 Hz), 6.93 (1H, d, J = 8.0 Hz), 6.22- 6.33 (2H, m), 5.67-5.79 (1H, m), 4.74 (2H, s), 4.63 (2H, brs), 1.42 (9H, s); LCMS: 99.3%, MS (ESI); m/z 422.2 [M + H]+.  68 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.28 (2H, d, J = 8.8 Hz), 7.02-7.06 (2H, m), 6.98 (1H, d, J = 8.4 Hz), 6.60 (1H, d, J = 2.0 Hz), 6.37 (1H, dd, J = 8.0, 2.0 Hz), 4.80 (2H, brs), 4.26 (2H, t, J = 4.8 Hz), 4.19 (2H, t, J = 5.2 Hz), 4.08 (4H, t, J = 7.2 Hz), 2.28-2.34 (2H, m); LCMS: 95.7%, MS (ESI); m/z 393.3 [M + H]+.  69 off-white powder; 1H NMR (DMSO-d6); δ 10.50 (1H, brs), 7.71 (2H, d, J = 8.8 Hz), 7.34 (2H, d, J = 8.8 Hz), 6.70 (1H, d, J = 8.0 Hz), 6.51 (1H, s), 6.19 (1H, d, J = 8.0 Hz), 5.84 (1H, s), 4.74 (2H, s), 4.42 (2H, brs), 1.43 (9H, s); LCMS: 92.7%, MS (ESI); m/z 422.0 [M + H]+.  70 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.26 (2H, d, J = 8.4 Hz), 7.02 (1H, d, J = 8.4 Hz), 6.95-7.05 (2H, m), 6.52 (1H, d, J = 2.0 Hz), 6.32 (1H, dd, J = 8.0, 2.0 Hz), 4.53 (2H, brs), 4.25 (2H, t, J = 4.2 Hz), 4.20 (2H, t, J = 4.8 Hz), 4.10 (4H, t, J = 7.6 Hz), 2.28-2.33 (2H, m); LCMS: 95.9%, MS (ESI); m/z 393.2 [M + H]+.  71 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.75 (1H, brs), 7.59 (2H, d, J = 2.4 Hz), 7.33-7.42 (2H, m), 6.77-6.83 (1H, m), 6.44 (1H, s), 6.17-6.24 (1H, m), 5.25-5.30 (1H, m), 4.45 (2H, brs), 3.70- 3.82 (1H, m), 3.50-3.62 (3H, m), 2.28-2.38 (1H, m), 2.16-2.22 (1H, m); LCMS: 95.9%, MS (ESI); m/z 413.3 [M + H]+.  72 off-white powder; 1H NMR (DMSO-d6); δ 7.38 (1H, d, J = 2.4 Hz), 7.25 (2H, d, J = 8.8 Hz), 6.91-6.99 (2H, m), 6.80 (1H, d, J = 2.0 Hz), 4.67 (2H, brs), 4.48 (2H, t, J = 5.6 Hz), 4.32 (2H, t, J = 5.6 Hz), 3.51- 3.63 (4H, m), 1.85-1.94 (4H, m); LCMS: 97.6%, MS (ESI); m/z 408.3 [M + H]+.  73 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.20 (1H, brs), 7.59 (1H, s), 7.30-7.40 (2H, m), 6.68-6.89 (1H, m), 6.10-6.48 (3H, m), 4.43 (2H, brs), 3.43-3.52 (2H, m), 2.99 (2H, t, J = 7.2 Hz); LCMS: 99.5%, MS (ESI); m/z 321.1 [M + H]+.  74 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.13-10.34 (1H, m), 7.49-7.61 (2H, m), 7.38 (1H, d, J = 8.4 Hz), 6.83-7.10 (1H, m), 6.80 (1H, dd, J = 8.4, 2.8 Hz), 6.31-6.43 (1H, m), 6.10-6.24 (1H, m), 5.08-5.25 (1H, m), 4.25-4.55 (2H, m), 1.40 (3H, d, J = 6.8 Hz); LCMS: 100%, MS (ESI); m/z 321.2 [M + H]+.  75 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.27 (1H, brs.), 7.28 (2H, d, J = 8.4 Hz), 7.05 (2H, d, J = 9.2 Hz), 6.84 (1H, d, J = 8.0 Hz), 6.45 (1H, s), 6.27 (1H, d, J = 7.6 Hz), 5.77 (2H, brs.), 5.06 (1H, brs), 4.13 (2H, t, J = 5.6 Hz), 3.38 (2H, t, J = 5.6 Hz); LCMS: 100%, MS (ESI); m/z 353.3 [M + H]+.  76 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.58 (1H, brs), 7.76 (2H, d, J = 8.8 Hz), 7.34 (2H, d, J = 8.4 Hz), 7.09 (1H, d, J = 8.4 Hz), 6.61 (1H, s), 6.54 (1H, d, J = 8.4 Hz), 3.78-3.95 (5H, m), 3.68 (3H, s), 2.27-2.40 (1H, m), 2.11-2.25 (1H, m); LCMS: 93.9%, MS (ESI); m/z 420.0 [M + H]+.  77 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 12.5 (2H, brs), 9.23 (1H, brs), 7.29-7.49 (2H, m), 7.31 (2H, d, J = 8.8 Hz), 7.18-7.21 (3H, m), 7.08 (2H, d, J = 9.6 Hz), 6.50-6.52 (2H, m), 5.20-5.21 (1H, m), 4.60 (2H, d, J = 6.0 Hz), 3.67-3.72 (1H, m), 3.30-3.42 (3H, overlap with H2O peak), 2.33-2.38 (1H, m), 1.90-2.23 (1H, m); LCMS: 98.1%, MS (ESI); m/z 487.3 [M + H]+.  78 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.56 (1H, d, J = 4.4 Hz), 7.98 (1H, d, J = 4.0 Hz), 7.30 (1H, d, J = 8.4 Hz), 7.24 (2H, d, J = 8.4 Hz), 6.85-6.95 (2H, m), 6.79 (1H, d, J = 2.0 Hz), 6.55-6.60 (1H, m), 5.17 (2H, brs), 4.68 (2H, t, J = 5.2 Hz), 4.30 (2H, t, J = 5.2 Hz); LCMS: 95.6%, MS (ESI); m/z 422.2 [M + H]+.  79 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.46 (2H, d, J = 8.8 Hz), 7.29 (2H, d, J = 8.0 Hz), 6.88 (1H, brs), 6.77 (1H, d, J = 8.4 Hz), 6.40 (1H, d, J = 1.6 Hz), 6.17 (1H, dd, J = 8.4, 2.4, Hz), 4.45 (2H, d, J = 6.0 Hz); LCMS: 95.7%, MS (ESI); m/z 323.1 [M + H]+.  80 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.72 (1H, t, J = 6.0 Hz), 7.49 (2H, d, J = 8.4 Hz), 7.35-7.45 (4H, m), 7.10-7.20 (2H, m), 6.95-7.09 (4H, m), 4.65 (2H, d, J = 6.0 Hz); LCMS: 100%, MS (ESI); m/z 331.2 [M + H]+.  81 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.35 (1H, brs), 8.09-8.18 (1H, m), 7.90-7.99 (1H, m), 7.82 (1H, d, J = 8.0 Hz), 7.49- 7.59 (3H, m), 7.46 (1H, t, J = 8.0 Hz), 6.66-6.91 (2H, m), 6.41 (1H, s), 6.10-6.20 (1H, m), 4.91 (2H, d, J = 4.4 Hz), 4.43 (2H, brs); LCMS: 96.0%, MS (ESI); m/z 289.1 [M + H]+.  82 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.60 (1H, d, J = 4.8 Hz), 7.99 (1H, d, J = 4.4 Hz), 7.38 (1H, d, J = 8.4 Hz), 7.15-7.28 (2H, m), 6.80-6.93 (2H, m), 6.70-6.80 (1H, m), 6.63-6.75 (1H, m), 4.91 (2H, brs), 4.78 (2H, t, J = 5.2 Hz), 4.29 (2H, t, J = 5.2 Hz); LCMS: 99.1%, MS (ESI); m/z 422.2 [M + H]+.  83 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.54 (1H, d, J = 2.4 Hz), 7.27 (2H, d, J = 8.4 Hz), 6.96-7.04 (3H, m), 4.78 (2H, brs), 4.38 (2H, t, J = 5.2 Hz), 4.26-4.34 (2H, m), 3.46-3.58 (4H, m), 1.85- 1.95 (4H, m); LCMS: 97.7%, MS (ESI); m/z 408.0 [M + H]+.  84 white powder; 1H NMR (CDCl3, 400 MHz); δ 7.65 (1H, d, J = 8.4 Hz), 7.14 (2H, d, J = 8.8 Hz), 6.75-6.90 (2H, m), 6.39 (1H, d, J = 8.4 Hz), 6.21 (1H, s), 4.55-4.65 (2H, m), 4.29 (1H, t, J = 4.2 Hz), 3.95- 4.05 (4H, m), 3.85-3.95 (4H, m), 2.35-2.45 (2H, m), 2.05-2.20 (4H, m); LCMS: 92%, MS (ESI); m/z 447.1 [M + H]+.  85 white powder; 1H NMR (CDCl3, 400 MHz); δ 7.12 (1H, d, J = 8.4 Hz), 7.08 (1H, d, J = 8.4 Hz), 6.81 (1H, d, J = 2.4 Hz), 6.75 (2H, d, J = 9.2 Hz), 6.31 (1H, dd, J = 8.8, 2.0 Hz), 4.55-4.65 (2H, m), 4.25-4.35 (2H, m), 3.90-4.00 (4H, m), 3.80-3.90 (4H, m), 2.35-2.45 (2H, m), 2.05-2.15 (4H, m); H NMR and NOE confirmed the structure; LCMS: 96.3%, MS (ESI); m/z 447.3 [M + H]+.  86 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); 7.40-7.45 (4H, m), 6.95-7.05 (4H, m), 6.90-6.98 (1H, brs), 6.81 (1H, d, J = 8.4 Hz), 6.43 (1H, s), 6.21 (1H, dd, J = 8.0, 2.0 Hz), 4.44 (2H, d, J = 4.8 Hz); LCMS: 99.5%, MS (ESI); m/z 365.1 [M + H]+.  87 pale yellow powder; hydroscopic; 1H NMR (DMSO-d6, 400 MHz); δ 12.60 (2H, brs), 9.24-9.38 (1H, m), 7.46 (2H, d, J = 8.8 Hz), 7.39 (2H, t, J = 7.6 Hz), 7.02 (2H, t, J = 8.4 Hz), 6.97-7.08 (4H, m), 6.74 (1H, s), 6.66 (1H, d, J = 8.4 Hz), 4.60 (2H, d, J = 6.4 Hz), 3.83-4.00 (2H, m), 3.71-3.82 (2H, m), 3.42-3.53 (1H, m); LCMS: 100%, MS (ESI); m/z 387.0 [M + H]+.  88 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.42 (2H, d, J = 8.8 Hz), 7.37 (2H, d, J = 8.0 Hz), 7.00-7.10 (4H, m), 6.90-7.00 (1H, brs), 6.82 (1H, d, J = 8.0 Hz), 6.44 (1H, d, J = 2.0 Hz), 6.20-6.25 (1H m), 4.45 (2H, d, J = 5.2 Hz); LCMS: 99.5%, MS (ESI); m/z 415.0 [M + H]+.  89 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.26 (2H, d, J = 8.8 Hz), 7.11 (1H, s), 6.90-7.00 (2H, m), 6.88 (1H, s), 4.61 (2H, t, J = 4.8 Hz), 4.35 (2H, t, J = 4.8 Hz), 3.74-3.76 (4H, m), 1.96-1.99 (4H, m); LCMS: 100%, MS (ESI); m/z 441.2 [M + H]+.  90 grey powder; mp >200° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.58- 7.65 (4H, m), 7.41-7.48 (4H, m), 7.34 (1H, t, J = 7.6 Hz), 6.75-6.85 (2H, m), 6.41 (1H, d, J = 2.0 Hz), 6.18 (1H, d, J = 6.8 Hz), 4.30-4.65 (4H, m); LCMS: 99.1%, MS (ESI); m/z 315.1 [M + H]+  91 white powder; mp >107.8° C.; 1H NMR (DMSO-d6, 400 MHz); δ 8.15 (1H, d, J = 7.6 Hz), 7.94 (1H, d, J = 2.4 Hz), 7.83 (1H, d, J = 8.0 Hz), 7.50-7.61 (3H, m), 7.44-7.48 (1H, m), 6.80 (1H, d, J = 8.0 Hz), 6.79 (1H, brs), 6.43 (1H, d, J = 2.0 Hz), 6.20 (1H, d, J = 6.8 Hz), 4.92 (2H, d, J = 5.6 Hz), 4.41 (2H, brs); LCMS: 99.3%, MS (ESI); m/z 289.1 [M + H]+.  92 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.56 (1H, brs), 7.36-7.42 (6H, m), 7.24-7.26 (2H, m), 6.86 (1H, d, J = 8.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 6.29 (1H, dd, J = 8.4, 2.0 Hz), 4.50 (2H, s); LCMS: 95.5%, MS (ESI); m/z 381.1 [M + H]+.  93 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.26 (2H, d, J = 8.8 Hz), 6.92-7.01 (2H, m), 6.88 (1H, d, J = 8.4 Hz), 6.69 (1H, d, J = 2.0 Hz), 6.49 (1H, d, J = 8.0, 2.0 Hz), 6.12 (2H, brs), 4.29 (2H, t, J = 5.2 Hz), 4.17-4.25 (2H, m), 4.04 (1H, brs), 1.17 (9H, s); LCMS: 100%, MS (ESI); m/z 409.1 [M + H]+.  94 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.37 (2H, d, J = 8.8 Hz), 7.16-7.24 (2H, m), 6.96-7.05 (2H, m), 6.94 (2H, d, J = 8.4 Hz), 6.70-6.79 (2H, m), 6.41 (1H, d, J = 2.0 Hz), 6.19 (1H, dd, J = 8.0, 1.6 Hz), 4.41 (2H, d, J = 6.0 Hz); LCMS: 99.2%, MS (ESI); m/z 349.2 [M + H]+.  95 mp >137.5° C.; 1H NMR (DMSO-d6, 400 MHz): δ 10.30-10.40 (1H, m), 7.35-7.45 (4H, m), 7.12 (1H, t, J = 7.6 Hz), 6.95-7.05 (4H, m), 6.70-6.90 (2H, m), 6.39 (1H, s), 6.20-6.30 (1H, m), 4.40-4.70 (3H, m), 3.45-3.50 (1H, m), 1.10 (6H, d, J = 6.4 Hz); LCMS: 99.4%, MS (ESI); m/z 373.2 [M + H]+.  96 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.30-10.45 (1H, m), 7.35-7.45 (4H, m), 7.12 (1H, t, J = 7.2 Hz), 6.95-7.05 (4H, m), 6.60-6.90 (2H, m), 6.32 (1H, d, J = 2.0 Hz), 6.15-6.25 (1H, m), 5.16 (1H, brs), 4.42 (2H, d, J = 6.0 Hz), 3.65-3.80 (1H, m), 2.25-2.35 (2H, m), 1.65-1.85 (4H, m); LCMS: 98.8%, MS (ESI); m/z 385.3 [M + H]+.  97 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.30-10.40 (1H, m), 7.30-7.40 (4H, m), 7.12 (1H, t, J = 7.6 Hz), 6.95-7.00 (4H, m), 6.60-6.95 (2H, m), 6.39 (1H, s), 6.15-6.30 (1H, m), 4.70-4.85 (1H, m), 4.40-4.50 (2H, m), 3.60-3.65 (1H, m), 1.75-1.95 (2H, m), 1.60-1.70 (2H, m), 1.45-1.55 (2H, m), 1.35-1.45 (2H, m); LCMS: 100%, MS (ESI); m/z 399.2 [M + H]+.  98 white solid; mp = 116.8-118.7° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.45 (1H, brs), 7.30-7.45 (4H, m), 7.12 (1H, t, J = 7.2 Hz), 6.75-7.05 (6H, m), 6.60 (1H, s), 6.40-6.50 (1H, m), 4.45 (2H, d, J = 6.0 Hz), 2.79 (6H, s); LCMS: 99.2%, MS (ESI); m/z 359.2 [M + H]+.  99 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.70 (1H, brs), 7.29 (2H, d, J = 8.8 Hz), 7.00-7.08 (2H, m), 6.95-7.00 (1H, m), 6.42- 6.48 (1H, m), 6.19-6.24 (1H, m), 5.12-51.9 (1H, m), 3.61-3.68 (1H, m), 3.30-3.40 (5H, m), 3.24-3.26 (2H, m), 2.32-2.35 (1H, m), 2.10- 2.19 (1H, m), 1.90-1.95 (4H, m); LCMS: 95.2%, MS (ESI); m/z 433.2 [M + H]+. 100 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.27 (2H, d, J = 4.2 Hz), 6.95-7.10 (3H, m), 6.66 (1H, d, J = 2.0 Hz), 6.35-6.45 (1H, m), 4.78 (2H, brs), 4.33 (4H, s), 3.83 (2H, t, J = 14.0 Hz), 3.64 (2H, J = 7.6 Hz), 2.40-2.55 (2H, M); LCMS: 95.3%, MS (ESI); m/z 443.2 [M + H]+. 101 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.30-7.40 (3H, m), 7.17 (1H, d, J = 7.6 Hz), 7.00-7.10 (2H, m), 6.92-7.01 (2H, m), 6.89 (1H, dd, J = 8.0, 2.0 Hz), 6.81 (1H, d, J = 8.0 Hz), 6.43 (1H, d, J = 1.6 Hz), 6.23 (1H, dd, J = 8.0, 2.0 Hz), 4.46 (2H, s); LCMS: 99.5% , MS (ESI); m/z 365.1 [M + H]+. 102 white powder; mp = 58.4-66.6° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.46 (3H, m), 7.22 (1H, dd, J = 6.4, 3.2 Hz), 6.96-7.03 (3H, m), 6.70-6.80 (2H, m), 6.41 (1H, d, J = 2.0 Hz), 6.19 (1H, d, J = 7.6 Hz), 4.30-4.55 (4H, m); LCMS: 95.7%, MS (ESI); m/z 383.1[M + H]+. 103 pale green powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.30-7.40 (3H, m), 7.10-7.20 (2H, m), 7.04 (1H, s), 6.98 (2H, dd, J = 8.8, 1.2 Hz), 6.71-6.82 (3H, m), 6.41 (1H, J = 1.6 Hz), 6.20 (1H, d, J = 8.0 Hz), 4.44 (2H, d, J = 6.4 Hz); LCMS: 97.3%, MS (ESI); m/z 331.2 [M + H]+. 104 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.44 (1H, brs), 7.30 (2H, d, J = 8.8 Hz), 7.06 (2H, d, J = 8.8 Hz), 6.90-6.99 (1H, m), 6.37-6.45 (1H, m), 6.07-6.28 (2H, m), 5.14-5.16 (1H, m), 3.62-3.67 (1H, m), 3.30-3.42 (3H, overlapped with H2O peak), 2.1 (3H, d, J = 4.0 Hz), 2.31-2.35 (1H, m), 2.14-2.17 (1H, m); LCMS: 96.2%, MS (ESI); m/z 393.1 [M + H]+. 105 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.30 (2H, d, J = 8.8 Hz), 7.06 (2H, d, J = 9.2 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.43 (1H, s) 6.25 (1H, d, J = 8.4 Hz), 5.14-5.17 (1H, m), 3.62-3.68 (1H, m), 3.30- 3.42 (3H, overlap with H2O peak), 2.99 (6H, s), 2.32-2.38 (1H, m), 2.14-2.17 (1H, m); LCMS: 100%, MS (ESI); m/z 407.1 [M + H]+. 106 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.35-10.49 (1H, brs), 7.64-7.73 (5H, m), 7.51-7.58 (4H, m), 6.78-7.01 (2H, m), 6.42 (1H, s), 6.18-6.22 (1H, m), 4.54-4.58 (2H, m), 4.42-4.45 (2H, m); LCMS: 99.1%, MS (ESI); m/z 343.1 [M + H]+. 107 white powder; mp >200.9° C.; 1H NMR (DMSO-d6, 400 MHz); δ 9.51 (1H, d, J = 8.8 Hz), 7.54-7.66 (2H, m), 7.33-7.51 (3H, m), 7.12-7.22 (1H, m), 4.15-4.29 (1H, m), 3.00-3.15 (2H, m), 1.29 (3H, d, J = 6.8 Hz); LCMS: 100%, MS (ESI); m/z 334.9 [M + H]+. 108 yellow solid; 1H NMR (DMSO-d6, 400 MHz); δ 7.41 (2H, d, J = 8.8 Hz), 7.29 (2H, d, J = 8.0 Hz), 7.23 (2H, d, J = 8.0 Hz), 6.94 (2H, d, J = 8.4 Hz), 6.80 (1H, d, J = 8.0 Hz), 6.64 (1H, brs), 6.42 (1H, d, J = 2.0 Hz), 6.19 (1H, d, J = 7.2 Hz), 4.34 (2H, d, J = 6.0 Hz), 4.04 (2H, d, J = 12.4 Hz), 2.68-2.75 (3H, m), 1.80-1.91 (2H, m), 1.65-1.80 (2H, m); LCMS: 98.0%, MS (ESI); m/z 482.1 [M + H]+. 109 white powder; mp >173° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.40 (1H, brs), 7.30-7.40 (4H, m), 7.18 (1H, s), 7.11 (1H, t, J = 7.2 Hz), 6.90-7.00 (5H, m), 6.70-6.85 (2H, m), 6.39 (1H, d, J = 2.0 Hz), 6.24 (1H, d, J = 7.6 Hz), 5.00 (1H, brs), 4.42 (2H, d, J = 6.0 Hz), 1.31 (6H, s); LCMS: 100%, MS (ESI); m/z 416.1 [M + H]+. 110 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.03-10.31 (1H, m), 7.30-7.55 (4H, m), 6.91-7.07 (4H, m), 6.60-6.88 (2H, m), 6.39 (1H, brs), 6.05-6.15 (1H, m), 4.80-4.90 (1H, m), 4.40 (2H, brs), 1.44 (3H, d, J = 6.8 Hz); LCMS: 100%, MS (ESI); m/z 379.0 111 white solid; mp = 156.4-158.5° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.40 (1H, d, J = 8.8 Hz), 7.21 (1H, d, J = 8.4 Hz), 6.95-7.04 (4H, m), 6.83 (1H, d, J = 8.4 Hz), 6.31 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 6.08 (2H, brs), 5.10 (2H, s), 4.47 (2H, brs); LCMS: 99.8%, MS (ESI); m/z 365.1 [M + H]+. 112 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.60 (1H, d, J = 8.8 Hz), 7.44 (2H, d, J =8.4 Hz), 7.40 (1H, brs), 7.23 (1H, d, J = 3.2 Hz), 7.07 (2H, d, J = 8.8 Hz), 6.96 (1H, dd, J = 8.8, 2.8 Hz), 6.85 (1H, d, J = 8.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.48 (2H, s); LCMS: 97.6%, MS (ESI); m/z 399.1 [M + H]+. 113 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.65 (1H, brs), 7.32-7.50 (3H, m), 7.08-7.20 (1H, m), 7.02 (2H, d, J = 8.4 Hz), 6.88 (1H, d, J = 8.4 Hz), 6.74-6.84 (1H, m), 6.48 (1H, d, J = 2.0 Hz), 6.29 (1H, dd, J = 8.0, 2.0 Hz), 4.48 (2H, s); LCMS: 98.7%, MS (ESI); m/z 367.1 [M + H]+. 114 white powder; mp >220° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.30 (1H, brs), 7.15-7.35 (4H, m), 7.06 (2H, d, J = 9.6 Hz), 6.95 (1H, d, J = 8.8 Hz), 6.78 (1H, d, J = 7.2 Hz), 6.50-6.70 (1H, m), 6.41 (1H, s), 6.15-6.25 (1H, m), 4.25-4.55 (4H, m), 3.25-3.40 (4H, m), 3.15-3.25 (4H, m); LCMS: 98.8%, MS (ESI); m/z 483.2 [M + H]+. 115 white powder; mp >220° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.30 (1H, brs), 7.30-7.55 (4H, m), 7.22 (2H, d, J = 8.4 Hz), 6.92 (2H, d, J = 8.4 Hz), 6.79 (1H, d, J = 8.0 Hz), 6.50-6.75 (1H, m), 6.41 (1H, d, J = 2.0 Hz), 6.15-6.25 (1H, m), 4.25-4.50 (2H, brs), 4.33 (2H, J = 6.0 Hz) 3.60-3.80 (2H, m), 2.60-2.75 (3H, m), 1.80-1.95 (2H, m), 1.65-1.80 (2H, m); LCMS: 98.7%, MS (ESI); m/z 432.1 [M + H]+. 116 pale yellow; mp >130.8° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.34 (2H, d, J = 8.4 Hz), 7.28 (2H, d, J = 8.4 Hz), 7.02 (1H, brs), 6.75-6.85 (1H, m), 6.44 (1H, s), 6.22 (1H, d, J = 8.0 Hz), 4.43 (2H, s), 1.25 (9H, s); LCMS: 99.6%, MS (ESI); m/z 295.0 [M + H]+. 117 off-white powder; mp >207.2° C.; 1H NMR (DMSO-d6, 400 MHz); δ 9.78 (1H, t, J = 6.0 Hz), 7.42-7.49 (4H, m), 7.36-7.42 (2H, m), 7.19 (1H, dd, J = 8.4, 2.0 Hz), 7.00 (2H, d, J = 8.8 Hz), 6.88-6.96 (2H, m), 4.66 (2H, d, J = 6.0 Hz), 1.27 (9H, s); LCMS; LCMS: 98.5%, MS (ESI); m/z 387.1 [M + H]+. 118 pale green powder; mp >113.2° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.56 (0.4H, brs), 10.40 (0.4H, brs), 7.35-7.50 (4H, m), 7.19-7.25 (1H, m), 6.90-7.05 (5H, m), 6.75-6.95 (2H, m), 6.39 (1H, s), 6.15-6.35 (1H, m), 4.97 (0.5H, brs), 5.07 (0.5H, brs), 4.38-4.49 (2H, m), 1.31 (6H, d, J = 3.6 Hz); LCMS: 99.5%, MS (ESI); m/z 450.0 [M + H]+. 119 white powder; mp >54.3° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.35-10.65 (1H, m), 7.30-7.60 (5H, m), 7.10-7.20 (1H, m), 6.90-7.10 (4H, m), 6.75-6.90 (1H, m), 6.40 (1H, s), 6.15-6.30 (1H, m), 5.00-5.25 (1H, m), 4.40-4.60 (2H, m), 3.85-4.05 (2H, m), 3.75-3.85 (1H, m), 3.60-3.75 (1H, m), 3.45-3.60 (1H, m), 2.05-2.25 (1H, m), 1.65-1.80 (1H, m); LCMS: 97.3%, MS (ESI); m/z 401.1 [M + H]+. 120 white powder; mp = 200.7-201.3° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.27 (2H, d, J = 8.8 Hz), 6.92-7.05 (2H, m), 6.87 (1H, d, J = 8.0 Hz), 6.48 (1H, s), 6.26 (2H, dd, J = 8.4, 2.4 Hz), 6.01 (1H, d, J = 6.8 Hz), 4.53 (2H, brs), 4.20-4.30 (2H, m), 4.13-4.20 (2H, m), 4.05-4.13 (1H, m), 1.85-2.05 (2H, m), 1.60-1.75 (2H, m), 1.45-1.60 (4H, m); LCMS: 98.6%, MS (ESI); m/z 421.1 [M + H]+. 121 white powder; mp >59.7° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.26 (2H, d, J = 8.4 Hz), 6.90 (2H, d, J = 8.4 Hz), 6.79 (1, d, J = 8.4 Hz), 6.69 (1H, brs), 6.42 (1H, d, J = 2.0 Hz), 6.19 (1H, dd, J = 8.0, 2.0 Hz), 4.39 (2H, d, J = 6.0 Hz), 1.26 (9H, s); LCMS: 99.5%, MS (ESI); m/z 311.1 [M + H]+. 122 off-white powder; mp >160.8° C.; 1H NMR (DMSO-d6); δ 9.73 (1H, t, J = 6.4 Hz), 7.52 (2H, d, J = 8.4 Hz), 7.35-7.46 (3H, m), 7.19 (1H, dd, J = 8.0, 2.0 Hz), 7.14 (1H, d, J = 8.4 Hz), 7.10 (2H, d, J = 8.8 Hz), 7.02 (1H, t, J = 2.4 Hz), 6.95 (1H, dd, J = 8.4, 2.4 Hz), 4.67 (2H, d, J = 6.0 Hz); LCMS: 100%, MS (ESI); m/z 365.0 [M + H]+. 123 yellow powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 7.35- 7.47 (4H, m), 6.95-7.05 (4H, m), 6.91 (1H, d, J = 8.0 Hz), 6.40 (1H, s), 6.34 (1H, d, J = 8.4 Hz), 5.79 (1H, brs), 4.22 (2H, s), 2.98 (6H, s); LCMS: 98.7%, MS (ESI); m/z 393.1 [M + H]+. 124 gray powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.14 (1H, brs), 7.30-7.40 (4H, m), 6.90-7.00 (4H, m), 6.55-6.87 (2H, m), 6.37 (1H, s), 6.14 (1H, d, J = 8.4 Hz), 4.20-4.70 (3H, m), 1.60-1.80 (2H, m), 0.87 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI); m/z 393.0 [M + H]+. 125 pale yellow powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.40 (1H, brs), 7.36-7.45 (4H, m), 6.95-7.06 (4H, m), 6.75-6.80 (2H, m), 6.26 (1H, s), 6.13 (1H, d, J = 7.6 Hz), 5.69 (1H, brs), 4.81 (2H, t, J = 6.0 Hz), 4.31-4.50 (5H, m); LCMS: 99.1%, MS (ESI); m/z 421.1 [M + H]+. 126 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 13.14 (2H, brs), 7.78 (2H, d, J = 8.8 Hz), 7.39 (2H, d, J = 8.4 Hz), 7.30 (1H, d, J = 8.8 Hz), 6.90-7.10 (6H, m), 4.42 (2H, s), 3.21 (6H, s); LCMS: 100%, MS (ESI); m/z 443.1 [M + H]+. 127 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 13.20 (2H, brs), 7.50 (2H, d, J = 8.8 Hz), 7.38 (2H, d, J = 8.4 Hz), 7.29 (1H, d, J = 8.8 Hz), 7.16 (1H, brs), 6.80-7.10 (5H, m), 4.71 (1H, d, J = 5.6 Hz), 3.20 (6H, s), 1.66 (3H, d, J = 6.0 Hz); LCMS: 100%, MS (ESI); m/z 457.1 [M + H]+. 128 pale green powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 12.66 (2H, brs), 7.36-7.47 (4H, m), 7.13 (1H, d, J = 7.6 Hz), 6.90-7.00 (4H, m), 6.60-6.85 (2H, m), 4.25-4.35 (1H, m), 3.15 (6H, s), 1.70-2.00 (2H, m), 0.87 (3H, t, J = 7.2 Hz); LCMS: 99.39%, MS (ESI); m/z 421.1 [M + H]+. 129 gray powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.35-10.50 (1H, m), 7.80-7.98 (4H, m), 7.66 (2H, d, J = 8.8 Hz), 7.57 (2H, d, J = 8.4 Hz), 6.75-7.00 (1H, m), 6.70-6.80 (1H, m), 6.39 (1H, s), 6.10-6.25 (1H, m), 4.45-4.55 (2H, m), 4.25-4.45 (2H, m); LCMS: 98.0%, MS (ESI); m/z 413.0 [M + H]+. 130 white powder; 1H NMR (DMSO-d6); δ 9.92 (1H, t, J = 6.0 Hz), 7.69- 7.83 (4H, m), 7.58-7.69 (4H, m), 7.39-7.51 (2H, m), 7.18 (1H, d, J = 8.8 Hz), 4.83 (2H, d, J = 6.0 Hz); LCMS: 100%, MS (ESI); m/z 377.0 [M + H]+. 131 pale green powder; 1H NMR (DMSO-d6, 400 MHz); δ 12.91 (2H, brs), 7.41-7.47 (4H, m), 7.22 (1H, d, J = 8.4 Hz), 6.86-6.99 (6H, m), 4.50-4.70 (1H, m), 3.17 (6H, s), 1.58 (3H, d, J = 5.2 Hz); LCMS: 99.7%, MS (ESI); m/z 407.0 [M + H]+. 132 pale green powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 12.76 (2H, brs), 7.43 (2H, d, J = 8.8 Hz), 7.38 (2H, d, J = 8.8 Hz), 7.16 (1H, d, J = 7.2 Hz), 7.02-7.08 (2H, m), 7.00 (2H, d, J = 8.8 Hz), 6.60-6.85 (2H, m), 4.30-4.40 (1H, m), 3.16 (6H, s), 1.75-2.10 (2H, m), 0.87 (3H, t, J = 7.2 Hz); LCMS: 99.6%, MS (ESI); m/z 471.1 [M + H]+. 133 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.52 (1H, brs), 7.85-7.99 (4H, m), 7.61-7.70 (2H, m), 7.56 (2H, d, J = 8.4 Hz), 6.96 (1H, brs), 6.84 (1H, d, J = 8.0 Hz), 6.23 (1H, s), 6.12 (1H, dd, J = 8.4, 2.0 Hz), 5.70 (1H, brs), 4.80 (2H, t, J = 6.0 Hz), 4.52 (2H, d, J = 6.0 Hz), 4.38-4.45 (1H, m), 4.30-4.38 (2H, m); LCMS: 95.3%, MS (ESI); m/z 469.0 [M + H]+. 134 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.24-10.59 (1H, m), 7.34-7.44 (4H, m), 6.94-7.09 (4H, m), 6.85-6.88 (2H, m), 6.42 (1H, d, J = 2.0 Hz), 6.20-6.25 (1H, m), 4.83 (1H, brs), 4.44 (2H, d, J = 6.4 Hz), 3.63-3.67 (1H, m), 2.51-2.53 (1H, m), 2.26-2.30 (1H, m), 1.21 (3H, d, J = 6.0 Hz); LCMS: 98.0%, MS (ESI); m/z 375.1 [M + H]+. 135 pale green powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.76 (1H, d, J = 2.8 Hz), 7.30-7.45 (4H, m), 7.05 (1H, d, J = 8.8 Hz), 6.97 (2H, d, J = 8.4 Hz), 6.85 (1H, d, J = 8.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.46 (2H, s); LCMS: 98.2%, MS (ESI); m/z 398.9 [M + H]+. 136 pale green powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.4 Hz), 7.41-7.52 (4H, m), 7.07 (2H, d, J = 8.8 Hz), 6.75-6.85 (2H, m), 6.42 (1H, d, J = 1.6 Hz), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 4.45 (2H, d, J = 5.6 Hz); LCMS: 97.8%, MS (ESI); m/z 366.0 [M + H]+. 137 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.47-10.63 (1H, m), 7.40 (4H, d, J = 8.8 Hz), 6.86-7.04 (6H, m), 6.40-6.45 (1H, m), 6.18-6.32 (1H, m), 5.91-6.08 (1H, m), 4.42-4.48 (2H, m), 2.59- 2.72 (2H, m), 2.27-2.40 (2H, m), 1.98-2.15 (2H, m); LCMS: 92.6%, MS (ESI); m/z 444.2 [M + H]+. 138 white powder; 1H NMR (DMSO-d6); δ 9.78 (1H, t, J = 6.0 Hz), 8.17 (1H, d, J = 2.4 Hz), 7.96 (1H, dd, J = 8.8, 2.4 Hz), 7.51 (2H, d, J = 8.4 Hz), 7.37-7.45 (2H, m), 7.08-7.20 (4H, m), 4.69 (2H, d, J = 6.0 Hz); LCMS: 99.6%, MS (ESI); m/z 365.9 [M + H]+. 139 white powder; 1H NMR (DMSO-d6); δ 8.41 (1H, d, J = 4.8 Hz), 7.71- 7.78 (1H, m), 7.53 (1H, d, J = 8.0 Hz), 7.29-7.35 (2H, m), 7.23-7.28 (2H, m), 7.16-7.22 (1H, m), 6.70-6.82 (2H, m), 6.40 (1H, s), 6.18 (1H, dd, J = 8.4, 2.0 Hz), 6.04 (1H, brs), 5.66 (1H, s), 4.38 (2H, d, J = 5.6 Hz); LCMS: 98.3%, MS (ESI); m/z 346.0 [M + H]+. 140 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.52 (1H, d, J = 2.0 Hz), 7.33 (1H, d, J = 8.0 Hz), 7.20-7.30 (4H, m), 7.03 (2H, d, J = 6.8 Hz), 6.86 (1H, d, J = 8.8 Hz), 6.31 (1H, d, J = 8.4 Hz), 6.15-6.27 (2H, m), 5.00-5.20 (2H, m), 4.46 (2H, brs), 4.10-4.25 (1H, m), 2.87- 3.08 (2H, m), 1.22 (3H, d, J = 6.4 Hz); LCMS: 100%, MS (ESI); m/z 425.1 [M + H]+. 141 pale yellow powder; 1H NMR (DMSO-d6); δ 8.70 (1H, d, J = 4.0 Hz), 8.01-8.10 (1H, m), 7.96 (1H, d, J = 8.0 Hz), 7.91 (2H, d, J = 8.4 Hz), 7.61-7.68 (1H, m), 7.50 (2H, d, J = 7.04 (brs), 6.77-6.84 (1H, m), 6.43 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.0, 2.0 Hz), 4.55 (2H, s); LCMS: 89.4%, MS (ESI); m/z 344.1 [M + H]+. 142 white amorphous; hydroscopic; 1H NMR (DSMO-d6, 400 MHz); δ 12.52 (2H, brs), 10.73 (1H, brs), 8.87 (1H, t, J = 6.0 Hz), 7.29 (2H, d, J = 8.4 Hz), 7.11-7.22 (1H, m), 7.05 (2H, d, J = 9.2 Hz), 6.41-6.59 (2H, m), 5.10-5.22 (1H, m), 3.89-4.00 (2H, m), 3.71-3.81 (2H, m), 3.61-3.70 (3H, m), 3.50-3.60 (4H, m), 3.11-3.24 (4H, m), 2.92-3.10 (2H, m), 2.50-2.60 (2H, m), 2.11-2.21 (1H, m), 1.95-2.08 (1H, m); LCMS: 99.5%, MS (ESI); m/z 506.3 [M + H]+. 143 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.30-10.43 (1H, m), 7.29 (2H, d, J = 8.8 Hz), 7.04 (2H, d, J = 9.2 Hz), 6.86-6.99 (1H, m), 6.34-6.45 (1H, m), 5.95-6.25 (2H, m), 5.10-5.20 (1H, m), 3.60- 3.69 (1H, m), 3.47-3.58 (4H, m), 3.30-3.37 (2H, m), 3.20-3.29 (2H, m), 2.53-2.61 (2H, m), 2.43-2.49 (2H, m), 2.28-2.40 (5H, m), 2.05- 2.17 (1H, m); LCMS: 100%, MS (ESI); m/z 492.1 [M + H]+. 144 pale-yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.53 (1H, d, J = 2.0 Hz), 7.33 (1H, d, J = 8.0 Hz), 7.15-7.28 (4H, m), 7.04 (2H, d, J = 7.6 Hz), 6.64 (1H, d, J = 8.0 Hz, 6.37-6.50 (2H, m), 6.05-6.15 (2H, m), 5.00-5.20 (2H, m), 4.40 (2H, brs), 4.15-4.29 (1H, m), 2.88- 3.04 (2H, m), 1.23 (3H, d, J = 6.8 Hz); LCMS: 98.1%, MS (ESI); m/z 425.1 [M + H]+. 145 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.62 (1H, brs), 7.35-7.45 (2H, m), 7.25 (1H, d, J = 8.8 Hz), 6.90-7.10 (4H, m), 6.78 (1H, d, J = 8.4 Hz), 6.40 (1H, s), 6.19 (1H, d, J = 6.4 Hz), 5.07 (1H, d, J = 8.0 Hz), 4.45 (2H, brs), 3.65-3.75 (1H, m), 3.40-3.55 (1H, m), 2.30-2.40 (1H, m), 1.75-2.00 (3H, m); LCMS: 97.0%, MS (ESI); m/z 405.1 [M + H]+. 146 gray powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.20-10.40 (1H, m), 7.30-7.45 (4H, m), 6.90-7.10 (4H, m), 6.60-6.75 (2H, m), 6.45- 6.55 (1H, m), 4.41 (2H, d, J = 6.0 Hz), 4.00-4.30 (2H, m), 3.70 (3H, s); LCMS: 99.5%, MS (ESI); m/z 394.9 [M + H]+. 147 off-white solid; mp = 191.4 C.-193.5 C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.35-10.60 (1H, m), 7.35-7.45 (4H, m), 6.90-7.05 (6H, m), 6.63 (1H, s), 4.52-4.70 (2H, m), 4.40-4.45 (2H, m); LCMS: 100%, MS (ESI); m/z 399.0 [M + H]+. 148 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.15-10.35 (1H, m), 7.28 (2H, d, J = 8.8 Hz), 7.04 (2H, d, J = 9.2 Hz), 6.86-6.98 (1H, m), 6.32-6.44 (1H, m), 6.12-6.26 (1H, m), 5.08-5.18 (1H, m), 3.60- 3.70 (3H, m), 3.51-3.59 (2H, m), 3.36-3.41 (2H, m), 3.30-3.35 (1H, m), 3.21-3.29 (4H, m), 2.27-2.36 (1H, m), 2.05-2.18 (1H, m); LCMS: 100%, MS (ESI); m/z 437.2 [M + H]+. 149 pink amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.29-10.47 (1H, m), 8.51 (1H, d, J = 4.0 Hz), 7.70 (1H, t, J = 8.0 Hz), 7.29-7.47 (5H, m), 7.22 (1H, t, J = 6.0 Hz), 6.92-7.06 (4H, m), 6.65-6.90 (2H, m), 6.34 (1H, s), 6.15-6.31 (1H, m), 5.60-5.86 (1H, m), 4.41 (2H, t, J = 6.8 Hz), 4.30 (2H, d, J = 5.6 Hz); LCMS: 99.5%, MS (ESI); m/z 456.1 [M + H]+. 150 pale-yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.60- 10.85 (1H, m), 8.15 (1H, d, J = 2.0 Hz), 7.87 (1H, dd, J = 8.4, 2.4 Hz), 7.38 (2H, d, J = 8.4 Hz), 7.22 (2H, d, J = 9.2 Hz), 7.01 (1H, d, J = 8.8 Hz), 6.75-6.94 (1H, m), 6.18-6.40 (2H, m), 5.46-5.69 (1H, m), 4.41- 4.55 (1H, m), 2.90-2.95 (6H, m), 1.42 (3H, d, J = 6.4 Hz); LCMS: 97.6%, MS (ESI); m/z 458.1 [M + H]+. 151 grey powder; mp >200° C.; 1H NMR (DMSO-d6, 400 MHz); δ 9.56 (1H, s), 6.83 (2H, d, J = 8.4 Hz), 6.61 (2H, d, J = 8.4 Hz), 6.39 (2H, d, J = 8.8 Hz), 6.21 (2H, d, J = 8.8 Hz), 5.97 (1H, brs), 5.90 (1H, d, J = 8.0 Hz), 5.53 (1H, d, J = 2.0 Hz), 5.32 (1H, d, J = 8.0 Hz), 3.62 (4H, d, J = 6.0 Hz); LCMS: 97.1%, MS (ESI); m/z 428.1 [M + H]+. 152 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.60- 10.85 (1H, m), 8.19 (1H, s), 7.93 (1H, dd, J = 8.8, 2.4 Hz), 7.42 (2H, d, J = 8.8 Hz), 7.00-7.10 (3H, m), 6.75-6.90 (1H, m), 6.19-6.36 (2H, m), 5.46-5.67 (1H, m), 4.36-4.50 (1H, m), 2.90-2.95 (6H, m), 1.42 (3H, d, J = 5.2 Hz); LCMS: 99.2%, MS (ESI); m/z 408.1 [M + H]+. 153 off-white powder; 1H NMR (DMSO-d6); δ 8.12-8.23 (1H, m), 7.79 (1H, s), 7.71-7.77 (1H, m), 7.64-7.71 (1H, m), 6.98 (1H, d, J = 8.8 Hz), 6.89 (1H, brs), 6.79 (1H, d, J = 8.0 Hz), 6.42 (1H, d, J = 2.0 Hz), 6.19 (1H, dd, J = 8.0 Hz), 4.59 (2H, d, J = 5.6 Hz), 3.96 (3H, s); LCMS: 93%, MS (ESI); m/z 319.9 [M + H]+. 154 grey amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.33-10.54 (1H, m), 8.60 (1H, d, J = 4.8 Hz), 7.40 (2H, d, J = 8.4 Hz), 7.22 (1H, t, J = 4.8 Hz), 7.10 (2H, d, J = 8.4 Hz), 6.70-6.94 (2H, m), 6.36-6.45 (1H, m), 6.11-6.22 (1H, m), 4.27-4.50 (4H, m); LCMS: 100%, MS (ESI); m/z 333.1 [M + H]+. 155 white solid; mp = 203.8-204.6° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.44 (1H, m), 7.19 (1H, d, J = 8.4 Hz), 6.90-7.04 (4H, m), 6.88 (1H, d, J = 8.4 Hz), 6.53 (1H, t, J = 5.2 Hz), 6.30 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 5.10 (2H, s), 5.02 (1H, brs), 4.51 (2H, brs), 3.50-3.60 (2H, m), 3.34-3.38 (2H, m); LCMS: 100%, MS (ESI); m/z 490.0 [M + H]+. 156 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.30 (1H, d, J = 8.8 Hz), 8.08 (1H, d, J = 2.0 Hz), 7.99 (1H, d, J = 9.2 Hz), 7.75 (1H, dd, J = 8.8, 2.4 Hz), 7.60 (1H, d, J = 8.4 Hz), 6.97 (1H, brs), 6.79 (1H, d, J = 8.0 Hz), 6.41 (1H, d, J = 2.0 Hz), 6.19 (1H, d, J = 6.4 Hz), 4.72 (2H, d, J = 5.6 Hz); LCMS: 93.1%, MS (ESI); m/z 323.9 [M + H]+. 157 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.45 (2H, d, J = 8.4 Hz), 7.32 (2H, d, J = 8.0 Hz), 7.08 (1H, d, J = 8.4 Hz), 6.46 (1H, d, J = 2.0 Hz), 6.41 (1H, dd, J = 8.4, 2.0 Hz), 4.77 (2H, brs), 3.50-3.60 (2H, m), 3.48 (3H, s), 2.88-3.01 (2H, m), 2.73-2.85 (1H, m), 1.80-1.95 (4H, m); LCMS: 100%, MS (ESI); m/z 390.9 [M + H]+. 158 off-white powder; mp = 101.8-104.0° C.; 1H NMR (DMSO-d6, 400 MHz); δ 10.49 (1H, brs), 8.56 (1H, d, J = 2.0 Hz), 7.87 (1H, dd, J = 8.4, 2.4 Hz), 7.40 (1H, d, J = 8.0 Hz), 6.85 (1H, brs), 6.79 (1H, d, J = 8.4 Hz), 6.41 (1H, d, J = 1.6 Hz), 6.19 (1H, d, J = 7.2 Hz), 4.54 (2H, d, J = 6.0 Hz), 4.42 (2H, brs); LCMS: 99.2%, MS (ESI); m/z 273.9 [M + H]+. 159 green solid; 1H NMR (DMSO-d6, 400 MHz); δ 8.84-8.86 (1H, m), 8.33 (1H, d, J = 8.4 Hz), 7.91-8.00 (2H, m), 7.61-7.64 (1H, m), 7.49 (1H, dd, J = 8.0, 4.0 Hz), 7.13 (1H, brs), 6.81 (1H, d, J = 8.4 Hz), 6.43 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.0, 2.0 Hz), 4.68 (2H, d, J = 6.0 Hz); LCMS: 93.2%, MS (ESI); m/z 290.3 [M + H]+. 160 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.64-10.85 (1H, m), 8.25 (1H, d, J = 2.4 Hz), 7.81 (1H, dd, J = 8.8, 2.4 Hz), 6.88 (1H, d, J = 8.4 Hz), 6.76-6.86 (1H, m), 6.44 (1H, d, J = 1.6 Hz), 6.14- 6.28 (1H, m), 5.50-5.56 (1H, m), 4.30-4.57 (2H, m), 3.70-3.81 (1H, m), 3.49-3.67 (3H, m), 2.26-2.37 (1H, m), 2.10-2.24 (1H, m); LCMS: 96.8%, MS (ESI); m/z 329.9 [M + H]+. 161 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.40 (2H, d, J = 8.8 Hz), 7.16 (2H, d, J = 8.8 Hz), 6.93-7.05 (4H, m), 6.89 (1H, d, J = 8.0 Hz), 6.22-6.30 (2H, m), 6.19 (1H, d, J = 6.8 Hz), 5.12 (2H, s), 4.47 (2H, brs), 4.06-4.19 (1H, m), 1.91-1.94 (2H, m), 1.48-1.56 (2H, m), 1.56-1.66 (4H, m); LCMS: 98.4%, MS (ESI); m/z 433.0 [M + H]+. 162 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 6.71-6.81 (2H, m), 6.69 (1H, brs), 6.35-6.45 (3H, m), 6.20 (1H, d, J = 8.4 Hz), 5.58 (1H, brs), 4.25 (2H, d, J = 6.0 Hz), 3.09-3.18 (2H, m), 2.55-2.65 (2H, m), 1.65-1.80 (2H, m); LCMS: 96.9%, MS (ESI); m/z 293.9 [M + H]+. 163 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.32 (2H, d, J = 8.8 Hz), 7.01 (1H, d, J = 8.4 Hz), 7.00 (2H, d, J = 8.8 Hz), 6.50 (1H, s), 6.40 (1H, d, J = 8.4 Hz), 4.73 (2H, brs), 3.90 (2H, d, J = 6.0 Hz), 3.40-3.50 (5H, m), 2.80-2.87 (2H, m), 1.94-2.00 (1H, m), 1.80-1.88 (2H, m), 1.46-1.55 (2H, m); LCMS 95%, MS (ESI); m/z 370.9 [M + H]+. 164 grey amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.30-10.40 (1H, m), 8.68 (1H, d, J = 1.2 Hz), 8.02 (2H, d, J = 8.4 Hz), 7.98 (2H, d, J = 1.6 Hz), 7.47 (2H, d, J = 8.0 Hz), 6.70-6.91 (2H, m), 6.41 (1H, d, J = 2.0 Hz), 6.10-6.22 (1H, m), 4.49 (2H, d, J = 6.0 Hz), 4.30-4.45 (2H, m); LCMS: 100%, MS (ESI); m/z 349.9 [M + H]+. 165 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.45 (2H, m), 7.20 (2H, d, J = 8.4 Hz), 6.94-7.04 (4H, m), 6.87 (1H, d, J = 8.3 Hz), 6.51 (1H, brs), 6.33 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.0, 2.0 Hz), 5.15 (2H, s), 3.27-3.30 (2H, m), 1.08 (6H, s); LCMS: 97.8%, MS (ESI); m/z 437.0 [M + H]+. 166 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.30-10.50 (1H, m), 8.16 (1H, d, J = 2.4 Hz), 7.92 (1H, dd, J = 8.8, 2.4 Hz), 7.38 (2H, d, J = 8.4 Hz), 7.01-7.09 (3H, m), 6.75-6.95 (2H, m), 6.24 (1H, d, J = 4.8 Hz), 6.08-6.20 (1H, m), 5.60-5.78 (1H, m), 4.81 (2H, t, J = 6.4 Hz), 4.35-4.50 (5H, m); LCMS: 98.13%, MS (ESI); m/z 422.0 [M + H]+. 167 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.36-7.44 (4H, m), 6.93-7.05 (4H, m), 6.86 (2H, d, J = 8.4 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.57 (2H, brs), 4.50 (2H, d, J = 6.0 Hz), 3.40 (3H, s); LCMS: 97.8%, MS (ESI); m/z 378.9 [M + H]+. 168 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.93 (1H, d, J = 8.4 Hz), 7.48 (1H, d, J = 8.4 Hz), 7.41 (1H, brs), 6.81 (1H, d, J = 8.4 Hz), 6.43 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 4.53 (2H, s), 3.73-3.84 (1H, m), 1.79-1.93 (2H, m), 1.65-1.77 (2H, m), 1.59 (4H, m); LCMS: 94%, MS (ESI); m/z 335.1 [M + H]+. 169 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.44 (2H, d, J = 7.2 Hz), 7.38 (2H, t, J = 7.6 Hz), 7.25-7.34 (1H, m), 7.23 (2H, d, J = 8.8 Hz), 6.93 (2H, d, J = 8.8 Hz), 6.84 (1H, d, J = 8.0 Hz), 6.52 (1H, brs), 6.45 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.54 (1H, t, J = 6.0 Hz), 3.59-3.70 (2H, m); LCMS: 97.4%, MS (ESI); m/z 378.9 [M + H]+. 170 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.38-7.45 (4H, m), 7.28 (1H, brs), 7.09 (1H, brs), 6.96-7.02 (4H, m), 6.88-6.96 (2H, m), 6.33 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.4, 2.0 Hz), 5.37 (1H, t, J = 6.0 Hz), 4.50 (2H, d, J = 5.6 Hz), 3.57 (2H, d, J = 5.6 Hz), 3.42 (3H, s); LCMS: 95.5%, MS (ESI): m/z 435.9 [M + H]+. 171 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.46 (4H, m), 6.95-7.04 (6H, m), 6.58 (1H, d, J = 2.0 Hz), 6.41 (1H, dd, J = 8.4, 2.1 Hz), 5.74 (1H, t, J = 7.2 Hz), 4.52 (2H, d, J = 6.0 Hz), 4.21 (2H, d, J = 7.2 Hz), 3.47 (3H, s); LCMS: 96.6%, MS (ESI); m/z 418.0 [M + H]+. 172 grey powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 7.27 (2H, d, J = 8.4 Hz), 6.87 (2H, d, J = 8.4 Hz), 6.77 (1H, d, J = 8.4 Hz), 6.66 (1H, brs), 6.40 (1H, d, J = 1.6 Hz), 6.17 (1H, d, J = 8.4 Hz), 4.62- 4.78 (1H, m), 4.34 (2H, d, J = 6.4 Hz), 2.56-2.74 (2H, m), 1.28 (3H, d, J = 6.0 Hz); LCMS: 99.4%, MS (ESI); m/z 364.9 [M + H]+. 173 pale-yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.32-10.50 (1H, m), 8.16 (2H, d, J = 8.4 Hz), 7.56 (1H, s), 7.47 (2H, d, J = 8.0 Hz), 7.17 (1H, s), 6.88-6.98 (0.5H, m), 6.70-6.84 (1.5H, m), 6.40 (1H, s), 6.10-6.23 (1H, m), 4.25-4.60 (4H, m), 3.97 (3H, s); LCMS: 90%, MS (ESI); m/z 347.1 [M + H]+. 174 off-white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 7.11-7.39 (6H, m), 6.93 (1H, d, J = 7.6 Hz), 6.42 (1H, d, J = 1.6 Hz), 6.34 (1H, d, J = 8.4 Hz), 4.66-4.83 (3H, m), 3.72 (1H, t, J = 8.8 Hz), 3.36-3.43 (4H, m), 2.91 (2H, d, J = 6.4 Hz); LCMS: 97.0%, MS (ESI); m/z 352.0 [M + H]+. 175 off-white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 8.03 (1H, s), 7.96 (2H, d, J = 8.4 Hz), 7.59 (2H, d, J = 8.4 Hz), 6.81 (1H, d, J = 8.0 Hz), 6.43 (1H, d, J = 1.6 Hz), 6.20 (1H, d, J = 7.6 Hz), 4.39 (2H, d, J = 5.6 Hz); LCMS: 100%, MS (ESI); m/z 340.1 [M + H]+. 176 grey powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 9.50- 9.62 (1H, m), 7.34-7.42 (3H, m), 7.31 (1H, s), 7.07 (1H, d, J = 7.6 Hz), 6.97 (2H, J = 8.4 Hz), 4.56 (2H, d, J = 5.6 Hz), 4.18 (2H, t, J = 6.0 Hz), 2.67-2.85 (2H, m); LCMS: 100%, MS (ESI); m/z 351.1 [M + H]+. 177 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.35-10.60 (1H, m), 8.16 (1H, d, J = 2.4 Hz), 7.92 (1H, dd, J = 8.8, 2.4 Hz), 7.39 (2H, d, J = 8.0 Hz), 7.14-7.25 (1H, m), 7.05-7.12 (3H, m), 6.77-6.97 (3H, m), 6.38 (1H, s), 6.15-6.33 (1H, m), 4.90-5.10 (1H, m), 4.40-4.70 (2H, m), 1.31 (6H, s); LCMS: 96.3%, MS (ESI); m/z 451.0 [M + H]+. 178 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (2H, d, J = 8.8 Hz), 7.54 (2H, d, J = 8.0 Hz), 6.83 (1H, d, J = 8.4 Hz), 6.44 (1H, d, J = 2.0 Hz), 6.22 (2H, dd, J = 8.0, 2.0 Hz), 4.28-4.35 (1H, m), 3.70- 3.79 (1H, m), 3.57-3.68 (1H, m), 3.45-3.51 (2H, m), 2.25-2.35 (1H, m), 2.08-2.20 (1H, m); LCMS: 99.5%, MS (ESI); m/z 390.9 [M + H]+. 179 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.60-10.89 (1H, m), 7.90 (2H, d, J = 8.0 Hz), 7.51 (2H, d, J = 8.0 Hz), 6.74-7.00 (1H, m), 6.14-6.45 (2H, m), 5.63-5.96 (1H, m), 4.31 (2H, d, J = 4.8 Hz), 3.83 (3H, s), 2.94 (3H, s), 2.93 (3H, s); LCMS: 99.3%, MS (ESI); m/z 394.9 [M + H]+. 180 off-white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.29 (1H, brs), 7.42 (2H, d, J = 7.2 Hz), 7.36 (2H, t, J = 7.6 Hz), 7.28 (1H, t, J = 7.2 Hz), 7.18-7.24 (2H, m), 6.83-6.95 (3H, m), 6.58 (1H, brs), 6.27 (1H, d, J = 1.6 Hz), 6.13 (1H, d, J = 8.0 Hz), 5.71 (1H, brs), 5.52 (1H, t, J = 6.4 Hz), 4.81 (2H, t, J = 6.0 Hz), 4.31-4.49 (3H, m), 3.63 (2H, t, J = 6.0 Hz); LCMS: 99.1%, MS (ESI); m/z 435.0 [M + H]+. 181 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.44 (1H, d, J = 4.0 Hz), 7.77 (1H, t, J = 7.2 Hz), 7.50 (1H, d, J = 8.0 Hz), 7.25- 7.36 (4H, m), 7.16-7.25 (1H, m), 6.78 (1H, d, J = 8.4 Hz), 6.72 (1H, brs), 6.41 (1H, s), 6.19 (1H, d, J = 8.0 Hz), 5.32 (1H, s), 4.40 (2H, d, J = 4.4 Hz), 3.29 (3H, s); LCMS: 96.7%, MS (ESI); m/z 359.9 [M + H]+. 182 pale green powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.12 (1H, brs), 7.40-7.55 (4H, m), 7.15 (1H, d, J = 8.4 Hz), 7.07 (2H, d, J = 8.4 Hz), 6.99-7.02 (2H, m), 6.65 (1H, s), 6.59 (1H, d, J = 8.8 Hz), 4.62 (2H, d, J = 5.6 Hz), 3.72-3.80 (2H, m), 3.60 (3H, s), 3.14-3.28 (2H, m), 1.95- 2.06 (2H, m); LCMS 96.6%, MS (ESI); m/z 419.0 [M + H]+. 183 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.27 (2H, d, J = 8.8 Hz), 7.00-7.12 (3H, m), 6.79 (1H, s), 6.95 (1H, d, J = 8.4 Hz), 4.49-4.61 (1H, m), 3.48-3.55 (1H, m), 3.19-3.24 (1H, m), 3.05 (6H, s), 2.73-2.89 (2H, m), 1.98-2.10 (1H, m), 1.80-1.90 (1H, m), 1.62-1.76 (1H, m), 1.45-1.58 (1H, m); LCMS: 100%, MS (ESI); m/z 421.0 [M + H]+. 184 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.44 (4H, m), 6.86-7.04 (6H, m), 6.17-6.28 (2H, m), 5.82 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.46-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.43 (3H, s); LCMS: 98.4%, MS (ESI); m/z 434.9 [M + H]+. 185 pale yellow powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.65-10.86 (1H, m), 7.26 (2H, d, J = 8.0 Hz), 7.05-7.18 (2H, m), 6.95-7.04 (2H, m), 6.81-6.95 (3H, m), 6.20-6.45 (2H, m), 5.45-5.66 (1H, m), 4.49 (2H, s), 4.04-4.21 (4H, m), 2.97 (3H, s), 2.94 (3H, s), 1.17 (3H, t, J = 7.2 Hz); Based on H NMR, it is a mixture of tautomers; LCMS: 99.3%, MS (ESI); m/z 462.1 [M + H]+. 186 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.91 (1H, s), 7.38-7.40 (2H, m), 7.30-7.33 (2H, m), 6.89 (1H, d, J = 8.4 Hz), 6.48 (1H, d, J = 2.0 Hz), 6.30 (1H, dd, J = 8.4, 2.0 Hz), 4.34 (2H, s), 4.13 (2H, s); LCMS: 100%, MS (ESI); m/z 354.1 [M + H]+. 187 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.39-7.43 (2H, m), 7.21 (2H, d, J = 8.4 Hz), 6.96-7.03 (5H, m), 6.36-6.40 (3H, m), 5.26 (2H, s), 3.53 (2H, s), 1.32 (6H, s); LCMS: 100%, MS (ESI); m/z 437.0 [M + H]+. 188 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.16-10.45 (1H, m), 8.44 (1H, d, J = 4.4 Hz), 7.77 (1H, t, J = 7.6 Hz), 7.51 (1H, d, J = 7.6 Hz), 7.26-7.35 (4H, m), 7.17-7.25 (1H, m), 6.55-6.88 (2H, m), 6.39 (1H, d, J = 1.6 Hz), 6.17 (1H, brs), 5.42 (1H, s), 4.20-4.63 (4H, m), 3.40-3.49 (2H, q, J = 6.8 Hz), 1.17 (3H, t, J = 7.0 Hz); LCMS: 95.4%, MS (ESI); m/z 373.8 [M + H]+. 189 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.29-10.48 (1H, m), 8.40-8.49 (1H, m), 7.72-7.82 (1H, m), 7.50 (1H, d, J = 7.6 Hz), 7.26-7.35 (4H, m), 7.19-7.26 (1H, m), 6.79-6.90 (2H, m), 6.24 (1H, d, J = 4.8 Hz), 6.06-6.17 (1H, m), 5.59-5.79 (1H, m), 5.32 (1H, s), 4.81 (2H, t, J = 6.0 Hz), 4.30-4.50 (5H, m), 3.29 (3H, s); LCMS: 95.7%, MS (ESI); m/z 416.0 [M + H]+. 190 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.67-10.95 (1H, m), 8.18 (2H, d, J = 8.8 Hz), 7.53 (2H, d, J = 8.4 Hz), 6.88-7.07 (1H, m), 6.12-6.54 (2H, m), 4.23-4.40 (1H, m), 3.53 (1H, t, J = 8.8 Hz), 3.37-3.43 (1H, m, overlap with H2O signal), 3.20-3.30 (2H, m, overlap with H2O signal), 2.97 (6H, s), 2.25-2.34 (1H, m), 2.10-2.21 (1H, m); LCMS: 97.4%, MS (ESI, TOF); m/z 419.1985 [M + H]+. 191 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.74-10.84 (1H, m), 7.32-7.42 (4H, m), 7.03 (2H, d, J = 9.2 Hz), 6.95 (2H, d, J = 8.4 Hz), 6.51-6.64 (1H, m), 6.05-6.18 (1H, m), 4.58-4.75 (1H, m), 4.43-4.50 (1H, m), 3.76-4.02 (1H, m), 2.96-2.98 (6H, m), 1.42-1.47 (3H, m); LCMS: 96.6%, MS (ESI); m/z 486.9 [M + H]+. 192 pale brown powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.35-7.51 (4H, m), 6.91-7.06 (6H, m), 6.25 (1H, d, J = 2.0 Hz), 6.09 (1H, dd, J = 8.4, 2.0 Hz), 5.50 (1H, d, J = 6.8 Hz), 4.46-4.57 (3H, m), 3.90-4.05 (2H, m), 3.44 (3H, s), 3.30-3.45 (2H, m); LCMS: 96.0%, MS (ESI); m/z 435.0 [M + H]+. 193 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.36-7.45 (4H, m), 7.01-7.09 (2H, m), 6.93-7.01 (4H, m), 6.43 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 4.51 (2H, d, J = 6.0 Hz), 4.17 (4H, t, J = 12.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 455.0 [M + H]+. 194 brown powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.92 (2H, d, J = 8.8 Hz), 7.08 (2H, d, J = 9.2 Hz), 6.95-7.05 (1H, m), 6.21-6.47 (2H, m), 5.20-5.30 (1H, m), 3.82 (3H, s), 3.60-3.70 (1H, m), 3.30-3.36 (3H, m), 2.97 (3H, s), 3.92 (3H, s), 2.37-2.40 (2H, m); LCMS: 95.3%, MS (ESI); m/z 308.8 [M + H]+. 195 off-white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.15 (1H, d, J = 2.8 Hz), 7.92 (1H, dd, J = 8.8, 2.8 Hz), 7.19 (2H, d, J = 8.4 Hz), 7.03- 7.12 (3H, m), 6.82 (1H, d, J = 8.4 Hz), 6.32 (1H, d, J = 1.6 Hz), 6.25 (1H, dd, J = 8.0, 2.0 Hz), 6.14 (2H, brs), 5.11 (2H, s), 4.49 (2H, brs); LCMS: 97.1%, MS (ESI); m/z 365.9 [M + H]+. 196 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.40-7.60 (5H, m), 7.06 (1H, d, J = 8.4 Hz), 6.45-6.60 (2H, m), 6.32-6.37 (1H, m), 4.34 (2H, s), 3.83 (3H, s), 3.10 (6H, s); LCMS: 98.1%, MS (ESI); m/z 346.8 [M + H]+. 197 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.74 (1H, brs), 8.68 (1H, s), 7.90-8.05 (4H, m), 7.49 (2H, d, J = 8.0 Hz), 6.87 (1H, d, J = 6.8 Hz), 6.37 (1H, s), 6.15-6.45 (1H, m), 5.78 (1H, brs), 4.29 (2H, d, J = 5.6 Hz), 2.93 (6H, s); LCMS: 100%, MS (ESI); m/z 377.9 [M + H]+. 198 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.37 (1H, brs), 7.20-7.38 (4H, m), 6.52-6.95 (2H, m), 6.41 (1H, d, J = 2.0 Hz), 6.18 (1H, d, J = 6.4 Hz), 5.63 (1H, d, J = 4.0 Hz), 4.67 (1H, d, J = 4.0 Hz), 4.17-4.56 (4H, m), 1.06 (3H, s), 0.86 (3H, s); LCMS: 100%, MS (ESI); m/z 379.1 [M + H]+. 199 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.14 (1H, d, J = 2.4 Hz), 7.92 (1H, dd, J = 8.4, 2.4 Hz), 7.21 (2H, d, J = 8.4 Hz), 7.01-7.02 (3H, m), 6.74 (1H, d, J = 8.4 Hz), 6.41 (1H, d, J = 1.2 Hz), 6.29 (2H, brs), 6.14 (1H, dd, J = 8.4, 2.0 Hz), 5.11 (2H, s), 4.39 (2H, brs); LCMS: 92.3%, MS (ESI); m/z 365.8 [M + H]+. 200 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.25-10.60 (1H, m), 7.35-7.60 (5H, m), 6.65-7.00 (2H, m), 6.41 (1H, s), 6.35 (1H, d, J = 1.6 Hz), 6.10-6.25 (1H, m), 4.25-4.60 (4H, m), 3.82 (3H, s); LCMS: 100%, MS (ESI); m/z 318.9 [M + H]+. 201 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.40-10.60 (1H, m), 7.40-7.50 (5H, m), 6.80-7.10 (2H, m), 6.35 (1H, d, J = 2.0 Hz), 6.26 (1H, s), 6.10-6.20 (1H, m), 5.60-5.80 (1H, m), 4.81 (1H, t, J = 6.0 Hz), 4.30-4.60 (5H, m), 3.83 (3H, s); LCMS: 99.8%, MS (ESI); m/z 374.9 [M + H]+. 202 red amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 10.76-10.90 (1H, m), 8.38 (2H, d, J = 6.0 Hz), 6.90-7.03 (3H, m), 6.37-6.47 (1H, m), 6.17-6.30 (1H, m), 5.24-5.26 (1H, m), 3.64-3.71 (1H, m), 3.30-3.32 (3H, m), 2.99 (3H, s), 2.97 (3H, s), 2.37-2.45 (1H, m), 2.16-2.25 (1H, m); LCMS: 100%, MS (ESI); m/z 324.1 [M + H]+. 203 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.05-7.10 (3H, m), 6.88 (1H, d, J = 8.0 Hz), 6.60 (1H, t, J = 6.0 Hz), 6.46 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.0, 2.0 Hz), 5.26 (1H, s), 4.40-4.60 (4H, m), 3.75 (2H, s), 1.19 (6H, s); LCMS: 100%, MS (ESI); m/z 438.0 [M + H]+. 204 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.43 (2H, m), 7.24 (2H, d, J = 8.8 Hz), 6.92-7.03 (5H, m), 6.62 (1H, t, J = 5.2 Hz), 6.14-6.21 (2H, m), 5.82 (1H, d, J = 6.8 Hz), 5.14 (2H, s), 5.00 (1H, brs), 4.77 (2H, t, J = 6.4 Hz), 4.38-4.48 (1H, m), 4.29-4.37 (2H, m), 3.52-3.59 (2H, m), 3.30-3.45 (2H, m); LCMS: 99.4%, MS (ESI); m/z 465.0 [M + H]+. 205 off-white amorphous; 1H NMR (DMSO-d6, t = 80° C., 400 MHz); δ 10.15 (1H, brs), 7.60-7.67 (2H, m), 7.46-7.52 (2H, m), 6.83 (1H, d, J = 8.4 Hz), 6.40-6.60 (2H, m), 6.24 (1H, d, J = 7.6 Hz), 4.56 (2H, s), 4.17 (2H, brs), 1.49-1.56 (6H, m); LCMS: 98.9%, MS (ESI); m/z 377.0 [M + H]+. 206 white powder; 1H NMR (DSMO-d6, 400 MHz); δ 7.42 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.4 Hz), 6.95-7.10 (5H, m), 6.38 (2H, d, J = 8.8 Hz), 6.32 (1H, s), 5.17-5.28 (2H, m), 4.99 (1H, brs), 4.25-4.35 (1H, m), 3.50-3.70 (2H, m), 3.10-3.22 (2H, m), 1.92-1.95 (1H, m), 1.70- 1.80 (1H, m); LCMS: 97.8%, MS (ESI); m/z 434.9 [M + H]+. 207 off-white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 7.38-7.43 (2H, m), 7.25 (2H, d, J = 8.4 Hz), 7.05 (1H, t, J = 6.4 Hz), 6.96-7.02 (4H, m), 6.89 (1H, d, J = 8.4 Hz), 6.32 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 5.14 (2H, s), 4.54 (2H, brs), 4.01 (2H, q, J = 7.2 Hz), 4.05 (2H, d, J = 6.0 Hz), 1.19 (3H, t, J = 7.2 Hz); LCMS: 98.5%, MS (ESI); m/z 451.0 [M + H]+. 208 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.41 (2H, d, J = 8.4 Hz), 7.08 (3H, d, J = 8.8 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.64 (1H, t, J = 6.0 Hz), 6.35 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.80 (1H, d, J = 7.6 Hz), 5.22 (1H, s), 4.83 (2H, t, J = 6.4 Hz), 4.47-4.59 (3H, m), 4.32-4.44 (2H, m), 3.80 (2H, s), 1.18 (6H, s); LCMS: 100%, MS (ESI); m/z 494.0 [M + H]+. 209 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.36-7.46 (4H, m), 6.95-7.04 (4H, m), 6.88 (1H, d, J = 8.4 Hz), 6.55 (1H, t, J = 6.0 Hz), 6.45 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 5.23 (1H, brs), 4.45-4.50 (4H, m), 3.74 (2H, s), 1.18 (6H, s); LCMS: 100%, MS (ESI); m/z 437.0 [M + H]+. 210 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.04-7.13 (3H, m), 6.82-6.97 (2H, m), 6.37 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.0, 1.6 Hz), 4.42-4.65 (4H, m), 3.42 (3H, s); LCMS: 99.7%, MS (TOF, ESI); m/z 380.1267 [M + H]+. 211 off-white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.95 (1H, dd, J = 2.4 Hz), 7.33-7.51 (3H, m), 7.05-7.18 (3H, m), 6.99 (1H, d, J = 8.8 Hz), 6.21-6.37 (2H, m), 5.99 (1H, d, J = 2.0 Hz), 4.86 (2H, t, J = 6.4 Hz), 4.48-4.61 (3H, m), 4.41 (2H, t, J = 6.0 Hz), 3.49 (3H, s); LCMS: 99.2%, MS (ESI); m/z 436.0 [M + H]+. 212 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.54-10.91 (1H, m), 7.43 (1H, s), 7.23 (2H, d, J = 8.4 Hz), 6.95-7.19 (5H, m), 6.75-7.91 (3H, m), 6.37 (1H, s), 6.28 (1H, d, J = 7.6 Hz), 5.52 (1H, brs), 4.05-4.21 (4H, m), 2.93 (6H, s); LCMS: 99.0%, MS (ESI); m/z 432.9 [M + H]+. 213 pale-yellow powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 8.04 (1H, s), 7.25 (2H, d, J = 8.4 Hz), 7.06-7.18 (5H, m), 6.88-6.97 (3H, m), 6.42 (1H, d, J = 1.6 Hz), 6.38 (1H, d, J = 8.4 Hz), 5.78 (1H, brs, 5.01 (2H, s), 4.15 (2H, s), 3.01 (6H, s); LCMS: 97.6%, MS (ESI); m/z 457.0 [M + H]+. 214 white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.64- 10.86 (1H, m), 10.19 (1H, brs), 7.63 (2H, d, J = 9.2 Hz), 7.41 (1H, d, J = 10.4 Hz), 7.33 (2H, d, J = 8.8 Hz), 6.80-6.96 (1H, m), 6.45-6.55 (1H, m), 6.24-6.40 (1H, m), 5.15-5.43 (1H, m), 4.02 (2H, t, J = 5.2 Hz), 2.96 (3H, s), 2.93 (3H, s); LCMS: 100%, MS (ESI); m/z 382.9 [M + H]+. 215 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.31-10.49 (1H, m), 7.29-7.46 (4H, m), 6.88-7.06 (4H, m), 6.65-6.88 (2H, m), 6.41 (1H, d, J = 6.4 Hz), 6.15-6.29 (1H, m), 4.50-4.81 (3H, m), 4.34-4.50 (2H, m), 3.55-3.71 (1H, m), 3.04-3.18 (1H, m), 2.70-2.91 (1H, m); LCMS: 100%, MS (ESI); m/z 439.0 [M + H]+. 216 white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 11.86 (1H, brs), 10.60-10.82 (1H, m), 7.19-7.25 (2H, m), 7.02-7.18 (4H, m), 6.74-7.00 (5H, m), 6.35-6.38 (1H, m), 6.18-6.31 (1H, m), 5.39-5.65 (1H, m), 4.80 (2H, s), 4.10 (2H, s), 2.94 (3H, s), 2.92 (3H, s); LCMS: 99.1%, MS (ESI); m/z 456.0 [M + H]+. 217 white amorphous; 1H NMR DMSO-d6, 400 MHz); δ 7.41 (2H, d, J = 8.8 Hz), 7.33 (1H, brs), 7.25 (1H, d, J = 8.0 Hz), 6.94-7.06 (5H, m), 6.89 (1H, d, J = 8.0 Hz), 6.77 (1H, t, J = 6.0 Hz), 6.32 (1H, s), 6.27 (1H, d, J = 8.4 Hz), 5.13 (2H, s), 4.53 (2H, brs), 3.84 (2H, d, J = 5.6 Hz); LCMS: 99.4%, MS (ESI); m/z 422.0 [M + H]+. 218 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.92 (1H, s), 7.98 (2H, d, J = 8.4 Hz), 7.55 (2H, d, J = 8.4 Hz), 7.09 (1H, d, J = 8.4 Hz), 6.49-6.59 (2H, m), 6.46 (1H, d, J = 2.0 Hz), 4.38 (2H, d, J = 5.2 Hz), 4.31 (2H, q, J = 7.2 Hz), 3.12 (6H, s), 1.30 (3H, t, J = 7.2 Hz); LCMS: 98.7%, MS (ESI); m/z 406.0 [M + H]+. 219 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.36-7.44 (1H, m), 7.17 (1H, d, J = 8.4 Hz), 6.95-7.03 (4H, m), 6.90 (1H, d, J = 8.4 Hz), 6.42 (1H, q, J = 4.4 Hz), 6.31 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 5.07 (2H, s), 4.50 (2H, brs), 2.85 (3H, d, J = 4.4 Hz); LCMS: 97.7%, MS (ESI); m/z 378.9 [M + H]+. 220 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, s), 7.92 (2H, d, J = 8.4 Hz), 7.52 (2H, d, J = 8.4 Hz), 7.35 (1H, s), 6.91 (1H, d, J = 8.0 Hz), 6.37 (1H, J = 2.0 Hz), 6.34 (1H, J = 8.0, 2.0 Hz), 5.92 (1H, brs), 4.31 (2H, s), 2.97 (6H, s); LCMS: 100%, MS (ESI); m/z 333.9 [M + H]+. 221 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 11.56 (1H, brs), 10.68-10.79 (1H, m), 7.70 (2H, d, J = 6.8 Hz), 7.45-7.53 (3H, m), 6.82-6.89 (1H, m), 6.50-6.60 (1H, m), 6.26-6.35 (3H, m), 5.71-5.83 (1H, m), 4.25-4.35 (2H, m), 2.94 (3H, s), 2.93 (3H, s); LCMS: 98.9%, MS (ESI); m/z 359.9 [M + H]+. 222 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.21 (1H, d, J = 2.4 Hz), 7.65 (1H, dd, J = 8.8, 2.4 Hz), 7.30 (2H, d, J = 8.4 Hz), 7.08 (2H, dd, J = 6.8, 2.4 Hz), 7.00 (1H, d, J = 8.4 Hz), 6.89 (1H, d, J = 8.8 Hz), 6.56 (1H, s), 6.43 (1H, d, J = 7.2 Hz), 4.42 (2H, d, J = 5.2 Hz), 4.20- 4.30 (1H, m), 4.10-4.18 (2H, m), 3.95-4.05 (2H, m), 3.80-3.90 (1H, m), 3.55-3.65 (1H, m), 2.80-2.90 (1H, m), 2.65-2.75 (1H, m); LCMS: 98.1%, MS (ESI); m/z 515.0 [M + H]+. 223 pale-yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.54 (1H, d, J = 2.8 Hz), 7.88 (1H, d, J = 8.8 Hz), 7.45-7.52 (3H, m), 7.17 (2H, d, J = 8.8 Hz), 6.84-6.93 (2H, m), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.50-4.58 (4H, m); 3.41 (3H, s); LCMS: 100%, MS (ESI); m/z 414.0 [M + H]+. 224 pale-yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.32-8.37 (2H, m), 7.35-7.46 (4H, m), 7.03 (2H, J = 8.8 Hz), 6.83-6.88 (2H, m), 6.36 (1H, d, J = 2.8 Hz), 6.24-6.28 (1H, m), 4.53 (2H, brs), 4.50 (2H, d, J = 6.0 Hz), 3.40 (3H, s); LCMS: 100%, MS (ESI); m/z 345.9 [M + H]+. 225 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.68 (1H, brs), 7.35-7.48 (5H, m), 6.96-7.17 (6H, m), 5.49 (2H, brs), 4.29 (2H, d, J = 6.4 Hz); LCMS: 100%, MS (ESI); m/z 423.0 [M + H]+. 226 pale-yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.53 (1H, d, J = 2.8 Hz), 7.87 (1H, d, J = 8.8 Hz), 7.45-7.54 (3H, m), 7.16 (2H, d, J = 8.8 Hz), 6.91-6.99 (2H, m), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.4 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.80-4.88 (2H, m), 4.48- 4.56 (3H, m), 4.39 (2H, t, J = 6.8 Hz), 3.44 (3H, s); LCMS: 100%, MS (ESI); m/z 469.9 [M + H]+. 227 pale-yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.32-8.36 (2H, m), 7.35-7.46 (4H, m), 7.03 (2H, d, J = 8.8 Hz), 6.89-6.96 (2H, m), 6.18-6.26 (2H, m), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, d, J = 6.4 Hz), 4.48-4.55 (3H, m), 4.39 (2H, t, J = 5.6 Hz), 3.43 (3H, s); LCMS: 100%, MS (ESI); m/z 402.2 [M + H]+. 228 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.71 (1H, s), 7.94 (2H, d, J = 8.4 Hz), 7.54 (2H, d, J = 8.0 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.27-6.43 (2H, m), 4.32 (2H, s), 2.97 (6H, s); LCMS: 97.9%, MS (ESI); m/z 377.9 [M + H]+. 229 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.04-7.12 (3H, m), 6.91 (1H, d, J = 8.4 Hz), 6.44 (1H, brs), 6.33 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.0, 1.6 Hz), 5.10 (2H, s), 4.51 (2H, brs), 2.86 (3H, d, J = 4.4 Hz); LCMS: 100.0%, MS (ESI); m/z 379.9 [M + H]+. 230 pale yellow powder; 1H NMR (DSMO-d6 + D2O, 400 MHz); δ 8.72 (1H, s), 7.94-8.11 (2H, m), 7.03 (1H, d, J = 8.0 Hz), 6.47 (1H, s), 6.32 (1H, d, J = 7.6 Hz), 4.40-4.54 (1H, m), 3.44-3.45 (1H, m), 3.29-3.40 (1H, m), 3.14-3.29 (2H, m), 2.97 (6H, s), 2.04-2.21 (1H, m), 2.22-2.35 (1H, m); LCMS: 100%, MS (ESI); m/z 369.9 [M + H]+. 231 white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 7.36- 7.43 (1H, m), 7.25 (1H, d, J = 8.8 Hz), 6.94-7.04 (2H, m), 6.89 (1H, d, J = 8.4 Hz), 6.14-6.23 (4H, m), 5.78 (1H, d, J = 6.8 Hz), 5.13 (2H, s), 4.78 (2H, t, J = 6.4 Hz), 4.38-4.80 (1H, m), 4.29-4.37 (2H, t, J = 6.0 Hz); LCMS: 98.8%, MS (ESI); m/z 421.0 [M + H]+. 232 white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.60- 10.80 (1H, m), 7.40-7.50 (1H, m), 7.27 (2H, d, J = 8.0 Hz), 7.17 (2H, d, J = 7.2 Hz), 6.80-6.95 (2H, m), 6.15-6.45 (2H, m), 5.45-5.75 (1H, m), 4.17 (2H, s), 3.30 (2H, s), 2.93 (3H, s), 2.91 (3H, s); LCMS: 95.2%, MS (ESI); m/z 324.0 [M + H]+. 233 pale-yellow powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 10.60-10.80 (1H, m), 8.14 (1H, s), 7.28 (2H, d, J = 8.4 Hz), 7.24 (1H, s), 6.95 (2H, d, J = 6.8 Hz), 6.77-6.91 (1H, m), 6.17-6.40 (2H, m), 5.44-5.65 (1H, m), 5.17 (2H, s), 4.13 (2H, s), 2.94 (3H, s), 2.91 (3H, s); LCMS: 98.8%, MS (ESI); m/z 364.1 [M + H]+. 234 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.26 (2H, d, J = 8.8 Hz), 7.05-7.13 (3H, m), 6.91 (1H, d, J = 8.4 Hz), 6.13-6.25 (4H, m), 5.79 (1H, d, J = 7.2 Hz), 5.16 (2H, s), 4.79 (2H, t, J = 6.4 Hz), 4.40-4.50 (1H, m), 4.35 (2H, t, J = 6.0 Hz); LCMS: 97.8%, MS (ESI); m/z 421.9 [M + H]+. 235 off-white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.24 (2H, d, J = 8.4 Hz), 7.07-7.13 (3H, m), 7.03 (1H, d, J = 8.4 Hz), 6.45 (1H, d, J = 7.6 Hz), 6.33 (2H, brs), 6.23 (1H, dd, J = 8.4, 2.0 Hz), 5.22 (2H, s), 4.15 (4H, t, J = 12.0 Hz); LCMS: 100.0%, MS (ESI); m/z 442.1 [M + H]+. 236 pale-yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.86 (1H, brs), 7.84 (1H, d, J = 2.0 Hz), 7.76 (1H, d, J = 8.8 Hz), 7.43 (1H, dd, J = 8.4, 2.0 Hz), 6.99 (1H, d, J = 8.4 Hz), 6.46 (1H, s), 6.27 (1H, d, J = 6.4 Hz), 3.85-4.00 (1H, m), 3.63-3.72 (2H, m), 3.35-3.43 (2H, m), 2.98 (3H, s), 2.33-2.45 (2H, m); LCMS: 99.0%, MS (ESI); m/z 382.0 [M + H]+. 237 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.72 (1H, brs), 7.25-7.40 (4H, m), 7.15 (1H, d, J = 6.8 Hz), 6.95 (1H, s), 6.87 (1H, d, J = 7.6 Hz), 6.37 (1H, s), 6.29 (1H, s), 5.63 (1H, brs), 4.19 (2H, d, J = 6.0 Hz), 3.68-3.79 (2H, m), 3.44-3.53 (2H, m), 2.94 (6H, s), 2.36-2.45 (2H, m), 1.71-1.83 (2H, m); LCMS: 97.1%, MS (ESI); m/z 394.1 [M + H]+. 238 white powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, s), 7.45-7.54 (2H, m), 7.23 (2H, d, J = 8.4 Hz), 7.08 (2H, d, J = 8.8 Hz), 6.31 (1H, s), 6.26 (1H, dd, J = 2.0, 8.0 Hz), 6.10 (2H, s), 5.11 (2H, s), 4.48 (2H, s); LCMS: 99.8%, MS (ESI); m/z 365.9 [M + H]+. 239 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.37 (1H, d, J = 2.8 Hz), δ 7.43-7.47 (3H, m), 7.00-7.07 (2H, m), 7.01 (1H, d, J = 8.8 Hz), 6.84 (1H, d, J = 8.0 Hz), 6.25-6.28 (2H, m), 6.09 (2H, brs), 5.18 (2H, s), 4.49 (2H, brs); LCMS: 100%, MS (ESI); m/z 366.0 [M + H]+. 240 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.08 (1H, s), 7.64 (1H, d, J = 8.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.04 (1H, d, J = 8.8 Hz), 6.82 (1H, d, J = 8.0 Hz), 6.37 (1H, s), 6.26 (1H, d, J = 8.4 Hz), 6.17 (2H, brs), 5.10 (2H, s), 4.49 (2H, brs); LCMS: 100%, MS (ESI); m/z 366.0 [M + H]+. 241 pale-yellow powder (amorphous) 1H NMR (DMSO-d6, 400 MHz); δ 7.41-7.52 (4H, m), 6.88 (2H, d, J = 8.4 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.31 (1H, d, J = 8.4 Hz), 5.75 (1H, brs), 4.25 (2H, d, J = 4.4 Hz), 3.94- 4.06 (2H, m), 3.60-3.71 (2H, m), 2.95 (6H, s), 1.96-2.13 (4H, m); LCMS: 97.5%, MS (ESI); m/z 376.1 [M + H]+. 242 pale white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.35-7.49 (4H, m), 7.13 (1H, d, J = 6.4 Hz), 6.95-7.09 (4H, m), 6.46 (1H, s), 6.32 (1H, d, J = 8.4 Hz), 4.53 (2H, d, J = 5.6 Hz), 4.22 (4H, t, J = 12.0 Hz); LCMS: 100%, MS (ESI); m/z 440.9 [M + H]+. 243 white powder; 1H NMR (DMSO-d6); δ 8.54 (1H, s), 8.21 (1H, dd, J = 8.8, 2.0 Hz), 7.19-7.28 (3H, m), 7.15 (2H, d, J = 8.4 Hz), 6.84 (1H, d, J = 8.4 Hz), 6.34 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 6.15 (2H, brs), 5.14 (2H, s), 4.50 (2H, brs); LCMS: 97.7%, MS (ESI); m/z 400.0 [M + H]+. 244 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 9.10 (2H, brs), 8.19 (1H, d, J = 2.4 Hz), 7.95 (1H, dd, J = 8.4, 2.4 Hz), 7.65 (1H, s), 7.48 (1H, d, J = 8.4 Hz), 7.39 (2H, d, J = 8.4 Hz), 7.29 (1H, d, J = 8.0 Hz), 7.06 (2H, d, J = 8.4 Hz), 7.00 (1H, d, J = 8.8 Hz), 4.42 (2H, t, J = 7.4 Hz), 3.01 (2H, t, J = 7.4 Hz); LCMS: 100%, MS (ESI); m/z 379.9 [M + H]+. 245 white powder; 1H NMR (DSMO-d6, 400 MHz); δ 7.36 (2H, d, J = 8.8 Hz), 7.23 (2H, d, J = 8.8 Hz), 6.98-7.11 (4H, m), 6.84 (1H, d, J = 8.0 Hz), 6.23 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 6.12 (2H, brs), 5.11 (2H, s), 4.49 (2H, brs); LCMS: 100%, MS (ESI); m/z 415.0 [M + H]+ 246 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.57-7.65 (1H, m), 7.42-7.54 (3H, m), 7.22-7.33 (4H, m), 6.86 (1H, d, J = 8.0 Hz), 6.33 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.0, 1.6 Hz), 6.18 (2H, brs), 5.18 (2H, s), 4.50 (2H, brs); LCMS: 99.7%, MS (ESI); m/z 372.0 [M + H]+. 247 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), δ 7.95 (1H, dd, J = 8.8, 2.8 Hz), 7.27 (2H, d, J = 8.8 Hz), 7.08-7.14 (3H, m), 6.82 (1H, d, J = 8.0 Hz), 6.19-6.24 (2H, m), 6.02 (2H, brs), 5.64 (1H, q, J = 7.2 Hz), 4.39 (2H, brs), 1.83 (3H, d, J = 7.2 Hz); LCMS: 99.8%, MS (ESI); m/z 380.0 [M + H]+. 248 purple powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.15 (1H, d, J = 2.4 Hz), δ 7.97 (1H, dd, J = 8.8, 2.4 Hz), 7.31 (1H, t, J = 8.4 Hz), 7.20 (1H, d, J = 8.8 Hz), 7.14 (1H, d, J = 11.2 Hz), 7.01 (1H, d, J = 8.0 Hz), 6.87 (1H, d, J = 8.4 Hz), 6.43 (2H, brs), 6.38 (1H, s), 6.30 (1H, d, J = 7.2 Hz), 5.18 (2H, s); LCMS: 95.5%, MS (ESI); m/z 383.9 [M + H]+. 249 off-white amorphous; 1H NMR (DMSO-d6, 400 Mhz); δ 8.20 (1H, d, J = 2.4 Hz), 7.80 (1H, dd, J = 8.8, 2.8 Hz), 7.38 (2H, d, J = 8.0 Hz), 7.14 (2H, d, J = 8.0 Hz), 6.91 (1H, d, J = 8.8 Hz), 6.79-6.85 (1H, m), 6.24 (2H, dd, J = 4.4, 2.0 Hz), 6.08 (2H, brs), 5.27 (2H, s), 5.11 (2H, s), 4.45 (2H, brs); LCMS: 100%, MS (ESI); m/z 379.9 [M + H]+. 250 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.19 (2H, d, J = 8.8 Hz), 7.04-7.13 (3H, m), 6.89 (1H, d, J = 8.0 Hz), 6.58 (1H, t, J = 5.6 Hz), 6.32 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 5.13 (2H, s), 5.05 (1H, brs), 4.52 (2H, brs), 3.53-3.64 (2H, m), 3.36-3.43 (2H, m); LCMS: 100%, MS (ESI); m/z 410.0 [M + H]+. 251 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.15 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.23 (2H, d, J = 8.4 Hz), 7.03-7.15 (3H, m), 6.96 (1H, d, J = 8.4 Hz), 6.64 (1H, t, J = 5.6 Hz), 6.21 (1H, s), 6.17 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J = 6.8 Hz), 5.16 (2H, s), 4.99 (1H, t, J = 5.2 Hz), 4.78 (2H, t, J = 6.0 Hz), 4.38-4.50 (1H, m), 4.33 (2H, d, J = 6.0 Hz), 3.54-3.63 (2H, m), 3.36-3.44 (2H, m); LCMS: 99.4%, MS (ESI); m/z 466.0 [M + H]+. 252 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.36-7.43 (2H, m), 7.22 (1H, d, J = 8.8 Hz), 6.95-7.02 (5H, m), 6.93 (1H, d, J = 8.4 Hz), 6.33 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.0, 2.0 Hz), 5.11 (2H, s), 4.55 (2H, brs), 3.54 (2H, q, J = 6.0 Hz), 2.88 (2H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI); m/z 418.0 [M + H]+. 253 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.4, 2.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 6.93- 7.16 (5H, m), 6.60 (1H, d, J = 1.6 Hz), 6.46-6.49 (1H, m), 4.54 (2H, d, J = 5.6 Hz), 3.49 (3H, s), 2.83 (6H, s); LCMS: 99.9%, MS (ESI); m/z 407.9 [M + H]+. 254 white amorphous; 1H NMR (DMSO-d6); δ 8.61 (1H, d, J = 2.4 Hz), 7.95 (1H, dd, J = 8.4, 2.4 Hz), 7.52 (1H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.97 (2H, d, J = 8.4 Hz), 6.82 (1H, d, J = 8.0 Hz), 6.29 (1H, d, J = 1.6 Hz), 6.24 (1H, dd, J = 8.0, 2.0 Hz), 6.08 (2H, brs), 5.14 (2H, s), 5.03 (2H, s), 4.45 (2H, s); LCMS: 100%, MS (ESI); m/z 379.9 [M + H]+. 255 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.14 (1H, d, J = 2.4 Hz), 7.97 (1H, dd, J = 8.4, 2.4 Hz), 7.26-7.37 (2H, m), 7.10-7.22 (2H, m), 6.85 (1H, d, J = 8.4 Hz), 6.35 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 1.6 Hz), 6.18 (2H, brs), 5.15 (2H, s), 4.53 (2H, brs); LCMS: 100%, MS (ESI); m/z 399.9 [M + H]+. 256 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.0 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.02- 7.10 (3H, m), 6.90 (1H, d, J = 8.4 Hz), 6.70 (1H, d, J = 8.0 Hz), 6.23 (1H, d, J = 2.0 Hz), 6.19 (1H, dd, J = 8.4, 2.0 Hz), 5.83 (1H, d, J = 7.2 Hz), 5.00-5.12 (1H, m), 4.83 (2H, t, J = 6.4 Hz), 4.45-4.55 (1H, m), 4.35-4.40 (2H, m), 3.46 (3H, s), 1.50 (3H, d, J = 6.8 Hz); LCMS: 99.6%, MS (ESI); m/z 450.1 [M + H]+. 257 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.41 (2H, d, J = 8.4 Hz), 6.90-7.00 (3H, m), 6.93 (1H, d, J = 8.4 Hz), 6.79 (1H, t, J = 6.0 Hz), 6.31 (1H, d, J = 1.6 Hz), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.82 (1H, d, J = 7.2 Hz), 5.03 (1H, brs), 4.83 (2H, t, J = 6.4 Hz), 4.45-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.98 (2H, t, J = 5.2 Hz), 3.59-3.70 (2H, m); LCMS: 100%, MS (ESI); m/z 466.1 [M + H]+. 258 off-white solid; 1H NMR (CDCl3, 400 MHz); δ 8.11 (1H, d, J = 2.4 Hz), 7.66 (1H, dd, J = 8.8, J = 2.8 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.31 (1H, d, J = 8.4 Hz), 7.11 (2H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.8 Hz), 6.66 (1H, d, J = 2.0 Hz), 6.54 (1H, dd, J = 8.4 Hz, J = 2.0 Hz), 4.67 (2H, d, J = 4.8 Hz), 4.29-4.38 (1H, m), 4.24 (1H, brs), 3.55 (2H, brs), 1.56 (6H, d, J = 6.8 Hz); LCMS: 99.6%, MS (ESI); m/z 408.1 [M + H]+. 259 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.05-7.10 (3H, m), 6.87 (1H, d, J = 8.0 Hz), 6.75 (1H, t, J = 5.2 Hz), 6.41 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 1.6 Hz), 5.06 (1H, t, J = 4.8 Hz), 4.57 (2H, brs), 4.50 (2H, d, J = 6.0 Hz), 3.95 (2H, t, J = 5.2 Hz), 3.64 (2H, q, J = 5.2 Hz); LCMS: 99.3%, MS (ESI); m/z 410.0 [M + H]+. 260 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.05- 7.10 (3H, m), 6.83 (1H, d, J = 8.4 Hz), 6.65 (1H, d, J = 8.0 Hz), 6.35 (1H, d, J = 1.6 Hz), 6.25 (1H, dd, J = 8.4, 2.0 Hz), 5.00-5.09 (1H, m), 4.55 (2H, brs), 3.44 (3H, s), 1.51 (3H, d, J = 7.2 Hz); LCMS: 98.2%, MS (ESI); m/z 394.0 [M + H]+. 261 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.04- 7.14 (3H, m), 7.01 (1H, d, J = 1.2 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.76 (1H, t, J = 5.6 Hz), 6.35 (1H, dd, J = 8.8, 2.4 Hz), 5.53-5.65 (1H, m), 5.04-5.17 (2H, m), 4.90-5.03 (2H, m), 4.71 (2H, brs), 4.45 (2H, d, J = 5.6 Hz); LCMS: 98.3%, MS (ESI); m/z 422.1 [M + H]+. 262 white powder; 1H NMR (DSMO-d6, 400 MHz); δ 7.39 (2H, d, J = 8.8 Hz), 7.27 (2H, d, J = 8.8 Hz), 7.07 (1H, t, J = 5.6 Hz), 6.94-7.02 (5H, m), 6.17-6.24 (2H, m), 5.87 (1H, d, J = 6.8 Hz), 5.14 (2H, s), 4.78 (2H, t, J = 6.4 Hz), 4.39-4.48 (1H, m), 4.34 (2H, t, J = 6.0 Hz), 3.55 (2H, q, J = 6.0 Hz), 2.88 (2H, t, J = 6.4 Hz); LCMS: 98.6%, MS (ESI); m/z 474.2 [M + H]+. 263 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.8 Hz), 7.05- 7.11 (3H, m), 6.86 (1H, d, J = 8.0 Hz), 6.78 (1H, t, J = 5.6 Hz), 6.41 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.49-4.51 (4H, m), 4.06 (2H, t, J = 5.6 Hz), 3.57 (2H, t, J = 4.8 Hz), 3.24 (3H, s); LCMS: 98.5%, MS (ESI); m/z 424.1 [M + H]+. 264 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.44 (2H, m), 7.18 (2H, d, J = 8.8 Hz), 6.95-7.03 (4H, m), 6.93 (1H, d, J = 8.4 Hz), 6.75 (1H, t, J = 5.6 Hz), 6.31 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 5.08 (2H, s), 4.5 (2H, brs), 3.53 (2H, q, J = 6.4 Hz), 2.59- 2.70 (2H, m); LCMS: 100%, MS (ESI); m/z 461.0 [M + H]+. 265 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.41 (2H, d, J = 8.8 Hz), 7.05- 7.10 (3H, m), 6.92 (1H, t, J = 6.0 Hz), 6.85 (1H, d, J= 8.4 Hz), 6.39 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.43-4.60 (4H, m), 3.93 (2H, q, J = 7.2 Hz), 1.20 (3H, t, J = 7.2 Hz); LCMS: 99.2%, MS (ESI); m/z 394.1 [M + H]+. 266 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.01- 7.16 (4H, m), 6.84-6.97 (2H, m), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 6.05 (1H, d, J = 6.0 Hz), 5.51-5.68 (1H, m), 5.04-5.12 (2H, m), 4.96-5.04 (2H, m), 4.82 (2H, t, J = 6.0 Hz), 4.39-4.54 (5H, m); LCMS: 98.8%, MS (ESI); m/z 478.1 [M + H]+. 267 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.97 (1H, dd, J = 8.8, 2.4 Hz), 7.36 (1H, d, J = 11.2 Hz), 7.24- 7.30 (2H, m), 7.20 (1H, d, J = 8.8 Hz), 6.97 (1H, t, J = 6.0 Hz), 6.87 (1H, d, J = 8.4 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.56 (2H, brs), 4.52 (2H, d, J = 5.6 Hz), 3.42 (3H, s); LCMS: 100%, MS (ESI); m/z 398.0 [M + H]+. 268 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.98 (1H, dd, J = 8.8, 2.8 Hz), 7.36 (1H, d, J = 11.2 Hz), 7.23-7.31 (2H, m), 7.20 (1H, d, J = 8.8 Hz), 7.04 (1H, t, J = 6.0 Hz), 6.95 (1H, d, J = 8.0 Hz), 6.27 (1H, d, J = 2.0 Hz), 6.23 (1H, dd, J = 8.0, 2.0 Hz), 5.87 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.46- 4.60 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 454.1 [M + H]+. 269 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.41 (2H, d, J = 8.0 Hz), 7.05-7.10 (3H, m), 6.93 (1H, d, J = 8.4 Hz) 6.84 (1H, t, J = 5.6 Hz), 6.31 (1H, s), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 4.10 (2H, t, J = 5.2 Hz), 3.58 (2H, t, J = 5.2 Hz), 3.25 (3H, s); LCMS: 100%, MS (ESI); m/z 480.2 [M + H]+. 270 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.40 (2H, d, J = 8.8 Hz), 7.05- 7.10 (3H, m), 6.99 (1H, t, J = 6.0 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.28 (1H, d, J = 2.0 Hz), 6.19 (1H, dd, J = 8.4, 2.0 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.47-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.97 (2H, q, J = 6.8 Hz), 1.20 (2H, d, J = 7.2 Hz); LCMS: 100%, MS (ESI); m/z 450.0 [M + H]+. 271 brown powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.40 (2H, d, J = 8.4 Hz), 7.05- 7.10 (3H, m), 6.94 (1H, d, J = 8.4 Hz), 6.84 (1H, t, J = 5.6 Hz), 6.47 (1H, d, J = 1.6 Hz), 6.16 (1H, dd, J = 8.4, 2.0 Hz), 5.80 (1H, d, J = 7.2 Hz), 4.83 (2H, t, J = 6.8 Hz), 4.56-4.65 (1H, m), 4.45-4.55 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 1.47 (2H, d, J = 6.8 Hz); LCMS: 98.8%, MS (ESI); m/z 464.1 [M + H]+. 272 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, d, J = 2.4 Hz), 7.97 (1H, dd, J = 8.8, 2.8 Hz), 7.48 (1H, t, J = 8.8 Hz), 7.13 (1H, d, J = 9.2 Hz), 7.10 (1H, dd, J = 11.2, 2.4 Hz), 6.95 (1H, dd, J = 8.4, 2.4 Hz), 6.83-6.92 (2H, m), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.4 Hz), 4.56 (2H, brs), 4.53 (2H, d, J = 6.0 Hz), 3.42 (3H, s); LCMS: 99.6%, MS (ESI); m/z 398.0 [M + H]+. 273 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, d, J = 2.4 Hz), 7.96 (1H, dd, J = 8.8, 2.4 Hz), 7.48 (1H, t, J = 8.4 Hz), 7.05-7.18 (2H, m), 6.89-7.02 (3H, m), 6.16-6.33 (2H, m), 5.87 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.46-4.62 (3H, m), 4.34-4.45 (2H, m), 3.46 (3H, s); LCMS: 98.6%, MS (ESI); m/z 454.1 [M + H]+. 274 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.01-7.12 (3H, m), 6.81 (1H, d, J = 8.4 Hz), 6.61 (1H, d, J = 2.4 Hz), 6.33 (1H, d, J = 1.6 Hz), 6.23 (1H, dd, J = 8.0, 2.0 Hz), 4.75-4.86 (1H, m), 4.52 (1H, brs), 3.44 (3H, s), 1.84-1.95 (1H, m), 1.70-1.83 (1H, m), 0.93 (3H, t, J = 7.2 Hz); LCMS: 97.2%, MS (ESI); m/z 408.0 [M + H]+. 275 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.02-7.12 (3H, m), 7.07 (1H, d, J = 8.4 Hz), 6.89 (1H, t, J = 8.4 Hz), 6.22 (1H, d, J = 2.0 Hz), 6.18 (1H, dd, J = 8.4, 2.0 Hz), 5.82 (1H, d, J = 7.2 Hz), 4.76-4.88 (3H, m), 4.45-4.51 (1H, m), 4.35-4.44 (2H, m), 3.48 (3H, s), 1.85-1.96 (1H, m), 1.73-1.84 (1H, m), 0.94 (3H, t, J = 7.2 Hz); LCMS: 95.9%, MS (ESI); m/z 464.2 [M + H]+. 276 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.55 (1H, s), 8.22 (1H, dd, J = 8.8, 2.4 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.23 (1H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.93 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.34 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, brs), 4.52 (2H, d, J = 6.0 Hz), 3.42 (3H, s); LCMS: 100%, MS (ESI); m/z 414.1 [M + H]+. 277 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.8 Hz), 7.05-7.13 (4H, m), 7.02 (1H, d, J = 8.4 Hz), 6.59 (1H, d, J = 2.0 Hz), 6.40 (1H, dd, J = 8.4, 2.0 Hz), 4.69-4.75 (2H, m), 4.54 (2H, d, J = 6.0 Hz), 4.43- 4.49 (2H, m), 4.34-4.41 (1H, m), 3.49 (3H, s), 2.70 (3H, s); LCMS: 98.7%, MS (ESI); m/z 450.0 [M + H]+. 278 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.0 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.43 (2H, d, J = 8.8 Hz), 7.13 (1H, t, J = 6.0 Hz), 7.05-7.10 (3H, m), 7.03 (1H, d, J = 8.4 Hz), 6.61 (1H, d, J = 2.0 Hz), 6.44 (1H, dd, J = 8.0, 2.0 Hz), 4.68 (2H, t, J = 6.4 Hz), 4.55 (2H, d, J = 6.0 Hz), 4.44-4.52 (1H, m), 4.36 (2H, t, J = 6.4 Hz), 3.49 (3H, s), 3.12 (2H, q, J = 6.8 Hz) 0.83 (3H, t, J = 7.2 Hz); LCMS: 99.8%, MS (ESI); m/z 464.1 [M + H]+. 279 white powder; mp = 155.5-159.8° C.; 1H NMR (DMSO-d6, 400 MHz); δ 7.37-7.43 (2H, m), 7.23 (2H, d, J = 8.4 Hz), 6.95-7.03 (5H, m), 6.80- 6.84 (1H, m), 6.16-6.23 (2H, m), 5.86 (1H, d, J = 6.8 Hz), 5.11 (2H, s), 4.78 (2H, t, J = 6.4 Hz), 4.41-4.48 (1H, m), 4.33 (2H, d, J = 6.0 Hz), 3.54 (2H, q, J = 6.8 Hz), 2.60-2.71 (2H, m); LCMS: 98.9%, MS (ESI); m/z 417.0 [M + H]+. 280 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.8 Hz), 7.41-7.52 (4H, m), 7.07 (2H, d, J = 8.8 Hz), 6.75-6.85 (2H, m), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, brs), 4.51 (1H, d, J = 5.6 Hz), 3.41 (3H, s); LCMS: 98.7%, MS (ESI); m/z 380.0 [M + H]+. 281 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.4 Hz), 7.41-7.56 (4H, m), 7.07 (2H, d, J = 8.4 Hz), 6.90-6.95 (2H, m), 6.25 (1H, s), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.46-4.57 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 98.1%, MS (ESI); m/z 436.1 [M + H]+. 282 brown powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.14 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.31 (1H, s), 7.25 (1H, d, J = 8.4 Hz), 7.07 (1H, d, J = 8.8 Hz), 7.00 (1H, d, J = 8.0 Hz), 6.83-6.90 (2H, m), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.54 (2H, brs), 4.48 (2H, d, J = 5.6 Hz), 3.41 (3H, s), 2.04 (3H, s); LCMS: 100%, MS (ESI); m/z 394.0 [M + H]+. 283 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.14 (1H, d, J = 2.8 Hz), 7.92 (1H, dd, J = 8.8, 2.8 Hz), 7.30 (1H, s), 7.25 (1H, d, J = 8.0 Hz), 7.07 (1H, d, J = 8.8 Hz), 7.00 (1H, d, J = 8.0 Hz), 6.89-6.96 (2H, m), 6.25 (1H, d, J = 1.6 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.46-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.45 (3H, s), 2.03 (3H, s); LCMS: 99.8%, MS (ESI); m/z 450.1 [M + H]+. 284 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.54 (1H, s), 8.21 (1H, dd, J = 8.8, 2.4 Hz), 7.45 (2H, d, J = 8.0 Hz), 7.22 (1H, d, J = 8.4 Hz), 7.13 (2H, d, J = 8.4 Hz), 6.98 (1H, t, J = 5.6 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.25 (1H, s), 6.21 (1H, dd, J = 8.0, 2.0 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.79-4.88 (2H, m), 4.45-4.57 (3H, m), 4.35-4.44 (2H, m), 3.45 (3H, s); LCMS: 99.6%, MS (ESI); m/z 470.0 [M + H]+. 285 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, d, J = 2.4 Hz), 7.97 (1H, dd, J = 8.8, 2.8 Hz), 7.46 (1H, d, J = 8.8 Hz), 7.33 (1H, d, J = 2.4 Hz), 7.14 (1H, d, J = 8.8 Hz), 7.10 (1H, dd, J = 8.8, 2.4 Hz), 6.97 (1H, t, J = 6.0 Hz), 6.85 (1H, d, J = 8.4 Hz), 6.38 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.51-4.61 (4H, m), 3.45 (3H, s); LCMS: 100%, MS (ESI); m/z 414.0 [M + H]+. 286 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.0 Hz), 7.13 (1H, t, J = 5.6 Hz), 7.06-7.10 (3H, m), 6.86 (1H, d, J = 8.4 Hz), 6.39 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, brs), 4.50 (2H, d, J = 5.6 Hz), 3.95 (2H, t, J = 6.8 Hz), 2.47-2.49 (2H, m), 2.20 (6H, s); LCMS: 100%, MS (ESI); m/z 437.0 [M + H]+. 287 white amorphous; 1H NMR (CDCl3, 400 MHz); δ 8.20 (1H, s), 7.83 (1H, dd, J = 8.4, 2.0 Hz), 7.35 (2H, d, J = 8.8 Hz), 7.26-7.29 (1H, m), 7.07 (2H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.54 (1H, dd, J = 8.0, 2.0 Hz), 6.45 (1H, d, J = 1.6 Hz), 4.65 (2H, d, J = 5.6 Hz), 4.21 (1H, t, J = 5.2 Hz), 3.58 (2H, brs), 3.41 (3H, s); LCMS: 100%, MS (ESI); m/z 380.0 [M + H]+. 288 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.44 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.92 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.58 (2H, brs), 4.51 (2H, d, J = 5.6 Hz), 3.41 (3H, s); LCMS: 99.7%, MS (ESI); m/z 381.0 [M + H]+. 289 pale yellow powder; 1H NMR (DSMO-d6, 400 MHz); δ 8.73 (2H, s), 8.32 (1H, s), 7.44 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.89- 7.01 (2H, m), 6.25 (1H, s), 6.21 (1H, dd, J = 2.4, 8.4 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.57 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 100%, MS (ESI); m/z 437.1 [M + H]+. 290 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.35 (1H, d, J = 8.4 Hz), 7.06 (1H, d, J = 8.8 Hz), 6.96 (1H, s), 6.91 (1H, d, J = 8.0 Hz), 6.86 (1H, d, J = 8.4 Hz), 6.73 (1H, t, J = 5.6 Hz), 6.37 (1H, s), 6.26 (1H, dd, J = 8.0, 1.2 Hz), 4.64 (2H, brs), 4.46 (2H, d, J = 5.2 Hz), 3.42 (3H, s), 2.34 (3H, s); LCMS: 98.8%, MS (ESI); m/z 394.1 [M + H]+. 291 off-white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.92 (1H, dd, J = 8.8, 2.4 Hz), 7.34 (1H, d, J = 8.4 Hz), 7.05 (1H, d, J = 8.8 Hz), 6.85-7.00 (3H, m), 6.81 (1H, t, J = 5.6 Hz), 6.26 (1H, d, J = 1.2 Hz), 6.22 (1H, d, J = 8.4 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.0 Hz), 4.44-4.56 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s), 2.34 (3H, s); LCMS: 99.6%, MS (ESI); m/z 450.0 [M + H]+. 292 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.44 (2H, d, J = 8.4 Hz), 7.37 (2H, d, J = 8.4 Hz), 7.01-7.12 (4H, m), 6.82-6.93 (2H, m), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, s), 4.50 (2H, d, J = 6.0 Hz), 3.41 (3H, s); LCMS: 98.5%, MS (ESI); m/z 429.1 [M + H]+. 293 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.44 (2H, d, J = 8.4 Hz), 7.37 (2H, d, J = 8.4 Hz), 6.98-7.10 (4H, m), 6.89-6.98 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.45-4.37 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 97.4%, MS (ESI); m/z 485.2 [M + H]+. 294 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.8 Hz), 7.96 (1H, dd, J = 8.8, 2.8 Hz), 7.45 (1H, d, J = 8.4 Hz), 7.32 (1H, d, J = 2.4 Hz), 7.13 (1H, d, J = 8.8 Hz), 7.09 (1H, dd, J = 8.4, 2.4 Hz), 7.01 (1H, t, J = 5.6 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.27 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.86 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.57 (2H, d, J = 5.6 Hz), 4.45-4.55 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.49 (3H, s); LCMS: 99.4%, MS (ESI); m/z 470.1 [M + H]+. 295 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.41 (1H, d, J = 1.2 Hz), 8.32 (1H, s), 7.45 (2H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.4 Hz), 6.90 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.54 (2H, brs), 4.51 (2H, d, J = 6.0 Hz), 3.41 (3H, s); LCMS: 98.7%, MS (ESI); m/z 381.0 [M + H]+. 296 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.41 (1H, s), 8.32 (1H, s), 7.44 (2H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.4 Hz), 6.89- 7.02 (2H, m), 6.24 (1H, s), 6.21 (1H, d, J = 8.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.58 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 97.5%, MS (ESI); m/z 437.0 [M + H]+. 297 white poder; 1H NMR (DMSO-d6, 400 MHz); δ 8.35 (1H, s), 7.43- 7.46 (4H, m), 7.01-7.07 (3H, m), 6.84 (1H, d, J = 8.0 Hz), 6.37 (1H, s), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.59 (2H, d, J = 6.0 Hz), 4.56 (2H, brs), 3.44 (3H, s); LCMS: 99.5%, MS (ESI); m/z 380.0 [M + H]+. 298 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.34 (1H, s), 7.41- 7.45 (4H, m), 7.03-7.07 (3H, m), 6.92 (1H, d, J = 8.8 Hz), 6.25 (1H, s), 6.21 (1H, d, J = 8.4 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.59 (2H, d, J = 5.6 Hz), 4.48-4.51 (1H, m), 4.39 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 436.0 [M + H]+. 299 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.39 (1H, d, J = 2.4 Hz), 8.18 (1H, d, J = 2.8 Hz), 7.98 (1H, dd, J = 8.8, 2.8 Hz), 7.58 (1H, dd, J = 8.8, 2.8 Hz), 7.46 (1H, d, J = 8.8 Hz), 7.20 (1H, d, J = 8.8 Hz), 7.04 (1H, t, J = 6.0 Hz), 6.85 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.60 (2H, d, J = 6.0 Hz), 4.55 (2H, brs), 3.45 (3H, s); LCMS: 99.3%, MS (ESI); m/z 381.0 [M + H]+. 300 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.39 (1H, d, J = 2.4 Hz), 8.17 (1H, d, J = 2.4 Hz), 7.98 (1H, dd, J = 8.8, 2.8 Hz), 7.58 (1H, dd, J = 8.4, 2.8 Hz), 7.45 (1H, d, J = 8.4 Hz), 7.19 (1H, d, J = 8.8 Hz), 7.09 (1H, t, J = 5.6 Hz), 6.92 (1H, d, J = 8.0 Hz), 6.26 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.84 (1H, t, J = 6.0 Hz), 4.61 (1H, d, J = 6.0 Hz), 4.45-4.57 (1H, m), 4.39 (1H, t, J = 6.0 Hz), 3.48 (3H, s); LCMS: 99.0%, MS (ESI); m/z 437.0 [M + H]+. 301 pale yellow solid; mp = 121.4-124.6° C.; 1H NMR (DMSO-d6, 400 MHz); δ 8.12 (1H, d, J = 3.2 Hz), 7.74-7.85 (1H, m), 7.42 (2H, d, J = 8.4 Hz), 7.02-7.12 (3H, m), 6.82-6.92 (2H, m), 6.36 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.54 (2H, brs), 4.50 (2H, d, J = 5.6 Hz), 3.41 (3H, s); LCMS: 98.8%, MS (ESI); m/z 364.0 [M + H]+. 302 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.11 (1H, d, J = 3.2 Hz), 7.76-7.85 (1H, m), 7.41 (2H, d, J = 8.4 Hz), 7.01-7.12 (3H, m), 6.90-6.97 (2H, m), 6.24 (1H, s), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.45-4.57 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 98.4%, MS (ESI); m/z 420.1 [M + H]+. 303 white power; 1H NMR (DSMO-d6, 400 MHz); δ 10.92 (1H, brs), 8.42 (1H, d, J = 2.4 Hz), 8.22 (1H, d, J = 8.8 Hz), 7.92-7.98 (3H, m), 7.48 (2H, d, J = 8.4 Hz), 7.04 (1H, t, J = 6.0 Hz), 6.91 (1H, d, J = 8.0 Hz), 6.25 (1H, s), 6.20 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.58 (2H, d, J = 6.0 Hz), 4.45-4.55 (1H, m), 4.39 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 463.2 [M + H]+. 304 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.21 (1H, d, J = 2.4 Hz), 7.80 (1H, dd, J = 8.8, 2.4 Hz), 7.33-7.42 (4H, m), 6.91 (1H, d, J = 8.4 Hz), 6.81-6.89 (2H, m), 6.36 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 5.29 (2H, s), 4.54 (2H, brs), 4.50 (2H, d, J = 6.0 Hz), 3.40 (3H, s); LCMS: 98.1%, MS (ESI); m/z 394.1 [M + H]+. 305 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.21 (1H, d, J = 2.4 Hz), 7.80 (1H, dd, J = 8.8, 2.8 Hz), 7.31-7.42 (4H, m), 6.97-6.85 (3H, m), 6.24 (1H, d, J = 2.0 Hz), 6.20 (1H, dd, J = 8.0, 2.0 Hz), 5.83 (1H, d, J = 6.8 Hz), 5.29 (2H, s), 4.84 (2H, t, J = 6.4 Hz), 4.44-4.58 (3H, m), 4.33-4.43 (2H, m), 3.43 (3H, s); LCMS: 99.1%, MS (ESI); m/z 450.0 [M + H]+. 306 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.21- 7.23 (1H, m), 7.05-7.09 (3H, m), 6.96-7.02 (2H, m), 6.93 (1H, d, J = 8.4 Hz), 6.33 (1H, d, J = 1.6 Hz), 6.29 (1H, dd, J = 8.4, 2.0 Hz), 5.14 (1H, brs), 4.52 (2H, d, J = 6.0 Hz), 3.40 (3H, s), 1.33 (6H, s); LCMS: 99.1%, MS (ESI); m/z 465.1 [M + H]+. 307 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.16 (1H, d, J = 2.4 Hz), 7.90 (1H, dd, J = 8.0, 2.4 Hz), 7.40-7.46 (2H, m), 7.09-7.16 (2H, m), 7.02 (1H, d, J = 8.0 Hz), 6.89-6.96 (2H, m), 6.24 (1H, d, J = 2.4 Hz), 6.21 (1H, dd, J = 8.4, 2.4 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.82- 4.86 (2H, m), 4.43-4.55 (3H, m), 4.38 (2H, t, J = 6.0 Hz), 3.41 (3H, s); LCMS: 99.0%, MS (ESI); m/z 436.1 [M + H]+. 308 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.25-8.30 (2H, m), 7.99 (1H, dd, J = 8.4, 2.8 Hz), 7.94 (1H, dd, J = 8.0, 2.4 Hz), 7.18 (1H, d, J = 8.8 Hz), 7.11 (1H, d, J = 8.0 Hz), 6.92 (1H, d, J = 6.0 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.55 (2H, brs), 4.50 (2H, t, J = 5.6 Hz), 3.39 (3H, s); LCMS: 99.0%, MS (ESI); m/z 381.0 [M + H]+. 309 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.25-8.35 (2H, m), 7.99 (1H, dd, J = 8.8, 2.8 Hz), 7.93 (1H, dd, J = 8.4, 2.4 Hz), 7.18 (1H, d, J = 8.8 Hz), 7.12 (1H, d, J = 8.4 Hz), 6.98 (1H, t, J = 5.6 Hz), 6.95 (1H, d, J = 8.0 Hz), 6.25 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.4, 2.4 Hz), 5.86 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.45-4.60 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.39 (3H, s); LCMS: 98.4%, MS (ESI); m/z 437.0 [M + H]+. 310 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 10.94 (1H, brs), 8.43 (1H, d, J = 2.4 Hz), 8.23 (1H, d, J = 8.8 Hz), 7.94-7.98 (3H, m), 7.49 (2H, d, J = 8.4 Hz), 6.99 (1H, t, J = 6.0 Hz), 6.84 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.25 (1H, dd, J = 8.0, 2.0 Hz), 4.58 (2H, d, J = 6.0 Hz), 4.55 (2H, brs), 3.43 (3H, s); LCMS: 98.6%, MS (ESI); m/z 407.0 [M + H]+. 311 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.62 (1H, d, J = 8.8 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.32 (1H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.82-6.92 (2H, m), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.46-4.55 (4H, m), 3.41 (3H, s), 2.54 (3H, s); LCMS: 97.7%, MS (ESI); m/z 361.1 [M + H]+. 312 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.61 (1H, d, J = 9.2 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.32 (1H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.8 Hz), 6.94 (2H, d, J = 8.0 Hz), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.4 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.57 (3H, m), 4.39 (2H, t, J = 5.6 Hz), 3.44 (3H, s), 2.53 (3H, s); LCMS: 96.4%, MS (ESI); m/z 417.1 [M + H]+. 313 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.0 Hz), 7.94 (1H, dd, J = 8.4, 2.4 Hz), 7.43 (2H, d, J = 8.8 Hz), 7.06- 7.10 (3H, m), 6.88-6.73 (2H, m), 6.39 (1H, d, J = 2.0 Hz), 6.31 (1H, dd, J = 8.0, 2.0 Hz), 4.90 (1H, brs), 4.66 (1H, t, J = 5.6 Hz), 4.51 (2H, d, J = 5.6 Hz), 3.57 (2H, q, J = 6.0 Hz), 3.45 (3H, s), 3.00-3.10 (2H, m); LCMS: 99.0%, MS (ESI); m/z 424.0 [M + H]+. 314 white solid; m.p = 96.6-100.9° C.; 1H NMR (DMSO-d6, 400 MHz); δ 8.62 (1H, d, J = 2.4 Hz), 7.95 (1H, dd, J = 8.4, 2.4 Hz), 7.53 (1H, d, J = 8.4 Hz), 7.31 (2H, d, J = 8.8 Hz), 6.96 (2H, d, J = 8.4 Hz), 6.85 (1H, d, J = 8.0 Hz), 6.75 (1H, t, J = 6.0 Hz), 6.35 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 5.16 (2H, s), 4.55 (2H, brs), 4.42 (2H, d, J = 5.6 Hz), 3.38 (3H, s); LCMS: 97.0%, MS (ESI); m/z 394.1 [M + H]+. 315 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.62 (1H, d, J = 2.4 Hz), 7.95 (1H, dd, J = 8.8, 2.8 Hz), 7.53 (1H, d, J = 8.4 Hz), 7.31 (2H, d, J = 8.8 Hz), 6.88-7.01 (3H, m), 6.81 (1H, t, J = 6.0 Hz), 6.23 (1H, d, J = 2.0 Hz), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.83 (1H, d, J = 6.8 Hz), 5.15 (2H, s), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.56 (1H, m), 4.34-4.45 (4H, m), 3.41 (3H, s); LCMS: 100%, MS (ESI); m/z 450.1 [M + H]+. 316 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.43 (2H, d, J = 8.4 Hz), 7.00- 7.13 (3H, m), 6.83-6.98 (2H, m), 6.42 (1H, d, J = 2.0 Hz), 6.32 (1H, dd, J = 8.0, 2.0 Hz), 4.94 (1H, t, J = 6.0 Hz), 4.52 (2H, d, J = 6.0 Hz), 3.50 (2H, t, J = 5.6 Hz), 3.45 (3H, s), 3.28 (3H, s), 3.18 (2H, q, J = 5.8 Hz); LCMS: 98.0%, MS (ESI); m/z 438.1 [M + H]+. 317 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.40 (2H, d, J = 8.8 Hz), 6.99- 7.15 (4H, m), 6.45 (1H, d, J = 1.6 Hz), 6.40 (1H, dd, J = 8.4, 2.4 Hz), 4.90 (1H, t, J = 5.6 Hz), 4.77 (2H, brs), 4.44 (2H, s), 3.59 (2H, q, J = 5.6 Hz), 3.52 (3H, s), 3.24 (1H, t, J = 6.0 Hz); LCMS: 100%, MS (ESI); m/z 424.0 [M + H]+. 318 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.40 (2H, d, J = 8.8 Hz), 7.12 (1H, d, J = 8.4 Hz), 7.04-7.10 (3H, m), 6.38 (1H, dd, J = 8.4, 2.0 Hz), 6.30 (1H, d, J = 2.0 Hz), 6.08 (1H, d, J = 6.8 Hz), 4.87 (1H, t, J = 6.4 Hz), 4.50-4.62 (1H, m), 4.45 (2H, brs), 4.40 (1H, t, J = 6.0 Hz), 3.53-3.62 (5H, m), 3.24 (2H, t, J = 6.0 Hz); LCMS: 100%, MS (ESI); m/z 480.1 [M + H]+. 319 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.41 (1H, d, J = 2.4 Hz), 7.80 (1H, dd, J = 8.8, 2.8 Hz), 7.19-7.33 (5H, m), 6.89 (1H, d, J = 8.4 Hz), 6.43 (1H, s), 6.33 (1H, d, J = 7.6 Hz), 4.53 (2H, d, J = 5.2 Hz), 3.44 (6H, s); LCMS: 100%, MS (ESI); m/z 421.1 [M + H]+. 320 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.41 (1H, d, J = 2.4 Hz), 7.99 (1H, dd, J = 8.8, 2.4 Hz), 7.18-7.30 (5H, m), 6.89-6.94 (2H, m), 6.24 (1H, s), 6.20 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.48-4.53 (3H, m), 4.38 (2H, t, J = 6.4 Hz), 3.42 (6H, s); LCMS: 100%, MS (ESI); m/z 477.1 [M + H]+. 321 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.33 (1H, d, J = 2.0 Hz), 8.13 (1H, d, J = 2.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.11 (2H, d, J = 8.8 Hz), 6.91 (1H, t, J = 6.0 Hz), 6.85 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz); LCMS: 100%, MS (ESI); m/z 414.0 [M + H]+. 322 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.32 (1H, d, J = 2.0 Hz), 8.12 (1H, d, J = 2.4 Hz), 7.43 (2H, d, J = 8.8 Hz), 7.11 (2H, d, J = 8.4 Hz), 6.89-7.00 (2H, m), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45- 4.57 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 99.7%, MS (ESI); m/z 470.0 [M + H]+. 323 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, dd, J = 10.0, 2.4 Hz), 8.02 (1H, d, J = 2.0 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.14 (2H, d, J = 8.8 Hz), 6.93 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.57 (2H, brs), 4.51 (2H, d, J = 6.0 Hz), 3.41 (3H, s); LCMS: 100%, MS (ESI); m/z 398.0 [M + H]+. 324 white power; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, dd, J = 10.0, 2.0 Hz), 8.01 (1H, d, J = 2.0 Hz), 7.43 (2H, d, J = 8.4 Hz), 7.13 (2H, d, J = 8.8 Hz), 6.89-7.00 (2H, m), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.4 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.8 Hz), 4.45-4.57 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 98.6%, MS (ESI); m/z 454.1 [M + H]+. 325 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.43 (2H, d, J = 8.4 Hz), 7.02- 7.11 (4H, m), 6.94 (1H, d, J = 8.4 Hz), 6.62 (1H, d, J = 2.0 Hz), 6.49 (1H, d, J = 8.4, 2.0 Hz), 4.75 (1H, t, J = 5.2 Hz), 4.54 (2H, d, J = 5.6 Hz), 3.46 (3H, s), 3.27 (2H, d, J = 5.6 Hz), 1.10 (6H, s); LCMS: 98.9%, MS (ESI); m/z 452.0 [M + H]+. 326 off-white solid; 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.05- 7.10 (3H, m), 7.02 (1H, t, J = 4.8 Hz), 6.92 (1H, d, J = 8.4 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.31 (1H, dd, J = 8.4, 2.0 Hz), 4.52 (2H, d, J = 5.2 Hz), 3.41 (3H, s), 1.40 (6H, s); LCMS: 93.1%, MS (ESI); m/z 466.1 [M + H]+. 327 yellow powder; 1H NMR (Methanol-d4, 400 MHz); δ 8.16 (1H, d, J = 2.8 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.55-7.62 (2H, m), 7.45 (1H, d, J = 8.4 Hz), 7.39 (1H, dd, J = 8.4, 2.0 Hz), 7.04 (1H, d, J = 8.8 Hz), 6.90 (1H, d, J = 2.0 Hz), 6.75 (1H, dd, J = 8.4, 2.4 Hz), 4.73 (2H, s), 3.84 (3H, s), 3.76 (3H, s); LCMS: 100%, MS (ESI); m/z 410.0 [M + H]+. 328 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.19 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.27 (1H, d, J = 8.4 Hz), 7.06 (1H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.0 Hz), 6.81 (1H, d, J = 2.0 Hz), 6.76 (1H, t, J = 6.0 Hz), 6.64 (1H, dd, J = 8.4, 2.4 Hz), 6.25 (1H, d, J = 1.6 Hz), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.84 (1H, t, J = 6.4 Hz), 4.49-4.57 (1H, m), 4.47 (2H, d, J = 6.0 Hz), 4.39 (1H, t, J = 6.0 Hz), 3.80 (3H, s), 3.47 (3H, s); LCMS: 98.9%, MS (ESI); m/z 466.0 [M + H]+. 329 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.51 (1H, dd, J = 4.8, 0.8 Hz), 8.17 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.70 (1H, dt, J = 8.0, 2.0 Hz), 7.43 (2H, d, J = 8.8 Hz), 7.32 (1H, d, J = 7.6 Hz), 7.18-7.25 (1H, m), 7.03-7.14 (3H, m), 6.87-6.97 (2H, m), 6.40 (1H, d, J = 2.0 Hz), 6.32 (1H, dd, J = 8.4, 2.4 Hz), 5.15 (1H, t, J = 6.0 Hz), 4.51 (2H, d, J = 6.0 Hz), 3.45 (3H, s), 3.35-3.40 (2H, m), 3.00 (2H, t, J = 7.2 Hz); LCMS: 96.1%, MS (ESI); m/z 485.1 [M + H]+. 330 white powder (amorphous); (note: HNMR showed 10% of methyl isomer); 1H NMR (DMSO-d6, 400 MHz); δ 7.84 (1H, d, J = 3.2 Hz), 7.48 (1H, dd, J = 8.8, 3.2 Hz), 7.39 (2H, d, J = 8.8 Hz), 6.93-7.05 (3H, m), 6.80-6.90 (2H, m), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.54 (2H, brs), 4.48 (2H, d, J = 6.0 Hz), 3.78 (3H, s), 3.40 (3H, s); LCMS: 98.8%, MS (ESI); m/z 376.1 [M + H]+. 331 white powder (amorphous); (Note: HNMR showed 10% of methyl isomer); 1H NMR (DMSO-d6, 400 MHz); δ 7.84 (1H, d, J = 2.8 Hz), 7.48 (1H, dd, J = 8.8, 3.2 Hz), 7.38 (2H, d, J = 8.8 Hz), 6.89-7.02 (5H, m), 6.24 (1H, d, J = 2.0 Hz), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.57 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.78 (3H, s), 3.44 (3H, s); LCMS: 100%, MS (ESI); m/z 432.1 [M + H]+. 332 white powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.40 (2H, d, J = 8.4 Hz), 7.21 (1H, t, J = 6.0 Hz), 7.06-7.10 (3H, m), 6.93 (1H, d, J = 8.4 Hz), 6.27 (1H, d, J = 1.6 Hz), 6.19 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.80-4.86 (2H, m), 4.47-4.55 (3H, m), 4.36-4.42 (2H, m), 3.99 (2H, t, J = 6.8 Hz), 2.51-2.54 (2H, m, overlapped with DMSO peak), 2.20 (6H, s); LCMS: 96.1%, MS (ESI); m/z 493.1 [M + H]+. 333 white powder (amorphous); 1H NMR (CDCl3, 400 MHz); δ 8.12 (1H, d, J = 2.8 Hz), 7.66 (1H, dd, J = 8.8, 2.4 Hz), 7.48 (2H, d, J = 8.4 Hz), 7.34 (1H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.92 (1H, d, J = 8.8 Hz), 6.53 (1H, dd, J = 8.4, 2.0 Hz), 6.40 (1H, d, J = 1.6 Hz), 4.70 (2H, d, J = 5.6 Hz), 4.14 (1H, t, J = 5.4 Hz), 3.45 (3H, s), 3.21 (2H, t, J = 5.6 Hz), 2.68 (2H, t, J = 5.8 Hz), 2.30-2.65 (8H, m), 2.31 (3H, s); LCMS: 100%, MS (ESI); m/z 506.2 [M + H]+. 334 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, d, J = 2.0 Hz), 7.94 (1H, dd, J = 8.8, 2.4 Hz), 7.07 (1H, d, J = 8.8 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.84 (2H, s), 6.36 (1H, s), 6.29 (1H, d, J = 8.0 Hz), 6.22 (1H, brs), 4.59 (2H, brs), 4.43 (2H, d, J = 4.0 Hz), 3.36 (3H, s), 2.38 (6H, s); LCMS: 100%, MS (ESI); m/z 408.1 [M + H]+. 335 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.20 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.07 (1H, d, J = 8.8 Hz), 7.01 (1H, d, J = 9.2 Hz), 6.84 (2H, s), 6.18-6.32 (3H, m), 5.86 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.48-4.58 (1H, m), 4.45 (2H, d, J = 4.4 Hz), 4.40 (2H, t, J = 6.0 Hz), 3.39 (3H, s), 2.37 (6H, s); LCMS: 99.4%, MS (ESI); m/z 464.1 [M + H]+. 336 pale yellow powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.71 (2H, s), 7.44 (2H, d, J = 8.4 Hz), 7.13 (2H, d, J = 8.8 Hz), 6.91 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.4 Hz), 6.36 (1H, d, J = 1.2 Hz), 6.26 (1H, dd, J = 8.0, 1.6 Hz), 4.55 (2H, brs), 4.51 (2H, d, J = 6.0 Hz), 3.41 (3H, s); LCMS: 100%, MS (ESI); m/z 365.0 [M + H]+. 337 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.71 (2H, s), 7.43 (2H, d, J = 8.0 Hz), 7.13 (2H, d, J = 8.4 Hz), 6.97 (1H, brs), 6.93 (1H, d, J = 8.0 Hz), 6.25 (1H, d, J = 1.6 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.82-4.86 (2H, m), 4.47-4.55 (3H, m), 4.36-4.42 (2H, m), 3.45 (3H, s); LCMS: 99.5%, MS (ESI); m/z 421.1 [M + H]+. 338 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.38 (1H, d, J = 8.8 Hz), 7.01- 7.12 (4H, m), 6.45 (1H, d, J = 1.6 Hz), 6.40 (1H, dd, J = 8.8, 2.0 Hz), 4.78 (2H, brs), 4.43 (2H, s), 3.53-3.47 (5H, m), 3.29-3.34 (2H, m), 3.21 (3H, s); LCMS: 99.6%, MS (ESI); m/z 438.1 [M + H]+. 339 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.18 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.4, 2.4 Hz), 7.37 (2H, d, J = 8.8 Hz), 7.13 (1H, d, J = 8.4 Hz), 7.00-7.10 (3H, m), 6.38 (1H, dd, J = 8.8, 2.4 Hz), 6.30 (1H, d, J = 2.0 Hz), 6.09 (1H, d, J = 6.4 Hz), 4.86 (2H, t, J = 6.4 Hz), 4.51-4.58 (1H, m), 4.44 (2H, s), 4.40 (2H, t, J = 6.0 Hz), 3.55 (3H, s), 3.49 (2H, t, J = 5.6 Hz), 3.28-3.33 (2H, m), 3.21 (3H, s); LCMS: 99.6%, MS (ESI); m/z 494.1 [M + H]+. 340 pale yellow powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.58 (2H, s), 7.46 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.81- 6.92 (2H, m), 6.36 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, brs), 4.51 (2H, d, J = 5.6 Hz), 3.40 (3H, s); LCMS: 100%, MS (ESI); m/z 381 [M + H]+. 341 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.57 (2H, s), 7.45 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.92-6.95 (2H, m), 6.14-6.28 (2H, m), 5.85 (1H, d, J = 6.4 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.35-4.45 (3H, m), 4.39 (2H, t, J = 5.6 Hz), 3.44 (3H, s); LCMS: 100%, MS (ESI); m/z 436.9 [M + H]+. 342 grey powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.15 (1H, s), 7.32 (2H, d, J = 8.4 Hz), 7.26 (1H, s), 6.97 (2H, d, J = 8.4 Hz), 6.85 (1H, d, J = 8.4 Hz), 6.77 (1H, brs), 6.35 (1H, s), 6.26 (1H, dd, J = 8.0, 2.4 Hz), 5.19 (2H, s), 4.55 (2H, brs), 4.42 (2H, d, J = 6.0 Hz), 3.38 (3H, s); LCMS: 100%, MS (ESI); m/z 350.2 [M + H]+. 343 white powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.15 (1H, s), 7.31 (2H, d, J = 8.4 Hz), 7.25 (1H, s), 6.90-7.02 (3H, m), 6.82 (1H, t, J = 6.0 Hz), 6.15-6.25 (2H, m), 5.83 (1H, d, J = 6.8 Hz), 5.19 (2H, s), 4.77-4.89 (2H, m), 4.34-4.55 (5H, m), 3.41 (3H, s); LCMS: 100%, MS (ESI); m/z 406.0 [M + H]+. 344 pale-yellow power; 1H NMR (DMSO-d6, 400 MHz); δ 8.61 (2H, d, J = 4.8 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.25 (1H, t, J = 4.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.92 (1H, d, J = 8.4 Hz), 6.43 (1H, s), 6.33 (1H, d, J = 8.0 Hz), 4.54 (2H, d, J = 5.6 Hz), 3.46 (3H, s); LCMS: 98.4%, MS (ESI); m/z 347.0 [M + H]+. 345 pale-yellow power; 1H NMR (DMSO-d6, 400 MHz); δ 8.61 (2H, d, J = 4.4 Hz), 7.43 (2H, d, J = 8.4 Hz), 7.24 (2H, t, J = 4.8 Hz), 7.11 (2H, d, J = 8.4 Hz), 6.93-6.98 (2H, m), 6.25 (1H, s), 6.21 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.49-4.53 (3H, m), 4.39 (2H, t, J = 5.6 Hz), 3.45 (3H, s); LCMS: 99.5%, MS (ESI); m/z 403.0 [M + H]+. 346 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.12 (1H, dd, J = 4.8, 1.2 Hz), 7.77-7.89 (1H, m), 7.43 (2H, d, J = 8.0 Hz), 7.04-7.12 (3H, m), 7.00 (1H, d, J = 8.4 Hz), 6.92 (1H, t, J = 5.2 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.0, 1.6 Hz), 4.36-4.83 (4H, m), 3.42 (3H, s); LCMS: 100%, MS (ESI); m/z 346.0 [M + H]+. 347 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.11 (1H, dd, J = 4.8, 1.6 Hz), 7.78-7.88 (1H, m), 7.41 (2H, d, J = 8.4 Hz), 7.03-7.13 (3H, m), 7.00 (1H, d, J = 8.8 Hz), 6.90-7.02 (2H, m), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.0, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.62 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 100%, MS (ESI); m/z 402.0 [M + H]+. 348 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.45 (2H, s), 7.45 (2H, d, J = 8.4 Hz), 7.13 (2H, d, J = 8.4 Hz), 6.96 (1H, d, J = 8.4 Hz), 6.47 (1H, s), 6.38 (1H, d, J = 8.4 Hz), 4.56 (2H, d, J = 5.2 Hz), 3.48 (3H, s), 2.20 (3H, s); LCMS: 97.8%, MS (ESI); m/z 361.0 [M + H]+. 349 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.44 (2H, s), 7.41 (2H, d, J = 8.0 Hz), 7.08 (2H, d, J = 8.4 Hz), 6.92-6.96 (2H, m), 6.25 (1H, s), 6.21 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.47-4.52 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s), 2.19 (3H, s); LCMS: 98.5%, MS (ESI); m/z 417.1 [M + H]+. 350 off white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.62 (1H, d, J = 2.0 Hz), 8.30 (1H, dd, J = 8.8, 2.4 Hz), 7.47 (2H, d, J = 8.0 Hz), 7.23 (1H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.85-6.94 (2H, m), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.45-4.61 (4H, m), 3.42 (3H, s); LCMS: 99.8%, MS (ESI); m/z 371.1 [M + H]+. 351 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.62 (1H, d, J = 2.0 Hz), 8.30 (1H, dd, J = 8.8, 2.4 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.23 (1H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.90-7.01 (2H, m), 6.26 (1H, s), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.48-4.59 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 98.3%, MS (ESI); m/z 427.1 [M + H]+. 352 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.95 (1H, d, J = 2.4 Hz), 7.65 (1H, dd, J = 8.4, 2.4 Hz), 7.41 (2H, d, J = 8.4 Hz), 7.03 (2H, d, J = 8.4 Hz), 6.95-6.83 (3H, m), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.54 (2H, s), 4.50 (2H, d, J = 6.0 Hz), 3.41 (3H, s), 2.23 (3H, s); LCMS: 98.3%, MS (ESI); m/z 360.0 [M + H]+. 353 a white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.95 (1H, s), 7.65 (1H, dd, J = 8.4, 2.4 Hz), 7.40 (2H, d, J = 8.4 Hz), 7.02 (2H, d, J = 8.4 Hz), 6.86-6.98 (3H, m), 6.16-6.31 (2H, m), 5.84 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.46-4.57 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.44 (3H, s), 2.23 (3H, s); LCMS: 98.0%, MS (ESI); m/z 416.2 [M + H]+. 354 pale yellow powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.77 (2H, s), 8.46 (1H, d, J = 2.8 Hz), 7.66 (1H, dd, J = 8.4, 2.8 Hz), 7.48 (1H, d, J = 8.8 Hz), 7.05 (1H, t, J = 6.0 Hz), 6.84 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.61 (2H, d, J = 6.0 Hz), 4.55 (2H, s), 3.45 (3H, s); LCMS: 99.5%, MS (ESI); m/z 382.0 [M + H]+. 355 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.76 (2H, s), 8.46 (1H, d, J = 2.4 Hz), 7.66 (1H, dd, J = 8.4, 2.8 Hz), 7.47 (1H, d, J = 8.8 Hz), 7.10 (1H, t, J = 6.0 Hz), 6.92 (1H, d, J = 8.0 Hz), 6.26 (1H, d, J = 1.6 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.62 (2H, d, J = 6.0 Hz), 4.547-4.55 (1H, m), 4.39 (2H, t, J = 6.0 Hz), 3.48 (3H, s); LCMS: 100%, MS (ESI); m/z 438.1 [M + H]+. 356 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.40-7.53 (3H, m), 7.25-7.40 (3H, m), 7.05-7.20 (2H, m), 6.82-6.96 (2H, m), 6.37 (1H, d, J = 1.2 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.40-4.65 (4H, m), 3.71 (3H, s), 3.42 (3H, s); LCMS: 100%, MS (ESI); m/z 399.1 [M + H]+. 357 white amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 7.40-7.52 (3H, m), 7.27-7.39 (3H, m), 7.06-7.19 (2H, m), 6.91-7.02 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.83 (1H, d, J = 7.6 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.62 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.70 (3H, s), 3.45 (3H, s); LCMS: 100%, MS (ESI); m/z 455.2 [M + H]+. 358 pale-yellow powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.44 (2H, d, J = 8.4 Hz), 7.22 (1H, brs), 7.14 (2H, d, J = 8.4 Hz), 6.96-7.05 (2H, m), 6.92 (1H, d, J = 8.4 Hz), 6.33 (1H, d, J = 1.6 Hz), 6.30 (1H, dd, J = 8.4, 2.0 Hz), 5.15 (1H, brs), 4.52 (2H, d, J = 6.4 Hz), 3.40 (3H, s), 1.32 (6H, s); LCMS: 99.1%, MS (ESI); m/z 466.1 [M + H]+. 359 yellow powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.44 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.0 Hz), 7.05 (1H, s), 6.87-7.00 (2H, m), 6.79 (1H, s), 6.57 (1H, s), 6.42 (1H, d, J = 8.4 Hz), 5.46 (1H, brs), 4.51 (2H, d, J = 5.6 Hz), 4.24 (2H, d, J = 4.8 Hz), 3.64 (3H, s), 3.44 (3H, s); LCMS: 99.53%, MS (ESI); m/z 475.1 [M + H]+. 360 white powder (amorphous); 1H NMR (DMSO-d6, 400 MHz); δ 8.11 (2H, s), 7.35 (1H, d, J = 8.4 Hz), 6.89 (2H, d, J = 8.8 Hz), 6.75-6.88 (2H, m), 6.62 (2H, brs), 6.35 (1H, d, J = 1.2 Hz), 6.25 (1H, dd, J = 8.0, 1.6 Hz), 4.53 (2H, brs), 4.44 (2H, d, J = 5.6 Hz), 3.38 (3H, s); LCMS: 97.1%, MS (ESI); m/z 362.1 [M + H]+. 361 pale-yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.78 (2H, s), 7.44 (2H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.4 Hz), 7.02 (1H, brs), 6.86 (1H, d, J = 8.0 Hz), 6.37 (1H, s), 6.27 (1H, dd, J = 8.4, 1.6 Hz), 4.77 (2H, brs), 4.51 (2H, d, J = 5.6 Hz), 3.42 (3H, s); LCMS: 98.8%, MS (ESI); m/z 425.0 [M + H]+. 362 pale-yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.77 (2H, s), 7.43 (2H, d, J = 8.0 Hz), 7.14 (2H, t, J = 8.4 Hz), 6.90-6.98 (2H, m), 6.25 (1H, s), 6.21 (1H, d, J = 8.4 Hz), 5.83 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.47-4.52 (3H, m), 4.39 (2H, t, J = 5.6 Hz), 3.45 (3H, s); LCMS: 100%, MS (ESI); m/z 482.9 [M + 3]+. 363 pale-yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.95 (1H, d, J = 4.8 Hz), 7.76 (1H, d, J = 5.2 Hz), 7.47 (2H,d, J = 8.4 Hz), 7.22 (2H, d, J = 8.8 Hz), 6.90 (1H, d, J = 8.0 Hz), 6.41 (1H, s), 6.31 (1H, d, J = 8.4 Hz), 4.55 (2H, d, J = 5.6 Hz), 3.45 (3H, s); LCMS: 97.7%, MS (ESI); m/z 415.1 [M + H]+. 364 pale-yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.96 (1H, d, J = 4.4 Hz), 7.75 (1H, d, J = 4.8 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 6.93-6.99 (2H, m), 6.25 (1H, s), 6.21 (1H, d, J = 8.8 Hz), 5.83 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.47-4.55 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 100%, MS (ESI); m/z 471.1 [M + H]+. 365 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.79 (2H, d, J = 5.2 Hz), 8.72 (2H, s), 7.44 (2H, d, J = 8.4 Hz), 7.39 (1H, t, J = 4.8 Hz), 7.12-7.17 (2H, m), 6.95 (1H, t, J = 6.0 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.50 (1H, d, J = 2.0 Hz), 6.39 (1H, dd, J = 8.4, 2.0 Hz), 5.63 (1H, t, J = 6.0 Hz), 4.52 (2H, d, J = 5.6 Hz), 4.45 (2H, d, J = 5.6 Hz), 3.43 (3H, s); LCMS: 96.7%, MS (ESI); m/z 473.1 [M + H]+. 366 pale-yellow power; 1H NMR (DMSO-d6, 400 MHz); δ 8.72 (2H, s), 7.43 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.96 (1H, t, J = 6.0 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.42 (1H, s), 6.27 (1H, dd, J = 8.8, 1.6 Hz), 5.76 (1H, d, J = 9.6 Hz), 4.70-4.78 (1H, m), 4.51 (2H, t, J = 6.0 Hz), 3.46 (3H, s), 3.30-3.35 (2H, m, after exchange with D2O), 3.25 (2H, t, J = 8.4 Hz); LCMS: 98.5%, MS (ESI); m/z 453.0 [M + H]+. 367 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.12 (2H, s), 7.47 (2H, d, J = 8.0 Hz), 7.19 (2H, d, J = 8.0 Hz), 6.93 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.4 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.52 (2H, d, J = 6.0 Hz), 3.41 (3H, s); LCMS: 99.3%, MS (ESI); m/z 372.1 [M + H]+. 368 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 9.12 (2H, s), 7.46 (2H, d, J = 8.4 Hz), 7.19 (2H, d, J = 8.4 Hz), 6.98 (1H, t, J = 6.0 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.0, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.47-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), (2H, m), 3.45 (3H, s); LCMS: 100%, MS (ESI); m/z 428.0 [M + H]+. 369 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.12 (2H, s), 7.35 (1H, d, J = 8.4 Hz), 6.80-7.00 (4H, m), 6.63 (1H, s), 6.75-6.88 (2H, m), 6.63 (2H, s), 6.24 (1H, d, J = 1.6 Hz), 6.21 (1H, dd, J = 8.8, 2.0 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.8 Hz), 4.50-4.60 (1H, m), 4.46 (2H, d, J = 6.0 Hz), 4.39 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 418.1 [M + H]+. 370 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.74 (1H, s), 8.67 (1H, d, J = 5.6 Hz), 7.48 (2H, d, J = 8.8 Hz), 7.09-7.21 (3H, m), 6.92 (1H, t, J = 6.0 Hz), 6.87 (1H, d, J = 8.4 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.49-4.61 (4H, m), 3.43 (3H, s); LCMS: 99.0%, MS (ESI); m/z 347.1 [M + H]+. 371 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.74 (1H, s), 8.67 (1H, d, J = 2.0 Hz), 7.47 (2H, d, J = 8.8 Hz), 7.09-7.26 (3H, m), 6.98 (1H, t, J = 5.6 Hz), 6.95 (1H, d, J = 8.0 Hz), 6.26 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.0, 1.6 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.44-4.69 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 403.2 [M + H]+. 372 yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.40-7.48 (4H, m), 7.10-7.20 (4H, m), 6.87-6.95 (2H, m), 6.41 (1H, s), 6.34 (1H, d, J = 8.4 Hz), 5.51 (1H, brs), 4.92-4.97 (1H, m), 4.74-4.80 (1H, m), 4.51 (2H, d, J = 6.0 Hz), 3.44 (3H, s), 3.17-3.25 (1H, m), 3.02-3.17 (1H, m); LCMS: 99.77%, MS (ESI); m/z 519.1 [M + H]+. 373 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.09 (2H, s), 7.47 (2H, d, J = 7.6 Hz), 7.20 (2H, d, J = 7.6 Hz), 6.90-6.99 (1H, m), 6.86 (1H, d, J = 8.0 Hz), 6.37 (1H, s), 6.26 (1H, d, J = 8.4 Hz), 4.45-4.65 (4H, m), 3.41 (3H, s); LCMS: 99.7%, MS (ESI); m/z 415.1 [M + H]+. 374 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.09 (2H, s), 7.46 (2H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 6.99 (1H, d, J = 6.0 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.17-6.28 (2H, m), 5.85 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.60 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 98.2%, MS (ESI); m/z 471.1 [M + H]+. 375 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.71 (1H, d, J = 5.6 Hz), 8.33 (1H, d, J = 8.8 Hz), 8.09 (1H, d, J = 2.0 Hz), 7.68 (1H, dd, J = 9.2, 2.4 Hz), 7.55 (2H, d, J = 8.4 Hz), 7.26 (2H, d, J = 8.4 Hz), 6.95 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.4 Hz), 6.60 (1H, d, J = 5.6 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.45-4.69 (4H, m), 3.43 (3H, s); LCMS: 99.3%, MS (ESI); m/z 430.0 [M + H]+. 376 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.95 (2H, s), 7.38 (2H, d, J = 8.0 Hz), 7.00 (2H, d, J = 8.4 Hz), 6.82-6.90 (2H, m), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 5.21 (2H, s), 4.55 (2H, brs), 4.48 (2H, d, J = 5.6 Hz), 3.40 (3H, s); LCMS: 94.7%, MS (ESI); m/z 362.0 [M + H]+. 377 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.24 (1H, d, J = 2.8 Hz), 7.95 (1H, dd, J = 8.8, 2.0 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.16 (1H, d, J = 9.2 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.83-6.95 (2H, m), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.56 (2H, brs), 4.52 (2H, d, J = 6.0 Hz), 3.42 (3H, s); LCMS: 99.9%, MS (ESI); m/z 430.1 [M + H]+. 378 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.23 (1H, d, J = 2.8 Hz), 7.95 (1H, dd, J = 8.8, 2.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.16 (1H, d, J = 8.8 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.90-7.01 (2H, m), 6.26 (1H, d, J = 1.6 Hz), 6.22 (2H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.0 Hz), 4.46-4.58 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 97.9%, MS (ESI); m/z 486.1 [M + H]+. 379 off-white powder; 1H NMR (DSMO-d6, 400 MHz); δ 8.73 (2H, s), 7.45 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.85-6.98 (2H, m), 6.42 (1H, d, J = 2.0 Hz), 6.31 (1H, dd, J = 8.4, 2.0 Hz), 4.82 (1H, t, J = 5.6 Hz), 4.52 (2H, d, J = 5.6 Hz), 3.59 (4H, t, J = 4.6 Hz), 3.45 (3H, s), 3.12 (2H, q, J = 6.0 Hz), 2.51-2.54 (2H, m), 2.35-2.46 (4H, m); LCMS: 99.5%, MS (ESI); m/z 494.1 [M + H]+. 380 grey powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.76 (2H, s), 7.50 (1H, t, J = 8.8 Hz), 7.21 (1H, dd, J = 10.8, 2.0 Hz), 7.03 (1H, dd, J = 8.4, 2.0 Hz), 6.84-6.93 (2H, m), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.48-4.62 (4H, m), 3.42 (3H, s); LCMS: 100%, MS (ESI); m/z 399.0 [M + H]+. 381 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.76 (2H, s), 7.50 (1H, t, J = 8.8 Hz), 7.21 (1H, dd, J = 11.2, 2.4 Hz), 7.03 (1H, dd, J = 8.4, 2.0 Hz), 6.92-7.00 (2H, m), 6.18-6.31 (2H, m), 5.86 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.46-4.61 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 455.1 [M + H]+. 382 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.38 (1H, d, J = 8.8 Hz), 7.76 (1H, dd, J = 9.2, 2.8 Hz), 7.68 (1H, dd, J = 9.2, 5.2 Hz), 7.53 (1H, td, J = 8.8, 3.2 Hz), 7.43-7.48 (2H, m), 7.31 (1H, d, J = 9.2 Hz), 7.15-7.21 (2H, m), 6.94 (1H, t, J = 5.8 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.46-4.65 (4H, m), 3.43 (3H, s); LCMS: 100%, MS (ESI); m/z 414.1 [M + H]+. 383 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.38 (1H, d, J = 8.8 Hz), 7.76 (1H, dd, J = 9.2, 2.8 Hz), 7.68 (1H, dd, J = 8.8, 5.2 Hz), 7.52 (1H, td, J = 8.8, 2.8 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.30 (1H, d, J = 8.8 Hz), 7.18 (2H, d, J = 8.4 Hz), 6.92-7.02 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.0 Hz), 4.56 (2H, d, J = 5.6 Hz), 4.47-4.55 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 470.1 [M + H]+. 384 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.70 (1H, d, J = 5.2 Hz), 8.32 (1H, d, J = 8.8 Hz), 8.08 (1H, d, J = 2.0 Hz), 7.68 (1H, dd, J = 9.2, 2.4 Hz), 7.54 (2H, d, J = 8.0 Hz), 7.26 (2H, d, J = 8.4 Hz), 7.02 (1H, t, J = 6.0 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.59 (1H, d, J = 5.2 Hz), 6.26 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.58 (2H, d, J = 6.0 Hz), 4.45-4.55 (1H, m), 4.40 (2H, d, J = 6.0 Hz), 3.46 (3H, s); LCMS: 97.1%, MS (ESI); m/z 481.2 [M + H]+. 385 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.75 (2H, s), 6.86-6.97 (3H, m), 6.36 (1H, s), 6.29 (1H, d, J = 8.0 Hz), 6.22 (1H, t, J = 4.8 Hz), 4.56 (2H, brs), 4.44 (2H, d, J = 4.8 Hz), 3.36 (3H, s), 2.39 (6H, s); LCMS: 100%, MS (ESI); m/z 409.2 [M + H]+. 386 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.44 (2H, d, J = 8.4 Hz), 7.15 (2H, t, J = 8.4 Hz), 7.01 (1H, brs), 6.96 (1H, d, J = 8.4 Hz), 6.30 (1H, s), 6.23 (1H, d, J = 8.4 Hz), 5.73 (1H, d, J = 4.8 Hz), 4.61-4.63 (1H, m), 4.53 (2H, d, J = 5.6 Hz), 3.44-3.52 (7H, m); LCMS: 98.9%, MS (ESI); m/z 469.2 [M + H]+. 387 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.78 (1H, d, J = 5.2 Hz), 8.30 (1H, d, J = 8.4 Hz), 8.02 (1H, d, J = 6.4 Hz), 7.63 (1H, t, J = 8.0 Hz), 7.55 (2H, d, J = 8.8 Hz), 7.27 (2H, d, J = 8.0 Hz), 6.94 (1H, t, J = 6.0 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.69 (1H, d, J = 4.8 Hz), 6.37 (1H, s), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.48-4.65 (4H, m), 3.43 (3H, s); LCMS: 98.7%, MS (ESI); m/z 430.1 [M + H]+. 388 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.78 (1H, d, J = 5.2 Hz), 8.30-8.35 (1H, m), 8.02 (1H, dd, J = 7.6, 1.6 Hz), 7.62 (1H, t, J = 8.4 Hz), 7.55 (2H, d, J = 8.4 Hz), 7.26 (2H, d, J = 8.4 Hz), 7.01 (1H, t, J = 6.0 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.68 (1H, d, J = 5.2 Hz), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.58 (2H, d, J = 6.0 Hz), 4.45-4.56 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 97.1%, MS (ESI); m/z 486.1 [M + H]+. 389 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.38 (1H, d, J = 9.2 Hz), 8.07 (1H, d, J = 1.6 Hz), 7.60-7.67 (2H, m), 7.47 (2H, d, J = 8.4 Hz), 7.32 (1H, d, J = 8.8 Hz), 7.19 (2H, d, J = 8.4 Hz), 6.92 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.4 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.50-4.60 (4H, m), 3.43 (3H, s); LCMS: 99.4%, MS (ESI); m/z 430.1 [M + H]+. 390 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.38 (1H, d, J = 9.2 Hz), 8.07 (1H, s), 7.60-7.66 (2H, m), 7.46 (2H, d, J = 8.4 Hz), 7.31 (1H, d, J = 9.2 Hz), 7.19 (2H, d, J = 8.4 Hz), 6.93-7.00 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.47-4.60 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 486.1 [M + H]+. 391 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.77 (2H, s), 7.59 (1H, d, J = 1.6 Hz), 7.43 (1H, dd, J = 8.4, 2.0 Hz), 7.35 (1H, d, J = 8.4 Hz), 6.99 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.4 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, d, J = 8.4, 2.0 Hz), 4.56 (2H, brs), 4.52 (2H, d, J = 6.0 Hz), 3.42 (3H, s); LCMS: 100%, MS (ESI); m/z 415.0 [M + H]+. 392 pale yellow amorphous; 1H NMR (DMSO-d6, 400 MHz); δ 8.77 (2H, s), 7.58 (1H, d, J = 2.0 Hz), 7.43 (1H, dd, J = 8.4, 2.0 Hz), 7.35 (1H, d, J = 2.4 Hz), 7.05 (1H, t, J = 6.0 Hz), 6.94 (1H, d, J = 8.4 Hz), 6.26 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.86 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz) 4.47-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz) 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 471.0 [M + H]+. 393 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.61 (1H, s), 7.46 (2H, d, J = 8.4 Hz), 7.37 (1H, s), 7.16 (2H, d, J = 8.8 Hz), 6.91 (1H, t, J = 5.6 Hz), 6.85 (1H, d, J = 8.0 Hz), 6.35 (1H, d, J = 2.0 Hz), 6.25 (1H, dd, J = 8.0, 2.0 Hz), 4.46-4.57 (4H, m), 3.40 (3H, s); LCMS: 100%, MS (ESI); m/z 381.00 [M + H]+. 394 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.63 (1H, s), 7.47 (2H, d, J = 8.8 Hz), 7.38 (1H, s), 7.18 (2H, d, J = 8.4 Hz), 6.98 (1H, t, J = 6.0 Hz), 6.94 (1H, d, J = 8.0 Hz), 6.26 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.45-4.61 (3H, m), 4.40 (2H, t, J = 5.6 Hz), 3.45 (3H, s); LCMS: 99.3%, MS (ESI); m/z 437.0 [M + H]+. 395 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.44 (1H, d, J = 1.6 Hz), 7.26 (1H, dd, J = 8.4, 1.6 Hz), 7.02-7.05 (2H, m), 6.87 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.4, 1.6 Hz), 4.51 (2H, d, J = 6.0 Hz), 3.43 (3H, s), 2.89-2.97 (1H, m), 1.11 (6H, d, J = 6.8 Hz); LCMS: 99.2%, MS (ESI); m/z 423.1 [M + H]+. 396 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.72 (2H, s), 7.43 (1H, d, J = 1.6 Hz), 7.25 (1H, dd, J = 8.0, 1.6 Hz), 7.02 (1H, d, J = 8.4 Hz), 6.92-6.95 (2H, m), 6.25 (1H, d, J = 1.6 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (2H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.49- 4.54 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.45 (3H, s), 2.89-2.96 (1H, m), 1.10 (6H, d, J = 6.8 Hz); LCMS: 99.3%, MS (ESI); m/z 479.2 [M + H]+. 397 white powder; 1H NMR (CDCl3, 400 MHz); δ 8.28 (1H, s), 7.48 (2H, d, J = 8.4 Hz), 7.32 (2H, d, J = 8.4 Hz), 7.15 (1H, d, J = 8.4 Hz), 6.56 (1H, d, J = 8.0 Hz), 6.48 (1H, s), 4.71 (2H, d, J = 3.6 Hz), 4.24 (1H, brs), 3.45 (3H, s), 2.41-2.52 (1H, m), 1.12-1.30 (4H, m); LCMS: 99.8%, MS (ESI); m/z 421.1 [M + H]+. 398 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.51 (1H, s), 7.42 (2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.91-7.00 (2H, m), 6.25 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.4, 1.6 Hz), 5.85 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.47-4.59 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.45 (3H, s), 2.38-2.46 (1H, m), 1.01-2.01 (2H, m), 0.80-1.05 (2H, m); LCMS: 99.7%, MS (ESI); m/z 447.1 [M + H]+. 399 off-white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.45 (1H, d, J = 8.0 Hz), 8.14 (1H, d, J = 8.4 Hz), 8.07 (1H, s), 8.03 (1H, t, J = 7.6 Hz), 7.86 (1H, t, J = 7.8 Hz), 7.48 (2H, d, J = 8.0 Hz), 7.22 (2H, d, J = 8.4 Hz), 7.01 (1H, brs), 6.88 (1H, d, J = 8.4 Hz), 6.38 (1H, d, J = 1.2 Hz), 6.28 (1H, dd, J = 8.0, 2.0 Hz), 4.55 (2H, d, J = 5.6 Hz), 3.43 (3H, s); LCMS: 99.8%, MS (ESI); m/z 430.1 [M + H]+. 400 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.45 (1H, d, J = 8.4 Hz), 8.14 (1H, d, J = 8.4 Hz), 8.07 (1H, s), 7.99-8.06 (1H, m), 7.86 (1H, t, J = 7.4 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.21 (2H, d, J = 8.4 Hz), 6.99 (1H, t, J = 6.2 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.47-4.60 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 486.1 [M + H]+. 401 white powder; 1H NMR (CDCl3, 400 MHz); δ 8.11 (1H, d, J = 2.4 Hz), 7.65 (1H, dd, J = 8.8, 2.8 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.32 (1H, d, J = 8.4 Hz), 7.11 (2H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.42 (1H, d, J = 8.4, 1.6 Hz), 6.28 (1H, d, J = 2.0 Hz), 4.67 (2H, d, J = 4.0 Hz), 4.35-4.47 (1H, m), 4.25 (1H, brs), 3.97 (2H, t, J = 7.2 Hz), 3.54 (2H, t, J = 7.0 Hz), 3.43 (3H, s); LCMS: 98.6%, MS (ESI); m/z 435.1 [M + H]+. 402 white powder; 1H NMR (CDCl3, 400 MHz); δ 7.52 (2H, d, J = 8.4 Hz), 7.45 (1H, d, J = 2.0 Hz), 7.33-7.40 (3H, m), 7.29 (1H, s), 7.22 (1H, dd, J = 8.4, 2.0 Hz), 6.55 (1H, dd, J = 8.4, 2.0 Hz), 6.47 (1H, d, J = 2.0 Hz), 4.61-4.82 (3H, m), 3.46 (3H, s); LCMS: 98.4%, MS (ESI); m/z 420 [M + H]+. 403 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.66 (1H, d, J = 8.4 Hz), 7.62 (1H, d, J = 2.0 Hz), 7.51 (2H, d, J = 8.8 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.32 (1H, dd, J = 8.8, 2.4 Hz), 7.00 (1H, t, J = 6.0 Hz), 6.94 (1H, d, J = 8.4 Hz), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.47- 4.60 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 99.2%, MS (ESI); m/z 476.2 [M + H]+. 404 white powder; 1H NMR (DSMO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.4 Hz), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.43 (2H, d, J = 8.8 Hz), 7.03-7.11 (3H, m), 6.91-7.00 (2H, m), 6.29 (1H, d, J = 2.0 Hz), 6.24 (1H, dd, J = 8.4, 2.0 Hz), 5.75-5.84 (2H, m), 5.73 (1H, d, J = 4.8 Hz), 4.52 (2H, d, J = 5.6 Hz), 4.10-4.30 (3H, m), 3.56 (2H, d, J = 4.0 Hz), 3.45 (3H, s); LCMS: 99.7%, MS (ESI); m/z 478.2 [M + H]+. 405 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.52 (1H, s), 8.26 (1H, d, J = 2.4 Hz), 7.91 (1H, dd, J = 9.2, 2.4 Hz), 7.75 (1H, d, J = 9.2 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.22 (2H, d, J = 8.4 Hz), 6.92 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.48-4.64 (4H, m), 3.43 (3H, s); LCMS: 99.4%, MS (ESI); m/z 431.1 [M + H]+. 406 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 9.51 (1H, s), 8.26 (1H, d, J = 2.4 Hz), 7.91 (1H, dd, J = 9.2, 2.4 Hz), 7.74 (1H, d, J = 9.2 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.21 (2H, d, J = 8.4 Hz), 6.93-7.04 (2H, m), 6.26 (1H, s), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.60 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 97.3%, MS (ESI); m/z 487.2 [M + H]+. 407 off-white powder; 1H NMR (CDCl3, 400 MHz); δ 8.50 (2H, s), 7.51 (2H, d, J = 8.4 Hz), 7.32 (1H, d, J = 8.4 Hz), 7.18 (2H, d, J = 8.4 Hz), 6.43 (1H, dd, J = 8.4, 1.6 Hz), 6.28 (1H, s), 4.71 (2H, d, J = 3.2 Hz), 4.34-4.46 (1H, m), 4.21 (1H, brs), 3.97 (2H, t, J = 7.2 Hz), 3.54 (2H, t, J = 7.2 Hz), 3.44 (3H, s); LCMS: 98.5%, MS (ESI); m/z 436.1 [M + H]+. 408 white powder; 1H NMR (CDCl3, 400 MHz); δ 8.50 (2H, s), 7.51 (1H, d, J = 8.4 Hz), 7.35 (1H, d, J = 8.4 Hz), 7.18 (2H, d, J = 8.8 Hz), 6.41 (1H, dd, J = 8.4, 2.0 Hz), 6.28 (1H, d, J = 2.0 Hz), 4.72 (2H, d, J = 5.6 Hz), 4.29-4.43 (5H, m), 4.26 (1H, t, J = 5.0 Hz), 3.93 (1H, brs), 3.76-3.86 (2H, m), 3.45 (3H, s); LCMS: 97.7%, MS (ESI); m/z 479.2 [M + H]+. 409 white powder; 1H NMR (DMSO-d6, 400 MHz); δ 7.43 (2H, d, J = 8.4 Hz), 7.27 (2H, d, J = 8.8 Hz), 7.03 (1H, d, J = 8.4 Hz), 6.90-6.98 (2H, m), 6.52 (1H, s), 6.42 (1H, d, J = 8.4 Hz), 6.25 (1H, s), 6.21 (1H, d, J = 8.4 Hz), 5.82 (1H, d, J = 6.8 Hz), 4.77-4.91 (4H, m), 4.47-4.57 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.54 (3H, s), 3.44 (3H, s); LCMS: 98.5%, MS (ESI); m/z 470.3 [M + H]+. 410 yellow powder; 1H NMR (CDCl3, 400 MHz); δ 8.50 (2H, s), 7.53 (2H, d, J = 8.4 Hz), 7.31 (1H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 6.55 (1H, dd, J = 8.0, 2.0 Hz), 6.47 (1H, d, J = 1.6 Hz), 4.72 (2H, d, J = 4.8 Hz), 4.18 (1H, brs), 3.43 (3H, s); LCMS: 96.9%, MS (ESI); m/z 431.1 [M + H]+. 411 pale yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 8.73 (2H, s), 7.15 (2H, s), 6.81-6.90 (2H, m), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.55 (2H, brs), 4.45 (2H, d, J = 6.0 Hz), 3.42 (3H, s), 2.02 (6H, s); LCMS: 100%, MS (ESI); m/z 409.1 [M + H]+. 412 yellow powder; 1H NMR (CDCl3, 400 MHz); δ 8.50 (2H, s), 7.52 (2H, d, J = 8.8 Hz), 7.34 (1H, d, J = 8.4 Hz), 7.19 (2H, d, J = 8.4), 6.40 (1H, dd, J = 8.4, 2.0 Hz), 6.24 (1H, d, J = 2.0 Hz), 5.03 (2H, t, J = 6.4 Hz), 4.73 (2H, d, J = 4.4 Hz), 4.63-4.70 (1H, m), 4.56 (2H, t, J = 6.0 Hz), 4.36 (1H, brs), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 487.3 [M + H]+. 413 1H NMR (DMSO-d6, 400 MHz); δ 8.17 (1H, d, J = 2.8 Hz), 8.02 (1H, s), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.45-7.42 (3H, m), 7.23 (1H, d, J = 2.4 Hz), 7.09-7.06 (3H, m), 7.05-6.98 (m, 2H) 6.85 (1H, dd, J = 8.8, 2.8 Hz), 5.73 (1H, d, J = 2.4 Hz), 4.53 (2H, d, J = 6.0 Hz), 3.71 (3H, s), 3.46 (3H, s); LCMS: 100%, MS (ESI); m/z 460.3 [M + H]+. 414 pale yellow solid; 1H NMR (DMSO-d6, 400 MHz); δ 8.74 (2H, s), 8.03 (1H, s), 7.48-7.45 (m, 3H), 7.23 (1H, d, J = 1.6 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.04-6.99 (2H, m), 6.86 (1H, dd, J = 8.8, 2.8 Hz), 5.74 (1H, d, J = 1.6 Hz), 4.56 (2H, d, J = 5.6 Hz) 3.73 (3H, s), 3.48 (3H, s); LCMS: 99.4%, MS (ESI); m/z 461.2 [M + H]+. 415 yellow powder; 1H NMR (DMSO-d6, 400 MHz); δ 11.48 (1H, s), 8.73 (2H, s), 7.92-7.91 (1H, m), 7.46 (2H, d, J = 8.4 Hz), 7.33 (1H, s), 7.16 (2H, d, J = 8.4 Hz), 7.02-6.07 (2H, m), 6.78-6.75 (1H, m), 5.55 (1H, s), 4.54 (2H, d, J = 5.2 Hz), 3.46 (s, 3H), 2.16 (s, 3H); LCMS: 95.5%, MS (ESI); m/z 461.2 [M + H]+. 416 pale yellow powder (amorphous); 1H-NMR (DMSO-d6, 400 MHz): δ 8.75 (2H, s), 6.86-6.97 (3H, m), 6.36 (1H, s), 6.29 (1H, d, J = 8.0 Hz), 6.22 (1H, t, J = 4.8 Hz), 4.56 (2H, brs), 4.44 (2H, d, J = 4.8 Hz), 3.36 (3H, s), 2.39 (6H, s); LCMS: 100%, MS (ESI); m/z 409.2 [M + H]+. 417 off-white powder (amorphous); 1H-NMR (DMSO-d6, 400 MHz): δ 8.74 (2H, s), 7.00 (1H, d, J = 8.8 Hz), 6.90 (2H, s), 6.29 (1H, t, J = 4.8 Hz), 6.19-6.25 (2H, m), 5.85 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.47-4.56 (1H, m), 4.44 (1H, d, J = 4.8 Hz), 4.39 (1H, t, J = 6.0 Hz), 3.37 (3H, s, D2O) added), 2.38 (6H, s); LCMS: 100%, MS (ESI): m/z 465.2 [M + H]+. 418 a white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 8.14 (2H, s), 6.94 (1H, d, J = 8.4 Hz), 6.90 (1H, t, J = 5.6 Hz), 6.25 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.0 Hz), 4.49-4.54 (1H, m), 4.46 (1H, d, J = 6.0 Hz), 4.40 (2H, t, J = 6.0 Hz), 3.45 (3H, s), 2.01 (6H, s); LCMS: 96.9%, MS (ESI): m/z 465.2 [M + H]+. 419 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.43 (1H, d, J = 9.2 Hz), 7.98 (1H, d, J = 8.4 Hz), 7.68 (1H, d, J = 2.4 Hz), 7.51 (1H, dd, J = 8.4, 2.0 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.28 (1H, d, J = 8.8 Hz), 7.20 (2H, d, J = 8.8 Hz), 6.93 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 2.0 Hz), 6.27 (1H, d, J = 8.4, 2.0 Hz), 4.50-4.55 (4H, m), 3.43 (3H, s); LCMS: 100%, MS (ESI): m/z 430.1 [M + H]+. 420 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.43 (1H, d, J = 8.8 Hz), 7.98 (1H, d, J = 8.4 Hz), 7.67 (1H, d, J = 2.0 Hz), 7.51 (1H, dd, J = 8.4, 2.0 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.28 (1H, d, J = 8.8 Hz), 7.19 (2H, d, J = 8.4 Hz), 6.93-7.02 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.56 (2H, d, J = 6.0 Hz), 4.46-4.54 (1H, m), 4.40 (2H, t, J = 5.8 Hz), 3.46 (3H, s); LCMS: 99.8%, MS (ESI): m/z 486.2 [M + H]+. 421 white amorphous; 1H-NMR (DMSO-d6, 400 MHz): δ 8.47 (1H, d, J = 9.2 Hz), 7.94 (1H, dd, J = 8.0, 1.2 Hz), 7.85 (1H, dd, J = 8.0, 1.2 Hz), 7.43-7.50 (3H, m), 7.29-7.33 (3H, m), 6.93 (1H, brs), 6.88 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.50- 4.65 (4H, m), 3.43 (3H, s); LCMS: 100%, MS (ESI): m/z 430.1 [M + H]+. 422 white amorphous; 1H-NMR (DMSO-d6, 400 MHz): δ 8.47 (1H, d, J = 9.2 Hz), 7.94 (1H, dd, J = 8.0, 1.2 Hz), 7.85 (1H, dd, J = 7.6, 1.2 Hz), 7.42-7.51 (3H, m), 7.27-7.34 (3H, m), 6.91-7.00 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.0, 2.0 Hz), 5.83 (1H, d, J = 7.6 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.57 (2H, d, J = 5.6 Hz), 4.47-4.55 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI): m/z 486.2 [M + H]+. 423 white solid; mp 138.9-140.8° C.; 1H-NMR (DMSO-d6, 400 MHz): δ 7.61 (1H, d, J = 2.0 Hz), 7.47 (2H, d, J = 8.8 Hz), 7.29-7.40 (3H, m), 7.12 (1H, dd, J = 8.8, 2.0 Hz), 6.90-7.02 (2H, m), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.4 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.59 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.71 (3H, s), 3.45 (3H, s); LCMS: 98.5%, MS (ESI): m/z 489.2 [M + H]+. 424 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.58 (1H, d, J = 8.8 Hz), 7.58-7.67 (3H, m), 7.48 (2H, d, J = 8.4 Hz), 7.40 (1H, d, J = 8.8 Hz), 7.21 (2H, d, J = 8.4 Hz), 6.93 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.0, 2.0 Hz), 4.49-4.60 (4H, m), 3.43 (3H, s); LCMS: 95.9%, MS (ESI): m/z 430.1 [M + H]+. 425 white solid; mp: 102.3-107.3° C.; 1H-NMR (DMSO-d6, 400 MHz): δ 8.43 (1H, d, J = 8.8 Hz), 7.98 (1H, d, J = 8.4 Hz), 7.67 (1H, d, J = 2.0 Hz), 7.51 (1H, dd, J = 8.4, 2.0 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.28 (1H, d, J = 8.8 Hz), 7.19 (2H, d, J = 8.4 Hz), 6.93-7.02 (2H, m), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.56 (2H, d, J = 6.0 Hz), 4.46-4.54 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 99.8%, MS (ESI): m/z 486.2 [M + H]+. 426 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.90 (1H, s), 8.15 (1H, s), 7.74-7.77 (2H, m), 7.49 (2H, d, J = 8.8 Hz), 7.27 (2H, dd, J = 6.8, 2.0 Hz), 6.95 (3H, t, J = 5.6 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.45-4.70 (4H, m), 3.43 (3H, s); LCMS: 100%, MS (ESI): m/z 431.1 [M + H]+. 427 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.90 (1H, s), 8.15 (1H, s), 7.74 (2H, s), 7.49 (2H, d, J = 8.4 Hz), 7.27 (2H, dd, J = 8.8 Hz), 6.99 (1H, t, J = 6.4 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.26 (1H, d, J = 2.0 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 5.83 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.70 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.46 (3H, s); LCMS: 100%, MS (ESI): m/z 487.2 [M + H]+. 428 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 7.61 (1H, d, J = 2.0 Hz), 7.48 (2H, d, J = 8.4 Hz), 7.30-7.40 (3H, m), 7.12 (1H, dd, J = 8.0, 2.0 Hz), 6.93 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.27 (1H, dd, J = 8.4, 2.4 Hz), 4.56 (1H, brs), 4.53 (2H, d, J = 5.6 Hz), 3.71 (3H, s), 3.42 (3H, s); LCMS: 100%, MS (ESI): m/z 433.2 [M + H]+ 429 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 13.10 (1H, brs), 9.39 (1H, t, J = 5.2 Hz), 8.88 (1H, s), 8.74 (2H, s), 7.78 (1H, d, J = 2.0 Hz), 7.53 (2H, d, J = 8.4 Hz), 7.21-7.31 (3H, m), 7.08 (1H, d, J = 8.4 Hz), 5.94 (2H, brs), 4.70 (2H, d, J = 6.0 Hz), 3.63 (3H, s); LCMS: 100%, MS (ESI): m/z 424.2 [M + H]+. 430 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.80 (2H, s), 7.12-7.21 (2H, m), 6.91 (1H, d, J = 8.0 Hz), 6.64 (1H, t, J = 5.2 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.29 (1H, dd, J = 8.4, 2.0 Hz), 4.57 (2H, brs), 4.51 (2H, d, J = 4.8 Hz); LCMS: 97.4%, MS (ESI): m/z 417.1 [M + H]+. 431 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.80 (2H, s), 7.17 (2H, d, J = 8.4 Hz), 6.99 (1H, d, J = 8.8 Hz), 6.70 (1H, t, J = 5.6 Hz), 6.20-6.25 (2H, m), 5.86 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.48-4.55 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.39 (3H, s); LCMS: 100%, MS (ESI): m/z 473.1 [M + H]+. 432 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.80 (2H, s), 7.70 (1H, s), 7.59 (1H, s), 7.02 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.39 (1H, d, J = 2.0 Hz), 6.28 (1H, dd, J = 8.0, 2.0 Hz), 4.50-4.66 (4H, m), 3.46 (3H, s); LCMS: 97.1%, MS (ESI): m/z 449.0 [M + H]+. 433 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.80 (2H, s), 7.70 (1H, s), 7.58 (1H, s), 7.08 (1H, t, J = 6.0 Hz), 6.94 (1H, d, J = 8.4 Hz), 6.28 (1H, d, J = 2.0 Hz), 6.23 (1H, dd, J = 8.0, 2.0 Hz), 5.88 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.57 (2H, d, J = 6.0 Hz), 4.46-4.54 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.50 (3H, s); LCMS: 100%, MS (ESI): m/z 507.0 [M + H]+. 434 off-white powder; 1H-NMR (CDCl3, 400 MHz): δ 9.67 (1H, s), 7.71- 7.80 (2H, m), 7.49-7.58 (3H, m), 7.29-7.33 (2H, m), 6.57 (1H, dd, J = 8.4, 2.0 Hz), 6.49 (1H, d, J = 2.0 Hz), 4.76 (2H, s), 4.63 (1H, brs), 3.48 (3H, s); LCMS: 97.5%, MS (ESI): m/z 431.2 [M + H] 435 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.68 (1H, s), 7.88 (1H, t, J = 8.0 Hz), 7.65-7.72 (2H, m), 7.47 (2H, d, J = 8.4 Hz), 7.22 (2H, d, J = 8.4 Hz), 6.98 (1H, brs), 6.95 (1H, d, J = 8.4 Hz), 6.25 (1H, s), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.58 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 99.1%, MS (ESI): m/z 487.2 [M + H]+. 436 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.58 (1H, s), 8.08- 8.17 (2H, m), 7.59 (1H, t, J = 8.0 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.27 (2H, d, J = 8.8 Hz), 6.90 (1H, t, J = 6.0 Hz), 6.88 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.0, 2.0 Hz), 4.47-4.61 (4H, m), 3.43 (3H, s); LCMS: 99.1%, MS (ESI): m/z 431.1 [M + H]+. 437 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.57 (1H, s), 8.06- 8.19 (2H, m), 7.59 (1H, t, J = 8.0 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.27 (2H, d, J = 8.4 Hz), 7.02-7.23 (1H, brs), 6.97 (1H, d, J = 8.0 Hz), 6.28 (1H, s), 6.24 (1H, d, J = 8.4 Hz), 5.89 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.46-4.62 (3H, m), 4.40 (2H, t, J = 6.0 Hz), 3.47 (3H, s); LCMS: 97.8%, MS (ESI): m/z 487.2 [M + H]+. 438 pale green powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.38 (1H, d, J = 8.8 Hz), 8.14 (1H, d, J = 2.0 Hz), 7.96 (1H, d, J = 6.0 Hz), 7.74 (1H, d, J = 9.2, 2.0 Hz), 7.40-7.55 (3H, m), 7.21 (2H, d, J = 8.4 Hz), 6.94 (1H, brs), 6.89 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 2.0 Hz), 6.28 (1H, d, J = 8.4, 2.0 Hz), 4.42-4.69 (4H, m), 3.45 (3H, s); LCMS: 100%, MS (ESI): m/z 430.1 [M + H]+. 439 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.36 (1H, d, J = 8.8 Hz), 8.12 (1H, d, J = 2.0 Hz), 7.93 (1H, d, J = 5.6 Hz), 7.71 (1H, dd, J = 8.8, 2.0 Hz), 7.47 (1H, d, J = 6.0 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.18 (2H, d, J = 8.4 Hz), 6.96 (1H, brs), 6.94 (1H, d, J = 8.0 Hz), 6.24 (1H, d, J = 1.6 Hz), 6.20 (1H, dd, J = 8.0, 2.0 Hz), 5.82 (1H, d, J = 7.6 Hz), 4.83 (2H, t, J = 6.4 Hz), 4.43-4.56 (3H, m), 4.38 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 99.1%, MS (ESI): m/z 486.2 [M + H]+. 440 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.55 (1H, s), 8.16 (1H, d, J = 8.4 Hz), 7.83 (1H, s), 7.63 (1H, dd, J = 8.8, 2.0 Hz), 7.47 (2H, d, J = 8.0 Hz), 7.22 (2H, d, J = 8.4 Hz), 6.98 (1H, brs), 6.89 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.0, 1.6 Hz), 4.67 (2H, brs), 4.55 (2H, d, J = 5.6 Hz), 3.43 (3H, s); LCMS: 98.1%, MS (ESI): m/z 431.2 [M + H]+. 441 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 13.90 (1H, brs), 10.08 (1H, s), 9.80 (1H, brs), 8.74 (2H, s), 7.40-7.65 (8H, m), 7.24 (2H, d, J = 8.8 Hz), 7.09-7.18 (1H, m), 4.79 (2H, d, J = 6.0 Hz), 3.73 (3H, s); LCMS: 100%, MS (ESI): m/z 423.2 [M + H]+. 442 off-white powder; 1H-NMR (CDCl3, 400 MHz): δ 8.48 (1H, d, J = 7.6 Hz), 7.95 (1H, s), 7.49 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.8 Hz), 7.02 (1H, brs), 6.89 (1H, d, J = 8.0 Hz), 6.84 (1H, dd, J = 7.6, 2.4 Hz), 6.74 (1H, d, J = 2.0 Hz), 6.39 (1H, d, J = 1.6 Hz), 6.29 (1H, dd, J = 8.0, 1.6 Hz), 4.54 (2H, d, J = 5.6 Hz), 3.43 (3H, s); LCMS: 98.7%, MS (ESI): m/z 419.1 [M + H]+. 443 white powder (hydroscopic); 1H-NMR (DMSO-d6, 400 MHz): δ 13.11 (1H, s), 9.40 (1H, t, J = 6.0 Hz), 8.74 (2H, s), 7.54 (2H, d, J = 8.4 Hz), 7.33-7.48 (4H, m), 7.12-7.28 (4H, m), 6.61 (1H, s), 6.54 (1H, d, J = 8.4 Hz), 4.70 (2H, d, J = 6.0 Hz), 4.40-4.50 (2H, m), 4.28-4.39 (1H, m), 3.77-3.86 (2H, m), 3.63 (3H, s); LCMS: 99.4%, MS (ESI): m/z 478.3 [M + H]+. 444 yellow powder; 1H NMR (DMSO-d6, 400 MHz): δ 9.55 (1H, s), 8.16 (1H, d, J = 8.8 Hz), 7.82 (1H, d, J = 1.6 Hz), 7.63 (1H, dd, J = 8.4, 2.0 Hz), 7.46 (2H, d, J = 8.4 Hz), 7.21 (2H, d, J = 8.4 Hz), 7.04 (1H, brs), 6.96 (1H, d, J = 8.0 Hz), 6.26 (1H, d, J = 1.6 Hz), 6.20-6.25 (1H, dd, J = 8.0, 2.0 Hz), 5.86 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.0 Hz), 4.56 (2H, d, J = 6.0 Hz), 4.47-4.54 (1H, m), 4.40 (2H, d, J = 6.0 Hz), 3.46 (3H, s); LCMS: 96.9%, MS (ESI): m/z 487.2 [M + H]+. 445 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.29 (1H, d, J = 2.4 Hz), 8.21 (1H, d, J = 2.4 Hz), 7.99 (1H, d, J = 3.6 Hz), 7.76 (2H, d, J = 8.4 Hz), 7.55 (2H, d, J = 8.8 Hz), 6.94 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.71 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 1.6 Hz), 6.26 (1H, d, J = 8.4, 2.0 Hz), 4.40-4.60 (4H, m), 3.43 (3H, s); LCMS: 99.3%, MS (ESI): m/z 430.1 [M + H]+. 446 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.28 (1H, d, J = 2.4 Hz), 8.21 (1H, d, J = 2.4 Hz), 7.99 (1H, d, J = 4.0 Hz), 7.76 (2H, d, J = 8.4 Hz), 7.55 (2H, d, J = 8.4 Hz), 7.00 (1H, t, J = 6.0 Hz), 6.94 (1H, d, J = 8.4 Hz), 6.70 (1H, d, J = 3.6 Hz), 6.26 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.8 Hz), 4.57 (2H, d, J = 6.0 Hz), 4.55-4.60 (1H, m), 4.39 (2H, d, J = 6.0 Hz), 3.46 (3H, s); LCMS: 98.3%, MS (ESI): m/z 459.3 [M + H]+. 447 pale yellow solid; 1H-NMR (DMSO-d6, 400 MHz): δ 8.72 (2H, s), 8.68 (1H, brs), 8.07 (1H, dd, J = 4.8, 1.2 Hz), 7.54 (1H, d, J = 2.0 Hz), 7.40-7.49 (3H, m), 7.11-7.20 (3H, m), 7.07 (1H, d, J = 8.0 Hz), 7.00 (1H, dd, J = 8.4, 2.0 Hz), 6.72 (1H, d, J = 8.4 Hz), 6.61 (1H, dd, J = 6.8, 6.0 Hz), 4.56 (2H, d, J = 6.0 Hz), 3.50 (3H, s); LCMS: 100%, MS (ESI): m/z 458.2 [M + H]+. 448 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.69 (1H, s), 8.17 (1H, d, J = 2.8 Hz), 8.08 (1H, dd, J = 4.8, 2.0 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.55 (1H, d, J = 2.0 Hz), 7.42-7.49 (3H, m), 7.15 (1H, t, J = 6.0 Hz), 7.06-7.11 (4H, m), 7.01 (1H, dd, J = 8.1, 2.0 Hz), 6.73 (1H, d, J = 8.4 Hz), 6.62 (1H, dd, J = 6.4, 5.2 Hz), 4.57 (2H, d, J = 6.0 Hz), 3.51 (3H, s); LCMS: 99.3%, MS (ESI): m/z 457.2 [M + H]+. 449 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.80 (1H, brs), 8.17 (1H, d, J = 2.8 Hz), 8.02 (1H, brs), 7.93 (1H, dd, J = 8.8, 2.8 Hz), 7.50 (1H, d, J = 2.4 Hz), 7.44 (2H, d, J = 8.4 Hz), 7.33 (1H, s), 7.06- 7.10 (3H, m), 6.97-7.03 (2H, m), 6.78 (1H, dd, J = 8.4, 2.0 Hz), 5.78 (1H, d, J = 2.4 Hz), 4.54 (2H, d, J = 5.6 Hz), 3.46 (3H, s); LCMS: 97.2%, MS (ESI): m/z 446.1 [M + H]+. 450 pale yellow solid; 1H-NMR (DMSO-d6, 400 MHz): δ 11.81 (1H, brs), 8.72 (2H, s), 8.02 (1H, s), 7.48 (1H, s), 7.45 (2H, d, J = 8.4 Hz), 7.33 (1H, s), 7.14 (2H, d, J = 8.4 Hz), 7.01 (1H, t, J = 6.0 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 8.8 Hz), 5.77 (1H, d, J = 2.0 Hz), 4.53 (2H, d, J = 6.0 Hz), 3.45 (3H, s); LCMS: 100%, MS (ESI): m/z 447.2 [M + H]+. 451 off-white solid; 1H-NMR (CDCl3, 400 MHz): δ 8.61 (1H, d, J = 2.8 Hz), 8.34 (1H, d, J = 8.8 Hz), 8.09 (1H, dd, J = 8.8, 2.4 Hz), 8.02 (1H, d, J = 3.2 Hz), 7.83 (1H, d, J = 8.8 Hz), 7.34 (1H, d, J = 8.4 Hz), 6.85- 6.95 (2H, m), 6.76 (1H, d, J = 3.6 Hz), 6.38 (1H, d, J = 1.6 Hz), 6.28 (1H, dd, J = 8.4, 2.0 Hz), 4.41-4.72 (4H, m), 3.43 (3H, s); LCMS: 99.6%, MS (ESI): m/z 403.2 [M + H]+. 452 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.71 (2H, s), 7.46 (2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.80 (1H, d, J = 8.0 Hz), 6.60 (1H, d, J = 8.4 Hz), 6.32 (1H, d, J = 1.6 Hz), 6.22 (1H, dd, J = 8.4, 2.0 Hz), 4.79 (1H, q, J = 8.0 Hz), 4.50 (2H, brs), 3.43 (3H, s), 1.65-1.96 (2H, m), 0.93 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI): m/z 409.2 [M + H]+. 453 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 7.49 (2H, d, J = 8.8 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.74 (1H, brs), 6.24 (1H, d, J = 1.6 Hz), 6.20 (1H, dd, J = 8.4, 2.0 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.75-4.91 (3H, m), 4.45-4.61 (1H, m), 4.39 (2H, td, J = 6.0, 2.4 Hz), 3.49 (3H, s), 1.69-2.01 (2H, m), 0.95 (3H, t, J = 7.2 Hz); LCMS: 98.7%, MS (ESI): m/z 465.3 [M + H]+. 454 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.39 (1H, s), 7.44 (2H, d, J = 8.4 Hz), 7.16 (2H, d, J = 8.8 Hz), 6.87-6.94 (1H, m), 6.85 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 2.0 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.55 (2H, brs), 4.51 (2H, d, J = 5.6 Hz), 3.97 (3H, s), 3.41 (3H, s); LCMS: 100%, MS (ESI): m/z 411.1 [M + H]+. 455 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.48 (1H, d, J = 7.6 Hz), 7.95 (1H, s), 7.48 (2H, d, J = 8.4 Hz), 7.12 (2H, d, J = 8.4 Hz), 6.91-6.98 (2H, m), 6.83 (1H, dd, J = 7.6, 2.4 Hz), 6.73 (1H, d, J = 2.4 Hz), 6.20-6.30 (2H, m), 5.83 (1H, d, J = 6.8 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.40 (2H, t, J = 6.0 Hz), 4.49-4.60 (3H, m), 3.45 (3H, s); LCMS: 97.2%, MS (ESI): m/z 475.0 [M + H]+. 456 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.72 (2H, s), 7.45 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.8 Hz), 6.90 (1H, t, J = 6.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.36 (1 H, d, J = 2.0 Hz), 6.26 (1 H, dd, J = 8.4, 2.0 Hz), 4.50-4.53 (4H, m), 3.41 (3H, s), 2.98 (6H, s); LCMS: 100%, MS (ESI): m/z 418.3 [M + H]+. 457 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.61 (1H, d, J = 2.4 Hz), 8.33 (1H, dd, J = 8.8 Hz), 8.08 (1H, dd, J = 8.8, 2.4 Hz), 8.01 (1H, d, J = 3.2 Hz), 7.82 (1H, d, J = 8.8 Hz), 7.64 (1H, s), 7.33 (1H, d, J = 8.4 Hz), 6.83-6.97 (2H, m), 6.75 (1H, d, J = 3.2 Hz), 6.25 (1H, s), 6.21 (1H, d, J = 8.4 Hz), 5.82 (1H, d, J = 7.6 Hz), 4.85 (2H, t, J = 6.4 Hz), 4.62 (2H, d, J = 6.0 Hz), 4.46-4.57 (1H, m), 4.40 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 97.8%, MS (ESI): m/z 459.1 [M + H]+. 458 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.80 (1H, s), 8.51 (2H, s), 7.61 (2H, d, J = 8.4 Hz), 7.31 (2H, d, J = 8.4 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.77 (1H, t, J = 5.8 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.4, 2.0 Hz), 4.56 (2H, brs), 4.44 (2H, d, J = 6.0 Hz), 3.40 (3H, s); LCMS: 98.5%, MS (ESI): 380.1 [M + H]+. 459 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.39 (1H, s), 7.43 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 6.90-6.97 (2H, m), 6.25 (1H, d, J = 2.0 Hz), 6.21 (1H, dd, J = 8.4, 2.0 Hz), 5.82 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.56 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.97 (3H, s), 3.44 (3H, s); LCMS: 99.5%, MS (ESI): m/z 467.1 [M + H]+. 460 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.95 (2H, s), 7.74-7.77 (2H, m), 7.54-7.59 (2H, m), 7.46 (2H, d, J = 8.8 Hz), 7.17 (2H, d, J = 8.8 Hz), 6.90 (1H, t, J = 5.8 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.4, 2.0 Hz), 4.47-4.58 (4H, m), 3.42 (3H, s); LCMS: 100%, MS (ESI): m/z 457.1 [M + H]+. 461 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.80 (1H, brs), 8.51 (2H, s), 7.61 (2H, d, J = 8.8 Hz), 7.30 (2H, d, J = 8.8 Hz), 6.93 (1H, d, J = 8.4 Hz), 6.81 (1H, t, J = 5.8 Hz), 6.24 (1H, d, J = 1.6 Hz), 6.20 (1H, dd, J = 8.4, 1.6 Hz), 5.82 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.48-4.56 (1H, m), 4.45 (2H, d, J = 6.0 Hz), 4.36-4.42 (2H, t, J = 5.8 Hz), 3.43 (3H, s); LCMS: 99.7%, MS (ESI): m/z 436.1 [M + H]+. 462 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.96 (1H, s), 8.65 (1H, brs), 7.47 (2H, d, J = 8.4 Hz), 7.18 (2H, d, J = 8.8 Hz), 6.92 (1H, brs), 6.88 (1H, d, J = 8.4 Hz), 6.37 (1H, d, J = 2.0 Hz), 6.27 (1H, dd, J = 8.0, 2.0 Hz), 4.50-4.70 (4H, m), 3.43 (3H, s), 2.80 (3H, d, J = 4.8 Hz); LCMS: 99.3%, MS (ESI): m/z 404.2 [M + H]+. 463 brown powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.40 (2H, s), 7.40 (2H, d, J = 8.4 Hz), 7.26 (2H, d, J = 8.4 Hz), 6.90 (1H, t, J = 5.8 Hz), 6.86 (1H, d, J = 8.4 Hz), 6.36 (1H, d, J = 1.6 Hz), 6.26 (1H, dd, J = 8.4, 1.6 Hz), 4.59 (2H, brs), 4.50 (2H, d, J = 5.6 Hz), 3.41 (6H, s); LCMS: 100%, MS (ESI): m/z 394.2 [M + H]+. 464 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.72 (2H, s), 7.90 (1H, d, J = 3.6 Hz), 7.59 (1H, s), 7.49 (1H, d, J = 1.6 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.34 (1H, d, J = 6.8 Hz), 7.10-7.19 (4H, m), 7.05 (1H, d, J = 8.8 Hz), 6.57-6.62 (1H, m), 4.57 (2H, d, J = 5.6 Hz), 3.49 (3H, s), 2.22 (3H, s); LCMS: 96.4%, MS (ESI): m/z 472.2 [M + H]+. 465 pale yellow solid; 1H-NMR (DMSO-d6, 400 MHz): δ 8.74 (2H, s), 7.91 (1H, brs), 7.47 (2H, d, J = 8.4 Hz), 7.22 (1H, d, J = 2.0 Hz), 7.16 (2H, d, J = 8.8 Hz), 7.04 (1H, t, J = 6.0 Hz), 6.99 (1H, d, J = 8.4 Hz), 6.84 (1H, dd, J = 8.4, 2.0 Hz), 5.58 (1H, s), 4.55 (2H, d, J = 5.6 Hz), 3.60 (3H, s), 3.48 (3H, s), 2.19 (3H, s); LCMS: 98.3%, MS (ESI): m/z 475.3 [M + H]+. 466 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.48 (1H, brs), 8.17 (1H, d, J = 2.0 Hz), 7.90-7.95 (2H, m), 7.44 (2H, d, J = 8.8 Hz), 7.32-7.35 (1H, m), 7.04-7.15 (3H, m), 6.92-7.04 (2H, m), 6.77 (1H, d, J = 8.0 Hz), 5.55 (1H, s), 4.54 (2H, d, J = 6.0 Hz), 3.46 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 460.3 [M + H]+. 467 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.48 (1H, s), 8.95 (2H, s), 7.92 (1H, s), 7.75 (2H, d, J = 8.4 Hz), 7.56 (2H, d, J = 8.4 Hz), 7.47 (2H, d, J = 8.4 Hz), 7.34 (1H, s), 7.17 (2H, d, J = 8.0 Hz), 7.01 (1H, t, J = 5.6 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 7.2 Hz), 5.55 (1H, s), 4.55 (2H, d, J = 5.6 Hz), 3.47 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 537.1 [M + H]+. 468 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.74 (2H, s), 8.38 (1H, brs), 7.47 (2H, d, J = 8.8 Hz), 7.24 (1H, d, J = 2.0 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.12 (1H, brs), 7.05 (2H, d, J = 8.4 Hz), 6.89 (1H, dd, J = 8.4, 2.0 Hz), 6.27 (1H, s), 4.57 (2H, d, J = 5.6 Hz), 3.85 (3H, s), 3.51 (3H, s); LCMS: 100%, MS (ESI): m/z 529.4 [M + H]+. 469 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.57 (1H, brs), 8.74 (2H, s), 7.94 (1H, brs), 7.35-7.51 (3H, m), 7.17 (2H, d, J = 8.4 Hz), 7.01 (1H, brs), 6.99 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 8.8 Hz), 5.53 (1H, s), 4.56 (2H, d, J = 5.6 Hz), 3.46 (3H, s), 1.26 (9H, s); LCMS: 97.9%, MS (ESI): m/z 503.2 [M + H]+. 470 yellow solid; 1H-NMR (DMSO-d6, 400 MHz): δ 11.52 (1H, brs), 8.72 (2H, s), 8.06 (1H, brs), 7.93 (1H, brs), 7.40-7.53 (3H, m), 7.18 (2H, d, J = 8.4 Hz), 7.01 (1H, d, J = 8.4 Hz), 6.84 (1H, d, J = 8.0), 5.53 (1H, s), 4.51 (2H, d, J = 3.6 Hz), 2.15 (3H, s); LCMS: 95.9%, MS (ESI): m/z 447.2 [M + H]+. 471 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.48 (1H, brs), 8.40 (2H, s), 7.91 (1H, brs), 7.41 (2H, d, J = 8.4 Hz), 7.33 (1H, s), 7.26 (2H, d, J = 8.0 Hz), 6.93-7.05 (2H, m), 6.77 (1H, d, J = 7.2 Hz), 5.55 (1H, s), 4.53 (2H, d, J = 5.2 Hz), 3.46 (3H, s), 3.42 (3H, s), 2.16 (3H, s); LCMS: 97.7%, MS (ESI): m/z 474.2 [M + H]+. 472 off-white solid; 1H-NMR (DMSO-d6, 400 MHz): δ 8.72 (2H, s), 7.21- 7.39 (3H, m), 7.08 (2H, d, J = 8.4 Hz), 6.84 (1H, d, J = 8.0 Hz), 6.37 (1H, brs), 6.26 (1H, d, J = 7.6 Hz), 4.55 (2H, brs), 3.43 (3H, s), 1.20- 1.38 (4H, m); LCMS: 99.8%, MS (ESI): m/z 407.1 [M + H]+. 473 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.49 (1H, brs), 8.77 (2H, s), 7.95 (1H, brs), 7.60 (1H, d, J = 1.6 Hz), 7.46 (1H, dd, J = 8.4, 2.0 Hz), 7.32-7.42 (2H, m), 7.10 (1H, brs), 6.99 (1H, d, J = 8.4 Hz), 6.75-6.80 (1H, m), 5.55 (1H, s), 4.55 (2H, d, J = 4.8 Hz), 3.47 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 495.2 [M + H]+. 474 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.42 (1H, brs), 8.72 (2H, s), 7.44 (2H, d, J = 8.8 Hz), 7.21-7.34 (2H, m), 7.14 (2H, d, J = 8.8 Hz), 7.02 (1H, brs), 6.95 (1H, d, J = 8.4 Hz), 6.76-6.88 (1H, m), 4.53 (2H, d, J = 5.6 Hz), 3.43 (3H, s), 2.08 (3H, s), 1.82 (3H, s); LCMS: 100%, MS (ESI): m/z 475.2 [M + H]+. 475 brown powder; 1H NMR (DMSO-d6): δ 12.78 (1H, brs), 8.73 (2H, s), 8.27 (1H, brs), 7.45 (2H, d, J = 8.4 Hz), 7.11-7.23 (3H, m), 7.07 (1H, d, J = 8.0 Hz), 6.85 (1H, brs), 6.66 (1H, d, J = 8.0 Hz), 6.08 (1H, s), 4.56 (2H, d, J = 6.0 Hz), 3.50 (3H, s); LCMS: 100%, MS (ESI): m/z 515.1 [M + H]+. 476 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.49 (1H, brs), 8.72 (2H, s), 7.91 (1H, brs), 7.43 (2H, d, J = 8.8 Hz), 7.37 (1H, s), 7.14 (2H, d, J = 8.4 Hz), 7.04 (1H, brs), 6.96 (1H, d, J = 8.4 Hz), 6.75 (1H, d, J = 8.0 Hz), 5.53 (1H, s), 4.54 (2H, d, J = 6.0 Hz), 3.96 (2H, q, J = 7.2 Hz), 2.14 (3H, s), 1.22 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 475.2 [M + H]+. 477 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.46 (1H, brs), 8.72 (2H, s), 7.89 (1H, s), 7.48 (2H, d, J = 8.4 Hz), 7.29 (1H, s), 7.13 (2H, d, J = 8.4 Hz), 6.92 (1H, d, J = 8.4 Hz), 6.70-6.74 (2H, m), 5.54 (1H, s), 4.80-4.87 (1H, m), 3.48 (3H, s), 2.15 (3H, s), 1.76-1.94 (2H, m), 0.94 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI): m/z 489.2 [M + H]+. 478 red powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.49 (1H, brs), 8.72 (2H, s), 7.91 (1H, brs), 7.40 (1H, brs), 7.21-7.38 (3H, m), 7.08 (2H, d, J = 8.8 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.75 (1H, d, J = 8.0 Hz), 5.55 (1H, s), 3.48 (3H, s), 2.16 (3H, s), 1.20-1.39 (4H, m); LCMS: 89.0%, MS (ESI): m/z 487.2 [M + H]+. 479 off-white powder; 1H-NMR (DMSO-d6): δ 11.48 (1H, brs), 9.09 (2H, s), 7.91 (1H, brs), 7.48 (2H, d, J = 8.8 Hz), 7.34 (1H, s), 7.21 (2H, d, J = 8.4 Hz), 7.03 (1H, t, J = 6.0 Hz), 6.97 (1H, d, J = 8.0 Hz), 6.77 (1H, d, J = 8.0 Hz), 5.55 (1H, s), 4.56 (2H, d, J = 6.0 Hz), 3.46 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 495.2 [M + H]+. 480 off-white powder; 1H NMR (DMSO-d6): δ 8.74 (2H, s), 7.79 (1H, brs), 7.59 (1H, brs), 7.42-7.50 (3H, m), 7.21 (3H, d, J = 8.4 Hz), 6.94 (1H, d, J = 9.2 Hz), 5.76 (1H, d, J = 2.0 Hz), 4.59 (2H, d, J = 6.0 Hz), 3.70 (3H, s); LCMS: 99.0%, MS (ESI): m/z 465.1 [M + H]+. 481 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 12.02 (1H, brs), 8.76 (2H, s), 7.52 (1H, brs), 7.47 (2H, d, J = 8.8 Hz), 7.30 (1H, s), 7.17 (2H, d, J = 8.0 Hz), 7.07 (1H, brs), 7.00 (1H, d, J = 8.8 Hz), 6.94 (1H, d, J = 8.0 Hz), 4.56 (2H, d, J = 6.0 Hz), 3.46 (3H, s), 2.18 (3H, s); LCMS: 95.4%, MS (ESI): m/z 475.2 [M + H]+. From LCMS, the product contains 4.6% impurity of de-Cl of compound 1. 482 off-white powder; 1H-NMR (CDCl3, 400 MHz): δ 8.50 (2H, s), 7.52 (2H, d, J = 8.4 Hz), 7.37 (1H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 7.07 (1H, s), 6.83 (1H, dd, J = 8.4, 1.6 Hz), 6.05 (1H, brs), 5.75 (1H, s), 4.73 (2H, s), 4.33 (1H, brs), 3.41 (3H, s), 2.28 (3H, s); LCMS: 98.0%, MS (ESI): m/z 511.1 [M + H]+. 483 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 12.25 (1H, brs), 8.95 (1H, s), 8.72 (2H, s), 8.11 (1H, s), 8.02 (1H, s), 7.55 (1H, s), 7.45 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.10 (1H, brs), 7.04 (1H, d, J = 8.8 Hz), 6.94 (1H, d, J = 8.4 Hz), 4.55 (2H, d, J = 5.6 Hz), 3.49 (3H, s), 2.64-2.81 (1H, m), 0.60-0.76 (2H, m), 0.41-0.53 (2H, m); LCMS: 100%, MS (ESI): m/z 530.4 [M + H]+. 484 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.43 (1H, brs), 10.60 (0.6H, brs), 10.48 (0.4H, brs), 8.74 (2H, s), 7.83 (0.6H, brs), 7.70 (0.4H, brs), 7.31-7.48 (2.6H, m), 7.10-7.26 (2.4H, m), 6.83-7.01 (2H, m), 6.62-6.80 (1H, m), 5.53 (1H, s), 4.41-4.55 (2H, m), 2.16 (3H, s); LCMS: 99.6%, MS (ESI): m/z 447.1 [M + H]+. 485 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.44 (1H, brs), 10.33-10.78 (1H, m), 8.74 (2H, s), 7.65-7.90 (1H, m), 7.44 (2H, d, J = 8.4 Hz), 7.21-7.40 (1H, m), 7.16 (2H, d, J = 8.8 Hz), 6.81-7.00 (2H, m), 6.73 (1H, d, J = 7.2 Hz), 5.53 (1H, s), 4.48 (2H, d, J = 5.6 Hz), 2.16 (3H, s); LCMS: 99.3%, MS (ESI): m/z 447.2 [M + H]+. 486 off-white powder; 1H NMR (DMSO-d6): δ 11.48 (1H, brs), 9.80 (1H, brs), 8.51 (2H, s), 7.91 (1H, brs), 7.62 (2H, d, J = 8.8 Hz), 7.25-7.39 (3H, m), 6.98 (1H, d, J = 8.4 Hz), 6.90 (1H, brs), 6.76 (1H, d, J = 7.2 Hz), 5.55 (1H, s), 4.47 (2H, d, J = 5.6 Hz), 3.44 (3H, s), 2.16 (3H, s); LCMS: 95.9%, MS (ESI): m/z 460.2 [M + H]+. 487 off-white powder; 1H NMR (DMSO-d6): δ 8.73 (2H, s), 7.56 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.37-7.43 (2H, m), 7.23 (1H, t, J = 6.0 Hz), 7.17 (2H, d, J = 8.4 Hz), 6.86 (1H, d, J = 8.8 Hz), 5.71 (1H, d, J = 2.4 Hz), 4.55 (2H, d, J = 6.0 Hz), 3.69 (3H, s), 3.68 (3H, s); LCMS: 98.6%, MS (ESI): m/z 479.2 [M + H]+. 488 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 12.27 (1H, brs), 8.91 (1H, s), 8.72 (2H, s), 8.14 (1H, brs), 7.53 (2H, brs), 7.45 (2H, d, J = 8.8 Hz), 7.10-7.21 (3H, m), 6.82-7.09 (3H, m), 4.55 (2H, d, J = 5.6 Hz), 3.49 (3H, s); LCMS: 100%, MS (ESI): m/z 489.9 [M + H]+. 489 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.49 (1H, brs), 8.54 (1H, s), 8.49 (1H, s), 7.95 (1H, brs), 7.47 (2H, d, J = 8.4 Hz), 7.35 (1H, s), 7.20 (2H, d, J = 8.4 Hz), 6.99 (1H, d, J = 8.8 Hz), 6.70-6.80 (1H, m), 5.56 (1H, s), 4.56 (2H, d, J = 6.0 Hz), 3.47 (3H, s), 2.16 (3H, s); LCMS: 99%, MS (ESI): m/z 461.2 [M + H]+. 490 light yellow powder; 1H NMR (DMSO-d6): δ 11.48 (1H, brs), 8.41 (1H, s), 8.32 (1H, s), 7.92 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.34 (1H, s), 7.17 (2H, d, J = 8.4 Hz), 7.03 (1H, brs), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 7.6 Hz), 5.55 (1H, s), 4.54 (2H, d, J = 5.6 Hz), 3.46 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 462.1 [M + H]+. 491 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.51 (1H, brs), 8.74 (2H, s), 7.97 (1H, brs), 7.47 (2H, d, J = 8.4 Hz), 7.31 (1H, s), 7.09-7.22 (3H, m), 7.01 (1H, d, J = 8.4 Hz), 6.86 (1H, d, J = 7.6 Hz), 5.57 (1H, s), 4.56 (2H, d, J = 5.2 Hz), 4.24 (2H, t, J = 7.2 Hz), 2.61- 2.80 (2H, m), 2.17 (3H, s); LCMS: 98.6%, MS (ESI): m/z 543.3 [M + H]+. 492 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.75 (1H, brs), 8.73 (2H, s), 7.62 (1H, s), 7.47 (1H, d, J = 8.8 Hz), 7.17 (1H, d, J = 8.8 Hz), 7.11 (1H, d, J = 8.0 Hz), 6.99 (1H, d, J = 8.0 Hz), 6.86 (1H, s), 4.58 (1H, d, J = 5.6 Hz), 3.52 (3H, s), 2.27 (3H, s). LCMS: 96.4%, MS (ESI): m/z 478.0 [M + H]+. 493 off-white powder; 1H NMR (DMSO-d6, 400 MHz): δ 10.24 (1H, brs), 8.73 (2H, s), 8.28-8.35 (1H, m), 7.46 (2H, d, J = 8.8 Hz), 7.38 (1H, d, J = 1.6 Hz), 7.27 (1H, t, J = 6.0 Hz), 7.16 (2H, d, J = 8.8 Hz), 7.13 (1H, s), 7.08-7.12 (1H, dd, J = 8.4, 2.0 Hz), 4.57 (2H, d, J = 6.0 Hz), 3.51 (3H, s); LCMS: 100%, MS (ESI): m/z 516.1 [M + H]+. 494 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 10.29 (1H, brs), 8.73 (2H, s), 7.45-7.60 (3H, m), 7.30-7.45 (2H, m), 7.10-7.25 (3H, m), 7.04 (1H, d, J = 8.8 Hz), 4.58 (1H, d, J = 6.0 Hz), 3.52 (3H, s); LCMS: 100%, MS (ESI): m/z 532.0 [M + H]+. 495 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.49 (1H, brs), 8.55 (1H, s), 8.20 (1H, dd, J = 8.8, 2.4 Hz), 7.93 (1H, brs), 7.47 (2H, d, J = 8.0 Hz), 7.33 (1H, s), 7.23 (1H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.4 Hz), 7.05 (1H, t, J = 5.6 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 8.0 Hz), 5.56 (1H, s), 4.50 (2H, d, J = 6.0 Hz), 3.47 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 494.2 [M + H]+. 496 off-white powder; 1H NMR (DMSO-d6, 400 MHz): δ 11.48 (1H, brs), 8.23 (1H, d, J = 2.4 Hz), 7.86-8.01 (2H, m), 7.45 (2H, d, J = 8.4 Hz), 7.34 (1H, s), 7.16 (1H, d, J = 9.2 Hz), 7.11 (2H, d, J = 8.8 Hz), 7.01 (1H, t, J = 5.6 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 7.2 Hz), 5.55 (1H, s), 4.54 (2H, d, J = 5.6 Hz), 3.46 (3H, s), 2.16 (3H, s); LCMS: 100%, MS (ESI): m/z 510.1 [M + H]+. 497 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.60 (1H, brs), 8.75 (2H, s), 8.22 (1H, brs), 7.95 (1H, s), 7.75 (1H, s), 7.61 (1H, brs), 7.48 (2H, d, J = 8.4 Hz), 7.19 (2H, d, J = 8.0 Hz), 5.57 (1H, s), 4.61 (2H, d, J = 4.4 Hz), 3.52 (3H, s), 2.19 (3H, s); LCMS: 96.4%, MS (ESI): m/z 462.0 [M + H]+. 498 off-white powder; 1H NMR (DMSO-d6, 400 MHz): δ 10.04 (1H, s), 8.73 (2H, s), 7.50 (1H, d, J = 2.0 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.25 (1H, t, J = 6.0 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.11 (1H, d, J = 8.4 Hz), 6.99 (1H, dd, J = 8.4, 2.0 Hz), 4.57 (2H, d, J = 6.0 Hz), 3.52 (3H, s), 2.38 (3H, s); LCMS: 99.2%, MS (ESI): m/z 463.0 [M + H]+. 499 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.56 (1H, brs), 8.73 (2H, s), 8.15 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.10-7.20 (3H, m), 7.05 (1H, s), 6.79 (1H, d, J = 13.6 Hz), 5.56 (1H, s), 4.56 (2H, d, J = 5.6 Hz), 3.46 (3H, s), 2.17 (3H, s); LCMS: 99.0%, MS (ESI): m/z 479.0 [M + H]+. 500 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.75 (1H, s), 8.68 (2H, s), 8.63 (1H, s), 7.81 (1H, t, J = 6.0 Hz), 7.50 (1H, d, J = 8.0 Hz), 7.41 (2H, d, J = 8.8 Hz), 7.07 (2H, d, J = 8.8 Hz), 7.01 (1H, d, J = 8.0 Hz), 5.57 (1H, s), 4.61 (2H, d, J = 6.0 Hz), 3.54 (3H, s), 2.17 (3H, s); LCMS: 93.0%, MS (ESI): m/z 462.1 [M + H]+. 501 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.83 (1H, brs), 8.73 (2H, s), 7.35-7.70 (4H, m), 7.00-7.25 (5H, m), 6.32 (1H, s), 4.58 (2H, d, J = 6.0 Hz), 3.52 (3H, s), 2.20 (3H, s); LCMS: 98.7%, MS (ESI): m/z 478.1 [M + H]+. 502 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.37 (1H, s), 8.18 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.23 (1H, d, J = 2.0 Hz), 7.01-7.16 (5H, m), 6.88 (1H, dd, J = 8.0, 2.0 Hz), 6.26 (1H, s), 4.55 (2H, d, J = 6.0 Hz), 3.84 (3H, s), 3.50 (3H, s); LCMS: 100%, MS (ESI): m/z 528.2 [M + H]+. 503 white powder; 1H-NMR (DSMO-d6, 400 MHz): δ 8.76 (2H, s), 8.39 (1H, brs), 7.52 (1H, t, J = 8.4 Hz), 7.20-7.25 (2H, m), 7.11 (1H, brs), 7.05 (2H, d, J = 8.0 Hz), 6.88 (1H, dd, J = 8.4, 2.0 Hz), 6.26 (1H, s), 4.58 (2H, d, J = 5.6 Hz), 3.83 (3H, s), 3.51 (3H, s); LCMS: 97.3%, MS (ESI): m/z 547.1 [M + H]+. 504 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.74 (2H, s), 8.38 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.24-7.35 (2H, m), 7.18 (2H, d, J = 8.4 Hz), 7.06 (1H, d, J = 8.0 Hz), 6.92 (1H, d, J = 8.4 Hz), 6.26 (1H, s), 4.58 (2H, d, J = 5.6 Hz), 4.03 (2H, q, J = 6.8 Hz), 3.84 (3H, s), 1.26 (3H, t, J = 6.8 Hz); LCMS: 98.4%, MS (ESI): m/z 543.0 [M + H]+. 505 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.72 (2H, s), 8.34 (1H, brs), 7.50 (2H, d, J = 8.4 Hz), 7.20 (1H, d, J = 1.6 Hz), 7.15 (2H, d, J = 8.8 Hz), 7.00 (1H, d, J = 8.4 Hz), 6.86 (1H, dd, J = 2.4, 0.4 Hz), 6.81 (1H, d, J = 8.4 Hz), 6.24 (1H, s), 4.82-4.88 (1H, m), 3.83 (3H, s), 3.52 (3H, s), 1.76-1.94 (2H, m), 0.95 (3H, t, J = 7.2 Hz); LCMS: 99.8%, MS (ESI): m/z 557.1 [M + H]+. 506 off-white solid; 1H-NMR (DMSO-d6, 400 MHz): δ 8.78 (2H, s), 8.56 (1H, brs), 7.51 (1H, t, J = 8.4 Hz), 7.35 (1H, brs), 7.27 (1H, d, J = 9.2 Hz), 7.09-7.20 (2H, m), 6.95-7.06 (1H, m), 6.28 (1H, s), 4.63 (2H, d, J = 5.2 Hz), 4.00-4.10 (2H, m), 3.85 (3H, s), 1.28 (3H, t, J = 6.8 Hz); LCMS: 99.8%, MS (ESI): m/z 561.0 [M + H]+. 507 off-white powder; 1H NMR (DMSO-d6, 400 MHz): δ 11.59 (1H, brs), 8.73 (1H, s), 8.70 (1H, s), 7.95 (1H, brs), 7.40-7.57 (3H, m), 7.22 (2H, d, J = 8.4 Hz), 7.07 (1H, t, J = 6.0 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.74 (1H, d, J = 8.4 Hz), 5.51 (1H, s), 4.57 (2H, d, J = 6.0 Hz), 3.97 (2H, q, J = 6.8 Hz), 1.21-1.28 (12H, m); LCMS: 98.9%, MS (ESI): m/z 551.0 [M + H]+. 508 off-white solid; 1H-NMR (DMSO-d6, 400 MHz): δ 12.09 (1H, brs), 8.74 (1H, s), 8.70 (1H, s), 7.60 (1H, brs), 7.49 (2H, d, J = 8.4 Hz), 7.43 (1H, s), 7.24 (2H, d, J = 8.4 Hz), 6.91-7.10 (2H, m), 4.59 (2H, d, J = 6.0 Hz), 4.00 (2H, q, J = 6.8 Hz), 2.18 (3H, s), 1.25 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 543.0 [M + H]+. 509 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.59 (1H, brs), 8.72 (2H, s), 7.94 (1H, brs), 7.50 (1H, s), 7.43 (2H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 7.04 (1H, brs), 6.96 (1H, d, J = 8.0 Hz), 6.72 (1H, d, J = 8.4 Hz), 5.49 (1H, s), 4.54 (2H, d, J = 5.6 Hz), 3.95-4.00 (2H, m), 1.20-1.25 (12H, m); LCMS: 98.7%, MS (ESI): m/z 517.1 [M + H]+. 510 off-white powder; 1H NMR (DMSO-d6): δ 8.41 (1H, d, J = 1.2 Hz), 8.35 (1H, s), 8.32 (1H, d, J = 1.6 Hz), 7.45 (2H, d, J = 8.8 Hz), 7.22 (1H, d, J = 1.6 Hz), 7.17 (2H, d, J = 8.4 Hz), 7.13 (1H, t, J = 5.6 Hz), 7.03 (1H, d, J = 8.4 Hz), 6.90 (1H, dd, J = 8.4, 2.0 Hz), 6.24 (1H, s), 4.56 (2H, d, J = 5.6 Hz), 4.01 (2H, q, J = 6.8 Hz), 3.82 (3H, s), 1.24 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 543.1 [M + H]+. 511 white powder; 1H-NMR (CDCl3, 400 MHz): δ 8.35 (1H, s), 8.17 (1H, d, J = 2.8 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.42 (2H, d, J = 8.4 Hz), 7.22 (1H, d, J = 1.6 Hz), 7.06-7.16 (4H, m), 7.04 (1H, d, J = 8.8 Hz), 6.90 (1H, dd, J = 8.0, 2.0 Hz), 6.24 (1H, s), 4.55 (2H, d, J = 6.0 Hz), 4.01 (2H, q, J = 6.8 Hz), 3.83 (3H, s), 1.24 (3H, t, J = 7.2 Hz); LCMS: 99.0%, MS (ESI): m/z 542.0 [M + H]+. 512 off-white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 12.05 (1H, brs), 8.74 (2H, s), 7.51 (1H, brs), 7.44 (2H, d, J = 8.4 Hz), 7.39 (1H, s), 7.16 (2H, d, J = 8.4 Hz), 7.10 (1H, s), 6.93-7.05 (2H, m), 4.60 (2H, d, J = 6.4 Hz), 3.97 (2H, q, J = 6.8 Hz), 2.17 (3H, s), 1.24 (3H, t, J = 7.2 Hz); LCMS: 97.6%, MS (ESI): m/z 508.9 [M + H]+. 513 off-white powder; 1H NMR (DMSO-d6, 400 MHz): δ 11.60 (1H, brs), 9.09 (2H, s), 7.96 (1H, brs), 7.51 (1H, s), 7.47 (2H, d, J = 8.0 Hz), 7.21 (2H, d, J = 8.4 Hz), 7.08 (1H, t, J = 6.0 Hz), 6.98 (1H, d, J = 8.4 Hz), 6.74 (1H, d, J = 8.4 Hz), 5.51 (1H, s), 4.57 (2H, d, J = 6.0 Hz), 3.98 (2H, q, J = 6.8 Hz), 1.20-1.28 (12H, m); LCMS: 94.2%, MS (ESI): m/z 551.1 [M + H]+. 514 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 11.59 (1H, brs), 8.41 (1H, s), 8.32 (1H, s), 7.95 (1H, brs), 7.50 (1H, s), 7.45 (2H, d, J = 8.4 Hz), 7.17 (2H, d, J = 8.8 Hz), 7.06 (1H, brs), 6.98 (1H, d, J = 8.0 Hz), 6.74 (1H, d, J = 8.4 Hz), 5.51 (1H, s), 4.55 (2H, d, J = 5.6 Hz), 3.97 (2H, q, J = 6.8 Hz), 1.21-1.26 (12H, m); LCMS: 99.4%, MS (ESI): m/z 517.0 [M + H]+. 515 off-white solid; 1H-NMR (DMSO-d6, 400 MHz): δ 12.07 (1H, brs), 8.43 (1H, s), 8.34 (1H, s), 7.55 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.40 (1H, s), 7.11-7.27 (3H, m), 6.95-7.04 (2H, m), 4.57 (2H, d, J = 5.6 Hz), 3.90-4.00 (2H, m), 2.18 (3H, s), 1.25 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 508.9 [M + H]+. 516 yellow solid; 1H-NMR (DMSO-d6, 400 MHz): δ 12.06 (1H, brs), 9.10 (2H, s), 7.44-7.59 (3H, m), 7.39 (1H, s), 7.22 (2H, d, J = 8.4 Hz), 7.12 (1H, brs), 6.97-7.06 (2H, m), 4.58 (2H, d, J = 6.0 Hz), 3.98 (2H, q, J = 6.8 Hz), 2.18 (3H, s), 1.25 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 543.0 [M + H]+. 517 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.41 (1H, d, J = 1.2 Hz), 8.36 (1H, brs), 8.32 (1H, d, J = 1.2 Hz), 7.50 (2H, d, J = 8.4 Hz), 7.20 (1H, s), 7.15 (2H, d, J = 8.8 Hz), 6.99 (1H, d, J = 8.4 Hz), 6.80-6.85 (2H, m), 6.24 (1H, s), 4.80-4.90 (1H, m), 3.83 (3H, s), 3.52 (3H, s), 1.74-1.97 (2H, m), 0.94 (3H, t, J = 8.8 Hz); LCMS: 100%, MS (ESI): m/z 557.0 [M + H]+. 518 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 12.02 (1H, brs), 8.17 (1H, d, J = 2.4 Hz), 7.94 (1H, dd, J = 8.8, 2.8 Hz), 7.49 (1H, s), 7.44 (2H, d, J = 8.8 Hz), 7.35 (1H, s), 7.01-7.11 (4H, m), 6.94-7.01 (2H, m), 4.54 (2H, d, J = 6.0 Hz), 3.45 (3H, s), 2.17 (3H, s); LCMS: 99.1%, MS (ESI): m/z 493.9 [M + H]+. 519 yellow powder; 1H-NMR (DSMO-d6, 400 MHz): δ 9.10 (2H, s), 8.39 (1H, brs), 7.50 (2H, d, J = 8.4 Hz), 7.25 (1H, d, J = 2.0 Hz), 7.22 (2H, d, J = 8.8 Hz), 7.14 (1H, brs), 7.05 (1H, d, J = 8.0 Hz), 6.89 (1H, dd, J = 8.4, 2.0 Hz), 6.27 (1H, s), 4.58 (2H, d, J = 6.0 Hz), 3.84 (3H, s), 3.51 (3H, s); LCMS: 100%, MS (ESI): m/z 563.0 [M + H]+. 520 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.09 (2H, s), 8.35 (1H, brs), 7.52 (2H, d, J = 8.4 Hz), 7.15-7.24 (3H, m), 6.99 (1H, d, J = 8.8 Hz), 6.78-6.89 (2H, m), 6.24 (1H, s), 4.79-4.95 (1H, m), 3.83 (3H, s), 3.53 (3H, s), 1.72-2.00 (2H, m), 0.96 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI): m/z 591.0 [M + H]+. 521 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.10 (2H, s), 8.36 (1H, brs), 7.48 (2H, d, J = 8.8 Hz), 7.21-7.27 (3H, m), 7.17 (1H, brs), 7.05 (1H, d, J = 8.4 Hz), 6.91 (1H, dd, J = 8.4, 2.0 Hz), 6.25 (1H, s), 4.59 (2H, d, J = 5.6 Hz), 4.03 (2H, q, J = 7.2 Hz), 3.84 (3H, s), 1.26 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI): m/z 577.0 [M + H]+. 522 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.72 (1H, s), 8.69 (1H, s), 8.36 (1H, brs), 7.53 (2H, d, J = 8.4 Hz), 7.19-7.24 (3H, m), 7.00 (1H, d, J = 8.0 Hz), 6.77-6.90 (2H, m), 6.24 (1H, s), 4.82-4.91 (1H, m), 3.83 (3H, s), 3.53 (3H, s), 1.73-1.99 (2H, m), 0.95 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI): m/z 590.9 [M + H]+. 523 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.73 (1H, s), 8.70 (1H, s), 8.35 (1H, brs), 7.48 (2H, d, J = 8.4 Hz), 7.20-7.30 (3H, m), 7.15 (1H, t, J = 6.0 Hz), 7.03 (1H, d, J = 8.4 Hz), 6.89 (1H, dd, J = 8.4, 2.4 Hz), 6.24 (1H, s), 4.57 (1H, d, J = 6.0 Hz), 4.02 (2H, q, J = 6.8 Hz), 3.83 (3H, s), 1.24 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI): m/z 577.1 [M + H]+. 524 a white powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 8.60 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.25 (1H, t, J = 6.0 Hz), 7.17 (2H, d, J = 8.4 Hz), 6.99 (1H, s), 6.87 (1H, d, J = 13.2 Hz), 6.29 (1H, s), 4.57 (2H, d, J = 6.0 Hz), 3.85 (3H, s), 3.50 (3H, s); LCMS: 100%, MS (ESI): m/z 546.9 [M + H]+. 525 off-white solid; 1H-NMR (DMSO-d6, 400 MHz): δ 9.10 (2H, s), 8.01 (1H, brs), 7.42-7.51 (3H, m), 7.20-7.31 (3H, m), 7.11 (1H, brs), 7.00 (1H, d, J = 8.4 Hz), 6.88 (1H, d, J = 8.4 Hz), 5.73 (1H, d, J = 2.0 Hz), 4.57 (2H, d, J = 5.6 Hz), 4.00 (2H, q, J = 6.8 Hz), 3.72 (3H, s), 1.25 (3H, t, J = 7.2 Hz); LCMS: 99.2%, MS (ESI): m/z 509.0 [M + H]+. 526 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.74 (2H, s), 8.02 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.23 (1H, brs), 7.17 (2H, d, J = 8.4 Hz), 7.10 (1H, d, J = 8.0 Hz), 6.83 (1H, d, J = 1.6 Hz), 6.69 (1H, dd, J = 8.4, 2.0 Hz), 6.14 (1H, s), 4.57 (2H, d, J = 6.0 Hz), 3.74 (3H, s), 3.50 (3H, s); LCMS: 98.4%, MS (ESI): m/z 529.1 [M + H]+. 527 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.13 (2H, s), 8.38 (1H, brs), 7.52 (1H, t, J = 8.8 Hz), 7.29 (1H, dd, J = 10.8, 2.4 Hz), 7.25 (1H, d, J = 2.0 Hz), 7.16 (1H, brs), 7.11 (1H, dd, J = 8.4, 1.6 Hz), 7.06 (1H, d, J = 8.4 Hz), 6.91 (1H, dd, J = 8.0, 2.0 Hz), 6.26 (1H, s), 4.61 (2H, d, J = 6.0 Hz), 4.04 (2H, q, J = 2.8 Hz), 3.84 (3H, s), 1.26 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 595.1 [M + H]+. 528 white solid; 1H NMR (DMSO-d6, 400 MHz): δ 9.12 (2H, s), 8.38 (1H, brs), 7.60 (1H, t, J = 8.8 Hz), 7.19-7.28 (2H, m), 7.06-7.13 (1H, m), 7.01 (1H, d, J = 8.4 Hz), 6.80-6.94 (2H, m), 6.25 (1H, s), 5.10-5.20 (1H, m), 3.83 (3H, s), 3.55 (3H, s), 1.74-1.98 (2H, m), 0.99 (3H, t, J = 7.2 Hz); LCMS: 99.2%, MS (ESI): m/z 609.0 [M + H]+. 529 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.53 (1H, brs), 8.71 (2H, s), 7.90 (1H, brs), 7.48 (2H, d, J = 8.4 Hz), 7.31 (1H, s), 7.13 (2H, d, J = 8.4 Hz), 6.92 (1H, d, J = 8.4 Hz), 6.60-6.81 (2H, m), 5.51 (1H, s), 4.83 (1H, q, J = 8.0 Hz), 3.47 (3H, s), 2.75-2.91 (1H, m), 1.70- 2.01 (2H, m), 1.18 (6H, d, J = 7.2 Hz), 0.94 (3H, t, J = 7.2 Hz); LCMS: 98.0%, MS (ESI): m/z 517.1 [M + H]+. 530 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.51 (1H, brs), 8.69 (2H, s), 7.85 (1H, brs), 7.45 (2H, d, J = 8.8 Hz), 7.23 (1H, s), 7.11 (2H, d, J = 8.4 Hz), 6.89 (1H, d, J = 8.4 Hz), 6.61-6.82 (2H, m), 5.41 (1H, s), 4.70-4.85 (1H, m), 3.66 (3H, s), 1.65-1.96 (3H, m), 0.76-0.99 (5H, m), 0.55-0.64 (2H, m); LCMS: 96.3%, MS (ESI): m/z 537.0 [M + Na]+. 531 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 11.50 (1H, brs), 9.09 (2H, s), 7.95 (1H, brs), 7.47 (2H, d, J = 8.4 Hz), 7.38 (1H, s), 7.21 (2H, d, J = 8.4 Hz), 7.14 (1H, brs), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, d, J = 8.0 Hz), 5.54 (1H, s), 4.57 (2H, d, J = 5.6 Hz), 3.95-4.00 (2H, m), 2.16 (3H, s), 1.24 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 509.0 [M + H]+. 532 light-yellow powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 8.23 (1H, brs), 7.46 (2H, d, J = 8.0 Hz), 7.07-7.35 (1H, m), 7.22 (1H, s), 7.16 (2H, d, J = 8.4 Hz), 7.08 (1H, brs), 7.02 (1H, d, J = 8.4 Hz), 6.84-6.89 (1H, m), 6.06 (1H, s), 4.54 (2H, d, J = 5.6 Hz), 3.78 (3H, s), 3.48 (3H, s); LCMS: 99.3%, MS (ESI): m/z 510.9 [M + H]+. 533 light-yellow powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 7.88 (1H, s), 7.45 (2H, d, J = 8.4 Hz), 7.12-7.40 (3H, m), 7.07 (1H, d, J = 8.0 Hz), 6.80 (1H, t, J = 55.2 Hz), 6.78 (1H, s), 6.62-6.68 (1H, m), 5.98 (1H, s), 4.56 (1H, d, J = 5.6 Hz), 3.69 (3H, s), 3.49 (3H, s); LCMS: 97.7%, MS (ESI): m/z 511.0 [M + H]+. 534 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.45 (1H, brs), 9.07 (2H, s), 7.89 (1H, brs), 7.50 (2H, d, J = 8.4 Hz), 7.29 (1H, s), 7.18 (2H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.60-6.81 (2H, m), 5.53 (1H, s), 4.80-4.90 (1H, m), 3.48 (3H, s), 2.14 (3H, s), 1.65- 1.96 (2H, m), 0.94 (3H, t, J = 6.8 Hz); LCMS: 96.7%, MS (ESI): 523.0 m/z [M + H]+. 535 pale yellow powder; 1H-NMR (CDCl3, 400 MHz): δ 8.43 (2H, s), 7.41 (2H, d, J = 8.4 Hz), 7.01-7.20 (3H, m), 6.41-6.85 (3H, m), 6.16 (1H, brs), 6.01 (1H, s), 4.90-5.06 (1H, m), 4.44 (1H, brs), 3.30 (3H, s), 1.76-2.11 (2H, m), 0.93 (3H, t, J = 7.2 Hz); LCMS: 96.1%, MS (ESI): 525.0 m/z [M + H]+. 536 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.51 (1H, brs), 8.76 (2H, s), 7.94 (1H, brs), 7.45-7.55 (1H, m), 7.40 (1H, s), 7.21 (1H, d, J = 10.8 Hz), 6.90-7.12 (3H, m), 6.71-6.82 (1H, m), 5.54 (1H, s), 4.58 (2H, d, J = 5.2 Hz), 3.95-4.00 (2H, m), 2.16 (3H, s), 1.24 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): 492.9 m/z [M + H]+. 537 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 11.48 (1H, brs), 8.76 (2H, s), 7.93 (1H, brs), 7.57 (1H, t, J = 8.8 Hz), 7.32 (1H, s), 7.17 (1H, d, J = 10.8 Hz), 7.05 (1H, d, J = 8.4 Hz), 6.94 (1H, d, J = 8.4 Hz), 6.50-6.85 (2H, m), 5.55 (1H, s), 5.08-5.20 (1H, m), 3.51 (3H, s), 2.16 (3H, s), 1.60-1.95 (2H, m), 0.98 (3H, t, J = 7.2 Hz); LCMS: 98.6%, MS (ESI): m/z 507.0 [M + H]+. 538 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 8.11 (1H, brs), 7.46 (2H, d, J = 8.0 Hz), 7.21 (1H, s), 7.16 (2H, d, J = 8.4 Hz), 7.07 (1H, brs), 7.02 (1H, d, J = 8.4 Hz), 6.85 (1H, d, J = 7.2 Hz), 5.96 (1H, d, J = 2.8 Hz), 5.43 (2H, d, J = 48.4 Hz), 4.55 (2H, d, J = 5.2 Hz), 3.73 (3H, s), 3.48 (3H, s); LCMS: 89.5%, MS (ESI): m/z 493.1 [M + H]+. 539 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 7.76 (1H, brs), 7.46 (2H, d, J = 8.4 Hz), 7.15-7.17 (3H, m), 7.05 (1H, d, J = 8.0 Hz), 6.74 (1H, s), 6.62 (1H, dd, J = 8.4, 1.6 Hz), 5.96 (1H, s), 5.19 (2H, d, J = 48.8 Hz), 4.56 (2H, d, J = 6.0 Hz), 3.65 (3H, s), 3.48 (3H, s); LCMS: 95.3%, MS (ESI): m/z 493.1 [M + H]+. 540 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 9.12 (2H, s), 7.95 (1H, brs), 7.51 (1H, t, J = 8.4 Hz), 7.37 (1H, s), 7.28 (1H, dd, J = 10.8, 2.0 Hz), 7.03-7.14 (2H, m), 6.98 (1H, d, J = 8.4 Hz), 6.77 (1H, dd, J = 8.4, 1.6 Hz), 5.54 (1H, s), 4.59 (2H, d, J = 5.2 Hz), 3.94-4.03 (2H, m), 2.16 (3H, q, 6.8 Hz), 1.24 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 527.0 [M + H]+. 541 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 11.48 (1 H, brs), 9.12 (2 H, s), 7.95 (1 H, brs), 7.58-7.62 (1 H, m), 7.32 (1 H, s), 7.24 (1 H, d, J = 10.8 Hz), 7.10 (1 H, d, J = 8.0 Hz), 6.95 (1 H, d, J = 8.0 Hz), 6.80-6.90 (1 H, brs), 6.76 (1 H, d, J = 7.6 Hz), 5.55 (1 H, s), 5.12- 5.13 (1 H, m), 3.52 (3 H, s), 2.33 (3 H, s), 1.80-1.92 (2 H, m), 0.97 (3 H, t, J = 7.2 Hz); LCMS: 95.9%, MS (ESI): m/z 541.0 [M + H]+. 542 white solid; 1H-NMR (DMSO-d6, 400 MHz): δ 9.11 (2H, s), 7.47 (1H, t, J = 8.4 Hz), 7.26 (1H, d, J = 10.8 Hz), 7.07 (1H, d, J = 8.4 Hz), 6.95-7.05 (1H, m), 6.93 (1H, d, J = 8.4 Hz), 6.28 (1H, s), 6.19 (1H, d, J = 8.4 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.83 (2H, t, J = 6.4 Hz), 4.45- 4.65 (3H, m), 4.38 (2H, t, J = 6.0 Hz), 3.90-4.10 (2H, m), 1.20 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 503.0 [M + H]+. 543 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.12 (2H, s), 7.58 (1H, t, J = 8.4 Hz), 7.23 (1H, d, J = 11.2 Hz), 7.09 (1H, d, J = 6.8 Hz), 6.90 (1H, d, J = 8.0 Hz), 6.76 (1H, brs), 6.15-6.25 (2H, m), 5.85 (1H, d, J = 5.2 Hz), 5.05-5.15 (1H, m), 4.70-4.90 (2H, m), 4.45-4.55 (1H, m), 4.30-4.40 (2H, m), 3.50 (3H, s), 1.60-2.00 (2H, m), 0.97 (3H, t, J = 7.2 Hz); LCMS: 98.15%, MS (ESI): m/z 517.0 [M + H]+. 544 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.54 (1H, s), 8.21 (1H, dd, J = 8.8, 2.0 Hz), 7.45 (2H, d, J = 8.4 Hz), 7.22 (1H, d, J = 8.8 Hz), 7.14 (2H, d, J = 8.4 Hz), 6.95-7.00 (1H, m), 6.94 (1H, d, J = 8.0 Hz), 6.25 (1H, s), 6.22 (1H, d, J = 8.4 Hz), 5.85 (1H, d, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.45-4.58 (3H, m), 4.39 (2H, t, J = 6.0 Hz), 3.45 (3H, s); LCMS: 100%, MS (ESI): m/z 470.0 [M + H]+. 545 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.83 (2H, s), 8.37 (1H, brs), 7.45 (2H, d, J = 8.4 Hz), 7.16-7.26 (3H, m), 7.05 (1H, d, J = 8.4 Hz), 6.91 (1H, d, J = 8.4 Hz), 6.25 (1H, s), 4.57 (2H, d, J = 4.8 Hz), 4.02-4.04 (2H, m), 3.83 (3H, s), 1.25 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 593.0 [M + H]+. 546 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.57 (1H, s), 8.24 (1H, dd, J = 8.8, 2.4 Hz), 7.50 (1H, t, J = 8.4 Hz), 7.28 (1H, d, J = 8.4 Hz), 7.18 (1H, dd, J = 10.8, 2.4 Hz), 7.01 (2H, dd, J = 8.4, 2.0 Hz), 6.95 (1H, d, J = 8.4 Hz), 6.26 (1H, d, J = 1.2 Hz), 6.23 (1H, d, J = 8.0, 1.2 Hz), 5.87 (1H, J = 6.8 Hz), 4.84 (2H, t, J = 6.4 Hz), 4.46-4.61 (3H, m), 4.34-4.44 (2H, m), 3.46 (3H, s); LCMS: 100%, MS (ESI): m/z 487.9 [M + H]+. 547 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.05 (2H, s), 7.47 (2H, d, J = 8.4 Hz), 7.15 (2H, d, J = 8.8 Hz), 6.86 (1H, dd, J = 8.0 Hz), 6.65 (1H, d, J = 8.4 Hz), 6.19 (1H, d, J = 1.6 Hz), 6.15 (1H, dd, J = 8.4, 2.0 Hz), 5.78 (1H, d, J = 7.2 Hz), 4.74-4.88 (3H, m), 4.35-4.50 (1H, m), 4.20-4.38 (2H, m), 3.44 (3H, s), 1.71-1.95 (2H, m), 0.91 (3H, t, J = 7.2 Hz); LCMS: 100%, MS (ESI); m/z 499.0 [M + H]+. 548 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.09 (2H, s), 7.45 (2H, d, J = 8.4 Hz), 7.20 (2H, d, J = 8.4 Hz), 7.04 (1H, brs), 6.93 (1H, d, J = 8.4 Hz), 6.29 (1H, d, J = 1.6 Hz), 6.19 (1H, dd, J = 8.0, 1.6 Hz), 5.84 (1H, d, J = 7.2 Hz), 4.84 (2H, t, J = 6.0 Hz), 4.47-4.57 (3H, m), 4.36-4.42 (2H, m), 3.98 (2H, q, J = 6.8 Hz), 1.20 (3H, t, J = 7.2 Hz); LCMS: 99.5%, MS (ESI): m/z 485.0 [M + H]+. 549 white powder; 1H-NMR (DSMO-d6, 400 MHz): δ 8.53 (1H, s), 8.18 (1H, dd, J = 8.8, 2.4 Hz), 7.46 (2H, d, J = 8.8 Hz), 7.19 (1H, d, J = 8.8 Hz), 7.10 (2H, d, J = 8.8 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.66 (1H, d, J = 8.4 Hz), 6.20 (1H, s), 6.16 (1H, dd, J = 8.4, 2.0 Hz), 5.80 (1H, d, J = 6.8 Hz), 4.72-4.85 (3H, m), 4.40-4.50 (1H, m), 4.33-4.41 (2H, m), 3.45 (3H, s), 1.69-1.96 (2H, m), 0.92 (3H, t, J = 7.6 Hz); LCMS: 100%, MS (ESI): m/z 498.1 [M + H]+. 550 white powder; 1H NMR (DMSO-d6, 400 MHz): δ 8.58 (1H, s.), 8.23 (1H, d, J = 8.8 Hz), 7.56 (1H, t, J = 8.4 Hz), 7.26 (1H, d, J = 8.8 Hz), 7.13 (1H, d, J = 10.8 Hz), 7.01 (1H, d, J = 8.0 Hz), 6.90 (1H, d, J = 8.0 Hz), 6.73 (1H, d, J = 8.0 Hz), 6.13-6.25 (2H, m), 5.83 (1H, d, J = 6.8 Hz), 5.06-5.15 (1H, m), 4.83 (2H, t, J = 6.4 Hz), 4.44-4.55 (1H, m), 4.33-4.41 (2H, m), 3.50 (3H, s), 1.68-1.96 (2H, m), 0.97 (3H, t, J = 7.2 Hz); LCMS: 99.3%, MS (ESI): m/z 516.0 [M + H]+. 551 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 9.08 (2H, s), 7.45 (2H, d, J = 8.4 Hz), 7.19 (2H, d, J = 8.4 Hz), 7.11 (1H, t, J = 6.0 Hz), 6.00-6.15 (3H, m), 4.83 (2H, t, J = 6.4 Hz), 4.46-4.57 (3H, m), 4.36 (2H, t, J = 6.0 Hz), 3.44 (3H, s); LCMS: 100%, MS (ESI): m/z 489.0 [M + H]+. 552 white powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.51 (1H, s), 8.18 (1H, dd, J = 8.4, 2.0 Hz), 7.42 (2H, d, J = 8.8 Hz), 7.19 (1H, d, J = 8.8 Hz), 7.02-7.16 (3H, m), 5.95-6.12 (3H, m), 4.81 (2H, t, J = 6.4 Hz), 4.42-4.56 (3H, m), 4.34 (2H, t, J = 6.4 Hz), 3.42 (3H, s); LCMS: 100.0%, MS (ESI): m/z 488.0 [M + H]+. 553 yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.14 (1H, d, J = 2.4 Hz), 7.91 (1H, dd, J = 8.4, 2.4 Hz), 7.40 (2H, d, J = 8.0 Hz), 6.97- 7.12 (3H, m), 5.95-6.27 (3H, m), 4.82 (2H, t, J = 6.4 Hz), 4.41-4.60 (3H, m), 4.35 (2H, t, J = 5.6 Hz), 3.44 (3H, s); LCMS: 86.5%, MS (ESI): m/z 476.0 [M + Na]+. 554 pale yellow powder; 1H-NMR (DMSO-d6, 400 MHz): δ 8.70 (2H, s), 7.41 (2H, d, J = 8.0 Hz), 7.12 (2H, d, J = 8.0 Hz), 7.07 (1H, t, J = 6.0 Hz), 5.95-6.10 (3H, m), 4.81 (2H, t, J = 6.0 Hz), 4.45-4.55 (3H, m), 4.34 (2H, t, J = 6.0 Hz), 3.42 (3H, s); LCMS: 99.3%, MS (ESI): m/z 455.0 [M + H]+. 555 white powder; .sup.1H-NMR (DMSO-d6, 400 MHz): δ 8.73 (2H, s), 7.42 (2H, d, J = 8.0 Hz), 7.16 (3H, d, J = 8.0 Hz), 5.98-6.17 (3H, m), 4.84 (2H, t, J = 6.4 Hz), 4.47-4.60 (3H, m), 4.34-4.42 (2H, m), 3.98 (2H, q, J = 6.8 Hz), 1.19 (3H, t, J = 6.8 Hz); LCMS: 100%, MS (ESI): m/z 469.0 [M + H]+. 556 pink powder; .sup.1H-NMR (DMSO-d6, 400 MHz): δ 11.57 (1H, brs), 8.74 (2H, s), 8.14 (1H, s), 7.47 (2H, d, J = 8.0 Hz), 7.15-7.25 (4H, m), 7.03 (1H, s), 5.55 (1H, s), 4.59 (2H, d, J = 5.6 Hz), 3.47 (3H, s), 2.17 (3H, s); LCMS: 100%, MS (ESI): m/z = 517.0 [M + Na]+.