QUINOLONE COMPOUND

Abstract

The present invention provides a compound represented by the formula (I)

##STR00001##

wherein X is a hydrogen atom or a fluorine atom; R is a hydrogen atom or alkyl; R.sup.1 is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms; R.sup.2 is alkyl, alkoxy, haloalkoxy, a halogen atom, cyano, etc.; and R.sup.3 is 7-oxo-7,8-dihydro-1,8-naphthyridinyl, 3-pyridyl, etc., or a salt thereof. The compound of the present invention has excellent antimicrobial activity against Clostridium difficile and is useful for the prevention or treatment of intestinal infection such as Clostridium difficile-associated diarrhea.

Claims

1. A compound represented by the formula (I) ##STR00589## wherein X is a hydrogen atom or a fluorine atom; R is a hydrogen atom or alkyl; R.sup.1 is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms; R.sup.2 is a hydrogen atom; alkyl optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom and hydroxyl; alkoxy; haloalkoxy; a halogen atom; cyano; cyclopropyl; nitro; amino; formyl; alkenyl or alkynyl; or R.sup.1 and R.sup.2 are bonded to form a 5- or 6-membered ring optionally substituted by alkyl; R.sup.3 is (l) a fused heterocyclic group of the formula ##STR00590## wherein custom-character represents a single bond or a double bond, X.sup.1 is C(R.sup.5) or N, R.sup.4 is a hydrogen atom or alkyl, and R.sup.5 is (a) a hydrogen atom, (b) a halogen atom, (c) cyano, (d) nitro, (e) hydroxy, (f) alkyl optionally substituted by 1 to 3 halogen atoms, (g) alkenyl or alkynyl, (h) aryl, or (i) alkoxy optionally substituted by 1 to 3 halogen atoms, when X.sup.1 is C(R.sup.5), R.sup.4 and R.sup.5 are optionally bonded to form a 5- or 6-membered ring optionally substituted by oxo, said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl, (2) a group of the formula ##STR00591## wherein X.sup.2 is C(R.sup.8) or N, and R.sup.6, R.sup.7 and R.sup.8 are each independently, (a) a hydrogen atom, (b) a halogen atom, (c) cyano, (d) nitro, (e) amino, (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkoxy and amino, (g) alkenyl, (h) alkynyl, (i) aryl, (j) formyl or CH═N—OH, (k) carboxy, (l) carbamoyl, (m) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, or (n) alkenyloxy, (3) a group of the formula ##STR00592## wherein X.sup.3 and X.sup.4 are N, or X.sup.3 is N and X.sup.4 is CR″, wherein R″ is hydrogen atom, amino, hydroxy, alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkoxy and dimethylamino or mercapto, or X.sup.3 is CH and X.sup.4 is N, R.sup.1 is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of substituted hydroxyl and amino, and R.sup.6 is as defined above, (4) a group of the formula ##STR00593## wherein custom-character represents a single bond or a double bond and R.sup.6 is as defined above, (5) 3-pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of (a) a halogen atom, (b) cyano, (c) nitro, (d) hydroxy, (e) amino, (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy, (g) alkenyl, alkynyl (h) aryl, (i) cycloalkyl, (j) alkoxy, (k) alkylamino, (l) dialkylamino, (m) phenylamino optionally substituted by 1 to 3 halogen atoms, (n) a cyclic amino group optionally substituted by alkoxycarbonyl, (o) formyl, (p) carbamoyl optionally substituted by alkyl optionally substituted by hydroxy, and (q) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, (6) 4-pyridyl optionally substituted by a halogen atom, (7) 5-pyrimidinyl optionally substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy, (8) 2-indolyl, 3-indolyl, 5-indolyl, 6-indolyl, benzofuranyl, benzothiophenyl, benzoxazolyl or benzothiazolyl, each optionally substituted by 1 or 2 substituents selected from the group consisting of (a) a halogen atom, (b) cyano, (c) nitro, (d) hydroxy, (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino, (f) alkoxy, (g) formyl, (h) carboxy, and (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkoxycarbonyl, (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl, (B) alkylamino, (C) dialkylamino, (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and (E) a halogen atom, (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy, (iv) cycloalkylcarbonyl, (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms, (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy, (vii) arylsulfonyl optionally substituted by alkoxy, (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo, (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and (x) —C(═N—CN)—SR.sup.9 wherein R.sup.9 is alkyl, (9) a group of the formula ##STR00594## wherein one of Y.sup.1, Y.sup.2, Y.sup.3 and Y.sup.4 is N or N.sup.+ (—O.sup.−), and the remaining three are each C(R.sup.25), C(R.sup.26) and C(R.sup.27), W is O, S, NH or N(R.sup.23) R.sup.23 is a hydrogen atom or alkyl, and R.sup.24, R.sup.2, R.sup.26 and R.sup.27 are each independently, (a) a hydrogen atom, (b) cyano, or (c) nitro, (10) a group of the formula ##STR00595## wherein R.sup.28 is a hydrogen atom or hydroxy, and R.sup.29 is a hydrogen atom or alkyl, (11) a group of the formula ##STR00596## wherein X.sup.5 is C(R.sup.11) or N, X.sup.6 is CH.sub.2, C(═O), O, S, SO.sub.2 or N(R.sup.12), X.sup.7 is CH(R.sup.13), C(═O) or N(R.sup.14), X.sup.8 is CH(R.sup.15) or C(═O), R.sup.10, R.sup.12 and R.sup.14 are each independently, (a) a hydrogen atom or (b) alkyl, and R.sup.11, R.sup.13 and R.sup.15 are each independently, (a) a hydrogen atom, (b) a halogen atom, (c) cyano, (d) nitro, (e) amino, (f) alkylamino, (g) dialkylamino, (h) alkyl optionally substituted by hydroxy, or (i) alkenyl, when X.sup.5 is C(R.sup.11), R.sup.10 and R.sup.11 are optionally bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo, and when X.sup.6 is N(R.sup.12) and X.sup.7 is CH(R.sup.13), R.sup.12 and R.sup.13 are optionally bonded to form a 5- or 6-membered ring, (12) a group of the formula ##STR00597## wherein R.sup.16 is (a) a hydrogen atom, (b) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino, (c) alkenyl optionally substituted by carboxy, (d) formyl, (e) carboxy, (f) carbamoyl, (g) —C(R.sup.17)═N—OH wherein R.sup.17 is a hydrogen atom, cyano or hydroxy, (h) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or (i) cyano, (13) a group of the formula ##STR00598## wherein R.sup.18 is a hydrogen atom or alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and phenyl, n is 0 or 1, R.sup.19, R.sup.2 and R.sup.33 are each independently, (a) a hydrogen atom, (b) a halogen atom, (c) cyano, (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of (i) a halogen atom, (ii) cyano, (iii) hydroxy, (iv) amino, (v) alkylamino, (vi) dialkylamino, and (vii) a cyclic amino group optionally substituted by alkyl, (e) alkoxy, (f) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkylcarbonyl optionally substituted by a cyclic amino group, (ii) alkylsulfonyl, (iii) carbamoyl, (iv) alkyl, cycloalkyl or cycloalkylalkyl, and (v) 5- to 10-membered saturated heterocyclic group, (g) carboxy, (h) alkoxycarbonyl, (i) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino, (j) formyl, (k) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, (l) —CH═N—OR.sup.21 wherein R.sup.21 is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino, (m) nitro, (n) a 5- to 10-membered saturated heterocyclic group optionally substituted by amino, (o) phenyl, or (p) —NHC(SMe) ═CHCN, (14) a group of the formula ##STR00599## wherein R.sup.30 is (a) a hydrogen atom, (b) a halogen atom, (c) cyano, (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and hydroxy, (e) alkenyl, (f) alkynyl, (g) alkoxy, (h) formyl, (i) —CH═N—OH, or (j) carbamoyl, (15) naphthyl or isochromenyl, (16) quinolyl or isoquinolyl, or their oxide derivatives, (17) a group of the formula ##STR00600## (18) a group of the formula ##STR00601## wherein U is O or S, and R.sup.31 is (a) a hydrogen atom, (b) a halogen atom, (c) alkyl optionally substituted by 1 to 3 halogen atoms, (d) carboxy, (e) nitro, (f) cyano, or (g) amino, (19) a group of the formula ##STR00602## wherein R.sup.32 is (a) a halogen atom, (b) phenyl, or (c) a group of the formula ##STR00603## (20) a group of the formula ##STR00604## wherein R.sup.34 and R.sup.35 are each independently, (a) a hydrogen atom, or (b) aminoalkyl, or R.sup.34 and R.sup.35 are bonded to form a 6-membered ring optionally substituted by amino or oxo, (21) a group of the formula ##STR00605## wherein R.sup.36 is (a) a hydrogen atom, (b) a halogen atom, (c) nitro, or (d) thienyl, or (22) a group of the formula ##STR00606## or a salt thereof.

2. The compound of claim 1, wherein X is a fluorine atom, or a salt thereof.

3. The compound of claim 1, wherein R.sup.3 is a fused heterocyclic group of the formula ##STR00607## wherein custom-character , X.sup.1 and R.sup.4 are as defined in claim 1, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl, or a salt thereof.

4. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00608## wherein X.sup.2, R.sup.6 and R.sup.7 are as defined in claim 1, or a salt thereof.

5. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00609## wherein X.sup.3, X.sup.4, R.sup.6 and R′ are as defined in claim 1, or a salt thereof.

6. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00610## wherein custom-character and R.sup.6 are as defined in claim 1, or a salt thereof.

7. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00611## wherein R.sup.22 is (a) a halogen atom, (b) cyano, (c) nitro, (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy, (e) alkenyl, alkynyl, (f) aryl, (g) cycloalkyl, (h) alkoxy, (i) formyl, or (j) carbamoyl optionally substituted by alkyl optionally substituted by hydroxyl, or a salt thereof.

8. The compound of claim 1, wherein R.sup.3 is 5-pyrimidinyl substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino, dialkylamino and carboxy, or a salt thereof.

9. The compound of claim 1, wherein R.sup.3 is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of (a) a halogen atom, (b) cyano, (c) nitro, (d) hydroxy, (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino, (f) alkoxy, (g) formyl, (h) carboxy, or (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkoxycarbonyl, (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl, (B) alkylamino, (C) dialkylamino, (D) a cyclic amino group optionally substituted by alkoxycarbonyl, and (E) a halogen atom, (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy, (iv) cycloalkylcarbonyl, (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms, (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy, (vii) arylsulfonyl optionally substituted by alkoxy, (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo, (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group optionally substituted by 1 to 3 alkyl, and (x) —C(═N—CN)—SR.sup.9 wherein R.sup.9 is alkyl, or a salt thereof.

10. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00612## wherein Y.sup.1, Y.sup.2, Y.sup.3, Y.sup.4, W and R.sup.24 are as defined in claim 1, or a salt thereof.

11. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00613## wherein R.sup.28 and R.sup.29 are as defined in claim 1, or a salt thereof.

12. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00614## wherein X.sup.5, X.sup.6, X.sup.7, X.sup.8 and R.sup.10 are as defined in claim 1, or a salt thereof.

13. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00615## wherein R.sup.16a is (a) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino, (b) alkenyl optionally substituted by carboxy, (c) formyl, (d) carboxy, (e) carbamoyl, (f) —C(R.sup.17)═N—OH wherein R.sup.17 is a hydrogen atom, cyano or hydroxy, (g) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl, or (h) cyano, or a salt thereof.

14. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00616## wherein R.sup.18a is alkyl, and R.sup.19a is (a) a halogen atom, (b) cyano, (c) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of (i) a halogen atom, (ii) cyano, (iii) hydroxy, (iv) amino, (v) alkylamino, (vi) dialkylamino, and (vii) a cyclic amino group optionally substituted by alkyl, (d) alkoxy, (e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of (i) alkylcarbonyl optionally substituted by a cyclic amino group, (ii) alkylsulfonyl, (iii) carbamoyl, and (iv) alkyl or cycloalkyl, (f) carboxy, (g) alkoxycarbonyl, (h) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino, (i) formyl, (j) a 5- to 10-membered aromatic heterocyclic group optionally substituted by alkyl, (k) —CH═N—OR.sup.21 wherein R.sup.21 is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino, or (l) nitro, or a salt thereof.

15. The compound of claim 1, wherein R.sup.3 is a group of the formula ##STR00617## wherein R.sup.30 is as defined in claim 1, or a salt thereof.

16. The compound of claim 1, wherein R.sup.3 is naphthyl or isochromenyl, or a salt thereof.

17. The compound of claim 1, wherein R.sup.3 is quinolyl or isoquinolyl, or their oxide derivatives, or a salt thereof.

18. The compound of claim 1, wherein R is a hydrogen atom, or a salt thereof.

19. The compound of claim 1, wherein R.sup.1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl, or a salt thereof.

20. The compound of claim 1, wherein R.sup.2 is methyl, methoxy or a chlorine atom, or a salt thereof.

21. A pharmaceutical composition comprising a compound of claim 1 or a salt thereof and a pharmaceutically acceptable carrier.

22. An antimicrobial agent comprising a compound of claim 1 or a salt thereof.

23. A compound of claim 1 or a salt thereof for use as a medicament.

24. A compound of claim 1 or a salt thereof for use as an antimicrobial agent.

25. A compound of claim 1 or a salt thereof for use in the prevention or treatment of a bacterial infection.

26. Use of a compound of claim 1 or a salt thereof for the manufacture of a medicament for preventing or treating a bacterial infection.

27. A method for preventing or treating a bacterial infection which comprises administering an effective amount of a compound of claim 1 or a salt thereof to a human or an animal.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0400] FIG. 1 is a graph showing the results of the animals administered with compound 2-18 in Experimental Example 2.

[0401] FIG. 2 is a graph showing the results of the animals administered with vancomycin in Experimental Example 2.

DETAILED DESCRIPTION OF THE INVENTION

[0402] Specific examples of groups in the formula (I) are as follows.

[0403] Examples of “halogen atom” include fluorine atom, chlorine atom, bromine atom, and iodine atom.

[0404] Examples of “alkyl” and “alkyl” moiety in “alkylamino”, “dialkylamino”, “alkylcarbonyl”, “cycloalkylalkylsulfonyl”, “cycloalkylalkyl”, “aminoalkyl” and “alkylsulfonyl” include straight or branched C.sub.1-6 alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-ethylpropyl, isopentyl, neopentyl, tert-pentyl, hexyl, 1,2,2-trimethylpropyl, 3,3-dimethylbutyl, 2-ethylbutyl, isohexyl, 3-methylpentyl, etc.

[0405] Examples of “alkenyl” include straight or branched C.sub.2-6 alkenyl such as vinyl, 1-propenyl, 2-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-pentenyl, 2-hexenyl, etc.

[0406] Examples of “alkynyl” include straight or branched C.sub.2-6 alkynyl such as ethynyl, 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 2-hexynyl, etc.

[0407] Examples of “alkoxy” and “alkoxy” moiety in “haloalkoxy”, “alkoxycarbonyl” and “alkoxycarbonylamino” include straight or branched C.sub.1-6 alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, isopentyloxy, neopentyloxy, tert-pentyloxy, hexyloxy, isohexyloxy, 3-methylpentyloxy, etc.

[0408] Examples of “haloalkoxy” include straight or branched C.sub.1-6 alkoxy substituted by 1 to 3 halogen atoms. Examples thereof include fluoromethoxy, difluoromethoxy, trifluoromethoxy, chloromethoxy, dichloromethoxy, trichloromethoxy, bromomethoxy, dibromomethoxy, dichlorofluoromethoxy, 2,2,2-trifluoroethoxy, 2-chloroethoxy, 3,3,3-trifluoropropoxy, 2-chloropropoxy, 3-chloropropoxy, 3-bromopropoxy, 4,4,4-trifluorobutoxy, 2-chlorobutoxy, 4-chlorobutoxy, 4-bromobutoxy, 5,5,5-trifluoropentyloxy, 5-chloropentyloxy, 6,6,6-trifluorohexyloxy, 6-chlorohexyloxy, etc. Preferable examples thereof include difluoromethoxy.

[0409] Examples of “alkenyloxy” include straight or branched C.sub.2-6 alkenyloxy such as vinyloxy, 1-propenyloxy, 2-propenyloxy, 1-butenyloxy, 2-butenyloxy, 3-butenyloxy, l-methyl-2-propenyloxy, 2-pentenyloxy, 2-hexenyloxy, etc.

[0410] Examples of “aryl” and “aryl” moiety in “arylsulfonyl” include C.sub.6-14 (preferably C.sub.6-10) aryl such as phenyl, naphthyl (e.g., 1-naphthyl, 2-naphthyl), etc. Preferable examples thereof include phenyl.

[0411] Examples of “5- to 10-membered aromatic heterocyclic group” and “5- to 10-membered aromatic heterocyclyl” moiety in “5- to 10-membered aromatic heterocyclylcarbonyl group” and “5- to 10-membered aromatic heterocyclylsulfonyl group” include 5- to 10-membered (preferably 5- or 6-membered) aromatic heterocyclic group containing 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples thereof include furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl), tetrazolyl, isoxazolyl, oxazolyl, furazanyl, isothiazolyl, thiazolyl, pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyridazinyl, pyrimidinyl, pyrazinyl, benzofuranyl, isobenzofuranyl, benzo[b]thiophenyl, benzo[c]thiophenyl, indolyl, isoindolyl, indolizinyl, indazolyl, benzimidazolyl, benzotriazolyl, benzoxazolyl, 1,2-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, purinyl, quinolyl, isoquinolyl, quinolizinyl, cinnolinyl, quinazolinyl, quinoxalinyl, phthalazinyl, naphthyridinyl, pteridinyl, etc. Preferable examples thereof include pyrrolyl, imidazolyl, oxazolyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl), tetrazolyl, pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), benzimidazolyl, etc.

[0412] Examples of “alkylamino” include C.sub.1-6 alkylamino such as methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino, tert-butylamino, pentylamino, isopentylamino, neopentylamino, tert-pentylamino, hexylamino, etc.

[0413] Examples of “dialkylamino” include di(C.sub.1-6 alkyl)amino such as dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, di(sec-butyl)amino, di(tert-butyl)amino, dipentylamino, di(tert-pentyl)amino, dihexylamino, ethylmethylamino, etc.

[0414] Examples of “aminoalkyl” include amino-C.sub.1-6 alkyl such as aminomethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, etc.

[0415] Examples of “cycloalkyl” and “cycloalkyl” moiety in “cycloalkyloxy”, “cycloalkylcarbonyl”, “cycloalkylalkyl” and “cycloalkylalkylsulfonyl” include C.sub.3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornanyl (e.g., 2-norbornanyl), etc.

[0416] Examples of “cycloalkylalkyl” include C.sub.3-8 cycloalkyl-C.sub.1-6 alkyl such as cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cycloheptylmethyl, cyclooctylmethyl, norbornanylmethyl (e.g., norbornan-2-ylmethyl), etc.

[0417] Examples of “cyclic amino group” includes a 4- to 7-membered (preferably 5- or 6-membered) cyclic amino group containing one nitrogen atom and optionally further containing one heteroatom selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples thereof include 1-azetidinyl, 1-pyrrolidinyl, 1-imidazolidinyl, 1-pyrazolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino, 1-azepanyl, 1,4-oxazepan-4-yl, etc. Preferable examples thereof include 1-pyrrolidinyl, piperidino, 1-piperazinyl, morpholino, thiomorpholino, etc.

[0418] Examples of “alkoxycarbonyl” include C.sub.1-6 alkoxy-carbonyl wherein the alkoxy moiety is C.sub.1-6 alkoxy. Examples thereof include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, hexyloxycarbonyl, etc.

[0419] Examples of “alkoxycarbonylamino” include C.sub.1-6 alkoxy-carbonylamino wherein the alkoxy moiety is C.sub.1-6 alkoxy. Examples thereof include methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, isobutoxycarbonylamino, sec-butoxycarbonylamino, tert-butoxycarbonylamino, pentyloxycarbonylamino, hexyloxycarbonylamino, etc.

[0420] Examples of “alkylcarbonyl” include C.sub.1-6 alkyl-carbonyl wherein the alkyl moiety is C.sub.1-6 alkyl. Examples thereof include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, tert-butylcarbonyl, pentylcarbonyl, hexylcarbonyl, etc.

[0421] Examples of “cycloalkyloxy” include C.sub.3-8 cycloalkyloxy such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, etc.

[0422] Examples of “cycloalkylcarbonyl” include C.sub.3-8 cycloalkylcarbonyl such as cyciopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl, cycloheptylcarbonyl, cyclooctylcarbonyl, etc.

[0423] Examples of “5- to 10-membered aromatic heterocyclylcarbonyl group” include a 5- to 10-membered (preferably 5- or 6-membered) aromatic heterocyclylcarbonyl group wherein the heterocyclyl moiety contains 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples of the heterocyclyl moiety are same as the examples of the 5- to 10-membered aromatic heterocyclic group mentioned above. Preferable examples of “5- to 10-membered aromatic heterocyclylcarbonyl group” include pyridylcarbonyl (e.g., 2-pyridylcarbonyl, 3-pyridylcarbonyl, 4-pyridylcarbonyl).

[0424] Examples of “arylsulfonyl” include C.sub.6-14 (preferably C.sub.6-10) arylsulfonyl such as phenylsulfonyl, naphthylsulfonyl (e.g., 1-naphthylsulfonyl, 2-naphthylsulfonyl), etc. Preferable examples thereof include phenylsulfonyl.

[0425] Examples of “cycloalkylalkylsulfonyl” include C.sub.3-8 cycloalkyl-C.sub.1-6 alkylsulfonyl such as cyclopropylmethylsulfonyl, cyclobutylmethylsulfonyl, cyclopentylmethylsulfonyl, cyclohexylmethylsulfonyl, cycloheptylmethylsulfonyl, cyclooctylmethylsulfonyl, norbornanylmethylsulfonyl (e.g., norbornan-2-ylmethylsulfonyl), etc.

[0426] Examples of “5- to 10-membered aromatic heterocyclylsulfonyl group” include a 5- to 10-membered (preferably 5- or 6-membered) aromatic heterocyclylsulfonyl group wherein the heterocyclyl moiety contains 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples of the heterocyclyl moiety are same as the examples of the 5- to 10-membered aromatic heterocyclic group mentioned above. Preferable examples of “5- to 10-membered aromatic heterocyclylsulfonyl group” include imidazolylsulfonyl.

[0427] Examples of “alkylsulfonyl” include C.sub.1-6 alkylsulfonyl wherein the alkyl moiety is C.sub.1-6 alkyl. Examples thereof include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl, tert-butylsulfonyl, pentylsulfonyl, hexylsulfonyl, etc.

[0428] Examples of “cyclopropyl optionally substituted by 1 to 3 halogen atoms” include cyclopropyl optionally substituted by 1 fluorine atom such as cyclopropyl, 2-fluorocyclopropyl, etc.

[0429] Examples of “phenyl optionally substituted by 1 to 3 halogen atoms” include phenyl substituted by two fluorine atoms such as 2,4-difluorophenyl, etc.

[0430] Examples of “5- to 10-membered saturated heterocyclic group” include a 5- to 10-membered (preferably 5- or 6-membered) saturated heterocyclic group containing 1 to 4 (preferably 1 to 3, more preferably 1 or 2) heteroatoms selected from a nitrogen atom, an oxygen atom and a sulfur atom. Examples thereof include pyrrolidinyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, etc.

[0431] Examples of “6-membered ring optionally substituted by amino or oxo” formed by R.sup.34 and R.sup.35 include a 6-membered ring optionally containing one nitrogen atom, and said ring is optionally substituted by amino or oxo. Examples thereof include cyclohexene and dihydropyridine, each optionally substituted by amino or oxo.

[0432] Examples of “5- or 6-membered ring optionally substituted by alkyl” formed by R.sup.1 and R.sup.2 include a 5- or 6-membered (preferably 6-membered) ring containing one nitrogen atom and optionally further containing one oxygen atom, and said ring is optionally substituted by alkyl. Preferably, R.sup.1 and R.sup.2 are optionally bonded to form —O—CH.sub.2—CH(CH.sub.3)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring as shown below.

##STR00041##

[0433] Examples of “5- or 6-membered ring optionally substituted by oxo” formed by R.sup.4 and R.sup.5 include a 5- or 6-membered (preferably 6-membered) ring containing one nitrogen atom and optionally further containing one oxygen atom, and said ring is optionally substituted by oxo. Preferably, R.sup.4 and R.sup.5 are optionally bonded to form —CH.sub.2—O—(C═O)— wherein the carbonyl is bonded to the phenyl ring of the quinolone ring as shown below.

##STR00042##

[0434] Examples of “5- or 6-membered ring optionally substituted by alkyl or oxo” formed by R.sup.10 and R.sup.11 include a 5- or 6-membered (preferably 5-membered) ring containing 2 or 3 nitrogen atoms, and said ring is optionally substituted by alkyl or oxo. Preferably, R.sup.10 and R.sup.11 are optionally bonded to form —(C═O)—NH—, —C(R.sup.31)═N— or —N═N— wherein R.sup.31 is a hydrogen atom or alkyl, and the nitrogen atom is bonded to the phenyl ring of the fused ring, as shown below.

##STR00043##

[0435] Examples of “5- or 6-membered ring” formed by R.sup.12 and R.sup.13 include a 5- or 6-membered (preferably 6-membered) ring containing one nitrogen atom. Preferably, R.sup.12 and R.sup.13 are optionally bonded to form —(CH.sub.2).sub.4— as shown below.

##STR00044##

[0436] X is a hydrogen atom or a fluorine atom, preferably, a fluorine atom.

[0437] R is a hydrogen atom or alkyl, preferably, a hydrogen atom.

[0438] R.sup.1 is (1) cyclopropyl optionally substituted by 1 to 3 halogen atoms or (2) phenyl optionally substituted by 1 to 3 halogen atoms, preferably, cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl.

[0439] R.sup.2 is a hydrogen atom; alkyl optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom and hydroxyl; alkoxy; haloalkoxy; a halogen atom; cyano; cyclopropyl; nitro; amino; formyl; alkenyl or alkynyl, preferably, alkyl, alkoxy, haloalkoxy, a chlorine atom or cyano, more preferably, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkoxy substituted by 1 to 3 halogen atoms, a chlorine atom or cyano, still more preferably, methyl, methoxy or a chlorine atom.

[0440] Examples of a fused heterocyclic group of the formula (A) or (B) include a fused heterocyclic group of the formula

##STR00045##

wherein X.sup.1 and R.sup.4 are as defined above, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl.

[0441] Preferable examples of a fused heterocyclic group of the formula (A) or (B) include a fused heterocyclic group of the formula

##STR00046##

wherein R.sup.4 and R.sup.5 are as defined above, and said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and alkyl.

[0442] Other preferable examples of a fused heterocyclic group of the formula (A) or (B) include a fused heterocyclic group of the formula

##STR00047##

[0443] Examples of a group of the formula (C) include a group of the formula

##STR00048##

wherein X.sup.2, R.sup.6 and R.sup.7 are as defined above.

[0444] Preferable examples of a group of the formula (C) include a group of the formula

##STR00049##

wherein R.sup.6, R.sup.7 and R.sup.8 are as defined above.

[0445] In the above formulas, R.sup.6, R.sup.7 and R.sup.8 are each independently, [0446] (a) a hydrogen atom, [0447] (b) a halogen atom, [0448] (c) cyano, [0449] (d) nitro, [0450] (e) amino, [0451] (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and amino, [0452] (g) alkenyl, [0453] (h) alkynyl, [0454] (i) aryl, [0455] (j) formyl, [0456] (k) carboxy, [0457] (l) carbamoyl, or [0458] (m) a 5- to 10-membered aromatic heterocyclic group (e.g., pyridyl, triazolyl) optionally substituted by alkyl.

[0459] Examples of a group of the formula (D) or (E) include a group of the formula

##STR00050##

wherein R.sup.6 is as defined above. R.sup.6 is preferably a hydrogen atom, a halogen atom, nitro or amino.

[0460] Preferably, R.sup.3 is 3-pyridyl optionally substituted by 1 or 2 substituents selected from the group consisting of [0461] (a) a halogen atom, [0462] (b) cyano, [0463] (c) nitro, [0464] (d) hydroxy, [0465] (e) amino, [0466] (f) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy, [0467] (g) alkenyl, [0468] (h) aryl, [0469] (i) cycloalkyl, [0470] (j) alkoxy, [0471] (k) alkylamino, [0472] (l) dialkylamino, [0473] (m) phenylamino optionally substituted by 1 to 3 halogen atoms, [0474] (n) a cyclic amino group (e.g., 1-piperazinyl, morpholino) optionally substituted by alkoxycarbonyl, [0475] (o) formyl, [0476] (p) carbamoyl, and [0477] (q) a 5- to 10-membered aromatic heterocyclic group (e.g., triazolyl) optionally substituted by alkyl.

[0478] More preferably, R.sup.3 is a group of the formula

##STR00051##

wherein R.sup.22 is [0479] (a) a halogen atom, [0480] (b) cyano, [0481] (c) nitro, [0482] (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, alkylamino, dialkylamino and hydroxy, [0483] (e) alkenyl, [0484] (f) aryl, [0485] (g) cycloalkyl, [0486] (h) alkoxy, [0487] (i) formyl, or [0488] (j) carbamoyl.

[0489] Preferably, R.sup.22 is [0490] (a) cyano, [0491] (b) nitro, [0492] (c) aryl, [0493] (d) formyl, or [0494] (e) carbamoyl.

[0495] Preferably, R.sup.3 is 5-pyrimidinyl substituted by 1 or 2 substituents selected from the group consisting of amino, alkylamino and dialkylamino.

[0496] Preferably, R.sup.3 is 2-indolyl, 3-indolyl, 5-indolyl or 6-indolyl, each optionally substituted by 1 or 2 substituents selected from the group consisting of [0497] (a) a halogen atom, [0498] (b) cyano, [0499] (c) nitro, [0500] (d) hydroxy, [0501] (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino, [0502] (f) alkoxy, [0503] (g) formyl, [0504] (h) carboxy, and [0505] (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of [0506] (i) alkoxycarbonyl, [0507] (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of [0508] (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl, [0509] (B) alkylamino, [0510] (C) dialkylamino, [0511] (D) a cyclic amino group (e.g., morpholino, 1-piperazinyl) optionally substituted by alkoxycarbonyl, and [0512] (E) a halogen atom, [0513] (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy, [0514] (iv) cycloalkylcarbonyl, [0515] (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group (e.g, pyridylcarbonyl) optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms, [0516] (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy, [0517] (vii) arylsulfonyl optionally substituted by alkoxy, [0518] (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo (e.g., camphorsulfonyl), [0519] (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group (e.g., imidazolylsulfonyl) optionally substituted by 1 to 3 alkyl, and [0520] (x) —C(═N—CN)—SR.sup.9 wherein R.sup.9 is alkyl.

[0521] More preferably, R.sup.3 is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of [0522] (a) a halogen atom, [0523] (b) cyano, [0524] (c) nitro, [0525] (d) hydroxy, [0526] (e) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, alkoxycarbonylamino, alkylamino and dialkylamino, [0527] (f) alkoxy, [0528] (g) formyl, [0529] (h) carboxy, and [0530] (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of [0531] (i) alkoxycarbonyl, [0532] (ii) alkylcarbonyl optionally substituted by a substituent selected from the group consisting of [0533] (A) cycloalkyloxy optionally substituted by 1 to 3 alkyl, [0534] (B) alkylamino, [0535] (C) dialkylamino, [0536] (D) a cyclic amino group (e.g., morpholino, 1-piperazinyl) optionally substituted by alkoxycarbonyl, and [0537] (E) a halogen atom, [0538] (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and alkoxy, [0539] (iv) cycloalkylcarbonyl, [0540] (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group (e.g, pyridylcarbonyl) optionally substituted by alkyl optionally substituted by 1 to 3 halogen atoms, [0541] (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and alkoxy, [0542] (vii) arylsulfonyl optionally substituted by alkoxy, [0543] (viii) cycloalkylalkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of alkyl and oxo (e.g., camphorsulfonyl), [0544] (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group (e.g., imidazolylsulfonyl) optionally substituted by 1 to 3 alkyl, and [0545] (x) —C(═N—CN)—SR.sup.9 wherein R.sup.9 is alkyl.

[0546] Examples of a group of the formula (F) or (G) include a group of the formula

##STR00052##

wherein
R.sup.23 is a hydrogen atom or alkyl, and
R.sup.24, R.sup.25, R.sup.26 and R.sup.27 are each independently, [0547] (a) a hydrogen atom, [0548] (b) cyano, or [0549] (c) nitro.

[0550] Examples of a group of the formula (K) include a group of the formula

##STR00053##

wherein X.sup.5, X.sup.6, X.sup.7, X.sup.8 and R.sup.10 are as defined above.

[0551] Preferable examples of a group of the formula (K) include a group of the formula

##STR00054##

wherein R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14 and R.sup.15 are as defined above.

[0552] When R.sup.10 and R.sup.11 are bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo, preferable examples of a group of the formula (K) include a group of the formula

##STR00055##

wherein R.sup.31 is a hydrogen atom or alkyl.

[0553] When R.sup.12 and R.sup.13 are bonded to form a 5- or 6-membered ring, preferable examples of a group of the formula (K) include a group of the formula

##STR00056##

[0554] More preferable examples of a group of the formula (K) include a group of the formula

##STR00057##

wherein R.sup.10a is [0555] (a) a hydrogen atom or [0556] (b) alkyl, and
R.sup.11a, R.sup.13a and R.sup.15a are each independently, [0557] (a) a hydrogen atom, [0558] (b) a halogen atom, [0559] (c) cyano, [0560] (d) nitro, [0561] (e) amino, [0562] (f) alkylamino, [0563] (g) dialkylamino, [0564] (h) alkyl optionally substituted by hydroxy, or [0565] (i) alkenyl,
R.sup.10a and R.sup.11a are optionally bonded to form a 5- or 6-membered ring optionally substituted by alkyl or oxo,
provided that R.sup.10a, R.sup.11a, R.sup.13a and R.sup.15a are not simultaneously hydrogen atom.

[0566] Preferably, R.sup.3 is a group of the formula

##STR00058##

wherein R.sup.16 is [0567] (a) a hydrogen atom, [0568] (b) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino, [0569] (c) alkenyl optionally substituted by carboxy, [0570] (d) formyl, [0571] (e) carboxy, [0572] (f) carbamoyl, [0573] (g) —C(R.sup.17)═N—OH wherein R.sup.17 is a hydrogen atom, cyano or hydroxy, or [0574] (h) a 5- to 10-membered aromatic heterocyclic group (e.g., tetrazolyl, pyrrolyl, oxazolyl, benzimidazolyl, triazolyl) optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl.

[0575] More preferably, R.sup.3 is a group of the formula

##STR00059##

wherein R.sup.16a is [0576] (a) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, alkylamino and dialkylamino, [0577] (b) alkenyl optionally substituted by carboxy, [0578] (c) formyl, [0579] (d) carboxy, [0580] (e) carbamoyl, [0581] (f) —C(R.sup.17)═N—OH wherein R.sup.17 is a hydrogen atom, cyano or hydroxy, or [0582] (g) a 5- to 10-membered aromatic heterocyclic group (e.g., tetrazolyl, pyrrolyl, oxazolyl, benzimidazolyl, triazolyl) optionally substituted by alkyl, alkoxycarbonyl, carboxy or phenyl.

[0583] Preferably, R.sup.3 is a group of the formula

##STR00060##

wherein
R.sup.18 is alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and phenyl, and
R.sup.19 and R.sup.20 are each independently, [0584] (a) a hydrogen atom, [0585] (b) a halogen atom, [0586] (c) cyano, [0587] (d) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of [0588] (i) a halogen atom, [0589] (ii) cyano, [0590] (iii) hydroxy, [0591] (iv) amino, [0592] (v) alkylamino, [0593] (vi) dialkylamino, and [0594] (vii) a cyclic amino group (e.g., 1-piperazinyl) optionally substituted by alkyl, [0595] (e) alkoxy, [0596] (f) amino optionally substituted by 1 or 2 substituents selected from the group consisting of [0597] (i) alkylcarbonyl optionally substituted by a cyclic amino group (e.g., morpholino), [0598] (ii) alkylsulfonyl, and [0599] (iii) carbamoyl, [0600] (g) carboxy, [0601] (h) alkoxycarbonyl, [0602] (i) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino, [0603] (j) formyl, [0604] (k) a 5- to 10-membered aromatic heterocyclic group (e.g., oxazolyl, benzimidazolyl), or [0605] (l) —CH═N—OR.sup.1 wherein R.sup.21 is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino.

[0606] More preferably, R.sup.3 is a group of the formula

##STR00061##

wherein
R.sup.18a is alkyl, and

R.SUP.19a .is

[0607] (a) a halogen atom, [0608] (b) cyano, [0609] (c) alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of [0610] (i) a halogen atom, [0611] (ii) cyano, [0612] (iii) hydroxy, [0613] (iv) amino, [0614] (v) alkylamino, [0615] (vi) dialkylamino, and [0616] (vii) a cyclic amino group (e.g., 1-piperazinyl) optionally substituted by alkyl, [0617] (d) alkoxy, [0618] (e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of [0619] (i) alkylcarbonyl optionally substituted by a cyclic amino group (e.g., morpholino), [0620] (ii) alkylsulfonyl, and [0621] (iii) carbamoyl, [0622] (f) carboxy, [0623] (g) alkoxycarbonyl, [0624] (h) carbamoyl optionally substituted by alkyl optionally substituted by amino, alkylamino, dialkylamino or alkoxycarbonylamino, [0625] (i) formyl, [0626] (j) a 5- to 10-membered aromatic heterocyclic group (e.g., oxazolyl, benzimidazolyl), or [0627] (k) —CH═N—OR.sup.21 wherein R.sup.21 is a hydrogen atom or alkyl optionally substituted by alkylamino or dialkylamino.

[0628] Preferable examples of compound (I) are as described below.

[Compound I-1]

[0629] A compound of the formula (I) wherein

R is a hydrogen atom;
R.sup.1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R.sup.2 is C.sub.1-6 alkyl (e.g., methyl), C.sub.1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R.sup.1 and R.sup.2 are optionally bonded to form —O—CH.sub.2—CH(CH.sub.3)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R.sup.3 is a fused heterocyclic group of the formula

##STR00062##

wherein
X.sup.1 is C(R.sup.5) or N,
R.sup.4 is a hydrogen atom or C.sub.1-6 alkyl, and

R.SUP.5 .is

[0630] (a) a hydrogen atom, [0631] (b) a halogen atom, [0632] (c) cyano, [0633] (d) nitro, [0634] (e) hydroxy, [0635] (f) C.sub.1-6 alkyl optionally substituted by 1 to 3 halogen atoms, [0636] (g) C.sub.2-6 alkynyl, [0637] (h) C.sub.6-14 aryl, or [0638] (i) C.sub.1-6 alkoxy optionally substituted by 1 to 3 halogen atoms,
when X.sup.1 is C(R.sup.5), R.sup.4 and R.sup.5 are optionally bonded to form —CH.sub.2—O—(C═O)— wherein the carbonyl is bonded to the phenyl ring of the quinolone ring,
said fused heterocyclic group is optionally substituted by 1 or 2 substituents selected from the group consisting of a halogen atom, cyano, nitro, hydroxy and C.sub.1-6 alkyl, or a salt thereof.

[Compound I-2]

[0639] A compound of the formula (I) wherein

R is a hydrogen atom;
R.sup.1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R.sup.2 is C.sub.1-6 alkyl (e.g., methyl), C.sub.1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R.sup.1 and R.sup.2 are optionally bonded to form —O—CH.sub.2—CH(CH.sub.3)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R.sup.3 is a group of the formula

##STR00063##

wherein
X.sup.2 is C(R.sup.8) or N, and
R.sup.6, R.sup.7 and R.sup.8 are each independently, [0640] (a) a hydrogen atom, [0641] (b) a halogen atom, [0642] (c) cyano, [0643] (d) nitro, [0644] (e) amino, [0645] (f) C.sub.1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and amino, [0646] (g) C.sub.2-6 alkenyl, [0647] (h) C.sub.2-6 alkynyl, [0648] (i) C.sub.6-14 aryl, [0649] (j) formyl, [0650] (k) carboxy, [0651] (l) carbamoyl, or [0652] (m) a 5- to 10-membered aromatic heterocyclic group (e.g., pyridyl, triazolyl) optionally substituted by C.sub.1-6 alkyl,
or a salt thereof.

[Compound I-3]

[0653] A compound of the formula (I) wherein

##STR00064##

wherein
X.sup.3 and X.sup.4 are N, or
X.sup.3 is N and X.sup.4 is CH, or
X.sup.3 is CH and X.sup.4 is N, and
R.sup.6 is a hydrogen atom, a halogen atom, nitro or amino, or a salt thereof.

[Compound I-4]

[0654] A compound of the formula (I) wherein

##STR00065##

or a salt thereof.

[Compound I-5]

[0655] A compound of the formula (I) wherein

R is a hydrogen atom;
R.sup.1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R.sup.2 is C.sub.1-6 alkyl (e.g., methyl), C.sub.1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R.sup.1 and R.sup.2 are optionally bonded to form —O—CH.sub.2—CH(CH.sub.3)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R.sup.3 is a group of the formula

##STR00066##

wherein R.sup.22 is [0656] (a) a halogen atom, [0657] (b) cyano, [0658] (c) nitro, [0659] (d) C.sub.1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino and hydroxy, [0660] (e) C.sub.2-6 alkenyl, [0661] (f) C.sub.6-14 aryl, [0662] (g) C.sub.3-8 cycloalkyl, [0663] (h) C.sub.1-6 alkoxy, [0664] (i) formyl, or [0665] (j) carbamoyl,
or a salt thereof.

[Compound I-6]

[0666] A compound of the formula (I) wherein

R is a hydrogen atom;
R.sup.1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R.sup.2 is C.sub.1-6 alkyl (e.g., methyl), C.sub.1-6 alkoxy (e.g., methoxy) or a chlorine atom; or
R.sup.1 and R.sup.2 are optionally bonded to form —O—CH.sub.2—CH(CH.sub.3)— wherein the oxygen atom is bonded to the phenyl ring of the quinolone ring; and
R.sup.3 is a group of the formula

##STR00067##

wherein R.sup.22 is [0667] (a) cyano, [0668] (b) nitro, [0669] (c) C.sub.6-14 aryl, [0670] (d) formyl, or [0671] (e) carbamoyl,
or a salt thereof.

[Compound I-7]

[0672] A compound of the formula (I) wherein

[Compound I-8]

[0673] A compound of the formula (I) wherein

R is a hydrogen atom;
R.sup.1 is cyclopropyl, 2-fluorocyclopropyl or 2,4-difluorophenyl;
R.sup.2 is C.sub.1-6 alkyl (e.g., methyl), C.sub.1-6 alkoxy (e.g., methoxy) or a chlorine atom; and
R.sup.3 is 2-indolyl optionally substituted by 1 or 2 substituents selected from the group consisting of [0674] (a) a halogen atom, [0675] (b) cyano, [0676] (c) nitro, [0677] (d) hydroxy, [0678] (e) C.sub.1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of amino, C.sub.1-6 alkoxy-carbonylamino, C.sub.1-6 alkylamino and di(C.sub.1-6 alkyl)amino, [0679] (f) C.sub.1-6 alkoxy, [0680] (g) formyl, [0681] (h) carboxy, and [0682] (j) amino optionally substituted by 1 or 2 substituents selected from the group consisting of [0683] (i) C.sub.1-6 alkoxy-carbonyl, [0684] (ii) C.sub.1-6 alkyl-carbonyl optionally substituted by a substituent selected from the group consisting of [0685] (A) C.sub.3-8 cycloalkyloxy optionally substituted by 1 to 3 C.sub.1-6 alkyl, [0686] (B) C.sub.1-6 alkylamino, [0687] (C) di(C.sub.1-6 alkyl)amino, [0688] (D) a cyclic amino group (e.g., morpholino, 1-piperazinyl) optionally substituted by C.sub.1-6 alkoxy-carbonyl, and [0689] (E) a halogen atom, [0690] (iii) phenylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of C.sub.1-6 alkyl and C.sub.1-6 alkoxy, [0691] (iv) C.sub.3-8 cycloalkyl-carbonyl, [0692] (v) a 5- to 10-membered aromatic heterocyclylcarbonyl group (e.g., pyridylcarbonyl) optionally substituted by C.sub.1-6 alkyl optionally substituted by 1 to 3 halogen atoms, [0693] (vi) benzylcarbonyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and C.sub.1-6 alkoxy, [0694] (vii) C.sub.6-14 arylsulfonyl optionally substituted by C.sub.1-6 alkoxy, [0695] (viii) C.sub.3-8 cycloalkyl-C.sub.1-6 alkylsulfonyl optionally substituted by 1 to 3 substituents selected from the group consisting of C.sub.1-6 alkyl and oxo (e.g., camphorsulfonyl), [0696] (ix) a 5- to 10-membered aromatic heterocyclylsulfonyl group (e.g., imidazolylsulfonyl) optionally substituted by 1 to 3 C.sub.1-6 alkyl, and [0697] (x) —C(═N—CN)—SR.sup.9 wherein R.sup.9 is C.sub.1-6 alkyl,
or a salt thereof.

[Compound I-9]

[0698] A compound of the formula (I) wherein

##STR00068##

wherein
R.sup.23 is a hydrogen atom or C.sub.1-6 alkyl, and
R.sup.24, R.sup.25, R.sup.26 and R.sup.27 are each independently, [0699] (a) a hydrogen atom, [0700] (b) cyano, or [0701] (c) nitro,
or a salt thereof.

[Compound I-10]

[0702] A compound of the formula (I) wherein

##STR00069##

wherein
R.sup.28 is a hydrogen atom or hydroxy, and
R.sup.29 is a hydrogen atom or C.sub.1-6 alkyl,
or a salt thereof.

[Compound I-11]

[0703] A compound of the formula (I) wherein

##STR00070##

wherein
R.sup.10, R.sup.12 and R.sup.14 are each independently, [0704] (a) a hydrogen atom or [0705] (b) C.sub.1-6 alkyl, and
R.sup.11, R.sup.13 and R.sup.15 are each independently, [0706] (a) a hydrogen atom, [0707] (b) a halogen atom, [0708] (c) cyano, [0709] (d) nitro, [0710] (e) amino, [0711] (f) C.sub.1-6 alkylamino, [0712] (g) di(C.sub.1-6 alkyl)amino, [0713] (h) C.sub.1-6 alkyl optionally substituted by hydroxy, or [0714] (i) C.sub.2-6 alkenyl, or
R.sup.10 and R.sup.11 are optionally bonded to form —(C═O)—NH—, —C(R.sup.31)═N— or —N═N— wherein R.sup.31 is a hydrogen atom or C.sub.1-6 alkyl, and the nitrogen atom is bonded to the phenyl ring of the fused ring,
or
R.sup.12 and R.sup.13 are optionally bonded to form —(CH.sub.2).sub.4—,
or a salt thereof.

[Compound I-12]

[0715] A compound of the formula (i) wherein

##STR00071##

wherein R.sup.10a is [0716] (a) a hydrogen atom or [0717] (b) C.sub.1-6 alkyl, and
R.sup.11a, R.sup.13a and R.sup.15a are each independently, [0718] (a) a hydrogen atom, [0719] (b) a halogen atom, [0720] (c) cyano, [0721] (d) nitro, [0722] (e) amino, [0723] (f) C.sub.1-6 alkylamino, [0724] (g) di(C.sub.1-6 alkyl)amino, [0725] (h) C.sub.1-6 alkyl optionally substituted by hydroxy, or [0726] (i) C.sub.2-6 alkenyl, and
provided that R.sup.10a, R.sup.11a, R.sup.13a and R.sup.15a are not simultaneously hydrogen atom,
or a salt thereof.

[Compound I-13]

[0727] A compound of the formula (I) wherein

##STR00072##

wherein R.sup.31 is a hydrogen atom or C.sub.1-6 alkyl,
or a salt thereof.

[Compound I-14]

[0728] A compound of the formula (I) wherein

##STR00073##

wherein R.sup.16a is [0729] (a) C.sub.1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of cyano, C.sub.1-6 alkylamino and di(C.sub.1-6 alkyl)amino, [0730] (b) C.sub.2-6 alkenyl optionally substituted by carboxy, [0731] (c) formyl, [0732] (d) carboxy, [0733] (e) carbamoyl, [0734] (f) —C(R.sup.17)═N—OH wherein R.sup.17 is a hydrogen atom, cyano or hydroxy, or [0735] (g) a 5- to 10-membered aromatic heterocyclic group (e.g., tetrazolyl, pyrroyl, oxazolyl, benzimidazolyl, triazolyl) optionally substituted by C.sub.1-6 alkyl, C.sub.1-6 alkoxy-carbonyl, carboxy or phenyl,
or a salt thereof.

[Compound I-15]

[0736] A compound of the formula (I) wherein

##STR00074##

wherein
R.sup.18a is C.sub.1-6 alkyl, and

R.SUP.19a .is

[0737] (a) a halogen atom, [0738] (b) cyano, [0739] (c) C.sub.1-6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of [0740] (i) a halogen atom, [0741] (ii) cyano, [0742] (iii) hydroxy, [0743] (iv) amino, [0744] (v) C.sub.1-6 alkylamino, [0745] (vi) di(C.sub.1-6 alkyl)amino, and [0746] (vii) a cyclic amino group (e.g., 1-piperazinyl) optionally substituted by C.sub.1-6 alkyl, [0747] (d) C.sub.1-6 alkoxy, [0748] (e) amino optionally substituted by 1 or 2 substituents selected from the group consisting of [0749] (i) C.sub.1-6 alkyl-carbonyl optionally substituted by a cyclic amino group (e.g., morpholino), [0750] (ii) C.sub.1-6 alkylsulfonyl, and [0751] (iii) carbamoyl, [0752] (f) carboxy, [0753] (g) C.sub.1-6 alkoxy-carbonyl, [0754] (h) carbamoyl optionally substituted by C.sub.1-6 alkyl optionally substituted by amino, C.sub.1-6 alkylamino, di(C.sub.1-6 alkyl)amino or C.sub.1-6 alkoxy-carbonylamino, [0755] (i) formyl, [0756] (j) a 5- to 10-membered aromatic heterocyclic group (e.g., oxazolyl, benzimidazolyl), or [0757] (k) —CH═N—OR.sup.21 wherein R.sup.21 is a hydrogen atom or C.sub.1-6 alkyl optionally substituted by C.sub.1-6 alkylamino or di(C.sub.1-6 alkyl)amino,
or a salt thereof.

[Compound I-16]

[0758] A compound of the formula (I) wherein

##STR00075##

wherein

R.SUP.30 .is

[0759] (a) a hydrogen atom, [0760] (b) a halogen atom, [0761] (C) cyano, [0762] (d) C.sub.1-C.sub.6 alkyl optionally substituted by 1 to 3 substituents selected from the group consisting of a halogen atom and hydroxy, [0763] (e) C.sub.2-6 alkenyl, [0764] (f) C.sub.2-6 alkynyl, [0765] (g) C.sub.2-C.sub.6 alkoxy, [0766] (h) formyl, or [0767] (i) —CH═N—OH,
or a salt thereof.

[0768] Examples of salts of the compound of the formula (I) include pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts of the compound of the formula (I) are conventional non-toxic salts and include, for example, a salt with a base or an acid addition salt such as a salt with an inorganic base, for example, an alkali metal salt (e.g., sodium salt, potassium salt, etc.), an alkaline earth metal salt (e.g., calcium salt, magnesium salt, etc.), an ammonium salt; a salt with an organic base, for example, an organic amine salt (e.g., trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, ethanolamine salt, triethanolamine salt, dicyclohexylamine salt, N,N′-dibenzylethylenediamine salt, etc.); an inorganic acid addition salt (e.g., hydrochloride, hydrobromide, sulfate, hydrogensulfate, phosphate, etc.); an organic carboxylic or sulfonic acid addition salt (e.g., formate, acetate, trifluoroacetate, maleate, tartrate, citrate, fumarate, methanesulfonate, benzenesulfonate, toluenesulfonate, etc.); and a salt with a basic or acidic amino acid (e.g., arginine, aspartic acid, glutamic acid, etc.).

[0769] Compound (I) can be produced, for example, by a method according to the following reaction schemes.

##STR00076##

wherein X, R.sup.1 and R.sup.2 are as defined above, R.sup.32 is alkyl and R.sup.33 is alkyl.

Step a

[0770] Compound (1) can be converted to acid halide by reacting compound (1) with a halogenating agent in the presence or absence of a solvent. The solvent includes aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as dichloromethane, chloroform and carbon tetrachloride; ethers such as dioxane, tetrahydrofuran and diethyl ether; N,N-dimethylformamide (DMF); dimethyl sulfoxide (DMSO); and the like. The halogenating agent may be any conventional halogenating agents which can convert hydroxy in carboxy group into a halogen atom, and includes, for example, thionyl chloride, phosphorus oxychloride, phosphorus oxybromide, phosphorus pentachloride, phosphorus pentabromide, and the like. The amounts of compound (1) and the halogenating agent are not particularly limited, but, in case of using no solvent, the halogenating agent is usually used in a large excess amount, and in case of using a solvent, the halogenating agent is usually used in an amount of at least 1 mole, preferably 2 to 4 moles, per 1 mole of compound (1). The reaction temperature and the reaction period of time are not particularly limited, but the reaction is usually carried out at a temperature of from room temperature to about 100° C. for about 30 minutes to about 6 hours.

[0771] The obtained acid halide is reacted with magnesium salt of malonic acid monoalkyl ester to give compound (2). Magnesium salt of malonic acid monoalkyl ester can be prepared in situ from potassium salt of malonic acid monoalkyl ester such as potassium ethyl malonate in the presence of magnesium chloride and a basic compound such as triethylamine. The reaction can be carried out in a suitable solvent. The solvent used in the reaction may be any conventional solvents unless they give any undesirable effect on the reaction, and includes, for example, esters such as ethyl acetate; ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme; alcohols such as methanol, ethanol and isopropanol; aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as n-hexane, heptane, cyclohexane and ligroin; amines such as pyridine and N,N-dimethylaniline; halogenated hydrocarbons such as chloroform, dichloromethane and carbon tetrachloride; aprotic polar solvents such as DMF, DMSO and hexamethylphosphoric triamide (HMPA); and a mixture of these solvents. The reaction is usually carried out at a temperature of from about 0° C. to about 150° C., preferably from about 0° C. to about 120° C., for about 0.5 to about 20 hours. Potassium salt of malonic acid monoalkyl ester is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of compound (1). Magnesium chloride and the basic compound are usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of compound (1).

Step b

[0772] Compound (3) can be prepared by reacting compound (2) with trialkyl orthoformate such as trimethyl orthoformate and triethyl orthoformate in acetic anhydride. The reaction is usually carried out at a temperature of from about 0° C. to about 200° C., preferably from about 0° C. to about 150° C., for about 0.5 to about 20 hours. Trialkyl orthoformate is usually used in an amount of at least 1 mole, preferably 1 to 10 moles, per 1 mole of compound (2).

Step c

[0773] Compound (4) can be prepared by reacting compound (3) with compound (6).

[0774] The reaction between compound (3) and compound (6) can be carried out in a suitable solvent. The solvent employed in the reaction may be any conventional solvents unless they give any undesirable effect on the reaction, and includes, for example, alcohols such as methanol, ethanol and propanol; ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme; aromatic hydrocarbons such as benzene, toluene and xylene; aliphatic hydrocarbons such as n-hexane, heptane, cyclohexane and ligroin; halogenated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride; aprotic polar solvents such as DMF, DMSO and HMPA; and the like. The reaction is usually carried out at a temperature of from about 0° C. to about 150° C., preferably from room temperature to about 100° C., for about 0.1 to about 15 hours. Compound (6) is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of compound (3).

Step d

[0775] Compound (5) can be prepared by cyclization of compound (4).

[0776] The cyclization of compound (4) can be carried out in a suitable solvent in the presence of a basic compound. The solvent employed in the reaction may be any conventional solvents unless they give any undesirable effect on the reaction, and includes, for example, ethers such as diethyl ether, dioxane, tetrahydrofuran, monoglyme and diglyme; aliphatic hydrocarbons such as n-hexane, heptane and ligroin; halogenated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride; aprotic polar solvents such as DMF, DMSO and HMPA; and the like. The basic compound employed in the reaction includes inorganic bases such as metallic sodium, metallic potassium, sodium hydride, sodium amide, sodium hydroxide, potassium hydroxide, sodium carbonate and potassium carbonate, metal alcoholates such as sodium methylate and sodium ethylate, organic bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), N-benzyltrimethylammnonium hydroxide and tetrabutylammonium hydroxide, and the like. The reaction is usually carried out at a temperature of from about 0° C. to about 200° C., preferably from room temperature to about 150° C., for about 0.5 to about 15 hours. The basic compound is usually used in an amount of at least 1 mole, preferably 1 to 2 moles, per 1 mole of the compound (4).

##STR00077##

wherein X, R.sup.1, R.sup.2, R.sup.3 and R.sup.32 are as defined above.

Step a

[0777] Compound (Ia) can be prepared by reacting compound (5) and compound (7) or compound (8) in an inert solvent or without using any solvents, in the presence or absence of a basic compound, in the presence of a palladium catalyst.

[0778] Examples of inert solvents include water; ethers such as dioxane, tetrahydrofuran, diethyl ether, 1,2-dimethoxyethane, diethylene glycol dimethyl ether and ethylene glycol dimethyl ether; aromatic hydrocarbons such as benzene, toluene and xylene; alcohols such as methanol, ethanol and isopropanol; ketones such as acetone and methyl ethyl ketone; and aprotic polar solvents such as DMF, DMSO, HMPA and acetonitrile. These inert solvents can be used singly or in combinations of two or more.

[0779] The palladium catalyst used in the reaction is not particularly limited, but include, for example, tetravalent palladium catalysts such as sodium hexachloropalladate(IV) tetrahydrate and potassium hexachloropalladate(IV); divalent palladium catalysts such as palladium(II) chloride, palladium(II) bromide, palladium(II) acetate, palladium(II) acetylacetonate, dichlorobis(benzonitrile)palladium(II), dichlorobis(acetonitrile)palladium(II), dichlorobis(triphenylphosphine)palladium(II), dichlorotetramine 75 palladium(IT), dichloro(cycloocta-1,5-diene)palladium(II), palladium(II) trifluoroacetate, and 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium(II) dichloromethane complex (Pd(dppf)Cl.sub.2.CH.sub.2Cl); zerovalent palladium catalysts such as tris(dibenzylideneacetone)dipalladium(0), tris(dibenzylideneacetone)dipalladium(0) chloroform complex and tetrakis(triphenylphosphine)palladium(0), etc. These palladium catalysts are used singly or in combinations of two or more.

[0780] In the reaction, the amount of the palladium catalyst is not particularly limited, but is typically in the range from 0.000001 to 20 moles in terms of palladium relative to 1 mole of compound (5). The amount of the palladium catalyst is preferably in the range from 0.0001 to 5 moles in terms of palladium relative to 1 mole of compound (5).

[0781] This reaction advantageously proceeds in the presence of a suitable ligand. Examples of ligands of the palladium catalyst include, for example, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), tri-o-tolylphosphine, bis(diphenylphosphino)ferrocene, triphenylphosphine, tri-t-butylphosphine and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos). These ligands are used singly or in combinations of two or more.

[0782] The proportion of the palladium catalyst and ligand is not particularly limited. The amount of the ligand is about 0.1 to about 100 moles per 1 mole of the palladium catalyst, and preferably about 0.5 to about 15 moles per 1 mole of the palladium catalyst.

[0783] Various known inorganic and organic bases can be used as basic compounds.

[0784] Inorganic bases include, for example, alkali metal hydroxides such as sodium hydroxide, potassium hydroxide, cesium hydroxide and lithium hydroxide; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and lithium carbonate; alkali metal hydrogen carbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metals such as sodium and potassium; phosphates such as sodium phosphate and potassium phosphate; amides such as sodium amide; and alkali metal hydrides such as sodium hydride and potassium hydride.

[0785] Organic bases include, for example, alkali metal lower alkoxides such as sodium methoxide, sodium ethoxide, sodium t-butoxide, potassium methoxide, potassium ethoxide and potassium t-butoxide, and amines such as triethylamine, tripropylamine, pyridine, quinoline, piperidine, imidazole, N-ethyldiisopropylamine, dimethylaminopyridine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo[4.3.0]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,4-diazabicyclo[2.2.2]octane (DABCO), etc.

[0786] Such basic compounds can be used singly or in combinations of two or more. More preferable basic compounds used in the reaction include alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate and lithium carbonate.

[0787] The basic compound is usually used in an amount of 0.5 to 10 moles per 1 mole of compound (5), and preferably 0.5 to 6 moles per 1 mole of compound (5).

[0788] Compound (7) or compound (8) is usually used in an amount of at least 1 mole per 1 mole of compound (5), and preferably about 1 to about 5 moles per 1 mole of compound (5).

[0789] The reaction can be conducted under normal pressure, under inert gas atmosphere including nitrogen, argon, etc., or under increased pressure.

[0790] The reaction proceeds usually from room temperature to about 200° C., and preferably from room temperature to about 150° C., and is usually completed in about 1 to about 30 hours. The reaction is also achieved by heating at about 100° C. to about 200° C. for about 5 minutes to about 1 hour using a microwave reactor.

Step b

[0791] Compound (Ib) can be prepared by hydrolysis of compound (Ia).

[0792] The hydrolysis of compound (Ia) can be carried out under the conditions of conventional hydrolysis, for example, in the presence of a basic compound such as sodium hydroxide, potassium hydroxide, barium hydroxide or potassium carbonate; a mineral acid such as sulfuric acid, hydrochloric acid or nitric acid; or an organic acid such as acetic acid or an aromatic sulfonic acid, in a solvent including water, alcohols such as methanol, ethanol and isopropanol; ketones such as acetone and methyl ethyl ketone; ethers such as dioxane and ethylene glycol diethyl ether; acetic acid; or a mixture thereof. The reaction is usually carried out at a temperature of from room temperature to about 200° C., preferably from room temperature to about 150° C., for about 0.1 to about 30 hours.

Preparation of Boronate and Boronic Acid

[0793] ##STR00078##

wherein R.sup.3 is as defined above, and Z is a bromine atom or an iodine atom.

[0794] Compound (7) can be prepared by reacting compound (9) with bis(pinacolato)diboron (10) in an inert solvent in the presence of a palladium catalyst and a basic compound.

[0795] Examples of inert solvents and palladium catalyst are same as those described in Step a in Reaction Scheme II.

[0796] The basic compound employed in the reaction includes potassium acetate, triethylamine, N-methylmorpholin, sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate, potassium phosphate and sodium hydrogen carbonate.

[0797] In the reaction, the amount of the palladium catalyst is not particularly limited, but is typically in the range from 0.000001 to 20 moles in terms of palladium relative to 1 mole of compound (9). The amount of the palladium catalyst is preferably in the range from 0.0001 to 5 moles in terms of palladium relative to 1 mole of compound (9).

[0798] The basic compound is usually used in an amount of 0.5 to 10 moles per 1 mole of compound (9), and preferably 0.5 to 6 moles per 1 mole of compound (9).

[0799] Bis(pinacolato)diboron (10) is usually used in an amount of at least 1 mole per 1 mole of compound (9), and preferably about 1 to about 5 moles per 1 mole of compound (9).

[0800] The reaction can be conducted under normal pressure, under inert gas atmosphere including nitrogen, argon, etc., or under increased pressure.

[0801] The reaction proceeds usually from room temperature to about 200° C., and preferably from room temperature to about 150° C., and is usually completed in about 1 to about 30 hours.

Step b

[0802] Compound (8) can be prepared by reacting compound (9) with trialkyl borate such as trimethyl borate, triethyl borate, tri(isopropyl) borate and tri(n-butyl) borate in an inert solvent in the presence of n-butyllithium or lithium diisopropylamide.

[0803] Examples of inert solvents are same as those described in Step a in Reaction Scheme II.

[0804] The trialkyl borate is usually used in an amount of at least 1 mole per 1 mole of compound (9), and preferably about 1 to about 5 moles per 1 mole of compound (9).

[0805] n-Butyllithium or lithium diisopropylamide is usually used in an amount of at least 1 mole per 1 mole of compound (9), and preferably about 1 to about 5 moles per 1 mole of compound (9).

[0806] The reaction is usually carried out at a temperature of from about −70° C. to about 0° C. for about 0.1 to about 15 hours.

[0807] Compound (I) of the present invention can easily be converted into a salt thereof by treating with a pharmaceutically acceptable acid or base. The acid includes inorganic acids such as hydrochloric acid, sulfuric acid, phosphoric acid and hydrobromic acid and organic acids such as oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, lactic acid, methanesulfonic acid and propionic acid. The base includes sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, potassium hydrogen carbonate, and the like.

[0808] The compound thus obtained can easily be isolated and purified by conventional methods, such as, for example, extraction with solvents, dilution method, recrystallization, column chromatography and preparative thin layer chromatography.

[0809] Compound (I) shows an excellent antimicrobial activity against mycoplasma, Pseudomonas aeruginosa, anaerobic bacteria, resistant cells against various antimicrobials, clinically isolated bacteria, and gram negative and gram positive bacteria such as Clostridium difficile, Enterococcus faecalis and Staphylococcus pyogenes and hence is useful as an antimicrobial agent for the treatment of diseases induced by these microorganisms. Compound (I) also shows low toxicity and less side effects and is characteristic in good absorbability and in sustained activity.

[0810] Since compound (I) shows an excellent antimicrobial activity against Clostridium difficile, it is useful for the prevention or treatment of intestinal infections including antibiotics-associated diarrhea (AAD) such as Clostridium difficile-associated diarrhea (CDAD).

[0811] The compounds of the present invention are usually used in the form of a usual pharmaceutical preparation. The pharmaceutical preparation can be prepared in admixture with conventional pharmaceutically acceptable diluents or carriers, such as fillers, bulking agents, binding agents, wetting agents, disintegrators, surfactants and lubricating agents. The pharmaceutical preparation includes various preparations suitable for treatment of the diseases, for example, tablets, pills, powders, solutions, suspensions, emulsions, granules, capsules, suppositories, injections such as solutions and suspensions, and the like. In the preparation of tablets, there may be used any conventional carriers, for example, excipients such as lactose, white sugar, sodium chloride, glucose, urea, starches, calcium carbonate, kaolin, crystalline cellulose and silicate, binding agents such as water, ethanol, propanol, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethyl cellulose, shellac, methyl cellulose, potassium phosphate and polyvinylpyrrolidone, disintegrators such as dry starch, sodium alginate, agar powder, laminaran powder, sodium hydrogen carbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, sodium lauryl sulfate, stearic monoglyceride, starches and lactose, disintegration inhibitors such as white sugar, stearin, cacao butter and hydrogenated oils, absorption promoters such as quaternary ammonium salts and sodium lauryl sulfate, wetting agents such as glycerin and starches, adsorbents such as starches, lactose, kaolin, bentonite and colloidal silicates, lubricants such as purified talc, stearates, boric acid powder and polyethylene glycol, and the like. The tablets may also be coated with conventional coating agents, for example, may be in the form of a sugar coated tablet, a gelatin-coated tablets, an enteric coating tablet, a film coating tablet, or a double or multiple layers tablet. In the preparation of pills, there may be used conventional carriers, including excipients such as glucose, lactose, starches, cacao butter, hydrogenated vegetable oils, kaolin and talc, binding agents such as gum arabic powder, tragacanth powder, gelatin and ethanol, disintegrators such as laminaran and agar, and the like. In the preparation of suppositories, there may be used conventional carriers, such as, for example, polyethylene glycol, cacao butter, higher alcohols, higher alcohol esters, gelatin and semi-synthesized glycerides. In the preparation of injections, the solutions, emulsions or suspensions of the compounds are sterilized and are preferably made isotonic with the body liquid. These solutions, emulsions and suspensions are prepared by admixing the active compound with a conventional diluent, such as water, aqueous lactic acid solution, ethyl alcohol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol or polyoxyethylene sorbitan fatty acid esters. The preparations may also be incorporated with sodium chloride, glucose or glycerin in an amount sufficient to make them isotonic with the body liquid. The preparations may also be incorporated with conventional solubilizers, buffering agents, anesthetizing agents, and further, with coloring agents, preservatives, perfumes, flavors, sweetening agents, and other medicaments. The preparations in the form of a paste, cream or gel may be prepared by using as a diluent such as white petrolatum, paraffin, glycerin, cellulose derivatives, polyethylene glycol, silicone, bentonite, or the like. When the compound of the active ingredient precipitates in the injection, an acid such as, for example, methanesulfonic acid, propionic acid, hydrochloric acid, succinic acid or lactic acid may be added to the injection as required to preserve the injection in a stable solution.

[0812] Compound (I) may be contained in any amount in the preparations, and are usually contained in an amount of from 1 to 70% by weight based on the whole weight of the preparations.

[0813] The pharmaceutical preparations of the present invention can be administered in any methods. Suitable method for administration may be selected in accordance with the preparation form, age and sex of patients, severity of the diseases, and the like. For instance, tablets, pills, solutions, suspensions, emulsions, granules and capsules are administered in oral route. In case of injection, it is administered intravenously in a single form or together with an auxiliary liquid such as glucose or amino solution. The injections may also be administered in intramuscular, intracutaneous, subcutaneous, or intraperitoneal route. Suppositories are administered in intrarectal route.

[0814] The dosage of the pharmaceutical preparations of the present invention may vary according to administration methods, age and sex of patients, severity of the diseases, and the like, usually in the range of about 0.1 to about 100 mg, more preferably in the range of about 0.1 to about 50 mg, of compound (I) per 1 kg body weight of the patient per day. The preparation is usually administered by dividing into 2 to 4 times per day.

[0815] The present invention is illustrated by the following Examples, Experimental Examples and Preparation Examples. It is to be understood that the present invention is not limited to these Examples, Experimental Examples or Preparation Examples and various changes and modifications can be made without departing from the scope and spirit of the present invention.

EXAMPLES

[0816] ##STR00079##

[0817] In our work, Suzuki coupling was employed as key reaction to construct our final products. For the coupling, the corresponding iodo-intermediates could be prepared through well-known methods that were wildly used to synthesis of quinolones before (General Scheme I).

Example 1: Synthesis of Intermediate 5a (R.SUP.2.=Me)

[0818] 1.1. Compound 2: A mixture of compound 1 (2 g, 6.71 mmol) and thionyl chloride (9.8 mL) was refluxed for 3 hr, and then concentrated to give acid chloride. To the residue was added dry EtOAc (10 mL) and then the mixture was concentrated.

[0819] A mixture of potassium ethyl malonate (1.6 g, 9.40 mmol) and MgCl.sub.2 (1.91 g, 20.13 mmol) in dry EtOAc was stirred for 30 min below 50° C. To the mixture was added Et.sub.3N (2.83 mL, 20.13 mmol) below 50° C. Then, the mixture was refluxed for 1 hr. To the mixture was added dropwise a solution of the acid chloride in dry EtOAc (10 mL) at 50-70° C. and then the mixture was refluxed for 1.5 hr. Water (30 mL) and 5 N HCl (30 mL) were added to the reaction mixture under ice-cooling. The EtOAc solution was washed with water, dried and concentrated to give compound 2 as a yellow oil, which was used in the next step without purification.

1.2. Compound 3: A mixture of compound 2 (11 g, 29.88 mmol), triethyl orthoformate (7.47 mL, 44.82 mmol) and acetic anhydride (6.77 mL, 71.72 mmol) was heated at 150° C. for 1 hr, and then concentrated to give compound 3, which was used in the next step without purification.
1.3. Compound 4: To compound 3 (obtained above) were added EtOH (50 mL) and cyclopropylamine (2.48 mL, 35.86 mmol). The mixture was stirred for 30 min and concentrated to give compound 4, which was used in the next step without purification.
1.4. Intermediate 5a: Compound 4 (obtained above) was dissolved in dry DMSO (100 mL). K.sub.2CO.sub.3 (16.52 g, 119.53 mmol) was added to the solution. The reaction mixture was stirred at 100° C. for 1 hr. When TLC (EtOAc/dipropyl ether=1/1) indicated the reaction was completed, the mixture was cooled to room temperature, poured into water, and extracted with EtOAc. The organic layer was washed with brine, dried and concentrated to give a yellow solid which was recrystallized from EtOAc. Intermediate 5a was obtained as a white solid in 75% overall yield. .sup.1H NMR (400 MHz, DMSO) δ 8.60 (s, 1H), 7.70 (d, J=7.8 Hz, 1H), 4.29-4.14 (m, 3H), 2.96 (s, 3H), 1.28 (t, J=7.1 Hz, 3H), 1.14 (q, J=7.0 Hz, 2H), 0.87-0.76 (m, 2H).

[0820] The following compounds were synthesized according to General Scheme I.

Example 2

[0821] Intermediate 5b (R.sup.2=OMe): .sup.1H NMR (400 MHz, DMSO) δ 8.51 (s, 1H), 7.69 (d, J=7.7 Hz, 1H), 4.23 (dd, J=14.0, 6.9 Hz, 2H), 4.03 (s, 1H), 3.80 (s, 3H), 1.28 (t, J=7.0 Hz, 3H), 1.09 (d, J=6.2 Hz, 2H), 0.97 (m, 2H).

Example 3

[0822] Intermediate 5c (R.sup.2=Cl): .sup.1H NMR (400 MHz, DMSO) δ 8.61 (s, 1H), 7.81 (d, J=7.6 Hz, 1H), 4.23 (m, 3H), 1.28 (t, J=7.1 Hz, 3H), 1.21-1.08 (dd, J=7.1, 2.2 Hz, 2H), 0.99-0.92 (m, 2H).

Example 4

[0823] Intermediate 5d: .sup.1H NMR (400 MHz, CDCl.sub.3) δ 8.59-8.51 (d, J=3.1 Hz, 1H), 8.03-7.92 (d, J=7.5 Hz, 1H), 4.98-4.73 (dddd, J=62.9, 6.3, 4.9, 3.4 Hz, 1H), 4.44-4.34 (q, J=7.1 Hz, 2H), 3.91-3.83 (dt, J=8.6, 5.4 Hz, 1H), 2.95-2.88 (s, 3H), 1.59-1.48 (m, 1H), 1.45-1.38 (t, J=7.1 Hz, 3H), 1.35-1.18 (m, 1H).

Example 5

[0824] Intermediate 5e: 1H NMR (400 MHz, CDCl.sub.3) δ 8.51-8.43 (d, J=2.0 Hz, 1H), 7.94-7.86 (d, J=7.6 Hz, 1H), 4.90-4.65 (dddd, J=62.7, 6.0, 5.1, 3.3 Hz, 1H), 4.37-4.28 (q, J 7.1 Hz, 2H), 3.80-3.76 (s, 3H), 3.75-3.69 (dt, J=8.7, 5.5 Hz, 1H), 1.61-1.47 (m, 2H), 1.46-1.30 (m, 4H).

Example 6

[0825] Intermediate 5f: .sup.1H NMR (400 MHz, DMSO) δ 8.65 (s, 1H), 7.48 (d, J=8.16 Hz, 1H), 4.79 (q, J=6.65 Hz, 1H), 4.62 (dd, J=1.82, 11.36 Hz, 1H), 4.44 (dd, J=2.20, 11.36 Hz, 1H), 4.23 (qd, J=2.95, 7.09 Hz, 2H), 1.40 (d, J=6.65 Hz, 3H), 1.28 (t, J=7.09 Hz, 3H).

##STR00080##

##STR00081##

[0826] General Scheme II outlined the preparation of required boronic acids and boronates. They are readily prepared through general methods.

Example 7 Synthesis of Boronic Acid 7

[0827] ##STR00082##

Reaction reagents and conditions: a. 1) NaH, THF, r.t.; 2) nBuLi, B(OiPr).sub.3. −70° C. to 0° C.

[0828] 7.1 Boronic acid 7: To a solution of compound 6 (10 g, 44.44 mmol) in dry tetrahydrofuran (350 mL) was added sodium hydride (2 g, 66.66 mmol, 80% dispersion) at 0° C. After the mixture was stirred at room temperature for 30 min, the mixture was cooled below −60° C. in a dry ice/acetone bath, and n-butyllithium (70 mL, 112 mmol, 1.6 M in hexane) was added over 30 min. The mixture was kept stirring for another 30 min, then triisopropyl borate (40 mL, 177 mmol) was added dropwise. The reaction mixture was stirred for 10 min, and then warmed to 0° C. slowly in an ice bath. HCl (5 N) was added to the mixture to adjust pH=: 3-4, and the mixture was stirred for 20 min. Aq. NaOH was added to the mixture to adjust pH=10. After filtration, the organic layer was separated. The aqueous layer was extracted with a mixture of ethyl acetate/THF (4/1; 2×120 mL) and EtOAc (100 mL). The aqueous layer was adjusted to 25 pH=5-6 with HCl. The precipitate thus formed was collected by filtration and dried to give boronic acid 7 (3.5 g, 41%) as a white solid.

Example 8 Synthesis of Boronate 10

[0829] ##STR00083##

8.1 Compound 9: 2-Aminonicotinonitrile 8 (100 g, 0.839 mol) was dissolved in HOAc (800 mL). To the solution was added Na.sub.2CO.sub.3 (88.97 g, 0.839 mol). Then, Br.sub.2 (46.4 mL, 0.923 mol) was added dropwise. The reaction mixture was stirred at room temperature for 50 min. To the mixture was added water (600 mL). The mixture was cooled to about 5° C. The precipitate thus formed was collected by filtration and dried to give compound 9 (207 g, 96%).
8.2 Boronate 10: Compound 9 (50 g, 0.224 mol), bis(pinacolato)diboron (85.6 g, 0.337 mol), KOAc (44.1 g, 0.449 mol) and Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 (2.77 g, 3.4 mmol) were charged into a flask. Dioxane (400 mL) was added. The reaction mixture was stirred at 100° C. for 2 hr under Ar. When LC-MS indicated that the reaction was completed, the mixture was cooled to room temperature. The mixture was filtered through diatomite, concentrated, diluted with a mixture of ethyl acetate and hexane in 3/1 ratio (1000 mL), filtered through silica gel (300-400 mesh), concentrated, crystallized and dried to give boronate 10 (32 g, 66%) as a white solid.

Example 9 Synthesis of Boronate 13

[0830] ##STR00084##

9.1 Compound 12: 3-Chloropyridin-2-amine (100 g, 0.778 mol) was dissolved in acetic acid (1200 mL). To the solution was added Na.sub.2CO.sub.3 (82.4 g, 0.778 mol). Then, Br.sub.2 (39.1 mL, 0.856 mmol) was added dropwise. After addition, the reaction mixture was stirred at room temperature for 30 min. To the mixture was added water (800 mL). The mixture was cooled to about 5° C. The resulting solid was collected by filtration and dried to give compound 12 (147 g, 91%) as a white solid. 9.2 Boronate 13: Compound 12 (4 g, 17.2 mmol), bis(pinacolato)diboron (4.79 g, 18.8 mmol), KOAc (3.37 g, 34.2 mmol) and Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 (0.210 g, 0.25 mmol) were charged into a flask. Dioxane (80 mL) was added. The mixture was stirred at 85° C. for 2 hr under Ar. When LC-MS indicated that the reaction was completed, the mixture was cooled to room temperature. The mixture was filtered through diatomite and concentrated. The residue was diluted with ethyl acetate and hexane (3/1, 100 mL), filtered through silica gel (300-400 mesh), concentrated and crystallized by n-hexane to give boronate 13 (3.4 g, 78%) as a white solid.

##STR00085##

Example 10 Synthesis of Compound 1-2

[0831] ##STR00086##

10.1 Compound 16: Intermediate 5a (30 g, 65 mmol), boronic acid 7 (17 g, 71.6 mmol) and K.sub.2CO.sub.3 (27, 195 mmol) were charged into a flask. Dioxane (600 mL) and water (60 mL) were added. The solution was deoxygenated with N.sub.2 for 15 min. Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 (2.8 g, 3.24 mmol) was added to the mixture. The reaction mixture was stirred at 85° C. overnight. When the reaction was completed, the reaction mixture was cooled to room temperature. The precipitate was filtered, dissolved in water, filtered, triturated with EtOH, filtered and dried to give compound 16 (16 g, 57%) as an off-white solid. The obtained compound was pure enough for use.

[0832] The organic filtrate was concentrated. To the residue were added water, dichloromethane and EtOAc. The precipitate thus formed was collected by filtration and dissolved in HCl (5 N). After filtration to remove Pd residue, the filtrate was basified with aq. NaOH (pH=7-8). The precipitate was collected by filtration and dried to give compound 16 (3 g, 11%) as an off-white solid.

10.2 Compound I-2: Compound 16 (33 g, 76.1 mmol) was suspended in EtOH (300 mL). Aq. NaOH (4 N, 100 mL) was added to the suspension, and the mixture was stirred at 60° C. for 2 hr. 200 mL of EtOH was evaporated under reduced pressure. To the residue was added HCl (5 N) to adjust pH=4. The resulting precipitate was filtered, triturated with EtOH, filtered and dried to give compound 1-2 (30 g, 97%) as an off-white solid. m.p.>300° C. 1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.39 (s, 1H), 8.92 (s, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.01 (m, 2H), 6.67 (d, J=9.4 Hz, 1H), 4.42 (s, 1H), 2.68 (s, 3H), 1.27 (d, J=6.4 Hz, 2H), 1.12-1.03 (m, 2H). .sup.13C NMR (101 MHz, DMSO) δ 176.92, 165.25, 162.85, 158.16, 155.72, 152.71, 150.92, 149.62, 139.29, 138.79, 137.62, 133.70, 133.52, 131.80, 127.47, 127.38, 123.75, 123.42, 113.89, 108.05, 107.81, 107.29, 41.29, 20.64, 20.62, 10.62. HPLC-MS m/z 406 (MH.sup.+). Anal. Calcd for C.sub.22H.sub.16FN.sub.3O.sub.4: C, 65.18, H, 3.98, N, 10.37. Found: C, 63.50, H, 4.00, N, 9.91.

Example 11 Synthesis of Compound 2-18

[0833] ##STR00087##

[0834] 11.1 Compound 17: Boronate 10 (14 g, 56.1 mmol), intermediate 5a (20 g, 46.7 mmol), Cs.sub.2CO.sub.3 (15.22 g, 46.7 mmol) and Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 (0.98 g, 1.2 mmol) were charged into a flask. Dioxane (500 mL) and water (5 mL) were added. The mixture was stirred at 110° C. overnight under Ar. The mixture was cooled to room temperature. The mixture was filtered, and the solid was washed with dioxane and ethyl acetate. The solid was dissolved in hot CH.sub.2Cl.sub.2 (1200 mL), and the solution was filtered through diatomite. The operation was repeated twice. The organic layers were combined and concentrated. To the residue was added ethyl acetate (200 mL). The solid was collected by filtration, washed with ethyl acetate (60 mL) and dried to give compound 17 (17.6 g, 90%) as a white solid. 11.2 Compound 2-18: Compound 17 (43 g, 0.101 mol) was dissolved in THF and EtOH (1/1, 500 mL). To the solution was added NaOH (60 mL, 4 N). The mixture was stirred at room temperature for 2 hr. HCl (63 mL, 4 N) was added to acidify the mixture (pH=3-4). The solid was collected by filtration, washed with EtOH (100 mL) and dried to give compound 2-18 (35.7 g, 99%) as a white solid. m.p.>300° C. .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.89 (s, 1H), 8.32-8.23 (m, 1H), 8.08 (d, J=2.09 Hz, 1H), 7.94 (d, J=8.87 Hz, 1H), 7.28 (s, 2H), 4.40 (tt, J=3.74, 7.17 Hz, 1H), 2.67 (s, 3H), 1.31-1.19 (m, 2H), 1.10-0.99 (m, 2H). .sup.13C NMR (101 MHz, DMSO) δ 176.95, 176.92, 165.32, 159.60, 158.29, 155.86, 154.07, 152.67, 143.59, 139.32, 133.39, 133.22, 131.73, 127.13, 127.05, 116.93, 116.52, 107.96, 107.71, 107.27, 89.15, 41.32, 20.64, 20.62, 10.65. HPLC-MS m/z 379 (MH.sup.+). Anal. Calcd for C.sub.20H.sub.15FN.sub.4O.sub.3: C, 63.49, H, 4.00, N, 14.81. Found: C, 62.04, H, 4.20, N, 13.97.

Example 12 Synthesis of Compound 3-11

[0835] ##STR00088##

[0836] 12.1 Compound 18: Boronate 13 (20 g, 75.4 mmol), intermediate 5a (24.1 g, 58.03 mmol), Cs.sub.2CO.sub.3 (26.5 g, 81.2 mmol) and Pd(dppf)Cl.sub.2.CH.sub.2Cl.sub.2 (1.42 g, 1.7 mmol) were charged into a flask. Dioxane (400 mL) and water (4 mL) were added. The mixture was stirred at 100*C overnight under Ar. The mixture was cooled to room temperature. The mixture was filtered, and the solid was washed with dioxane and ethyl acetate. The solid was dissolved in hot CH.sub.2Cl.sub.2 (1200 mL), and the solution was filtered through diatomite. The operation was repeated twice. The organic layers were combined and concentrated. To the residue was added ethyl acetate (200 mL). The solid was collected by filtration, washed with ethyl acetate (60 mL) and dried to give compound 18 (21 g, 85%) as a white solid.

12.2 Compound 19: Compound 18 (39 g, 91.91 mmol) was dissolved in THF and EtOH (1/1, 600 mL) added. To the mixture was added NaOH (4 N, 60 mL). The mixture was stirred at room temperature for 2 hr. HCl (4 N, 62 mL) was added to acidify the solution (pH=3-4). The solid was collected by filtration, washed with EtOH (100 mL) and dried to give compound 19 (34 g, 98%) as a white solid.
12.3 Compound 3-11: Chloroacetaldehyde (40% in water, 80 mL) was added to a solution of compound 19 (34 g, 91.9 mmol) in EtOH (600 mL). The mixture was refluxed for 3 hr. When LC-MS indicated that the reaction was completed, the mixture was cooled to 5° C. and filtered. The solid was dried to give compound 3-11 (21 g). The mother liquid was basified (pH=7-8) with aq. NaOH. The precipitate was collected by filtration, washed with EtOH and dried to give compound 3-11 (11.5 g) as a white solid. In total, 32.5 g of compound 3-11 was obtained in 93% yield. m.p.: 307-311° C. .sup.1H NMR (400 MHz, DMSO) δ 14.53 (s, 1H), 8.98-8.84 (m, 2H), 8.28 (d, J=1.16 Hz, 1H), 7.98 (d, J=8.83 Hz, 1H), 7.90 (d, J=0.89 Hz, 1H), 7.77 (s, 18), 4.43 (tt, J=3.70, 7.10 Hz, 1H), 3.50-3.36 (m, 1H), 2.72 (s, 3H), 1.26 (d, J=6.80 Hz, 2H), 1.07 (d, J=18.24 Hz, 2H). .sup.13C NMR (101 MHz, DMSO) δ 176.91, 176.88, 165.23, 158.22, 155.77, 152.84, 139.98, 139.17, 139.16, 132.44, 132.15, 131.98, 131.54, 127.86, 127.78, 127.38, 120.72, 118.97, 116.37, 108.15, 107.91, 107.37, 41.38, 20.54, 20.52, 10.72. HPLC-MS: m/z 412 (MH.sup.+). Anal. Calcd for C.sub.21H.sub.15ClFN.sub.3O.sub.3: C, 61.25, H, 3.67, N, 10.20. Found: C, 58.59, H, 3.86, N, 9.76.

[0837] Compounds listed in the following Tables were synthesized according to General Scheme III.

TABLE-US-00001 TABLE 1 [00089] embedded image Compound MS No. R.sup.3 = R.sup.2 = R.sup.1 = NMR (MH.sup.+) HPLC 1-1 [00090] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 12.41 (s, 1H), 8.82 (s, 1H), 8.69 (s, 1H), 8.38 (s, 1H), 8.05 (d, J = 9.6 Hz, 1H), 7.99 (d, J = 9.1 Hz, 1H), 6.66 (dd, J = 9.5, 1.6 Hz, 1H), 4.24 (s, 1H), 3.42 (s, 3H), 1.19 (d, J = 7.2 Hz, 4H). 422 98% 1-2 [00091] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.39 (s, 1H), 8.92 (s, 1H), 8.58 (s, 1H), 8.28 (s, 1H), 8.01 (m, 2H), 6.67 (d, J = 9.4 Hz, 1H), 4.42 (s, 1H), 2.68 (s, 3H), 1.27 (d, J = 6.4 Hz, 2H), 1.12-1.03 (m, 2H). 406 98% 1-3 [00092] OMe [00093] .sup.1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 12.41 (s, 1H), 8.85 (d, J = 1.3 Hz, 1H), 8.67 (s, 1H), 8.36 (s, 1H), 8.05 (d, J = 9.6 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 6.77-6.54 (m, 1H), 5.24-4.97 (m, 1H), 4.29-4.10 (m, 1H), 3.44 (s, 3H), 1.89-1.59 (m, 2H). 440 98% 1-4 [00094] embedded image Me [00095] .sup.1H NMR (400 MHz, DMSO) δ 14.50 (s, 1H), 12.39 (s, 1H), 8.90 (d, J = 3.0 Hz, 1H), 8.58 (s, 1H), 8.27 (s, 1H), 8.02 (m, 2H), 6.74-6.61 (m, 1H), 5.17 (dd, J = 64.3, 3.1 Hz, 1H), 4.39 (m, 1H), 2.60 (s, 3H), 1.84-1.50 (m, 2H). 424 98% 1-5 [00096] Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.22 (s, 1H), 12.42 (s, 1H), 8.94 (s, 1H), 8.61 (d, J = 2.0 Hz, 1H), 8.31 (d, J = 2.0 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 9.6 Hz, 1H), 6.67 (d, J = 9.5 Hz, 1H), 4.51-4.34 (m, 1H), 1.29-1.19 (m, 2H), 1.17-1.05 (m, 2H). 426 98% 1-7 [00097] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 11.27 (s, 1H), 8.91 (s, 1H), 8.04 (d, J = 9.5 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.78 (s, 2H), 6.69 (d, J = 9.5 Hz, 1H), 4.49-4.30 (m, 1H), 2.65 (s, 3H), 1.25 (d, J = 6.7 Hz, 2H), 1.08 (s, 2H). 439 98% 1-8 [00098] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 11.99 (s, 1H), 8.91 (s, 1H), 8.03 (d, J = 9.1 Hz, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.60 (s, 1H), 7.57 (d, J = 11.5 Hz, 1H), 6.66 (d, J = 9.6 Hz, 1H), 4.51-4.29 (m, 1H), 1.25 (d, J = 6.3 Hz, 2H), 1.15-0.94 (m, 2H). 423 98% 1-9 [00099] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 11.30 (s, 1H), 8.82 (s, 1H), 8.15- 8.03 (m, 1H), 8.00-7.93 (d, J = 9.1 Hz, 1H), 7.93-7.80 (d, J = 12.9 Hz, 2H), 6.79-6.51 (d, J = 9.4 Hz, 1H), 4.28-4.15 (m, 1H), 3.51-3.38 (s, 3H), 1.31-1.09 (m, 4H). 455 93% 1-10 [00100] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69-14.59 (s, 1H), 12.08-11.94 (s, 1H), 8.90- 8.74 (s, 1H), 8.13-8.01 (d, J = 1.8 Hz, 1H), 7.99-7.91 (d, J = 9.1 Hz, 1H), 7.77-7.71 (s, 1H), 7.68-7.59 (d, J = 11.6 Hz, 1H), 6.71-6.62 (d, J = 9.6 Hz, 1H), 4.30-4.17 (ddd, J = 11.2, 7.5, 4.7 Hz, 1H), 3.47-3.39 (s, 3H), 1.22-1.11 (m, 4H). 439 95% 1-11 [00101] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 9.92 (s, 1H), 8.91 (s, 1H), 8.09 (d, J = 9.6 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.81 (s, 1H), 7.62-7.53 (m, 4H), 7.52- 7.47 (m, 1H), 7.46 (s, 1H), 6.65 (d, J = 9.5 Hz, 1H), 4.65-4.23 (m, 1H), 2.70 (s, 3H), 1.24 (d, J = 7.0 Hz, 2H), 1.07 (s, 2H). 481 98% 1-12 [00102] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 12.23 (s, 1H), 8.92 (s, 1H), 8.10 (d, J = 9.5 Hz, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.87 (s, 1H), 7.70 (s, 1H), 6.70 (d, J = 9.3 Hz, 1H), 4.43 (s, 1H), 2.64 (s, 3H), 1.23 (s, 2H), 1.07 (d, J = 12.5 Hz, 2H). 489 98% 1-13 [00103] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.55 (s, 1H), 8.91 (s, 1H), 8.04 (d, J = 9.5 Hz, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.84 (s, 1H), 7.74 (s, 1H), 6.68 (d, J = 9.4 Hz, 1H), 4.75 (s, 1H), 4.40 (m, 1H), 2.64 (s, 3H), 1.25 (d, J = 6.9 Hz, 2H), 1.08 (s, 2H). 429 90% 1-14 [00104] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.06 (s, 1H), 8.91 (s, 1H), 8.05- 7.87 (m, 2H), 7.31 (s, 1H), 7.16 (s, 1H), 6.60 (d, J = 9.5 Hz, 1H), 4.40 (dd, J = 7.0, 3.4 Hz, 1H), 3.94 (s, 3H), 2.65 (s, 3H), 1.25 (d, J = 7.1 Hz, 2H), 1.08 (s, 2H). 435 90% 1-15 [00105] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 10.97 (s, 1H), 8.92 (s, 1H), 8.28- 8.06 (m, 2H), 8.01 (d, J = 8.8 Hz, 1H), 7.95 (s, 1H), 6.74 (d, J = 8.5 Hz, 1H), 4.49- 4.33 (m, 1H), 2.64 (s, 3H), 1.25 (d, J = 6.8 Hz, 2H), 1.10 (s, 2H). 473 90% 1-16 [00106] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.95 (s, 1H), 8.91 (s, 1H), 7.99 (d, J = 7.9 Hz, 2H), 7.76 (s, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 6.59 (d, J = 9.5 Hz, 1H), 4.40 (s, 1H), 2.63 (s, 3H), 1.25 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H). 405 98% 1-17 [00107] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.76 (s, 1H), 8.92 (s, 1H), 8.03 (d, J = 9.7 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.93 (s, 1H), 7.83 (s, 1H), 6.68 (d, J = 9.4 Hz, 1H), 2.65 (s, 3H), 1.25 (m, 2H), 1.07 (m, 2H). 482; 484 96% 1-18 [00108] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 11.86 (s, 1H), 8.92 (s, 1H), 8.16 (m, 3H), 8.00 (d, J = 8.7 Hz, 1H), 6.80 (s, 1H), 4.42 (s, 1H), 2.65 (s, 3H), 1.26 (m, 2H), 1.09 (m, 2H). 430 96% 1-19 [00109] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.10 (s, 1H), 8.90 (s, 1H), 7.97 (t, J = 9.04 Hz, 2H), 7.58 (s, 1H), 7.39 (s, 1H), 6.59 (d, J = 9.48 Hz, 1H), 4.39 (dt, J = 3.29, 6.75 Hz, 1H), 3.36 (s, 3H), 2.63 (s, 3H), 1.25 (d, J = 6.45 Hz, 2H), 1.06 (s, 2H). 419 96% 1-20 [00110] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 8.93 (s, 1H), 8.21 (s, 1H), 8.18 (s, 1H), 8.15 (d, J = 9.7 Hz, 1H), 8.02 (d, J = 8.9 Hz, 1H), 6.81 (d, J = 9.7 Hz, 1H), 6.24 (s, 2H), 4.41 (m, 2H), 2.65 (s, 4H), 1.25 (m, 2H), 1.10 (m, 2H). 461 90% 1-21 [00111] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 12.18 (s, 1H), 8.91 (s, 1H), 8.14 (s, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 7.7 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.41 (d, J = 7.9 Hz, 1H), 7.28 (d, J = 7.4 Hz, 1H), 4.43 (s, 1H), 2.71 (s, 3H), 1.24 (s, 2H), 1.05 (s, 2H). 405 98% 1-22 [00112] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 8.91 (s, 1H), 8.16 (s, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.90 (s, 1H), 7.85 (d, J = 7.3 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.38 (d, J = 6.7 Hz, 1H), 4.42 (s, 1H), 3.74 (s, 3H), 2.69 (s, 3H), 1.23 (s, 2H), 1.05 (s, 2H). 419 95% 1-23 [00113] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 12.04 (s, 1H), 8.93 (s, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.68 (t, J = 7.5 Hz, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.35 (d, J = 9.7 Hz, 1H), 7.17 (d, J = 7.1 Hz, 1H), 6.49 (d, J = 9.7 Hz, 1H), 4.39 (s, 1H), 2.50 (s, 3H), 1.16 (m, 4H). 405 96% 1-24 [00114] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 10.88 (s, 1H), 8.95 (s, 1H), 8.20- 7.94 (m, 2H), 7.86 (d, J = 30.6 Hz, 1H), 7.44 (d, J = 7.5 Hz, 1H), 7.36 (s, 1H), 6.57 (s, 1H), 4.41 (s, 1H), 2.67 (s, 3H), 1.47-0.92 (m, 4H). 405 90% 1-25 [00115] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 12.12 (s, 1H), 8.94 (s, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.45 (d, J = 7.0 Hz, 1H), 7.13 (s, 1H), 7.02 (d, J = 8.0 Hz, 1H), 6.65 (s, 1H), 4.40 (m, 1H), 2.62 (s, 3H), 1.28-1.04 (m, 4H). 405 90% 1-26 [00116] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.88 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.86 (d, J = 7.8 Hz, 1H), 7.29 (s, 1H), 7.22 (d, J = 7.6 Hz, 1H), 6.60 (d, J = 9.6 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.24 (d, J = 5.6 Hz, 2H), 1.07 (s, 2H). 405 94% 1-27 [00117] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 11.57 (s, 1H), 11.48 (s, 1H), 8.97 (s, 1H), 8.04 (d, J = 8.5 Hz, 1H), 7.82 (s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.49 (d, J = 8.2 Hz, 1H), 5.86 (s, 1H), 4.45 (s, 1H), 2.68 (s, 3H), 1.30 (d, J = 5.7 Hz, 2H), 1.13 (s, 2H). 421 98% 1-28 [00118] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 10.73 (s, 1H), 8.90 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.89 (s, 1H), 7.43 (s, 1H), 7.28 (d, J = 7.6 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.24 (s, 2H), 1.06 (s, 2H). 466 96% 1-29 [00119] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.96 (s, 1H), 8.81 (s, 1H), 8.01 (d, J = 9.6 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.87 (s, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.57 (dd, J = 9.5, 1.7 Hz, 1H), 4.32-4.10 (m, 1H), 3.38 (s, 3H), 1.18 (m, 4H). 421 98% 1-30 [00120] embedded image Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.41 (s, 1H), 11.96 (s, 1H), 8.91 (s, 1H), 8.20 (d, J = 8.8 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J = 8.6 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 6.62 (dd, J = 9.5, 1.7 Hz, 1H), 4.32-4.10 (m, 1H), 1.30 (m, 2H), 1.18 (m, 2H). 425 96% 1-31 [00121] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.89 (s, 1H), 8.82 (s, 1H), 8.17- 7.90 (m, 2H), 7.85 (d, J = 8.0 Hz, 1H), 7.48 (s, 1H), 7.35 (d, J = 7.9 Hz, 1H), 6.60 (d, J = 11.2 Hz, 1H), 4.28-4.14 (m, 1H), 3.41 (s, 4H), 1.18 (m, 4H). 421 90% 1-32 [00122] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.78 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.77 Hz, 1H), 7.72 (s, 1H), 7.54 (s, 1H), 7.50-7.44 (m, 1H), 6.48 (s, 1H), 2.63 (s, 3H), 2.44 (s, 3H), 1.28-1.21 (m, 2H), 1.12-1.02 (m, 2H). 419 96% 1-33 [00123] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 13.15 (s, 1H), 8.92 (s, 1H), 8.87 (s, 1H), 8.77 (d, J = 1.74 Hz, 1H), 8.38 (d, J = 1.97 Hz, 1H), 8.02 (d, J = 8.86 Hz, 1H), 4.42 (tt, J = 3.74, 7.15 Hz, 1H), 2.66 (s, 3H), 1.25 (q, J = 6.85 Hz, 2H), 1.08 (s, 2H). 431 96% 1-34 [00124] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.11 (s, 1H), 8.92 (s, 1H), 8.31 (d, J = 8.86 Hz, 1H), 8.16 (d, J = 8.54 Hz, 1H), 8.03 (d, J = 8.91 Hz, 1H), 6.51 (s, 1H), 4.44 (tt, J = 3.64, 7.02 Hz, 2H), 2.69 (s, 3H), 2.51 (s, 3H), 1.24 (d, J =0 6.83 Hz, 2H), 1.10 (s, 2H). 420 95% 1-35 [00125] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75-14.55 (m, 1H), 9.83-9.67 (d, J = 3.2 Hz, 1H), 8.89-8.73 (s, 1H), 7.96-7.86 (d, J = 9.1 Hz, 1H), 7.58-7.47 (s, 1H), 7.42- 7.34 (s, 1H), 4.30-4.14 (tt, J = 7.3, 4.5 Hz, 1H), 3.52-3.39 (s, 3H), 3.11- 2.95 (t, J = 7.5 Hz, 2H), 2.62-2.56 (dd, J = 8.5, 6.3 Hz, 2H), 1.21-1.12 (m, 4H). 457 99% 1-36 [00126] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, CDCl.sub.3) δ 14.52-14.39 (s, 1H), 8.87-8.82 (s, 1H), 8.01- 7.92 (m, 1H), 7.75-7.69 (s, 1H), 7.39-7.34 (t, J = 1.7 Hz, 1H), 7.21-7.18 (s, 1H), 6.79-6.69 (dd, J = 17.3, 11.0 Hz, 1H), 5.70-5.62 (d, J = 17.3 Hz, 1H), 5.54-5.44 (d, J = 11.0 Hz, 1H), 4.09-3.99 (d, J = 3.7 Hz, 1H), 3.45-3.36 (s, 3H), 3.03-2.95 (dd, J = 8.5, 6.5 Hz, 2H), 2.68-2.59 (dd, J = 8.7, 6.5 Hz, 2H), 449 85% 1.26-1.21 (dd, J = 5.2, 1.8 Hz, 2H), 1.11-1.03 (dt, J = 4.0, 1.9 Hz, 2H). 1-37 [00127] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.73-14.60 (s, 1H), 10.38-10.26 (s, 1H), 8.84- 8.76 (s, 1H), 7.96-7.86 (d, J = 9.1 Hz, 1H), 7.36-7.28 (d, J = 11.2 Hz, 1H), 7.25-7.19 (s, 1H), 4.29-4.18 (ddd, J = 11.3, 7.3, 4.4 Hz, 1H), 3.47-3.43 (s, 3H), 3.07-2.99 (t, J = 7.4 Hz, 2H), 2.60-2.53 (dd, J = 8.5, 6.5 Hz, 2H), 1.21- 1.08 (d, J = 5.3 Hz, 4H). 441 85% 1-38 [00128] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 9.62 (s, 1H), 8.79 (s, 1H), 7.89 (d, J = 9.2 Hz, 1H), 7.20 (d, J = 8.5 Hz, 2H), 4.39-4.16 (m, 1H), 3.42 (s, 3H), 3.03-2.88 (m, 2H), 2.54 (m, 5H), 1.16 (m, 4H). 436 99% 1-39 [00129] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.13-14.27 (m, 1H), 10.76-10.64 (s, 5H), 8.98- 8.88 (s, 1H), 8.19-8.14 (d, J = 2.2 Hz, 1H), 8.00-7.94 (d, J = 8.7 Hz, 1H), 7.75-7.70 (d, J = 2.1 Hz, 1H), 4.49-4.32 (tt, J = 7.3, 3.8 Hz, 1H), 3.03-2.95 (m, 2H), 2.69-2.64 (s, 3H), 2.62-2.56 (t, J = 7.5 Hz, 2H), 1.28-1.22 (m, 2H), 1.09-1.03 (m, 2H). 408 90% 1-40 [00130] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 12.01 (s, 1H), 8.92 (s, 1H), 8.53 (s, 1H), 8.08-7.98 (m, 2H), 7.72 (s, 1H), 6.85 (d, J = 9.75 Hz, 1H), 4.41 (s, 1H), 3.34 (s, 1H), 2.65 (s, 3H), 2.54 (s, 3H), 1.24 (d, J = 6.54 Hz, 2H), 1.09 (s, 2H). 406 96% 1-41 [00131] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.85-14.51 (s, 1H), 9.00-8.91 (m, 2H), 8.60-8.53 (s, 1H), 8.18-8.09 (t, J = 8.4 Hz, 2H), 8.09-8.02 (m, 1H), 7.95- 7.84 (s, 1H), 7.79-7.68 (s, 1H), 4.51-4.31 (s, 1H), 2.79-2.61 (s, 3H), 1.36-1.20 (d, J = 6.9 Hz, 2H), 1.16-1.04 (s, 2H). 389 100% 1-42 [00132] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.01-14.88 (d, J = 2.6 Hz, 1H), 8.95-8.82 (d, J = 2.5 Hz, 1H), 8.05-7.94 (d, J = 6.7 Hz, 1H), 7.89-7.77 (d, J = 9.4 Hz, 1H), 7.62-7.40 (m, 3H), 6.33-6.21 (s, 1H), 5.59-5.49 (s, 2H), 4.48- 4.35 (s, 1H), 2.86-2.76 (s, 3H), 1.30-1.15 392 100% (d, J = 7.0 Hz, 2H), 1.00-0.88 (s, 2H). 1-43 [00133] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 9.05-8.91 (s, 1H), 8.87-8.77 (s, 1H), 8.43- 8.36 (s, 1H), 8.14-8.06 (d, J = 7.3 Hz, 1H), 8.02-7.88 (d, J = 21.7 Hz, 2H), 7.74-7.62 (d, J = 8.7 Hz, 1H), 7.59-7.51 (s, 1H), 4.35-4.15 (s, 1H), 2.73- 2.53 (m, 3H), 1.05-0.93 (s, 2H), 0.85-0.71 389 97% (d, J = 8.0 Hz, 2H). 1-44 [00134] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72-14.59 (s, 1H), 9.01-8.91 (s, 1H), 8.88- 8.80 (s, 1H), 8.66-8.56 (d, J = 8.6 Hz, 1H), 8.25-8.16 (d, J = 8.0 Hz, 1H), 8.14-8.09 (s, 1H), 8.08-8.01 (d, J = 8.6 Hz, 1H), 7.95-7.89 (d, J = 8.7 Hz, 1H), 7.88-7.79 (d, J = 7.7 Hz, 1H), 4.51-4.35 (s, 1H), 2.75-2.67 (s, 3H), 1.30-1.19 (d, J = 6.8 Hz, 2H), 1.16-1.07 (s, 2H). 405 97.5% 1-45 [00135] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.85-14.58 (s, 1H), 9.00-8.88 (s, 1H), 8.19- 8.07 (d, J = 8.3 Hz, 1H), 8.07-7.94 (m, 4H), 7.68-7.58 (d, J = 6.0 Hz, 2H), 7.57-7.48 (d, J = 8.2 Hz, 1H), 4.49-4.33 (s, 1H), 2.72-2.59 (s, 3H), 1.33-1.19 (d, 388 98% J = 7.4 Hz, 2H), 1.16-1.00 (s, 2H). 1-46 [00136] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.69-9.59 (s, 1H), 9.01-8.92 (d, J = 2.5 Hz, 1H), 8.69-8.58 (d, J = 2.4 Hz, 1H), 8.47-8.34 (d, J = 7.6 Hz, 1H), 8.14- 8.04 (d, J = 8.1 Hz, 1H), 7.95-7.80 (t, J = 8.7 Hz, 2H), 7.57-7.46 (d, J = 7.9 Hz, 1H), 4.48-4.34 (s, 1H), 2.52-2.50 (s, 3H), 1.29-1.01 (m, 4H). 389 98% 1-47 [00137] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.96-14.46 (s, 1H), 12.04-11.50 (s, 1H), 8.98- 8.89 (s, 1H), 8.34-8.17 (d, J = 12.3 Hz, 1H), 8.17-8.01 (m, 2H), 7.97-7.90 (d, J = 8.1 Hz, 1H), 4.48-4.36 (dd, J = 7.3, 4.1 Hz, 1H), 2.66-2.56 (s, 3H), 1.31-1.17 (d, J = 7.1 Hz, 2H), 1.15-1.03 (s, 2H). 422 99% 1-48 [00138] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.19-9.11 (s, 1H), 8.98-8.92 (s, 1H), 8.45- 8.39 (s, 1H), 8.13-8.00 (dd, J = 16.7, 8.4 Hz, 2H), 7.80-7.69 (t, J = 7.7 Hz, 1H), 7.66-7.55 (t, J = 7.7 Hz, 1H), 7.38-7.29 (d, J = 8.3 Hz, 1H), 4.47- 4.34 (s, 1H), 2.65-2.54 (s, 3H), 1.28-1.07 (m, 4H). 405 98% 1-49 [00139] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69-14.45 (s, 1H), 10.31-10.19 (s, 1H), 9.06-8.94 (d, J = 3.6 Hz, 2H), 8.73-8.62 (d, J = 8.2 Hz, 1H), 8.61-8.43 (m, 2H), 8.32-8.21 (t, J = 7.5 Hz, 1H), 8.21-8.11 (m, 2H), 7.83-7.71 (d, J = 8.3 Hz, 1H), 4.67-4.52 (s, 3H), 4.50-4.39 (d, J = 7.6 Hz, 1H), 2.52- 2.50 (m, 3H), 1.32-1.03 (m, 4H). 404 100% 1-50 [00140] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72-14.45 (s, 1H), 9.88-9.78 (s, 1H), 9.58- 9.48 (s, 1H), 9.02-8.92 (s, 1H), 8.70-8.60 (d, J = 9.0 Hz, 1H), 8.59- 8.51 (d, J = 8.2 Hz, 1H), 8.46-8.36 (t, J = 7.9 Hz, 1H), 8.24-8.06 (t, J = 9.7 Hz, 2H), 4.78-4.67 (s, 2H), 4.53-4.40 (s, 1H), 2.82-2.71 (s, 3H), 1.37- 1.18 (d, J = 6.4 Hz, 2H), 1.16-1.07 (m, 2H). 404 98% 1-51 [00141] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.10-9.01 (d, J = 4.0 Hz, 1H), 8.98-8.91 (d, J = 2.6 Hz, 1H), 8.30-8.19 (d, J = 8.4 Hz, 1H), 8.14-8.07 (s, 1H), 8.05- 7.97 (t, J = 7.7 Hz, 1H), 7.96-7.89 (d, J = 8.4 Hz, 1H), 7.78-7.68 (d, J = 6.8 Hz, 1H), 7.65-7.57 (m, 1H), 4.45-4.33 (s, 1H), 2.48-2.40 (d, J = 2.8 Hz, 3H), 1.28-1.03 (m, 4H). 389 93.6% 1-52 [00142] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.78-14.66 (s, 1H), 9.06-8.97 (s, 1H), 8.96- 8.88 (s, 1H), 8.54-8.46 (d, J = 8.1 Hz, 1H), 8.26-8.14 (d, J = 8.3 Hz, 1H), 8.14-8.06 (s, 1H), 8.06-7.98 (d, J = 8.6 Hz, 1H), 7.74-7.58 (d, J = 8.3 Hz, 2H), 4.51-4.29 (s, 1H), 2.73-2.60 (s, 3H), 1.29-1.18 (d, J = 7.0 389 100% Hz, 2H), 1.15-1.07 (s, 2H). 1-53 [00143] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.96-8.88 (d, J = 2.4 Hz, 1H), 8.85-8.78 (s, 1H), 8.57-8.47 (d, J = 8.2 Hz, 1H), 8.25-8.13 (d, J = 8.3 Hz, 1H), 8.03- 7.95 (d, J = 8.3 Hz, 1H), 7.86-7.77 (m, 2H), 7.69-7.54 (d, J = 8.7 Hz, 1H), 4.44-4.31 (s, 1H), 2.48-2.42 (s, 3H), 1.29-1.16 (d, J = 7.6 Hz, 2H), 1.15-1.02 (s, 2H). 389 98% 1-54 [00144] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.17-9.09 (s, 1H), 9.01-8.91 (d, J = 2.7 Hz, 1H), 8.26-8.17 (d, J = 8.5 Hz, 1H), 8.15-8.06 (d, J = 8.5 Hz, 1H), 7.94- 7.84 (s, 1H), 2.48-2.42 (m, 2H), 7.72-7.59 (d, J = 9.2 Hz, 2H), 7.56-7.45 (d, J = 8.3 Hz, 1H), 4.45-4.35 (s, 1H), 2.52-2.45 (s, 3H), 1.29-1.03 (dd, J = 16.6, 7.5 Hz, 4H). 389 98% 1-55 [00145] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.08-14.78 (s, 1H), 8.95-8.83 (s, 2H), 8.48- 8.37 (d, J = 6.0 Hz, 1H), 8.33-8.19 (d, J = 8.2 Hz, 1H), 8.14-8.02 (d, J = 8.5 Hz, 1H), 7.94-7.76 (m, 2H), 7.68-7.59 (d, J = 7.1 Hz, 1H), 7.58-7.49 (t, J = 7.2 Hz, 1H), 4.47-4.34 (s, 1H), 2.73-2.56 (s, 3H), 1.31-0.99 (m, 4H). 405 95% 1-56 [00146] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.00-8.91 (s, 1H), 8.85-8.75 (d, J = 6.1 Hz, 1H), 8.73-8.64 (d, J = 8.6 Hz, 1H), 8.13-8.05 (d, J = 8.4 Hz, 1H), 7.97- 7.86 (d, J = 8.1 Hz, 1H), 7.80-7.71 (s, 1H), 7.65-7.58 (d, J = 5.8 Hz, 1H), 7.57-7.48 (d, J = 8.4 Hz, 1H), 4.46-4.35 (s, 1H), 2.57-2.52 (s, 3H), 1.28-1.04 (m, 4H). 405 96% 1-57 [00147] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.95-14.35 (m, 1H), 9.01-8.90 (t, J = 2.0 Hz, 1H), 8.80-8.63 (m, 2H), 8.13-8.06 (m, 1H), 8.04-7.95 (t, J = 7.8 Hz, 1H), 7.84-7.75 (d, J = 6.5 Hz, 1H), 7.52-7.41 (ddd, J = 10.0, 5.1, 2.5 Hz, 1H), 7.38-7.29 (d, J = 8.4 Hz, 1H), 4.46-4.32 (d, J = 6.9 Hz, 1H), 2.49- 2.44 (s, 3H), 1.29-0.99 (m, 4H). 405 93.3% 1-58 [00148] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.98-8.89 (s, 1H), 8.73-8.64 (d, J = 6.6 Hz, 1H), 8.58-8.52 (s, 1H), 8.35-8.26 (d, J = 8.2 Hz, 1H), 8.12-7.99 (t, J = 10.7 Hz, 2H), 7.83-7.75 (d, J = 8.3 Hz, 1H), 7.65-7.53 (s, 1H), 4.46-4.36 (s, 1H), 2.65-2.59 (s, 3H), 1.29-1.19 (d, J = 7.8 Hz, 2H), 1.14-1.07 (s, 2H). 405 96.2% 1-59 [00149] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.96-8.87 (s, 1H), 8.75-8.64 (d, J = 7.2 Hz, 2H), 8.28-8.19 (s, 1H), 8.10-7.99 (d, J = 8.5 Hz, 2H), 7.90-7.80 (d, J = 9.0 Hz, 1H), 7.63-7.52 (s, 1H), 4.48-4.34 (s, 1H), 2.65-2.57 (s, 3H), 1.30- 1.18 (d, J = 7.1 Hz, 2H), 1.14-1.02 (s, 2H). 405 99% 1-60 [00150] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.77-9.61 (s, 1H), 9.00-8.90 (d, J = 3.1 Hz, 1H), 8.75-8.62 (d, J = 5.8 Hz, 1H), 8.57-8.42 (d, J = 8.2 Hz, 1H), 8.31- 8.21 (s, 1H), 8.22-8.13 (d, J = 5.3 Hz, 1H), 8.11-8.01 (d, J = 8.7 Hz, 1H), 7.94-7.81 (d, J = 8.4 Hz, 1H), 4.49-4.34 (s, 1H), 2.68-2.59 (s, 389 93.6% 3H), 1.34-1.18 (d, J = 7.6 Hz, 2H), 1.15-1.00 (s, 2H). 1-61 [00151] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.19-9.10 (s, 1H), 9.03-8.95 (s, 1H), 8.37- 8.27 (d, J = 6.9 Hz, 1H), 8.18-8.05 (m, 4H), 7.81-7.73 (d, J = 8.4 Hz, 1H), 4.52-4.42 (t, J = 5.2 Hz, 1H), 2.74-2.65 (s, 3H), 1.36-1.27 (d, J = 7.1 Hz, 2H), 1.19-1.10 (s, 2H). 405 1005 1-62 [00152] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.82-14.70 (s, 1H), 11.54-11.41 (s, 1H), 9.03-8.93 (s, 1H), 8.44-8.33 (d, J = 8.2 Hz, 1H), 8.14-8.01 (d, J = 8.0 Hz, 1H), 7.84-7.75 (s, 1H), 7.58-7.51 (d, J = 7.6 Hz, 1H), 7.39-7.26 (s, 1H), 6.76-6.64 (d, J = 6.6 Hz, 1H), 4.52-4.40 (s, 1H), 2.70-2.61 (s, 3H), 1.37-1.22 (d, J = 6.8 Hz, 2H), 1.19-1.04 (s, 2H). 405 100% 1-63 [00153] embedded image .sup.1H NMR (400 MHz, DMSO) δ 15.18 (s, 1H), 12.31 (s, 1H), 9.09 (s, 1H), 8.82 (d, J = 2.0 Hz, 1H), 8.45 (d, J = 1.7 Hz, 1H), 8.03 (t, J = 9.3 Hz, 2H), 7.76 (d, J = 8.4 Hz, 1H), 6.63 (d, J = 9.4 Hz, 1H), 5.00 (d, J = 6.7 Hz, 1H), 4.58 (d, J = 10.8 Hz, 1H), 4.45 (d, J = 10.0 Hz, 1H), 2.54 (s, 1H), 1.52 (d, J = 6.7 Hz, 3H). 390 98% 1-64 [00154] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.96 (s, 1H), 12.35 (s, 1H), 9.10 (s, 1H), 8.68 (s, 1H), 8.34 (s, 1H), 8.01 (d, J = 9.53 Hz, 1H), 7.79 (d, J = 9.70 Hz, 1H), 6.64 (d, J = 9.45 Hz, 1H), 5.01 (d, J = 6.68 Hz, 1H), 4.60-4.54 (m, 1H), 4.46 (d, J = 9.78 Hz, 1H), 1.49 (d, J = 6.71 Hz, 3H). 408 96% 1-65 [00155] embedded image .sup.1H NMR (400 MHz, DMSO) δ 9.27 (s, 1H), 8.95 (s, 1H), 8.87 (d, J = 15.4 Hz, 1H), 8.41-8.22 (m, 3H), 8.01 (t, J = 7.3 Hz, 1H), 7.85 (t, J = 7.3 Hz, 1H), 7.73 (d, J = 8.2 Hz, 1H), 4.45 (m, 1H), 2.77 (s, 3H), 1.31 (d, J = 6.2 Hz, 2H), 1.11 (s, 2H). 371 97%

TABLE-US-00002 TABLE 2 [00156] embedded image Com- pound MS No. R.sup.3 = R.sup.2 = R.sup.1 = NMR (MH.sup.+) HPLC 2-1 [00157] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.28 (s, 1H), 7.98 (s, 1H), 7.80 (s, 1H), 7.33 (d, J = 8.90 Hz, 1H), 7.16 (d, J = 9.30 Hz, 1H), 3.66 (d, J = 3.58 Hz, 1H), 1.96 (s, 3H), 0.58 (d, J = 5.78 Hz, 2H), 0.37 (d, J = 1.61 Hz, 2H). 357 94% 2-2 [00158] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.48 (d, J = 2.77 Hz, 1H), 8.13 (s, 1H), 8.01 (d, J = 8.72 Hz, 1H), 7.61 (s, 1H), 4.50-4.30 (m, 1H), 3.49 (d, J = 5.30 Hz, 5H), 3.36-3.29 (m, 5H), 2.66 (d, J = 15.95 Hz, 3H), 1.43 (s, 9H), 1.28-1.21 (m, 2H), 1.08 (s, 2H). 523 98% 2-3 [00159] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.79 (d, J = 5.61 Hz, 2H), 8.01 (d, J = 8.93 Hz, 1H), 7.50 (d, J = 5.50 Hz, 2H), 4.40 (s, 1H), 2.61 (s, 3H), 1.24 (d, J = 5.97 Hz, 2H), 1.07 (s, 2H). 339 98% 2-4 [00160] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.00 (s, 2H), 8.92 (s, 1H), 8.49 (d, J = 2.73 Hz, 1H), 8.12 (s, 1H), 7.98 (t, J = 11.57 Hz, 1H), 7.56 (s, 1H), 4.44-4.34 (m, 1H), 3.64 (s, 5H), 3.26 (s, 4H), 2.62 (s, 3H), 1.23 (d, J = 6.27 Hz, 2H), 1.07 (s, 2H). 423 95% 2-5 [00161] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.71 (t, J = 26.47 Hz, 1H), 8.04 (d, J = 8.68 Hz, 2H), 7.61 (d, J = 45.28 Hz, 1H), 4.44-4.38 (m, 1H), 2.55 (s, 2H), 2.34 (d, J = 9.33 Hz, 3H), 1.23 (s, 2H), 1.06 (dd, J = 4.45, 8.57 Hz, 2H). 353 95% 2-6 [00162] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.92 (s, 1H), 8.83 (t, J = 8.69 Hz, 1H), 8.65 (dt, J = 8.70, 17.42 Hz, 1H), 8.05 (d, J = 8.87 Hz, 1H), 7.73-7.52 (m, 1H), 4.41 (tt, J = 3.77, 7.16 Hz, 1H), 2.64 (s, 3H), 1.31-1.16 (m, 2H), 1.10-0.97 (m, 2H). 357 98% 2-7 [00163] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.85-8.61 (m, 2H), 8.03 (d, J = 6.60 Hz, 1H), 7.96 (s, 2H), 7.69 (dd, J = 5.19, 7.64 Hz, 1H), 4.41 (ddd, J = 3.87, 7.26, 10.97 Hz, 2H), 2.75-2.72 (m, 5H), 1.33-1.20 (m, 3H), 1.13-1.03 (m, 2H). 339 98% 2-8 [00164] Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 8.79 (s, 1H), 7.92-7.71 (m, 2H), 7.55 (t, J = 17.62 Hz, 1H), 6.84 (t, J = 36.31 Hz, 1H), 4.16-4.04 (m, 1H), 3.02 (s, 5H), 1.09-1.01 (m, 2H), 0.81 (q, J = 7.23 Hz, 2H). 355 98% 2-9 [00165] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 8.06 (t, J = 38.62 Hz, 2H), 7.68 (dd, J = 8.35, 33.76 Hz, 2H), 7.47 (d, J = 8.87 Hz, 1H), 7.13-6.77 (m, 2H), 4.33 (s, 1H), 3.97 (d, J = 7.85 Hz, 3H), 2.20-1.90 (m, 2H), 1.35-1.22 (m, 1H), 1.05 (s, 1H). 369 98% 2-10 [00166] Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 9.06 (s, 1H), 8.33 (s, 1H), 8.01 (d, J = 9.18 Hz, 1H), 7.67 (t, J = 24.14 Hz, 2H), 7.17 (s, 1H), 4.37 (s, 1H), 3.94 (s, 3H), 2.66 (s, 3H), 1.32 (d, J = 6.60 Hz, 2H), 1.07 (s, 2H). 369 98% 2-11 [00167] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 9.05 (s, 1H), 8.29 (s, 2H), 8.09 (d, J = 7.83 Hz, 1H), 7.94 (d, J = 23.80 Hz, 2H), 7.39-7.20 (m, 2H), 7.09 (s, 1H), 4.36 (s, 1H), 2.77 (s, 3H), 1.30 (s, 2H), 1.09 (s, 2H). 466 98% 2-12 [00168] Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 9.02 (s, 1H), 8.40 (d, J = 92.33 Hz, 2H), 8.16-8.03 (m, 2H), 7.98-7.80 (m, 1H), 7.75-7.50 (m, 2H), 4.34 (s, 1H), 3.82 (d, J = 24.28 Hz, 4H), 3.45 (s, 4H), 2.70 (d, J = 23.16 Hz, 3H), 1.27 (dd, J = 11.61, 24.61 Hz, 3H), 1.09 (s, 2H). 424 98% 2-13 [00169] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.91 (s, 1H), 8.69 (s, 1H), 7.97 (d, J = 8.46 Hz, 1H), 7.79 (s, 1H), 7.63 (s, 1H), 4.40 (s, 1H), 3.82 (d, J = 6.95 Hz, 2H), 3.21 (s, 2H), 2.63 (d, J = 43.98 Hz, 3H), 1.22 (d, J = 5.36 Hz, 2H), 1.05 (s, 2H). 380 97% 2-14 [00170] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 2H), 8.91 (s, 1H), 8.49 (s, 2H), 8.24 (s, 2H), 7.98 (d, J = 8.62 Hz, 1H), 4.41 (s, 1H), 2.65 (d, J = 31.48 Hz, 3H), 1.24 (d, J = 6.48 Hz, 2H), 1.07 (s, 2H). 399 99% 2-15 [00171] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.91 (s, 1H), 8.13 (d, J = 25.11 Hz, 1H), 8.07 (s, 1H), 7.95 (dd, J = 8.95, 25.35 Hz, 2H), 7.06 (d, J = 8.71 Hz, 1H), 4.41 (s, 1H), 2.65 (d, J = 25.72 Hz, 3H), 1.22 (d, J = 5.45 Hz, 2H), 1.05 (s, 2H). 354 99% 2-16 [00172] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.74 (s, 1H), 8.54 (t, J = 24.30 Hz, 2H), 7.99 (d, J = 8.68 Hz, 1H), 4.41 (s, 1H), 3.10 (d, J = 17.91 Hz, 3H), 2.70 (s, 3H), 1.25 (d, J = 5.66 Hz, 2H), 1.07 (s, 2H). 413 99% 2-17 [00173] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 9.79 (s, 2H), 8.92 (s, 1H), 8.61 (s, 1H), 8.01 (d, J = 13.11 Hz, 2H), 4.67 (d, J = 32.94 Hz, 4H), 4.40 (s, 1H), 2.62 (s, 3H), 1.23 (s, 3H), 1.07 (s, 2H). 380 97% 2-18 [00174] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.89 (s, 1H), 8.27 (s, 1H), 8.07 (t, J = 6.62 Hz, 1H), 7.94 (d, J = 8.87 Hz, 1H), 7.28 (s, 2H), 4.40 (tt, J = 3.75, 7.16 Hz, 1H), 3.31 (s, 1H), 2.67 (s, 3H), 1.31-1.19 (m, 2H), 1.10-1.00 (m, 2H). 379 99% 2-19 [00175] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.28 (s, 1H), 8.93 (s, 1H), 8.70 (s, 1H), 8.36 (s, 1H), 8.03 (d, J = 8.65 Hz, 1H), 4.41 (s, 2H), 2.65 (s, 3H), 2.44 (s, 3H), 1.25 (d, J = 6.79 Hz, 2H), 1.10 (s, 2H). 420 97% 2-20 [00176] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.19 (d, J = 11.25 Hz, 3H), 7.99 (d, J = 8.83 Hz, 1H), 7.62 (s, 1H), 4.41 (s, 2H), 2.69 (s, 3H), 1.25 (d, J = 5.80 Hz, 2H), 1.05 (s, 2H). 397 99% 2-21 [00177] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.89 (s, 1H), 8.11-7.87 (m, 2H), 7.74 (s, 1H), 6.71 (s, 2H), 4.39 (s, 1H), 2.63 (d, J = 29.40 Hz, 3H), 1.20 (t, J = 25.86 Hz, 2H), 0.99 (d, J = 41.43 Hz, 2H). 388 98% 2-22 [00178] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.90 (s, 1H), 8.26 (s, 1H), 7.95 (d, J = 8.81 Hz, 1H), 7.86 (s, 1H), 6.89 (s, 2H), 4.39 (s, 1H), 2.66 (s, 3H), 1.24 (d, J = 5.61 Hz, 2H), 1.06 (s, 2H). 422 98% 2-23 [00179] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.98 (s, 1H), 8.13-8.02 (m, 2H), 7.92 (d, J = 14.79 Hz, 3H), 4.47 (s, 1H), 2.71 (d, J = 23.60 Hz, 3H), 2.31 (s, 3H), 1.29 (d, J = 5.54 Hz, 2H), 1.15 (d, J = 22.69 Hz, 2H). 368 99% 2-24 [00180] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.79 (s, 1H), 8.11 (s, 1H), 7.90 (s, 1H), 7.82 (s, 1H), 6.73 (s, 2H), 4.22 (s, 1H), 3.46 (s, 3H), 3.31 (s, 2H), 1.16 (s, 4H). 404 98% 2-25 [00181] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.80 (s, 1H), 8.39 (s, 1H), 8.13-7.81 (m, 2H), 6.91 (s, 2H), 4.23 (s, 1H), 3.31 (s, 3H), 1.17 (d, J = 6.99 Hz, 3H). 438 99% 2-26 [00182] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.74 (d, J = 61.68 Hz, 1H), 8.76 (d, J = 28.90 Hz, 1H), 8.39 (s, 1H), 7.97 (s, 1H), 7.92 (d, J = 9.13 Hz, 1H), 4.23 (s, 1H), 3.46 (s, 3H), 1.17 (d, J = 7.13 Hz, 4H). 395 98% 2-27 [00183] Me Cyclopeopyl .sup.1H NMR (400 MHz, DMSO), 8.89 (s, 1H), 7.95-7.93 (m, 2H), 7.83 (s, 1H), 7.60- 6.57 (d, 1H), 4.39 (s, 1H), 2.63 (d. J = 29.40 Hz, 3H), 1.20 (t, J = 25.86 Hz, 2H), 0.99 (d, J = 41.43 Hz, 2H). 372 98% 2-28 [00184] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.95 (s, 1H), 8.94-8.66 (m, 1H), 8.49-8.39 (m, 1H), 8.26 (d, J = 1.30 Hz, 1H), 7.91 (dd, J = 19.79, 31.75 Hz, 2H), 4.27-4.17 (m, 1H), 3.50-3.42 (m, 3H), 1.17 (dt, J = 7.59, 17.65 Hz, 3H). 398 98% 2-29 [00185] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.95 (s, 1H), 8.92 (d, J = 13.25 Hz, 1H), 8.32 (d, J = 1.05 Hz, 1H), 8.17 (d, J = 1.69 Hz, 1H), 8.00 (t, J = 18.18 Hz, 1H), 7,83 (d, J = 33.09 Hz, 1H), 4.40 (dt, J = 3.59, 10.71 Hz, 1H), 2.68 (d, J = 12.78 Hz, 3H), 1.25 (q, J = 6.89 Hz, 2H), 1.14-0.93 (m, 2H). 382 98% 2-30 [00186] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 2H), 8.90 (s, 1H), 7.97 (d, J = 8.81 Hz, 1H), 7.64 (d, J = 1.21 Hz, 1H), 7.34 (s, 1H), 4.40 (td, J = 3.75, 7.19 Hz, 1H), 3.90 (s, 3H), 2.78-2.61 (m, 3H), 1.23 (q, J = 7.19 Hz, 2H), 1.16-0.97 (m, 2H). 384 95% 2-31 [00187] Me [00188] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 2H), 8.90 (s, 1H), 7.97 (d, J = 8.81 Hz, 1H), 7.64 (d, J = 1.21 Hz, 1H), 7.34 (s, 1H), 4.40 (td, J = 3.75, 7.19 Hz, 1H), 3.90 (s, 3H), 2.78-2.61 (m, 3H), 1.23 (q, J = 7.19 Hz, 2H), 1.16-0.97 (m, 2H). 406 99% 2-32 [00189] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.90 (s, 1H), 7.99 (d, J = 1.60 Hz, 1H), 7.95 (t, J = 10.20 Hz, 1H), 7.70-7.53 (m, 1H), 4.39 (td, J = 3.61, 7.03 Hz, 1H), 2.62 (d, J = 19.25 Hz, 3H), 1.84 (ddd, J = 5.42, 8.33, 13.56 Hz, 1H), 1.21 (t, J = 6.56 Hz, 1H), 1.05 (d, J = 8.64 Hz, 1H), 1.03-0.96 (m, 2H), 0.78-0.65 (m, 2H). 394 98% 2-33 [00190] embedded image Me [00191] .sup.1H NMR (400 MHz. DMSO) δ 8.88 (d, J = 3.01 Hz, 1H), 8.18 (s, 1H), 8.13 (s, 1H), 8.09 (s, 1H), 7.99 (d, J = 8.77 Hz, 1H), 7.54 (s, 1H), 5.29-5.01 (m, 1H), 4.50- 4.31 (m, 1H), 2.71-2.57 (m, 2H), 1.76 (ddd, J = 9.04, 15.14, 17.62 Hz, 1H), 1.53 (d, J = 26.94 Hz, 1H). 415 98% 2-34 [00192] embedded image Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.11 (d, J = 8.56 Hz, 1H), 8.02 (d, J = 0.96 Hz, 1H), 7.81 (d, J = 1.67 Hz, 1H), 4.44-4.39 (m, 2H), 1.32-1.17 (m, 2H), 1.17-1.04 (m, 2H). 408 94% 2-35 [00193] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.80 (s, 1H), 7.99 (s, 1H), 7.92 (d, J = 9.3 Hz, 1H), 7.69 (d, J = 12.0 Hz, 1H), 4.29-4.14 (m, 1H), 3.47 (s, 3H), 1.24-1.04 (m, 4H). 387 99% 2-36 [00194] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.92 (s, 1H), 8.37 (s, 1H), 8.30 (d, J = 2.3 Hz, 1H), 8.11-7.88 (m, 3H), 7.51 (s, 1H), 4.55-4.30 (m, 3H), 3.20 (m, 2H), 2.68 (s, 3H), 1.25 (d, J = 6.4 Hz, 2H), 1.08 (d, J = 7.0 Hz, 2H). 441 98% 2-37 [00195] OMe [00196] .sup.1H NMR (400 MHz, DMSO) δ 14.52 (s, 1H), 8.82 (d, J = 1.51 Hz, 1H), 8.38 (s, 1H), 8.11 (s, 1H), 7.94 (d, J = 9.20 Hz, 1H), 7.36 (s, 2H), 5.10 (ddd, J = 5.42, 8.45, 64.07 Hz, 1H), 4.24-4.12 (m, 1H), 1.86-1.55 (m, 2H). 413 98% 2-38 [00197] embedded image OMe [00198] .sup.1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.82 (d, J = 1.46 Hz, 1H), 8.15 (d, J = 36.97 Hz, 1H), 7.92 (d, J = 9.24 Hz, 1H), 7.80 (s 1H), 6.75 (s, 2H), 5.10 (ddd, J = 5.43, 8.45, 64.08 Hz, 1H), 4.29-4.12 (m, 1H), 1.93-1.53 (m, 2H). 422 98% 2-39 [00199] Me [00200] .sup.1H NMR (400 MHz, DMSO) δ 14.39 (s, 1H), 8.80 (s, 1H), 8.16-8.08 (m, 2H), 7.98- 7.86 (m, 2H), 7.69-7.59 (m, 1H), 7.37 (dd, J = 5.20, 11.82 Hz, 1H), 7.26 (s, 2H), 1.67 (s, 3H). 451 99% 2-40 [00201] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, CDCl.sub.3) δ 14.60-14.29 (s, 1H), 8.96-8.89 (s, 1H), 8.05-7.96 (m, 2H), 7.48-7.40 (m, 4H), 7.40-7.33 (dt, J = 8.5, 2.8 Hz, 1H), 7.33-7.29 (s, 1H), 4.88-4.75 (s, 2H), 4.17-3.98 (s, 1H), 2.73-2.62 (s, 3H), 1.28-1.20 (m, 2H), 1.02-0.93 (s, 2H). 430 99% 2-41 [00202] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.83-14.68 (s, 1H), 8.99-8.81 (s, 1H), 7.96- 7.89 (d, J = 8.9 Hz, 1H), 7.88-7.81 (s, 1H), 7.36-7.20 (s, 1H), 6.19-6.08 (s, 2H), 4.47-4.31 (s, 1H), 2.75-2.60 (s, 3H), 1.36-1.10 (m, 6H), 1.10-0.94 (t, J = 3.1 Hz, 2H). 382 93% 2-42 [00203] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.83-14.67 (s, 3H), 8.97-8.85 (s, 3H), 8.00- 7.85 (m, 6H), 7.72-7.60 (t, J = 1.7 Hz, 3H), 6.97-6.81 (dd, J = 17.3, 11.0 Hz, 3H), 6.45-6.27 (s, 6H), 5.85-5.70 (m, 4H), 5.44-5.26 (dd, J = 11.0, 1.2 Hz, 3H), 4.47-4.33 (s, 1H), 2.76-2.60 (s, 9H), 1.30-1.18 (m, 6H), 1.12-0.98 (m, 5H), 1.32-1.20 (m, 7H). 380 99% 2-43 [00204] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.95-8.90 (s, 1H), 8.36-8.31 (m, 1H), 8.13-8.07 (d, J = 2.0 Hz, 1H), 8.02-7.97 (d, J = 8.8 Hz, 1H), 4.49-4.36 (m, 3H), 2.90-2.79 (s, 5H), 2.76-2.67 (s, 3H), 1.33-1.20 (q, J = 6.9 Hz, 2H), 1.10-0.98 (m, 2H). 397 98% 2-44 [00205] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.93-8.91 (s, 1H), 8.24-8.20 (m, 1H), 8.01-7.96 (d, J = 8.8 Hz, 1H), 7.93-7.87 (t, J = 2.8 Hz, 1H), 4.49-4.38 (tt, J = 7.2, 3.9 Hz, 1H), 4.24-4.14 (t, J = 5.5 Hz, 2H), 2.85-2.77 (s, 6H), 1.29-1.20 (m, 2H), 1.09-0.98 (m, 2H). 411 97% 2-45 [00206] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.94-8.89 (s, 1H), 8.15-8.09 (d, J = 2.1 Hz, 1H), 8.02-7.96 (d, J = 8.9 Hz, 1H), 7.92-7.88 (s, 1H), 4.46-4.37 (m, 1H), 4.57-4.46 (s, 2H), 2.71-2.65 (s, 3H), 1.25-1.18 (d, J = 6.7 Hz, 2H), 1.10-0.98 (m, 2H). 384 90% 2-46 [00207] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.89 (s, 1H), 8.35 (s, 2H), 7.94 (d, J = 8.67 Hz, 1H), 7.09 (s, 2H), 4.39 (s, 1H), 2.70 (s, 3H), 1.24 (d, J = 5.31 Hz, 2H), 1.03 (s, 2H). 354 99% 2-47 [00208] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.89 (s, 1H), 8.41 (s, 2H), 7.95 (d, J = 8.41 Hz, 1H), 7.60 (d, J = 28.12 Hz, 1H), 4.40 (s, 1H), 2.88 (s, 3H), 2.70 (s, 3H), 1.25 (d, J = 5.56 Hz, 2H), 1.03 (s, 2H). 369 99% 2-48 [00209] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.89 (s, 1H), 8.39 (s, 2H), 7.95 (d, J = 8.73 Hz, 1H), 7.64 (s, 1H), 4.39 (s, 1H), 2.70 (s, 3H), 2.53 (d, J = 9.32 Hz, 3H), 1.24 (d, J = 6.11 Hz, 2H), 1.17 (t, J = 6.98 Hz, 2H), 1.03 (s, 2H). 383 97% 2-49 [00210] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 2H), 8.90 (s, 1H), 8.48 (s, 2H), 7.96 (d, J = 8.59 Hz, 1H), 4.39 (s, 1H), 3.24 (d, J = 22.01 Hz, 6H), 2.70 (s, 3H), 1.25 (d, J = 6.03 Hz, 2H), 1.04 (d, J = 7.73 Hz, 2H), 383 98% 2-50 [00211] Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.35 (s, 2H), 8.13 (d, J = 8.6 Hz, 1H), 7.15 (s, 2H), 4.41 (m, 3.8 Hz, 1H), 1.37-1.17 (m, 2H), 1.18-1.02 (m, 2H). 375 99% 2-51 [00212] embedded image Me [00213] .sup.1H NMR (400 MHz, DMSO) δ 8.87 (d, J = 3.2 Hz, 1H), 8.35 (d, J = 1.0 Hz, 2H), 7.97 (d, J = 8.9 Hz, 1H), 7.08 (s, 2H), 5.33-4.97 (m, 2H), 4.37 (m, 1H), 2.65 (s, 3H), 1.89-1.41 (m, 2H). 373 99% 2-52 [00214] MeO [00215] .sup.1H NMR (400 MHz, DMSO) δ 14.54 (s, 1H), 8.82 (d, J = 1.2 Hz, 1H), 8.44 (s, 2H), 7.93 (d, J = 9.2 Hz, 1H), 7.10 (s, 2H), 5.09 (m, 1H), 4.37-3.96 (m, 1H), 3.50 (s, 3H), 1.98-1.52 (m, 2H). 389 98% 2-53 [00216] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.91 (d, J = 4.9 Hz, 1H), 8.76 (s, 2H), 8.15-7.85 (m, 1H), 4.63-4.29 (m, 1H), 2.50 (s, 3H), 1.29-1.15 (m, 2H), 1.06 (d, J = 7.0 Hz, 2H). 384 99% 2-54 [00217] MeO Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.86 (s, 1H), 8.52 (s, 2H), 8.00 (d, J = 9.2 Hz, 1H), 7.18 (s, 2H), 4.29 (m, 1H), 3.55 (s, 3H), 1.27-1.11 (m, 4H). 371 99% 2-55 [00218] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.79 (s, 1H), 8.19 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.81 (s, 1H), 6.91 (t, J = 5.6 Hz, 1H), 4.29-4.11 (m, 1H), 3.53- 3.41 (m, 5H), 1.26-1.06 (m, 7H). 432 98% 2-56 [00219] .sup.1H NMR (400 MHz, DMSO) δ 9.06 (s, 1H), 8.38 (s, 1H), 8.13 (d, J = 1.75 Hz, 1H), 7.72 (d, J = 9.80 Hz, 1H), 7.29 (s, 2H), 5.06- 4.90 (m, 1H), 4.58 (d, J = 10.62 Hz, 1H), 4.44 (d, J = 9.71 Hz, 1H), 1.48 (d, J = 6.75 Hz, 3H). 381 95% 2-57 [00220] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.95 (s, 1H), 8.91 (s, 1H), 8.37-8.33 (d, J = 2.5 Hz, 1H), 8.24-8.19 (d, J = 8.3 Hz, 1H), 8.14-8.10 (d, J = 2.5 Hz, 1H), 7.58-7.51 (d, J = 8.3 Hz, 1H), 7.22 (s, 2H), 4.42-4.36 (tt, J = 7.1, 3.7 Hz, 1H), 2.71 (s, 3H), 1.30- 1.25 (m, 2H), 1.05-0.94 (m, 2H). 361 95% 2-58 [00221] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.95 (s, 1H), 8.89 (s, 1H), 8.32 (d, J = 3.5 Hz, 1H), 8.21 (d, J = 8.2 Hz, 1H), 8.06 (s, 1H), 7.79 (s, 1H), 7.53 (d, J = 8.2 Hz, 1H), 6.61 (s, 2H), 4.39 (s, 1H), 2.72 (s, 3H), 1.27 (d, J = 6.1 Hz, 2H), 1.03 (s, 2H). 370 99% 2-59 [00222] .sup.1H NMR (400 MHz, DMSO) δ 15.00 (s, 1H), 9.08 (s, 1H), 8.17 (s, 1H), 7.80 (s, 1H), 7.72 (d, J = 9.8 Hz, 1H), 6.86 (t, J = 5.7 Hz, 1H), 4.98 (d, J = 6.7 Hz, 1H), 4.57 (d, J = 10.2 Hz, 1H), 4.48-4.32 (m, 1H), 3.55-3.37 (m, 2H), 1.48 (d, J = 6.8 Hz, 2H), 1.17 (t, J = 7.1 Hz, 2H). 418 98% 2-60 [00223] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.82 (d, J = 1.6 Hz, 1H), 8.18 (s, 1H), 7.92 (d, J = 9.3 Hz, 1H), 7.80 (s, 1H), 6.92 (t, J = 5.7 Hz, 1H), 5.10 (ddd, J = 64.1, 8.4, 5.4 Hz, 1H), 4.32-4.06 (m, 1H), 3.58-3.37 (m, 5H), 1.93-1.51 (m, 2H), 1.19 (t, J = 7.1 Hz, 3H). 450 98%

TABLE-US-00003 TABLE 3 [00224] embedded image Com- pound MS No. R.sup.3 = R.sup.2 = R.sup.1 = NMR (MH.sup.+) HPLC 3-1 [00225] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 9.08 (s, 1H), 8.94 (s, 1H), 8.33 (d, J = 1.3 Hz, 1H), 8.16 (d, J = 1.7 Hz, 1H), 8.06 (t, J = 8.5 Hz, 2H), 7.85 (d, J = 9.4 Hz, 1H), 4.49-4.38 (m, 1H), 2.70 (s, 3H), 1.25 (d, J = 6.6 Hz, 2H), 1.09 (s, 2H). 378 98% 3-2 [00226] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 9.38 (s, 1H), 8.91 (d, J = 25.3 Hz, 1H), 8.79 (s, 1H), 8.13 (s, 1H), 8.06 (d, J = 8.8 Hz, 1H), 8.01 (s, 1H), 4.44 (s, 1H), 2.75 (s, 3H), 1.25 (s, 2H), 1.09 (s, 2H). 379 95% 3-3 [00227] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 9.41 (s, 1H), 9.00 (s, 1H), 8.80 (s, 1H), 8.36 (s, 1H), 8.17 (s, 1H), 8.07 (s, 2H), 7.86 (s, 1H), 7.61 (s, 1H), 4.49 (s, 1H), 2.79 (s, 3H), 1.31 (s, 3H), 1.17 (s, 2H). 456 98% 3-4 [00228] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.57 (d, J = 5.1 Hz, 1H), 9.05 (d, J = 6.5 Hz, 1H), 8.94 (s, 1H), 8.44 (s, 1H), 8.23 (s, 1H), 8.11 (s, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.54 (d, J = 6.4 Hz, 1H), 4.43 (s, 1H), 2.68 (s, 3H), 1.24 (d, J = 5.0 Hz, 2H), 1.11 (s, 2H). 378 97% 3-5 [00229] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 9.13 (d, J = 6.3 Hz, 1H), 8.90 (s, 1H), 8.53 (s, 1H), 8.31 (d, J = 11.7 Hz, 2H), 8.09 (d, J = 9.1 Hz, 1H), 7.72 (d, J = 5.8 Hz, 1H), 4.30 (s, 1H), 3.57 (s, 3H), 1.25 (s, 4H). 394 95% 3-6 [00230] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.30 (s, 1H), 8.93 (s, 1H), 8.64 (s, 1H), 8.04 (t, J = 9.2 Hz, 2H), 7.75 (d, J = 9.2 Hz, 1H), 4.42 (s, 1H), 2.69 (s, 3H), 1.24 (s, 2H), 1.09 (s, 2H). 379 97% 3-7 [00231] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 9.33 (s, 1H), 8.83 (s, 1H), 8.64 (s, 1H), 8.06 (d, J = 9.2 Hz, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.86 (d, J = 9.3 Hz, 1H), 4.24 (s, 1H), 3.48 (s, 3H), 1.19 (d, J = 5.2 Hz, 4H). 395 98% 3-8 [00232] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 9.11 (s, 1H), 8.93 (s, 1H), 8.22 (d, J = 1.2 Hz, 1H), 8.17 (s, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.84 (d, J = 1.1 Hz, 1H), 4.43 (tt, J = 7.1, 3.7 Hz, 1H), 2.70 (s, 3H), 1.26 (d, J = 6.8 Hz, 2H), 1.09 (s, 2H). 379 98% 3-9 [00233] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 9.07 (s, 1H), 8.93 (s, 1H), 8.22 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.81 (s, 1H), 7.80 (s, 1H), 4.49-4.37 (m, 1H), 2.70 (d, J = 21.5 Hz, 3H), 1.27 (t, J = 9.8 Hz, 2H), 1.14-1.05 (m, 2H). 446 97% 3-10 [00234] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.94 (s, 2H), 8.35 (s, 1H), 8.23 (s, 1H), 8.05 (d, J = 8.7 Hz, 1H), 7.75 (s, 1H), 4.43 (s, 1H), 2.69 (s, 3H), 2.66 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H). 392 98% 3-11 [00235] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 8.92 (s, 1H), 8.79 (d, J = 1.2 Hz, 1H), 8.16 (d, J = 1.1 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 1.1 Hz, 1H), 7.58 (s, 1H), 4.42 (tt, J = 7.2, 3.8 Hz, 1H), 2.70 (d, J = 20.2 Hz, 3H), 1.26 (d, J = 6.9 Hz, 2H), 1.15-1.03 (m, 2H). 412 99% 3-12 [00236] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.40 (s, 1H), 8.94 (s, 1H), 8.88 (s, 1H), 8.18 (d, J = 9.3 Hz, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.89 (d, J = 9.3 Hz, 1H), 4.43 (s, 1H), 2.69 (s, 3H), 1.24 (d, J = 6.1 Hz, 2H), 1.12 (s, 2H). 423 96% 3-13 [00237] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 8.90 (s, 1H), 8.83 (s, 1H), 8.22 (d, J = 1.0 Hz, 1H), 7.98 (d, J = 9.2 Hz, 1H), 7.75 (d, J = 1.0 Hz, 1H), 7.66 (s, 1H), 4.29-4.18 (m, 1H), 3.51 (d, J = 13.2 Hz, 3H), 1.25-1.14 (m, 4H). 428 100% 3-14 [00238] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 9.19 (s, 1H), 8.83 (s, 1H), 8.28 (s, 1H), 8.01 (d, J = 9.2 Hz, 1H), 7.92 (s, 1H), 7.81 (s, 1H), 4.25 (dt, J = 11.0, 5.7 Hz, 1H), 3.50 (d, J = 12.8 Hz, 3H), 1.19 (m, 4H). 462 98% 3-15 [00239] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.61 (s, 1H), 8.93 (s, 1H), 8.51 (s, 1H), 8.13 (s, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.97 (d, J = 9.2 Hz, 1H), 7.62 (d, J = 9.2 Hz, 1H), 7.55 (s, 1H), 4.42 (s, 1H), 2.69 (s, 3H), 1.24 (s, 2H), 1.10 (s, 2H). 421 98% 3-16 [00240] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.87-13.95 (m, 2H), 9.60 (s, 1H), 8.94 (s, 1H), 8.44 (s, 1H), 8.05 (t, J = 9.5 Hz, 2H), 7.71 (d, J = 9.4 Hz, 1H), 4.46-4.39 (m, 1H), 2.71 (m, 3H), 2.46 (s, 3H), 1.25 (d, J = 6.3 Hz, 2H), 1.11 (s, 2H). 459 98% 3-17 [00241] Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.44-13.91 (m, 1H), 9.16 (s, 1H), 8.95 (s, 1H), 8.37 (s, 1H), 8.23 (d, J = 8.6 Hz, 1H), 8.08 (s, 1H), 7.81 (s, 1H), 4.43 (m, 1H), 1.23 (m, 2H), 1.16 (s, 2H). 398 98% 3-18 [00242] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.92 (s, 1H), 8.68 (s, 1H), 8.19 (d, J = 2.9 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.73 (d, J = 1.0 Hz, 1H), 7.32 (d, J = 11.7 Hz, 1H), 4.42 (m, 1H), 2.72 (s, 3H), 1.25 (d, 2H), 1.12-1.04 (m, 2H). 396 98% 3-19 [00243] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.29 (s, 1H), 8.94 (s, 1H), 8.54 (s, 1H), 8.36 (s, 1H), 8.05 (d, J = 8.9 Hz, 1H), 8.00 (s, 1H), 4.49-4.38 (m, 1H), 2.74 (s, 3H), 1.25 (d, J = 6.9 Hz, 2H), 1.11 (s, 2H). 423 98% 3-20 [00244] embedded image Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.95 (s, 1H), 8.88 (t, J = 4.2 Hz, 1H), 8.22 (t, J = 2.4 Hz, 1H), 8.20 (d, J = 8.5 Hz, 1H), 7.82 (s, 1H), 7.68 (s, 1H), 4.48-4.36 (m, 1H), 1.26-1.19 (m, 2H), 1.14 (m, 2H). 432 98% 3-21 [00245] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 9.32 (d, J = 1.2 Hz, 1H), 8.93 (s, 1H), 8.71 (s, 1H), 8.06 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 4.43 (tt, J = 7.0, 3.6 Hz, 1H), 2.70 (d, J = 17.8 Hz, 3H), 1.30-1.20 (m, 2H), 1.15-1.05 (m, 2H). 413 98% 3-22 [00246] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 9.22 (s, 1H), 8.93 (s, 1H), 8.71 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.85 (d, J = 10.8 Hz, 1H), 4.47-4.37 (m, 1H), 2.72 (s, 3H), 1.29-1.22 (m, 2H), 1.10 (s, 2H). 397 99% 3-23 [00247] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 9.26 (s, 1H), 8.84 (s, 1H), 8.72 (s, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.92 (d, J = 10.9 Hz, 1H), 4.28-4.18 (m, 1H), 3.51 (s, 3H), 1.20 (d, J = 5.5 Hz, 4H). 413 95% 3-24 [00248] embedded image OMe [00249] .sup.1H NMR (400 MHz, DMSO) δ 14.47 (s, 1H), 8.89 (t, J = 1.3 Hz, 1H), 8.86 (d, J = 1.8 Hz, 1H), 8.23 (d, J = 1.3 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.75 (d, J = 1.2 Hz, 1H), 7.63 (t, J = 1.3 Hz, 1H), 5.31- 4.93 (dtd, J = 64.0, 5.5, 3.3 Hz, 1H), 4.26-4.12 (dt, J = 8.9, 5.4 Hz, 1H), 3.54 (s, 3H), 1.93-1.49 (m, 2H). 446 98% 3-25 [00250] embedded image Me [00251] .sup.1H NMR (400 MHz, CDCl.sub.3) δ 14.07 (s, 1H), 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 17.0 Hz, 1H), 7.66 (dd, J = 11.6, 4.8 Hz, 2H), 7.49 (d, J = 4.4 Hz, 1H), 7.13-7.03 (m, 2H), 7.01 (d, J = 0.8 Hz, 1H), 5.22 (s, 1H), 1.72 (s, 3H). 484 98% 3-26 [00252] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 9.09 (s, 1H), 8.93 (s, 1H), 8.58 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.54 (s, 1H), 4.46-4.36 (m, 1H), 2.70 (s, 3H), 2.64 (s, 3H), 1.25 (d, J = 6.2 Hz, 2H), 1.09 (s, 2H). 393 98% 3-27 [00253] embedded image Me [00254] .sup.1H NMR (400 MHz, DMSO) δ 14.48 (s, 1H), 8.90 (d, J = 3.0 Hz, 1H), 8.78 (s, 1H), 8.16 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.75 (s, 1H), 7.57 (s, 1H), 5.16 (d, J = 64.5 Hz, 1H), 4.44-4.33 (m, 1H), 2.65 (s, 3H), 1.83-1.68 (m, 1H), 1.62 (m, 1H). 430 98% 3-28 [00255] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 9.63 (s, 1H), 8.94 (s, 1H), 8.81 (s, 1H), 8.30 (s, 1H), 8.04 (d, J = 8.9 Hz, 1H), 4.50-4.37 (m, 1H), 2.73 (s, 3H), 1.24 (t, J = 9.6 Hz, 2H), 1.12 (s, 2H). 447 98% 3-29 [00256] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.33 (s, 1H), 8.94 (s, 1H), 8.74 (s, 1H), 8.63 (s, 2H), 8.05 (d, J = 8.8 Hz, 1H), 7.84 (s, 1H), 4.51 (s, 2H), 4.46-4.36 (m, 1H), 2.71 (s, 3H), 1.26 (d, J = 6.8 Hz, 2H), 1.09 (s, 2H). 408 95% 3-30 [00257] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.58 (s, 1H), 9.37 (s, 1H), 8.84 (s, 1H), 8.72 (s, 1H), 8.13 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 4.29-4.18 (m, 1H), 3.51 (s, 3H), 1.20 (d, J = 5.4 Hz, 4H). 429 96% 3-31 [00258] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.43 (s, 1H), 8.99 (s, 1H), 8.89 (s, 1H), 8.14-8.01 (m, 2H), 7.54 (d, J = 9.8 Hz, 1H), 4.49 (s, 2H), 2.77 (s, 3H), 1.30 (s, 2H), 1.14 (s, 2H). 379 88% 3-32 [00259] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.42 (s, 1H), 8.92 (s, 1H), 8.83 (s, 1H), 8.00 (s, 2H), 7.57 (d, J = 9.3 Hz, 1H), 4.23 (s, 1H), 3.51 (s, 3H), 1.18 (s, 4H). 395 95% 3-33 [00260] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.98 (s, 1H), 8.74 (s, 1H), 8.48 (s, 1H), 8.23 (s, 1H), 8.04 (d, J = 8.9 Hz, 1H), 4.39 (s, 2H), 2.64 (s, 3H), 1.29 (s, 2H), 1.07 (s, 2H). 379 99% 3-34 [00261] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.02-14.73 (m, 1H), 9.01 (s, 1H), 8.10 (s, 3H), 7.54 (s, 1H), 4.51 (s, 1H), 1.33 (s, 2H), 1.18 (s, 2H). 379 95% 3-35 [00262] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 14.19 (s, 1H), 8.93 (s, 1H), 8.53 (s, 1H), 8.44 (s, 1H), 8.40 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 4.42 (s, 1H), 2.64 (s, 3H), 1.22 (m, 2H), 1.12 (m, 2H). 423 98% 3-36 [00263] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 12.87 (s, 1H), 8.97 (s, 1H), 8.10 (s, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.02 (s, 1H), 6.48 (s, 1H), 4.46 (s, 1H), 2.70 (s, 2H), 1.30 (s, 2H), 1.12 (s, 2H). 393 98% 3-37 [00264] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.83 (s, 1H), 13.45 (b, 1H), 8.98 (s, 1H), 8.26 (s, 1H), 8.04 (d, J = 8.6 Hz, 1H), 7.90 (s, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.42 (d, J = 8.4 Hz, 1H), 4.46 (s, 1H), 2.68 (s, 3H), 1.31 (d, J = 5.7 Hz, 2H), 1.14 (s, 2H). 378 92% 3-38 [00265] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 13.83 (s, 1H), 8.91 (s, 1H), 8.31 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.83 (s, 1H), 7.53 (s, 1H), 4.46- 4.34 (m, 1H), 2.63 (s, 3H), 1.25 (d, J = 6.9 Hz, 2H), 1.09 (s, 2H). 412 98% 3-39 [00266] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 14.27 (s, 1H), 8.90 (s, 1H), 8.62 (d, J = 10.6 Hz, 3H), 8.07 (d, J = 9.1 Hz, 1H), 4.31 (s, 1H), 3.44 (s, 3H), 1.26 (s, 4H). 439 95% 3-40 [00267] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.77 (s, 1H), 13.23 (s, 1H), 8.91 (s, 1H), 8.49 (s, 1H), 7.98 (d, J = 8.3 Hz, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.67 (s, 1H), 7.25 (d, J = 7.9 Hz, 1H), 4.40 (s, 1H), 2.61 (s, 2H), 1.25 (s, 2H), 1.09 (s, 2H). 378 98% 3-41 [00268] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 9.52 (s, 1H), 8.92 (s, 1H), 8.30 (s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.25 (d, J = 5.9 Hz, 2H), 1.08 (s, 2H). 395 95% 3-42 [00269] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.77 (s, 1H), 11.96 (s, 1H), 8.92 (s, 1H), 8.24 (s, 1H), 8.06 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.61 (s, 1H), 6.57 (s, 1H), 4.41 (s, 1H), 2.64 (s, 3H), 1.26 (d, J = 6.1 Hz, 2H), 1.09 (s, 2H). 378 98% 3-43 [00270] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.76-14.48 (s, 1H), 8.97-8.90 (d, J = 2.7 Hz, 2H), 8.63-8.55 (s, 1H), 8.07-7.97 (t, J = 9.2 Hz, 2H), 7.69-7.58 (m, 1H), 4.48-4.39 (s, 2H), 2.73-2.65 (s, 3H), 1.27- 1.20 (m, 2H), 1.14-1.06 (s, 2H). 403 95% 3-44 [00271] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 10.02-9.98 (s, 1H), 9.48-9.43 (s, 1H), 8.95-8.90 (s, 1H), 8.67- 8.62 (s, 1H), 8.12-8.07 (d, J = 9.2 Hz, 1H), 8.07-8.01 (d, J = 8.9 Hz, 1H), 7.82-7.75 (dd, J = 9.4, 1.7 Hz, 1H), 4.48-4.36 (s, 1H), 2.72- 2.67 (s, 3H), 1.25-1.21 (t, J = 3.8 Hz, 2H), 1.14- 1.06 (m, 2H). 406 90% 3-45 [00272] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 9.93 (s, 1H), 8.83 (s, 1H), 8.40 (s, 1H), 8.09-8.05 (dd, J = 9.2, 1.0 Hz, 1H), 8.05-8.00 (d, J = 8.7 Hz, 1H), 7.81-7.72 (dd, J = 9.3, 1.7 Hz, 1H), 5.35-5.16 (s, 1H), 4.53- 4.33 (m, 1H), 2.75-2.64 (s, 3H), 1.28-1.20 (d, J = 6.2 Hz, 2H), 1.15-1.03 (d, J = 3.8 Hz, 2H). 402 98% 3-46 [00273] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70-14.56 (s, 1H), 9.23-9.15 (m, 1H), 8.99-8.89 (s, 1H), 8.72- 8.65 (s, 1H), 8.08-7.99 (d, J = 8.8 Hz, 1H), 7.84- 7.77 (s, 1H), 7.16-7.04 (m, 1H), 6.93-6.82 (m, 1H), 5.82-5.69 (dd, J = 11.2, 1.6 Hz, 1H), 4.49- 4.36 (t, J = 3.5 Hz, 1H), 2.75-2.68 (s, 3H), 1.33- 1.19 (t, J = 6.5 Hz, 2H), 1.16-1.03 (s, 2H). 405 97% 3-47 [00274] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.76-14.48 (s, 1H), 8.96-8.91 (s, 4H), 8.86-8.79 (s, 4H), 8.64- 8.56 (d, J = 2.3 Hz, 4H), 8.06-7.99 (d, J = 8.8 Hz, 4H), 7.86-7.79 (d, J = 9.4 Hz, 4H), 7.52-7.43 (s, 3H), 4.48-4.37 (s, 1H), 2.74-2.67 (s, 12H), 1.29- 1.20 (d, J = 6.8 Hz, 9H), 1.11-1.01 (t, J = 3.0 Hz, 6H). 422 96% 3-48 [00275] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.76-14.48 (s, 1H), 8.95-8.89 (s, 1H), 8.84-8.78 (s, 1H), 8.63- 8.58 (s, 1H), 8.05-8.00 (d, J = 8.8 Hz, 1H), 7.90- 7.84 (d, J = 9.4 Hz, 1H), 7.53-7.45 (d, J = 9.3 Hz, 1H), 4.47-4.40 (s, 1H), 2.73-2.68 (s, 3H), 1.27- 1.21 (d, J = 6.6 Hz, 2H), 1.12-1.02 (s, 2H). 446 90% 3-49 [00276] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.66 (s, 1H), 8.06-7.99 (d, J = 8.7 Hz, 1H), 7.99-7.95 (s, 1H), 7.94-7.88 (d, J = 9.3 Hz, 1H), 7.55-7.47 (dd, J = 9.3, 1.6 Hz, 1H), 4.52-4.32 (m, 1H), 2.77-2.61 (s, 3H), 1.33-1.17 (d, J = 6.6 Hz, 2H), 1.19-1.05 (t, J = 3.3 Hz, 2H). 412 98% 3-50 [00277] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.60 (s, 1H), 8.06-8.00 (d, J = 8.7 Hz, 1H), 8.00-7.96 (s, 1H), 7.92-7.86 (d, J = 9.3 Hz, 1H), 7.56-7.48 (d, J = 9.4 Hz, 1H), 4.55-4.26 (m, 1H), 2.81-2.60 (s, 3H), 1.37-1.21 (d, J = 6.5 Hz, 2H), 1.15-1.05 (m, 2H). 456, 458 97% 3-51 [00278] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71-14.62 (s, 1H), 8.96-8.88 (s, 1H), 8.83-8.75 (s, 1H), 8.25- 8.16 (d, J = 7.5 Hz, 2H), 8.15-8.07 (s, 1H), 8.07- 7.97 (d, J = 8.8 Hz, 1H), 7.77-7.71 (s, 1H), 7.57- 7.42 (m, 4H), 4.50-4.33 (s, 1H), 2.82-2.71 (s, 3H), 1.31-1.22 (d, J = 6.7 Hz, 2H), 1.15-1.04 (s, 2H). 454 99% 3-52 [00279] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71-14.60 (s, 1H), 8.95-8.88 (s, 1H), 8.73-8.65 (s, 1H), 8.10- 7.96 (m, 2H), 7.74-7.68 (s, 1H), 7.40-7.32 (s, 1H), 7.11-7.02 (m, 1H), 6.96-6.83 (m, 1H), 5.70-5.60 (dd, J = 11.2, 2.0 Hz, 1H), 4.47-4.38 (t, J = 3.5 Hz, 1H), 2.78-2.69 (s, 3H), 1.31-1.20 (d, J = 6.9 Hz, 2H), 1.14-1.01 (s, 2H). 405 93% 3-53 [00280] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71-14.60 (s, 1H), 8.95-8.88 (s, 1H), 8.73-8.65 (s, 1H), 8.10- 7.96 (m, 2H), 7.74-7.68 (s, 1H), 7.40-7.32 (s, 1H), 7.11-7.02 (m, 1H), 6.96-6.83 (m, 1H), 5.70-5.60 (dd, J = 11.2, 2.0 Hz, 1H), 4.47-4.38 (t, J = 3.5 Hz, 1H), 2.78-2.69 (s, 3H), 1.31-1.20 (d, J = 6.9 Hz, 2H), 1.14-1.01 (s, 2H). 403 95% 3-54 [00281] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.76-14.39 (s, 1H), 9.20-9.07 (d, J = 7.0 Hz, 1H), 8.95-8.90 (s, 1H), 8.67-8.60 (s, 1H), 8.08-8.00 (m, 2H), 7.32- 7.24 (m, 1H), 4.47-4.36 (s, 1H), 2.75-2.61 (s, 3H), 1.30-1.19 (m, 2H), 1.15-1.03 (q, J = 3.8, 3.1 Hz, 2H). 379 98% 3-55 [00282] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.76-14.36 (s, 1H), 9.68-9.65 (d, J = 1.5 Hz, 1H), 8.95-8.92 (s, 1H), 8.84-8.81 (s, 1H), 8.63-8.59 (d, J = 1.5 Hz, 1H), 8.06-8.01 (d, J = 8.8 Hz, 1H), 4.46-4.39 (s, 1H), 2.76-2.69 (s, 3H), 1.30-1.20 (m, 2H), 1.14- 1.05 (s, 2H). 404 98% 3-56 [00283] embedded image OMe [00284] .sup.1H NMR (400 MHz, DMSO) δ 14.73-14.06 (s, 1H), 9.21-9.18 (m, 1H), 8.87-8.83 (d, J = 1.86 Hz, 1H), 8.32-8.27 (d, J = 1.33 Hz, 1H), 8.20-8.16 (s, 1H), 8.04-7.97 (d, J = 9.06 Hz, 1H), 7.87-7.80 (d, J = 1.20 Hz, 1H), 5.31-4.87 (m, 1H), 4.32-4.12 (m, 1H), 3.67-3.47 (s, 3H), 1.95-1.56 (m, 2H). 437 98% 3-57 [00285] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 8.83 (s, 1H), 8.77 (s, 1H), 8.23 (d, J = 2.1 Hz, 1H), 7.99 (d, J = 9.2 Hz, 1H), 7.73 (d, J = 1.0 Hz, 1H), 7.40 (d, J = 11.8 Hz, 1H), 4.46-4.08 (m, 1H), 3.51 (d, J = 10.5 Hz, 3H), 1.19 (d, J = 6.9 Hz, 4H). 412 90% 3-58 [00286] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.83-14.57 (s, 1H), 9.82-9.48 (s, 2H), 9.01-8.84 (d, J = 2.6 Hz, 1H), 8.05-7.90 (dd, J = 8.5, 2.7 Hz, 1H), 7.65- 7.57 (d, J = 7.5 Hz, 1H), 7.51-7.46 (s, 1H), 7.45- 7.36 (d, J = 7.7 Hz, 1H), 4.72-4.50 (s, 4H), 4.47- 4.28 (d, J = 6.8 Hz, 1H), 2.64-2.53 (d, J = 2.7 Hz, 3H), 1.31-1.14 (d, J = 6.1 Hz, 2H), 1.14-0.96 (s, 2H). 379 95% 3-59 [00287] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.95-8.83 (d, J = 2.4 Hz, 1H), 7.98-7.86 (d, J = 8.8 Hz, 1H), 7.25- 7.15 (s, 1H), 7.14-7.01 (d, J = 7.9 Hz, 1H), 6.97- 6.81 (d, J = 7.9 Hz, 1H), 3.65-3.50 (m, 2H), 4.45- 4.29 (dp, J = 9.2, 4.7, 3.9 Hz, 1H), 3.16-2.99 (t, J = 8.4 Hz, 2H), 2.65-2.56 (s, 3H), 1.28-1.16 (d, J = 6.6 Hz, 3H), 1.12-0.97 (m, 2H). 379 99% 3-60 [00288] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.01-14.39 (m, 1H), 12.95-12.53 (s, 2H), 9.03-8.82 (t, J = 1.9 Hz, 1H), 8.73-8.47 (s, 2H), 8.10-7.90 (d, J = 8.4 Hz, 1H), 7.62-7.44 (m, 1H), 4.51-4.23 (m, 1H), 7.44-7.31 (s, 1H), 7.31-7.11 (d, J = 8.6 Hz, 1H), 2.65-2.55 (s, 3H), 1.30-1.16 (m, 2H), 1.16-0.96 (s, 2H). 393 90% 3-61 [00289] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, MeOD) δ 9.17-9.06 (d, J = 2.8 Hz, 1H), 8.30-8.15 (m, 1H), 7.94-7.80 (m, 2H), 7.65-7.49 (dt, J = 7.5, 3.3 Hz, 2H), 4.47- 4.32 (d, J = 6.9 Hz, 1H), 2.96-2.81 (d, J = 2.8 Hz, 3H), 1.43-1.27 (dd, J = 10.8, 4.5 Hz, 2H), 1.21-1.05 (s, 2H). 378 100% 3-62 [00290] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.63-14.42 (s, 1H), 8.99-8.89 (s, 1H), 8.33-8.25 (d, J = 7.8 Hz, 1H), 8.25-8.18 (d, J = 8.0 Hz, 1H), 8.14-8.05 (d, J = 8.7 Hz, 1H), 7.71-7.56 (dt, J = 22.8, 7.4 Hz, 2H), 4.51-4.31 (s, 1H), 2.85-2.70 (s, 3H), 1.30- 1.20 (d, J = 7.0 Hz, 2H), 1.13-0.97 (s, 2H). 395 100% 3-63 [00291] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.01-14.28 (s, 2H), 9.04-8.82 (t, J = 2.3 Hz, 1H), 8.05-7.98 (d, J = 8.3 Hz, 1H), 7.98-7.92 (dd, J = 10.5, 2.5 Hz, 1H), 7.90-7.83 (s, 1H), 7.56-7.47 (d, J = 8.2 Hz, 1H), 4.46-4.34 (t, J = 6.3 Hz, 1H), 2.87-2.78 (t, J = 2.1 Hz, 3H), 2.64-2.55 (s, 3H), 1.29-1.16 (m, 2H), 1.16-1.03 (s, 2H). 392 100% 3-64 [00292] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.01-14.28 (s, 2H), 9.04-8.82 (t, J = 2.3 Hz, 1H), 8.05-7.98 (d, J = 8.3 Hz, 1H), 7.98-7.92 (dd, J = 10.5, 2.5 Hz, 1H), 7.90-7.83 (s, 1H), 7.56-7.47 (d, J = 8.2 Hz, 1H), 4.46-4.34 (t, J = 6.3 Hz, 1H), 2.87-2.78 (t, J = 2.1 Hz, 3H), 2.64-2.55 (m, 6H), 1.29-1.16 (m, 2H), 1.16-1.03 (s, 2H). 421 100% 3-65 [00293] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.05-14.35 (m, 1H), 10.46-9.91 (m, 1H), 9.02-8.80 (s, 1H), 8.80- 8.47 (d, J = 15.2 Hz, 1H), 8.12-7.64 (m, 3H), 7.44-7.25 (dd, J = 23.7, 8.0 Hz, 1H), 4.84-4.63 (d, J = 8.8 Hz, 2H), 4.49-4.32 (s, 1H), 3.01-2.77 (d, J = 17.9 Hz, 6H), 1.37-1.13 (d, J = 6.9 Hz, 2H), 1.17-0.86 (s, 2H). 449 96% 3-66 [00294] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.97-14.24 (s, 2H), 9.14-8.97 (m, 2H), 8.98-8.88 (s, 2H), 8.07- 7.89 (dd, J = 24.1, 8.9 Hz, 6H), 7.86-7.79 (s, 1H), 7.52-7.37 (t, J = 9.6 Hz, 3H), 4.57-4.31 (t, J = 6.8 Hz, 5H), 2.66-2.55 (s, 7H), 1.60-1.40 (m, 7H), 1.30-1.16 (m, 2H), 1.16-0.98 (s, 2H). 406 97% 3-67 [00295] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.97-14.24 (s, 2H), 9.14-8.97 (m, 2H), 8.98-8.88 (s, 2H), 8.07- 7.89 (dd, J = 24.1, 8.9 Hz, 6H), 7.86-7.79 (s, 1H), 7.52-7.37 (t, J = 9.6 Hz, 3H), 4.57-4.31 (t, J = 6.8 Hz, 5H), 2.66-2.55 (s, 3H), 1.60-1.40 (m, 7H), 1.30-1.16 (m, 2H), 1.16-0.98 (s, 2H). 392 100% 3-68 [00296] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.95-8.91 (s, 1H), 8.65-8.59 (s, 1H), 8.31-8.25 (s, 1H), 8.23-8.17 (s, 1H), 8.05-7.98 (m, 1H), 4.48-4.35 (s, 1H), 2.68- 2.61 (s, 3H), 1.30-1.22 (s, 2H), 1.16-1.06 (s, 2H). 423 97% 3-69 [00297] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.96-14.48 (m, 1H), 10.94-10.65 (d, J = 25.6 Hz, 2H), 9.01-8.77 (m, 1H), 8.05-7.81 (d, J = 8.6 Hz, 1H), 7.18-7.00 (d, J = 7.8 Hz, 1H), 7.00-6.78 (m, 2H), 4.47-4.25 (td, J = 6.9, 3.6 Hz, 1H), 2.67-2.54 (s, 3H), 1.27- 1.10 (d, J = 6.3 Hz, 2H), 1.14-0.88 (s, 2H). 394 94% 3-70 [00298] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.02-14.18 (s, 1H), 9.00-8.67 (m, 2H), 8.12-7.68 (m, 3H), 7.49- 7.25 (dd, J = 16.6, 8.2 Hz, 1H), 5.04-4.75 (m, 1H), 4.62-4.23 (m, 9H), 3.77-3.55 (m, 2H), 3.57-3.23 (d, J = 7.0 Hz, 1H), 2.70-2.53 (s, 3H), 1.37-1.15 (t, J = 8.0 Hz, 2H), 1.15-0.84 (td, J = 16.0, 7.8 Hz, 9H). 494 90% 3-71 [00299] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.45-14.13 (s, 1H), 11.09-10.85 (s, 1H), 8.73-8.58 (d, J = 2.7 Hz, 1H), 7.85-7.61 (m, 2H), 7.31-7.15 (m, 1H), 7.07- 6.83 (m, 2H), 4.27-4.07 (s, 1H), 3.82-3.71 (d, J = 2.5 Hz, 3H), 1.27-1.08 (m, 2H), 1.08-0.86 (s, 2H). 408 93% 3-72 [00300] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.07-14.72 (s, 1H), 9.21-8.97 (s, 1H), 8.95-8.73 (m, 1H), 8.41- 8.14 (m, 1H), 8.12-7.95 (s, 1H), 3.40-3.18 (m, 4H), 7.95-7.79 (d, J = 8.6 Hz, 1H), 7.79-7.60 (dd, J = 8.5, 3.9 Hz, 2H), 4.34-4.10 (d, J = 6.3 Hz, 1H), 1.30-1.02 (s, 4H). 376 95% 3-73 [00301] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.68-10.51 (s, 1H), 9.04-8.78 (m, 1H), 8.01- 7.81 (m, 1H), 7.36-7.11 (m, 2H), 7.11-6.87 (dd, J = 7.8, 2.7 Hz, 1H), 4.47-4.29 (s, 1H), 3.72-3.47 (s, 2H), 1.27-1.08 (m, 2H), 1.08-0.86 (s, 2H). 393 97% 3-74 [00302] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.68-10.51 (s, 1H), 9.04-8.78 (m, 1H), 8.01-7.81 (m, 1H), 7.36-7.11 (m, 2H), 7.11-6.87 (dd, J = 7.8, 2.7 Hz, 1H), 4.47-4.29 (s, 1H), 3.72- 3.47 (s, 2H), 2.66-2.57 (d, J = 2.7 Hz, 3H), 2.55- 2.45 (d, J = 3.4 Hz, 4H). 424 97% 3-75 [00303] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.80-14.62 (m, 1H), 8.38-8.18 (m, 1H), 8.03-7.83 (m, 1H), 8.96- 8.82 (m, 1H), 7.77-7.59 (m, 1H), 7.37-7.22 (m, 1H), 4.48-4.29 (m, 1H), 3.24-3.08 (m, 2H), 3.94- 3.70 (m, 2H), 1.32-1.12 (m, 2H), 1.12-0.86 (m, 2H). 394 100% 3-76 [00304] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.11-14.26 (d, J = 53.0 Hz, 1H), 10.22-9.45 (m, 1H), 9.01-8.84 (m, 1H), 8.77-8.58 (s, 1H), 8.09-7.92 (d, J = 8.5 Hz, 1H), 7.88-7.68 (s, 1H), 7.51-7.33 (s, 1H), 4.84-4.58 (s, 2H), 4.53-4.25 (s, 1H), 2.96-2.72 (s, 6H), 2.72-2.56 (s, 3H), 1.34-1.17 (d, J = 6.5 Hz, 2H), 1.17-0.93 (d, J = 10.1 Hz, 2H). 435 94% 3-77 [00305] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.87-14.59 (s, 1H), 12.20-12.00 (s, 1H), 9.01-8.79 (s, 1H), 8.09- 7.83 (d, J = 8.6 Hz, 1H), 7.74-7.59 (s, 1H), 7.39- 7.20 (m, 2H), 4.48-4.31 (s, 1H), 2.72-2.56 (s, 3H), 1.36-1.12 (d, J = 6.9 Hz, 2H), 1.12-0.79 (s, 2H). 411 98% 3-78 [00306] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.68-10.51 (s, 1H), 9.04-8.78 (m, 1H), 8.01-7.81 (m, 1H), 7.36-7.11 (m, 2H), 7.11-6.87 (dd, J = 7.8, 2.7 Hz, 1H), 4.47-4.29 (s, 1H), 3.72- 3.47 (s, 2H), 1.27-1.08 (m, 2H), 1.08-0.86 (s, 2H). 393 95% 3-79 [00307] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.82-14.60 (s, 1H), 11.50-11.28 (s, 1H), 8.99-8.81 (s, 1H), 8.09- 7.90 (m, 2H), 7.66-7.53 (d, J = 1.1 Hz, 1H), 6.91- 6.78 (s, 1H), 6.17-5.99 (d, J = 15.7 Hz, 1H), 5.38- 5.23 (d, J = 9.0 Hz, 1H), 4.48-4.31 (dd, J = 8.4, 4.4 Hz, 1H), 3.61-3.41 (s, 1H), 2.71-2.56 (s, 3H), 1.32-1.16 (s, 2H), 1.14-0.97 (s, 2H). 421 97% 3-80 [00308] embedded image MeO Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.82-14.60 (s, 1H), 11.50-11.28 (s, 1H), 8.99-8.81 (s, 1H), 8.09- 7.90 (m, 2H), 7.66-7.53 (d, J = 1.1 Hz, 1H), 6.91- 6.78 (s, 1H), 6.17-5.99 (d, J = 15.7 Hz, 1H), 5.38- 5.23 (d, J = 9.0 Hz, 1H), 4.48-4.31 (dd, J = 8.4, 4.4 Hz, 1H), 3.61-3.41 (s, 1H), 2.71-2.56 (s, 3H), 1.14-0.97 (s, 4H). 437 90% 3-81 [00309] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.85-14.61 (s, 1H), 10.95-10.69 (s, 1H), 9.06-8.79 (s, 2H), 8.05- 7.90 (d, J = 8.7 Hz, 1H), 7.28-7.09 (s, 1H), 6.85- 6.63 (s, 1H), 4.46-4.29 (tt, J = 7.4, 4.0 Hz, 1H), 2.72-2.54 (s, 3H), 1.32-1.14 (d, J = 5.8 Hz, 2H), 1.14-0.97 (d, J = 3.8 Hz, 2H). 394 94% 3-82 [00310] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.89-14.50 (s, 2H), 11.09-10.63 (s, 1H), 9.21-8.97 (s, 1H), 8.97- 8.73 (s, 1H), 8.07-7.85 (m, 1H), 3.48-3.31 (m, 5H), 7.42-7.26 (m, 1H), 7.04-6.87 (m, 1H), 4.31- 4.13 (p, J = 5.6 Hz, 1H), 2.72-2.54 (s, 3H), 1.27- 1.01 (d, J = 5.6 Hz, 4H). 410 98% 3-83 [00311] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 15.05-14.39 (s, 1H), 13.02-12.32 (s, 1H), 8.97-8.77 (s, 1H), 8.47- 8.20 (s, 1H), 7.85-7.39 (m, 2H), 7.33-6.98 (d, J = 8.0 Hz, 1H), 4.47-4.23 (s, 1H), 2.74-2.52 (s, 3H), 1.34-1.13 (m, 2H), 1.13-0.71 (s, 2H). 428 100% 3-84 [00312] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75 (d, J = 8.7 Hz, 1H), 8.91 (s, 1H), 8.13 (s, 1H), 7.99 (t, J = 11.1 Hz, 1H), 7.78 (t, J = 13.2 Hz, 1H), 7.72 (s, 1H), 7.33 (d, J = 8.5 Hz, 1H), 7.07 (s, 1H), 4.40 (m, 1H), 2.61 (s, 3H), 1.24 (d, J = 5.7 Hz, 2H), 1.08 (s, 2H). 378 98% 3-85 [00313] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.90 (s, 1H), 8.21 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 8.1 Hz, 1H), 7.94 (s, 1H), 7.90 (s, 1H), 7.56 (s, 1H), 7.38 (d, J = 7.9 Hz, 1H), 4.38 (s, 1H), 2.65 (s, 3H), 1.17 (m, 2H), 1.06 (m, 2H). 394 98% 3-86 [00314] .sup.1H NMR (400 MHz, DMSO) δ 15.38-14.22 (s, 1H), 9.14-9.08 (s, 1H), 9.00-8.94 (s, 1H), 8.32- 8.24 (s, 1H), 7.93-7.90 (s, 1H), 7.90-7.86 (s, 1H), 7.83-7.76 (d, J = 9.72 Hz, 1H), 5.07-4.96 (d, J = 6.74 Hz, 1H), 4.65-4.56 (d, J = 11.26 Hz, 1H), 4.53-4.43 (d, J = 9.86 Hz, 1H), 1.54-1.46 (d, J = 6.76 Hz, 3H). 414 99% 3-87 [00315] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.87 (s, 1H), 8.93 (s, 1H), 8.77 (s, 1H), 8.27 (d, J = 8.2 Hz, 1H), 8.15 (s, 1H), 7.73 (d, J = 0.9 Hz, 1H), 7.63 (m, 2H), 4.46- 4.36 (m, 1H), 2.76 (s, 3H), 1.29 (d, J = 6.5 Hz, 2H), 1.08 (t, J = 7.4 Hz, 2H). 394 99%

TABLE-US-00004 TABLE 4 [00316] embedded image Com- pound No. R.sup.3 = NMR MS (MH.sup.+) HPLC 4-1 [00317] .sup.1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 11.38 (s, 1H), 8.70 (s, 1H), 7.78 (d, J = 9.1 Hz, 1H), 7.42 (d, J = 7.9 Hz, 1H), 7.26 (d, J = 8.1 Hz, 1H), 7.00- 6.92 (m, 1H), 6.86 (t, J = 7.5 Hz, 1H), 6.51 (s, 1H), 4.24-4.16 (m, 1H), 2.56 (s, 3H), 1.03 (dd, J = 12.0, 4.6 Hz, 2H), 0.86 (d, J = 7.4 Hz, 2H). 377 95% 4-2 [00318] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.59 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.64 (d, J = 7.5 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.19 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 7.3 Hz, 1H), 6.73 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H). 377 100% 4-3 [00319] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.93 (s, 1H), 8.05 (d, J = 8.6 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.30-7.24 (m, 1H), 7.14 (t, J = 7.3 Hz, 1H), 6.68 (s, 1H), 4.41 (s, 1H), 3.58 (s, 3H), 2.65 (s, 3H), 1.24 (s, 4H). 391 98% 4-4 [00320] .sup.1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 11.36 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.57 (s, 3H), 7.46 (s, 1H), 7.07 (d, J = 8.5 Hz, 1H), 6.53 (s, 1H), 4.39 (s, 1H), 2.62 (s, 3H), 1.24 (s, 2H), 1.00 (d, J = 18.8 Hz, 2H). 377 87% 4-5 [00321] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.55 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.09 (t, J = 7.4 Hz, 1H), 6.87 (d, J = 6.9 Hz, 1H), 6.75 (s, 1H), 4.42 (s, 1H), 2.79 (s, 3H), 2.09 (s, 3H), 1.28 (d, J = 6.0 Hz, 2H), 1.07 (s, 2H). 391 90% 4-6 [00322] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.43 (s, 1H), 8.91 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.37 (d, J = 8.6 Hz, 1H), 7.13 (s, 1H), 6.84 (d, J = 8.7 Hz, 1H), 6.63 (s, 1H), 4.41 (s, 1H), 3.78 (s, 4H), 2.77 (s, 3H), 1.26 (d, J = 5.7 Hz, 2H), 1.07 (s, 2H). 407 92.3% 4-9 [00323] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 12.23 (d, J = 30.1 Hz, 1H), 8.93 (s, 1H), 8.20 (d, J = 11.8 Hz, 1H), 7.65 (s, 1H), 7.53 (s, 2H), 6.87 (d, J = 26.1 Hz, 1H), 4.38 (d, J = 31.7 Hz, 1H), 2.74 (d, J = 19.6 Hz, 3H), 1.24 (d, J = 8.9 Hz, 2H), 1.07 (s, 2H). 402 92.8% 4-10 [00324] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.70 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 8.9 Hz, 1H), 7.52- 7.44 (m, 1H), 7.41 (d, J = 9.8 Hz, 1H), 7.04 (t, J = 9.3 Hz, 1H), 6.72 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 6.4 Hz, 2H), 1.07 (s, 2H). 395 89.7% 4-11 [00325] .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 11.98 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.47 (d, J = 7.3 Hz, 1H), 7.19 (q, J = 7.8 Hz, 2H), 6.76 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.2 Hz, 2H), 1.08 (s, 2H). 411 97% 4-12 [00326] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.30 (s, 1H), 8.93 (s, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.86 (d, J = 6.8 Hz, 1H), 7.64 (s, 1H), 7.36 (s, 1H), 6.91 (s, 1H), 4.43 (s, 1H), 2.78 (s, 3H), 1.28 (s, 2H), 1.09 (s, 2H). 402 99% 4-13 [00327] .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 11.93 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 9.1 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.17 (d, J = 6.5 Hz, 1H), 6.87 (t, J = 8.9 Hz, 1H), 6.80 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.4 Hz, 2H), 1.07 (s, 2H). 395 87% 4-14 [00328] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.43 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.46 (s, 1H), 6.98 (s, 2H), 6.67 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 6.3 Hz, 2H), 1.09 (s, 2H). 391 92.7% 4-15 [00329] .sup.1H NMR (400 MHz, DMSO) δ 11.07 (s, 1H), 9.02 (s, 1H), 8.04 (s, 1H), 7.55 (s, 2H), 7.29 (s, 1H), 6.96 (s, 1H), 6.67 (s, 1H), 2.85 (s, 3H), 2.47 (s, 3H), 1.34 (s, 2H), 1.09 (s, 2H). 391 99% 4-16 [00330] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 12.41 (s, 1H), 8.93 (s, 1H), 8.69 (s, 1H), 8.07 (d, J = 13.8 Hz, 2H), 7.67 (s, 1H), 7.05 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.26 (s, 2H), 1.08 (s, 2H). 422 100% 4-17 [00331] .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.70 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.65 (s, 1H), 7.24 (d, J = 10.1 Hz, 1H), 6.96 (t, J = 9.1 Hz, 1H), 6.76 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 5.7 Hz, 2H), 1.07 (s, 2H). 395 88% 4-18 [00332] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 12.08 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 8.9 Hz, 1H), 7.47 (d, J = 6.4 Hz, 1H), 7.04 (d, J = 9.3 Hz, 2H), 6.79 (s, 1H), 4.42 (s, 1H), 2.76 (s, 3H), 1.26 (d, J = 6.2 Hz, 2H), 1.08 (s, 2H). 395 89.1% 4-19 [00333] .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 12.66 (s, 1H), 11.98 (s, 1H), 8.93 (s, 1H), 8.12 (s, 1H), 8.03 (d, J = 8.8 Hz, 1H), 7.70 (q J = 8.2 Hz, 2H), 6.83 (s, 1H), 4.43 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.2 Hz, 2H), 1.08 (s, 2H). 421 100% 4-20 [00334] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 11.78 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 9.0 Hz, 1H), 7.66 (d, J = 8.6 Hz, 1H), 7.51 (s, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 4.42 (s, 1H), 2.77 (s, 3H), 1.26 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H). 411 90% 4-21 [00335] .sup.1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 12.71 (s, 1H), 8.92 (s, 1H), 8.15 (s, 1H), 8.04 (d, J = 9.4 Hz, 2H), 7.43 (s, 1H), 7.29 (s, 1H), 4.42 (s, 1H), 2.79 (s, 3H), 1.27 (s, 2H), 1.08 (s, 2H). 422 97% 4-22 [00336] embedded image .sup.1H NMR (400 MHz, MeOD) δ 8.96 (s, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.55 (d, J = 12.6 Hz, 2H), 7.47 (s, 1H), 7.34 (d, J = 8.1 Hz, 1H), 6.77 (s, 1H), 6.57 (d, J = 7.9 Hz, 1H), 6.51 (s, 1H), 4.29 (s, 1H), 2.78 (s, 3H), 1.38-1.24 (m, 2H), 1.20 (s, 2H). 393 90% 4-23 [00337] .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 11.82 (s, 1H), 8.92 (s, 1H), 8.01 (d, J = 8.5 Hz, 1H), 7.70 (s, 1H), 7.50 (d, J = 8.3 Hz, 1H), 7.19 (d, J = 9.4 Hz, 1H), 6.73 (s, 1H), 4.42 (s, 1H), 2.76 (s, 3H), 1.26 (d, J = 6.1 Hz, 2H), 1.07 (s, 2H). 411 90% 4-24 [00338] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 11.61 (s, 1H), 8.95 (d, J = 9.5 Hz, 1H), 8.41 (s, 1H), 7.99 (s, 1H), 7.67 (d, J = 9.1 Hz, 1H), 6.52 (s, 1H), 4.43 (s, 1H), 2.78 (s, 3H), 1.25 (s, 2H), 1.08 (s, 2H). 422 90% 4-25 [00339] .sup.1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 11.31 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.48 (s, 1H), 7.41 (s, 1H), 6.99 (d, J = 7.9 Hz, 1H), 6.53 (s, 1H), 4.40 (s, 1H), 2.63 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H). 377 100% 4-26 [00340] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 12.37 (s, 1H), 8.93 (s, 1H), 8.19 (t, J = 9.0 Hz, 2H), 8.01 (d, J = 8.0 Hz, 1H), 7.34 (s, 1H), 7.00 (s, 1H), 4.43 (s, 1H), 2.75 (s, 3H), 1.24 (s, 2H), 1.11 (s, 2H). 422 99% 4-27 [00341] .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.45 (s, 1H), 9.17 (s, 1H), 8.92 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.77 (s, 1H), 7.35 (d, J = 8.5 Hz, 1H), 7.24 (s, 1H), 6.64 (s, 1H), 4.42 (s, 1H), 2.77 (s, 2H), 1.46 (d, J = 29.9 Hz, 9H), 1.25 (s, 2H), 1.06 (s, 2H). 492 100% 4-28 [00342] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.94 (s, 1H), 9.97 (s, 2H), 8.93 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.65 (s, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.19-7.13 (m, 1H), 6.84 (s, 1H), 4.42 (s, 2H), 2.76 (s, 3H), 1.14-1.00 (m, 4H). 392 94% 4-29 [00343] .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.94 (s, 1H), 9.97 (s, 2H), 8.93 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.65 (s, 1H), 7.60 (d, J = 8.6 Hz, 1H), 7.19- 7.13 (m, 1H), 6.84 (s, 1H), 4.42 (s, 2H), 2.76 (s, 3H), 1.14-1.00 (m, 4H). 391 100% 4-30 [00344] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.38 (s, 1H), 9.33 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.81 (s, 1H), 7.48 (d, J = 8.3 Hz, 1H), 7.09 (d, J = 8.7 Hz, 1H), 6.64 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.51 (s, 10H), 1.25 (d, J = 8.9 Hz, 2H), 1.08 (dd, J = 14.0, 6.3 Hz, 2H). 492 97% 4-31 [00345] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.31 (s, 1H), 11.68 (s, 1H), 8.94 (s, 1H), 8.17 (d, J = 8.7 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 7.21 (t, J = 7.5 Hz, 1H), 7.08 (t, J = 7.4 Hz, 1H), 6.80 (s, 1H), 4.44 (s, 1H), 1.25 (d, J = 6.4 Hz, 2H), 1.12 (s, 2H). 397 100% 4-32 [00346] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.74 (s, 1H), 9.35 (s, 2H), 8.92 (s, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.66 (d, J = 8.5 Hz, 1H), 7.34 (s, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.76 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 5.6 Hz, 3H), 1.06 (s, 2H). 392 97% 4-33 [00347] .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.56 (s, 1H), 9.17 (s, 1H), 8.93 (s, 1H), 8.00 (d, J = 7.7 Hz, 1H), 7.46 (s, 2H), 7.12 (d, J = 20.9 Hz, 2H), 5.18-4.56 (m, 1H), 4.44 (s, 1H), 2.80 (s, 3H), 1.24 (s, 2H), 1.07 (s, 2H). 492 91% 4-34 [00348] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.77 (s, 1H), 8.93 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.23- 7.03 (m, 2H), 6.88(s, 1H), 6.76 (d, J = 6.4 Hz, 1H), 4.43 (m, 1H), 2.77(s, 3H), 1.24 (d, J = 6.6 Hz, 2H), 1.12 (s, 2H). 392 99% 4-35 [00349] .sup.1H NMR (400 MHz, DMSO) δ 14.28 (s, 1H), 11.79 (s, 1H), 8.94 (s, 1H), 8.17 (d, J = 8.8 Hz, 1H), 7.56- 7.38 (m, 2H), 7.06 (t, J = 8.8 Hz, 1H), 6.79 (s, 1H), 4.44 (s, 1H), 1.24 (d, J = 6.6 Hz, 2H), 1.12 (s, 2H). 415 91% 4-36 [00350] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.28 (s, 1H), 12.16 (s, 1H), 8.95 (s, 1H), 8.18 (d, J = 8.0 Hz, 1H), 7.49 (d, J = 4.2 Hz, 1H), 7.05 (d, J = 8.5 Hz, 2H), 6.85 (s, 1H), 4.43 (s, 1H), 1.24 (s, 2H), 1.13 (s, 2H). 415 95% 4-37 [00351] .sup.1H NMR (400 MHz, DMSO) δ 14.26 (s, 1H), 12.07 (s, 1H), 8.95 (s, 1H), 8.19 (d, J = 8.5 Hz, 1H), 7.49 (d, J = 7.6 Hz, 1H), 7.29-7.07 (m, 2H), 6.81 (s, 1H), 4.44 (s, 1H), 1.25 (s, 2H), 1.13 (s, 2H). 431 95% 4-38 [00352] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.28 (s, 1H), 12.04 (s, 1H), 8.95 (s, 1H), 8.19 (d, J = 8.7 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.20 (s, 1H), 6.93-6.81 (m, 2H), 4.44 (s, 1H), 1.24 (s, 2H), 1.13 (s, 2H). 415 87% 4-39 [00353] .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.66 (s, 1H), 10.06 (s, 1H), 8.92 (s, 1H), 8.02 (s, 3H), 7.46 (s, 1H), 7.31 (s, 1H), 7.19 (s, 1H), 7.06 (s, 1H), 6.90 (s, 1H), 4.42 (s, 1H), 3.85 (s, 3H), 2.79 (s, 3H), 1.26 (s, 2H), 1.07 (s, 2H). 526 95.6% 4-40 [00354] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.62 (s, 1H), 10.05 (s, 1H), 8.93 (s, 1H), 7.99 (d, J = 9.2 Hz, 1H), 7.70 (d, J = 7.5 Hz, 2H), 7.28-6.87 (m, 6H), 4.42 (s, 1H), 3.75 (s, 3H), 2.68 (s, 3H), 1.25 (d, J = 9.3 Hz, 2H), 1.05 (d, J = 18.8 Hz, 2H). 562 96% 4-41 [00355] .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.66 (s, 1H), 9.62 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 8.7 Hz, 1H), 7.72 (s, 1H), 7.21 (s, 1H), 7.12 (s, 1H), 7.04 (s, 1H), 4.44 (s, 1H), 3.05 (s, 1H), 2.82 (d, J = 25.3 Hz, 3H), 1.12 (d, J = 24.4 Hz, 10H). 462 87% 4-42 [00356] embedded image .sup.1H NMR (400 MHz, DMSO) δ 11.87 (s, 1H), 9.18 (s, 1H), 8.08-7.63 (m, 2H), 7.48 (s, 2H), 7.20 (s, 2H), 6.95 (s, 2H), 4.54 (s, 1H), 4.24 (s, 2H), 2.81 (s, 3H), 1.29 (s, 2H), 1.06 (s, 2H). 406 97% 4-43 [00357] .sup.1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 11.70 (s, 1H), 8.98 (s, 1H), 8.06 (d, J = 9.0 Hz, 1H), 7.49 (s, 1H), 7.43 (d, J = 7.4 Hz, 1H), 7.20 (s, 1H), 7.00 (d, J = 6.8 Hz, 1H), 6.91 (s, 1H), 4.49 (s, 3H), 2.84 (s, 3H), 1.46 (s, 9H), 1.30 (s, 2H), 1.13 (s, 2H). 506 98% 4-44 [00358] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 12.92 (s, 1H), 8.92 (s, 1H), 8.79 (s, 1H), 8.07 (s, 1H), 7.99 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.3 Hz, 1H), 7.37 (d, J = 8.0 Hz, 1H), 4.40 (s, 1H), 2.62 (s, 3H), 1.25 (d, J = 5.7 Hz, 2H), 1.10 (s, 2H). 422 100% 4-45 [00359] .sup.1H NMR (400 MHz, DMSO) δ 11.65 (s, 1H), 9.57 (s, 1H), 8.82 (s, 1H), 7.93 (d, J = 8.3 Hz, 1H), 7.71 (d, J = 5.5 Hz, 1H), 7.19 (s, 1H), 7.09 (s, 1H), 7.00 (s, 1H), 4.32 (s, 1H), 2.72 (d, J = 18.9 Hz, 3H), 1.89-1.77 (m, 5H), 1.65 (s, 1H), 1.45 (d, J = 10.5 Hz, 2H), 1.35-1.16 (m, 6H), 0.97 (s, 2H). 502 89% 4-46 [00360] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.94 (s, 1H), 9.39 (s, 1H), 8.92 (s, 1H), 8.00 (d, J = 7.8 Hz, 1H), 7.72 (s, 1H), 7.28 (s, 1H), 7.15 (s, 1H), 6.81 (s, 1H), 4.43 (s, 1H), 4.27-4.13 (m, 2H), 2.79 (s, 3H), 2.33 (s, 1H), 2.17 (s, 1H), 1.59 (d, J = 14.2 Hz, 2H), 1.26 (s, 5H), 1.07 (s, 2H), 0.85 (dd, J = 54.3, 14.6 Hz, 14H). 588 86.3% 4-47 [00361] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.74 (s, 1H), 10.60 (s, 1H), 9.30 (s, 1H), 8.92 (s, 1H), 8.61 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 7.9 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.59 (d, J = 6.7 Hz, 1H), 7.37 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 6.97 (s, 1H), 4.43 (s, 1H), 2.79 (s, 3H), 1.25 (s, 2H), 1.07 (s, 2H). 565 96% 4-48 [00362] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.74 (s, 1H), 9.76 (s, 1H), 8.93 (s, 1H), 8.01 (d, J = 8.7 Hz, 1H), 7.29 (d, J = 6.6 Hz, 1H), 7.23-7.01 (m, 3H), 4.43 (s, 1H), 3.49 (d, J = 14.6 Hz, 1H), 3.06 (d, J = 14.8 Hz, 1H), 2.37 (dd, J = 27.4, 15.5 Hz, 2H), 2.04 (s, 1H), 1.91 (d, J = 17.7 Hz, 2H), 1.51 (d, J = 11.3 Hz, 1H), 1.41 (d, J = 10.3 Hz, 1H), 1.25 (s, 2H), 1.09 (d, J = 11.8 Hz, 3H), 0.98 (s, 2H), 0.77 (d, J = 22.2 Hz, 3H). 606 88% 4-49 [00363] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 11.58 (s, 1H), 10.29 (s, 1H), 8.91 (s, 1H), 8.40 (s, 1H), 8.05 (dd, J = 15.6, 8.6 Hz, 2H), 7.97 (s, 2H), 7.83 (d, J = 8.2 Hz, 1H), 7.72-7.56 (m, 2H), 7.18 (d, J = 8.0 Hz, 1H), 7.04 (t, J = 8.0 Hz, 1H), 6.98 (d, J = 7.5 Hz, 1H), 6.81 (s, 1H), 4.35 (s, 1H), 2.54 (s, 3H), 1.23 (s, 2H), 1.04 (s, 2H). 582 100% 4-50 [00364] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.68 (s, 1H), 10.26 (s, 1H), 8.92 (s, 1H), 8.00 (s, 1H), 7.74 (s, 1H), 7.29 (s, 1H), 7.19 (s, 1H), 7.03 (s, 1H), 6.93 (s, 2H), 4.43 (s, 1H), 2.79 (s, 3H), 2.31 (s, 6H), 2.10 (s, 3H), 1.24 (s, 2H), 1.07 (s, 2H). 538 90% 4-51 [00365] .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.62 (s, 1H), 10.08 (s, 1H), 8.93 (s, 1H), 8.00 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 8.6 Hz, 2H), 7.18 (d, J = 7.7 Hz, 2H), 7.02 (d, J = 18.7 Hz, 2H), 4.44 (s, 1H), 3.63 (s, 3H), 2.76 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H). 536 99% 4-52 [00366] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 11.68 (s, 1H), 9.29 (s, 1H), 8.93 (s, 1H), 8.81 (s, 1H), 8.31 (s, 1H), 8.03 (d, J = 8.9 Hz, 1H), 7.15 (s, 2H), 7.02 (dd, J = 24.0, 8.3 Hz, 2H), 6.94 (s, 1H), 4.44 (s, 1H), 3.91 (s, 3H), 2.80 (s, 3H), 1.25 (d, J = 15.5 Hz, 2H), 1.08 (s, 2H). 575 96% 4-53 [00367] embedded image .sup.1H NMR 400 MHz, DMSO) δ 14.71 (s, 1H), 11.72 (s, 1H), 10.04 (s, 1H), 8.94 (s, 1H), 8.02 (d, J = 10.3 Hz, 1H), 7.71 (d, J = 7.0 Hz, 1H), 7.24 (s, 1H), 7.15 (d, J = 7.3 Hz, 1H), 7.04 (s, 1H), 4.44 (s, 1H), 3.98 (s, 2H), 3.76 (s, 2H), 3.43 (s, 2H), 3.07 (d, J = 24.3 Hz, 4H), 2.78 (s, 3H), 2.69 (d, J = 10.9 Hz, 1H), 1.26 (s, 2H), 1.08 (s, 2H). 533 99% 4-54 [00368] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.72 (s, 1H), 10.03 (s, 1H), 8.94 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.70 (s, 1H), 7.24 (s, 1H), 7.14 (s, 1H), 7.03 (s, 1H), 5.33 (s, 1H), 4.43 (s, 1H), 4.03 (s, 2H), 3.03 (s, 4H), 2.78 (s, 3H), 2.00 (d, J = 7.6 Hz, 2H), 1.24 (s, 9H), 1.08 (s, 2H), 0.85 (s, 2H). 632 96% 4-55 [00369] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.72 (s, 1H), 10.04 (s, 1H), 9.57 (s, 1H), 8.94 (s, 1H), 8.02 (d, J = 8.9 Hz, 1H), 7.71 (d, J = 7.8 Hz, 1H), 7.26 (d, J = 7.6 Hz, 1H), 7.15 (d, J = 9.1 Hz, 1H), 7.03 (d, J = 9.6 Hz, 1H), 4.44 (s, 1H), 2.99 (s, 1H), 2.82 (s, 3H), 2.78 (s, 2H), 2.54 (s, 2H), 1.26 (s, 2H), 1.08 (s, 2H). 491 91% 4-56 [00370] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.87 (s, 1H), 10.45 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.47 (d, J = 7.2 Hz, 1H), 7.23 (s, 1H), 7.07 (d, J = 7.9 Hz, 1H), 6.68 (s, 1H), 4.42 (s, 1H), 2.78 (s, 3H), 2.68 (s, 3H), 1.26 (s, 2H), 1.08 (s, 2H). 490 96% 4-57 [00371] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 11.75 (s, 1H), 9.64 (s, 1H), 8.92 (s, 1H), 7.99 (d, J = 8.7 Hz, 1H), 7.83 (s, 1H), 7.70 (s, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.18 (d, J = 8.6 Hz, 1H), 4.48 (s, 2H), 4.40 (s, 1H), 2.72 (d, J = 27.2 Hz, 7H), 2.62 (s, 3H), 1.25 (s, 2H), 1.08 (s, 2H). M—(Me).sub.2N 389 100% 4-58 [00372] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.79 (s, 1H), 9.84 (s, 1H), 8.92 (s, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.77 (d, J = 8.1 Hz, 1H), 7.62 (s, 1H), 7.56 (s, 1H), 7.20 (d, J = 8.0 Hz, 1H), 6.63 (s, 1H), 4.64 (s, 2H), 4.39 (s, 1H), 3.57 (s, 2H), 2.88 (s, 6H), 2.65 (d, J = 22.8 Hz, 3H), 1.24 (s, 2H), 1.08 (s, 2H). 448 100% 4-59 [00373] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 11.62 (s, 1H), 9.68 (s, 1H), 8.92 (s, 1H), 7.99 (s, 1H), 6.95 (s, 2H), 6.77 (s, 1H), 6.46 (s, 1H), 4.43 (s, 1H), 2.80 (s, 3H), 1.27 (s, 2H), 1.07 (s, 4H). 393 99% 4-60 [00374] .sup.1H NMR (400 MHz, DMSO) δ 14.77 (s, 1H), 11.29 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 9.0 Hz, 1H), 7.13 (s, 1H), 6.97 (s, 1H), 6.61 (s, 1H), 4.42 (s, 1H), 3.80 (d, J = 13.7 Hz, 7H), 2.78 (s, 3H), 1.26 (s, 2H), 1.06 (s, 2H). 437 99% 4-61 [00375] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 11.29 (s, 1H), 8.91 (s, 1H), 8.81 (s, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.27 (d, J = 8.8 Hz, 1H), 6.93 (s, 1H), 6.71 (d, J = 8.4 Hz, 1H), 6.53 (s, 1H), 4.41 (s, 2H), 2.77 (s, 3H), 1.25 (s, 2H), 1.06 (s, 2H). 393 98% 4-62 [00376] .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 11.50 (s, 1H), 9.79 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.07 (d, J = 6.7 Hz, 1H), 6.86 (s, 1H), 6.60 (s, 2H), 4.41 (s, 1H), 2.76 (s, 3H), 1.23 (s, 2H), 1.08 (s, 2H). 393 100% 4-63 [00377] embedded image .sup.1H NMR (400 MHz, DMSO) δ 12.18 (s, 1H), 10.24 (s, 1H), 8.93 (s, 1H), 8.04 (d, J = 8.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.78 (d, J = 7.0 Hz, 1H), 7.46 (d, J = 7.3 Hz, 2H), 7.35 (s, 1H), 4.43 (s, 1H), 2.77 (s, 3H), 1.27 (s, 2H), 1.09 (s, 2H). 405 85% 4-64 [00378] .sup.1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 13.88 (s, 1H), 8.94 (s, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.01 (dd, J = 14.5, 7.6 Hz, 2H), 7.62 (s, 1H), 4.44 (s, 1H), 2.71 (s, 3H), 1.24 (s, 2H), 1.08 (s, 2H). 447 89% 4-65 [00379] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.44 (s, 1H), 11.53 (s, 1H), 8.84 (s, 1H), 8.16 (d, J = 9.1 Hz, 1H), 7.95 (d, J = 7.2 Hz, 1H), 7.69 (d, J = 9.7 Hz, 1H), 7.58 (t, J = 10.6 Hz, 1H), 7.42 (d, J = 7.4 Hz, 2H), 7.16 (t, J = 7.5 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H), 6.62 (s, 1H), 5.77 (s, 1H), 1.77 (d, J = 17.9 Hz, 3H). 449 94.06% 4-66 [00380] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.79 (s, 1H), 11.42 (s, 1H), 8.70 (s, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.25 (s, 1H), 6.96 (d, J = 8.1 Hz, 1H), 6.86 (d, J = 7.7 Hz, 1H), 6.61 (s, 1H), 4.23 (s, 1H), 2.70 (s, 3H), 1.06 (s, 2H), 0.81 (s, 2H). 359 91.2% 4-67 [00381] embedded image .sup.1H NMR (400 MHz, DMSO) δ 11.76 (s, 1H), 8.71 (s, 1H), 8.16 (d, J = 4.8 Hz, 1H), 7.81 (d, J = 8.8 Hz, 1H), 7.36 (s, 1H), 5.94 (dd, J = 3.4, 1.8 Hz, 1H), 5.10 (s, 1H), 4.22-4.08 (m, 1H), 2.33 (s, 3H), 1.09-0.88 (m, 4H). 378 97% 4-68 [00382] .sup.1H NMR (400 MHz, DMSO) δ 12.33 (s, 1H), 8.92 (s, 1H), 8.35 (d, J = 4.4 Hz, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.87 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.21 (dd, J = 7.7, 4.0 Hz, 1H), 4.47-4.34 (m, 2H), 2.69 (s, 3H), 1.28 (d, J = 6.6 Hz, 2H), 1.10 (s, 2H). 378 98% 4-69 [00383] embedded image .sup.1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 8.39 (t, J = 3.1 Hz, 1H), 8.08 (t, J = 9.0 Hz, 2H), 7.22 (dd, J = 8.1, 4.1 Hz, 1H), 6.74 (d, J = 2.9 Hz, 1H), 4.48-4.36 (m, 1H), 2.67 (s, 3H), 1.26 (d, J = 7.0 Hz, 4H), 1.09 (s, 4H). 392 98% 4-70 [00384] .sup.1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 8.39 (t, J = 3.1 Hz, 1H), 8.07 (t, J = 9.0 Hz, 1H), 7.21 (dt, J = 7.7, 3.7 Hz, 1H), 6.74 (d, J = 2.9 Hz, 1H), 4.50-4.32 (m, 1H), 2.67 (s, 3H), 1.33-1.19 (d, J = 7.0 Hz, 2H), 1.09 (s, 2H). 392 96% 4-71 [00385] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 11.96 (s, 1H), 8.92(s, 1H), 8.24 (s, 1H), 8.06 (s, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.61 (t, J = 2.8 Hz, 1H), 6.57 (s, 1H), 4.59-4.15 (dm, 1H), 2.64 (s, 3H), 1.26 (d, J = 6.8 Hz, 2H), 1.09 (m, 2H). 378 98% 4-72 [00386] .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 13.15 (s, 1H), 8.93 (s, 1H), 8.27 (d, J = 6.1 Hz, 1H), 8.01 (d, J = 8.8 Hz, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.19 (t, J = 7.1 Hz, 1H), 6.88 (s, 1H), 4.49-4.33 (m, 1H), 2.77 (s, 3H), 1.39-1.21 (d, J = 7.0 Hz, 2H), 1.15- 1.01 (m, 2H). 394 98% 4-73 [00387] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 12.94 (s, 1H), 8.93 (s, 1H), 8.72 (s, 1H), 8.65 (s, 1H), 8.04 (d, J = 8.7 Hz, 1H), 6.93 (s, 1H), 4.53-4.29 (m, 1H), 2.77 (s, 3H), 1.32-1.19 (m, 3H), 1.17- 0.95 (m, 2H). 403 92% 4-74 [00388] .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 13.00 (s, 1H), 8.94 (s, 1H), 8.53 (s, 7H), 8.04 (d, J = 8 Hz, 1H), 7.69 (dd, J = 4.4, 2.4 Hz, 1H), 7.01 (s, 6H), 4.58-4.31 (m, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.6 Hz, 15H), 1.18-1.01 (m, 16H). 403 92% 4-75 [00389] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.57(s, 1H), 13.95 (s, 1H), 8.94 (s, 1H), 8.58 (s, 2H), 8.09 (d, J = 8.7 Hz, 1H), 7.60-7.51 (m, 1H), 4.53-4.33 (m, 1H), 2.73 (s, 3H), 1.35-1.17 (m, 2H), 1.15-1.01 (m, 2H). 423 86% 4-76 [00390] .sup.1H NMR (400 MHz, DMSO) δ 13.25 (s, 1H), 8.99 (s, 1H), 8.36 (d, J = 5.9 Hz, 1H), 8.07 (d, J = 8.7 Hz, 1H), 7.95 (s, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.28 (t, J = 6.8 Hz, 1H), 4.54-4.44 (m, 1H), 2.76 (s, 3H), 1.34 (d, J = 6.8 Hz, 2H), 1.26-1.06 (m, 2H). 394 98% 4-77 [00391] embedded image .sup.1H NMR (400 MHz, DMSO) δ 12.56 (s, 1H), 8.93 (s, 1H), 8.38 (t, J = 3.6 Hz, 1H), 8.20 (d, J = 7.4 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 7.26 (dd, J = 8.0, 4.1 Hz, 1H), 6.83 (s, 1H), 4.57-4.33 (m, 1H), 2.78 (s, 3H), 1.35-1.19 (d, J = 6.9 Hz, 2H), 1.15-1.01 (s, 2H). 378 98% 4-78 [00392] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 12.47 (s, 1H), 11.98 (s, 1H), 8.91(s, 1H), 7.95 (m, 2H), 6.76 (s, 1H), 4.51-4.36 (m, 1H), 2.78 (s, 3H), 1.26 (d, J = 6.9 Hz, 2H), 1.17-1.01 (m, 2H). 395 95% 4-79 [00393] .sup.1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 13.19 (d, J = 8.5 Hz, 1H), 9.29 (d, J = 2.9 Hz, 1H), 9.02 (d, J = 2.4 Hz, 1H), 8.94 (s, 1H), 8.05 (d, J = 8.8 Hz, 1H), 7.06 (s, 1H), 4.49-4.35 (m, 1H), 2.77 (s, 3H), 1.26 (d, J = 7.2 Hz, 2H), 1.13-0.99 (s, 2H). 379 98% 4-80 [00394] embedded image .sup.1H NMR (400 MHz, DMSO) δ 15.167 (s, 1H), 14.59 (s, 1H), 13.80 (s, 1H), 9.32 (s, 1H), 8.96 (d, J = 2.3 Hz, 1H), 8.40 (d, J = 6.1 Hz, 1H), 8.25 (d, J = 6.0 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 7.27 (s, 1H), 4.51- 4.39 (m, 1H), 2.76 (m 3H), 1.29-1.17 (d, J = 7.0 Hz, 2H), 1.17-0.97 (m, 2H). 378 85% 4-81 [00395] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.56 (s, 1H), 13.05 (s, 1H), 8.95 (s, 1H), 8.68 (s, 1H), 8.08 (d, J = 9.1 Hz, 1H), 7.62 (s, 1H), 7.12 (s, 1H), 4.51-4.36 (m, 1H), 2.76 (s, 3H), 1.33-1.19 (d, J = 7.1 Hz, 2H), 1.13-1.05 (s, 2H). 378 85% 4-82 [00396] .sup.1H NMR (400 MHz, DMSO) δ 14.88 (s, 1H), 14.57 (s, 1H), 13.46 (s, 1H), 9.41 (s, 1H), 8.96 (s, 1H), 8.52 (d, J = 6.5 Hz, 1H), 8.21-7.93 (m, 2H), 7.38 (s, 1H), 4.53-4.29 (m, 1H), 2.77 (s, 3H), 1.35- 1.17 (d, J = 6.7 Hz, 2H), 1.19-1.03 (s, 2H). 378 98% 4-83 [00397] embedded image 421 90% 4-84 [00398] 421 98% 4-85 [00399] 482 93% 4-86 [00400] .sup.1H NMR (400 MHz, DMSO) δ 14.60 (s, 1H), 10.06 (s, 1H), 8.81 (s, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.21 (s, 1H), 7.05 (d, J = 8.1 Hz, 1H), 6.80 (d, J = 8.1 Hz, 1H), 4.36 (m, 1H), 3.08 (s, 2H), 1.06 (m, 4H). 392 95% 4-87 [00401] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 8.91 (s, 1H), 8.03 (d, J = 9.3 Hz, 1H), 7.80 (d, J =7.7 Hz, 1H), 7.73 (d, J = 8.3 Hz, 1H), 7.56-7.22 (m, 3H), 4.57-4.32 (m, 1H), 2.84 (s, 3H), 1.27 (m, 2H), 1.06 (m, 2H). 378 98% 488 [00402] .sup.1H NMR (400 MHz, DMSO) δ 14.50 (s, 1H), 13.22 (s, 1H), 8.84 (s, 1H), 8.10-7.80 (m, 2H), 7.74-7.58 (s, 1H), 7.49 (s, 1H), 4.38 (m, 1H), 2.78 (s, 3H), 1.30-1.12 (m, 2H), 1.00 (m, 2H). 422 98% 4-89 [00403] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.56 (s, 1H), 8.93 (s, 1H), 8.02 (d, J = 9.2 Hz, 1H), 7.76 (dd, J = 8.8, 3.5 Hz, 1H), 7.61 (d, J = 8.6 Hz, 1H), 7.41 (s, 1H), 7.28 (t, J = 9.3 Hz, 1H), 4.43 (m, 1H), 2.82 (s, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.05 (s, 2H). 396 98% 4-90 [00404] .sup.1H NMR (400 MHz, DMSO) δ 8.88 (s, 1H), 7.95 (d, J = 8.9 Hz, 1H), 7.76 (s, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.36 (s, 1H), 7.20 (t, J = 9.0 Hz, 1H), 4.35 (m, 1H), 2.76 (s, 3H), 1.30-1.09 (m, 3H), 0.96 (s, 2H). 396 98% 4-91 [00405] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.57 (s, 1H), 8.86 (s, 1H), 7.96 (m, 3H), 7.59 (s, 1H), 7.41 (d, J = 5.1 Hz, 2H), 4.35 (m, 1H), 2.72 (s, 3H), 1.17 (m, 2H), 1.00 (m, 2H). 394 96% 4-92 [00406] .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.86 (s, 1H), 8.08 (d, J = 7.6 Hz, 1H), 7.97 (m, 2H), 7.36 (m, 3H), 4.32 (m, 1H), 2.57 (s, 3H), 1.03 (m, 4H). 394 98% 4-93 [00407] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.51 (s, 1H), 8.92 (ss, 1H), 8.32 (d, J = 8.1 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 8.05 (t, J = 13.1 Hz, 1H), 7.90 (s, 1H), 7.70 (t, J = 8.2 Hz, 1H), 4.45 (m, 1H), 2.86 (s, 3H), 1.26 (t, J = 11.6 Hz, 2H), 1.10 (d, J = 21.6 Hz, 2H). 423 98% 4-94 [00408] .sup.1H NMR (400 MHz, DMSO) δ 14.46 (s, 1H), 8.69 (s, 1H), 8.14 (s, 1H), 7.75 (d, J = 9.2 Hz, 1H), 7.52 (dd, J = 8.8, 3.5 Hz, 1H), 7.20-7.11 (m, 3H), 4.43 (s, 1H), 2.64 (s, 3H), 1.26 (d, J = 6.4 Hz, 3H), 1.05 (s, 2H). 378 98% 4-95 [00409] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.94 (s, 1H), 8.05 (d, J = 9.3 Hz, 1H), 7.64 (d, J =2.9 Hz, 1H), 7.54 (s, 1H), 7.36 (d, J = 6.6 Hz, 2H), 4.44 (m, 1H), 2.85 (s, 3H), 1.34-1.19 (m, 2H), 1.06 (s, 2H). 396 96% 4-96 [00410] .sup.1H NMR (400 MHz, DMSO) δ 8.91 (s, 1H), 8.38 (s, 1H), 8.04 (d, J = 9.2 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.5 Hz, 1H), 7.55 (s, 1H), 4.44 (m, 1H), 2.83 (s, 3H), 1.35-1.18 (m, 2H), 1.06 (m, 2H). 403 98% 4-97 [00411] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.56 (s, 1H), 8.94 (s, 1H), 8.04 (d, J = 9.1 Hz, 1H), 7.95-7.77 (m, 2H), 7.53-7.33 (m, 2H), 4.45 (m, 1H), 2.83 (s, 3H), 1.27 (d, J = 6.3 Hz, 2H), 1.05 (s, 2H). 462 98% 4-98 [00412] .sup.1H NMR (400 MHz, DMSO) δ 14.61 (s, 1H), 8.86 (s, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.43 (s, 1H), 7.03 (t, J = 8.1 Hz, 1H), 6.77 (d, J = 7.4 Hz, 1H), 6.39 (d, J = 7.1 Hz, 1H), 4.38 (m, 1H), 2.77 (s, 3H), 1.19 (m, 2H), 0.98 (m, 1H). 393 96%

TABLE-US-00005 TABLE 5 [00413] embedded image Com- pound MS No. R.sup.3 = R.sup.2 = R.sup.1 = NMR (MH.sup.+) HPLC 5-1 [00414] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 10.91 (s, 1H), 8.89 (s, 1H), 7.94 (d, J = 6.60 Hz, 1H), 7.13-6.90 (m, 3H), 4.67 (s, 2H), 4.38 (s, 1H), 2.62 (s, 3H), 1.23 (d, J = 5.80 Hz, 2H), 1.04 (s, 2H). 409 97% 5-2 [00415] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 10.78 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 8.72 Hz, 1H), 7.41 (s, 1H), 7.22 (d, J = 8.03 Hz, 1H), 7.13 (d, J = 8.17 Hz, 1H), 4.38 (s, 1H), 3.57 (s, 2H), 2.62 (s, 3H), 1.24 (d, J = 6.14 Hz, 2H), 1.05 (s, 2H). 425 98% 5-3 [00416] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 10.64 (s, 1H), 8.98 (s, 1H), 8.05 (d, J = 8.72 Hz, 1H), 7.90 (s, 1H), 7.62 (s, 1H), 4.92 (s, 2H), 4.46 (s, 1H), 2.71 (s, 3H), 1.30 (s, 3H), 1.15 (s, 2H). 454 97% 5-4 [00417] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 11.39 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.72 Hz, 1H), 7.57 (s, 1H), 7.43 (s, 1H), 4.75 (s, 2H), 4.39 (s, 1H), 2.62 (s, 3H), 1.23 (d, J = 5.26 Hz, 2H), 1.06 (s, 2H). 434 98% 5-5 [00418] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 10.94 (s, 1H), 8.80 (s, 1H), 7.90 (s, 1H), 7.11 (d, J = 26.18 Hz, 2H), 4.67 (s, 2H), 1.15 (s, 4H). 425 98% 5-6 [00419] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 10.87 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.58 Hz, 1H), 7.14 (d, J = 8.35 Hz, 1H), 6.97 (d, J = 8.15 Hz, 1H), 6.89 (s, 1H), 4.69 (s, 2H), 4.39 (s, 1H), 2.62 (s, 3H), 1.23 (s, 2H), 1.04 (s, 2H). 409 98% 5-9 [00420] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 10.28 (s, 1H), 8.90 (s, 1H), 7.94 (d, J = 8.20 Hz, 1H), 7.23 (s, 1H), 7.17 (s, 1H), 7.03 (s, 1H), 4.38 (s, 2H), 2.97 (s, 2H), 2.63 (s, 2H), 1.23 (s, 2H), 1.04 (s, 2H). 407 85% 5-10 [00421] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 11.47 (s, 1H), 11.39 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.50 Hz, 1H), 7.89 (s, 1H), 7.70 (d, J = 8.10 Hz, 1H), 7.35 (d, J = 8.11 Hz, 1H), 4.40 (s, 1H), 3.49 (d, J = 87.04 Hz, 2H), 2.62 (s, 3H), 1.23 (s, 2H), 1.08 (s, 3H). 422 98% 5-11 [00422] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 11.96 (s, 1H), 11.63 (s, 1H), 8.92 (s, 1H), 8.69 (s, 1H), 8.34 (s, 1H), 8.00 (d, J = 8.65 Hz, 1H), 4.41 (s, 1H), 2.61 (d, J = 29.62 Hz, 3H), 1.24 (d, J = 5.11 Hz, 2H), 1.09 (s, 2H). 423 99% 5-12 [00423] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 12.44- 11.74 (m, 2H), 8.91 (s, 1H), 7.98 (d, J = 8.01 Hz, 1H), 7.53-7.03 (m, 3H), 4.39 (s, 1H), 2.61 (s, 3H), 1.20 (d, J = 26.27 Hz, 3H), 1.05 (s, 2H). 422 96% 5-13 [00424] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.83 (s, 1H), 8.88 (s, 1H), 7.90 (s, 2H), 6.70 (s, 3H), 4.27 (d, J = 77.51 Hz, 4H), 2.60 (d, J = 25.07 Hz, 3H), 1.23 (s, 2H), 1.02 (s, 2H). 395 98% 5-14 [00425] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 8.76 (s, 1H), 7.83 (d, J = 9.18 Hz, 1H), 6.92-6.81 (m, 2H), 6.70 (d, J = 7.26 Hz, 1H), 6.19 (d, J = 22.26 Hz, 1H), 4.16 (s, 4H), 3.39 (s, 3H), 2.50 (s, 7H). 411 96% 5-15 [00426] embedded image 8-N Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.55 (s, 1H), 8.61 (s, 1H), 8.19 (d, J = 11.38 Hz, 1H), 7.55 (d, J = 8.31 Hz, 1H), 7.47 (s, 1H), 6.68 (s, 1H), 6.54 (d, J = 8.26 Hz, 1H), 4.00 (s, 2H), 3.73 (s, 1H), 1.15-0.91 (m, 5H). 382 94% 5-16 [00427] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.90 (s, 1H), 8.94 (s, 1H), 7.94 (d, J = 9.06 Hz, 1H), 6.95 (d, J = 8.81 Hz, 2H), 6.63 (d, J = 7.73 Hz, 1H), 6.14 (s, 1H), 4.43 (s, 1H), 3.31 (s, 2H), 2.79 (s, 2H), 2.70 (s, 3H), 1.90 (s, 2H), 1.30 (s, 2H), 1.08 (s, 2H). 393 94% 5-17 [00428] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.89 (s, 1H), 8.60 (s, 1H), 7.94 (d, J = 8.81 Hz, 1H), 7.67 (s, 1H), 7.10 (s, 1H), 4.38 (s, 1H), 4.27 (s, 2H), 3.63 (s, 2H), 2.66 (s, 3H), 1.24 (d, J = 5.67 Hz, 2H), 1.07 (s, 2H). 440 97% 5-18 [00429] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 10.19 (s, 1H), 8.89 (s, 1H), 7.91 (d, J = 8.74 Hz, 1H), 6.33 (s, 1H), 6.24 (s, 1H), 4.57 (s, 2H), 4.38 (s, 2H), 2.64 (s, 3H), 1.23 (d, J = 5.42 Hz, 3H), 1.03 (s, 2H). 424 97% 5-19 [00430] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.88 (s, 1H), 7.91 (s, 1H), 6.29 (s, 1H), 6.18 (s, 1H), 4.37 (s, 2H), 4.18 (s, 3H), 3.10 (s, 2H), 2.65 (d, J = 16.81 Hz, 6H), 1.23 (s, 3H), 1.03 (s, 2H). 424 97% 5-20 [00431] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.97 (s, 1H), 8.01 (d, J = 9.26 Hz, 1H), 7.85-7.65 (m, 2H), 7.64-7.40 (m, 1H), 7.36 (s, 1H), 4.46 (s, 1H), 4.32 (s, 3H), 3.63 (s, 3H), 2.74 (s, 3H), 1.30 (d, J = 5.75 Hz, 2H), 1.11 (s, 2H). 396 98% 5-21 [00432] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.85 (d, J = 23.76 Hz, 1H), 7.87 (t, J = 19.93 Hz, 1H), 7.17 (s, 1H), 6.99 (d, J = 9.29 Hz, 2H), 4.37 (s, 1H), 4.20 (s, 2H), 3.59 (s, 1H), 3.44 (s, 2H), 2.63 (s, 3H), 1.24 (s, 2H), 1.07 (d, J = 23.80 Hz, 2H). 420 95% 5-22 [00433] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.78 (s, 1H), 7.87 (d, J = 9.24 Hz, 1H), 7.26 (d, J = 10.63 Hz, 1H), 7.11 (s, 1H), 7.04 (s, 1H), 4.20 (s, 3H), 2.00 (dd, J = 7.56, 15.22 Hz, 1H), 1.21 (d, J = 14.05 Hz, 4H). 436 98% 5-24 [00434] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.77 (s, 1H), 7.87 (d, J = 9.25 Hz, 1H), 7.75 (s, 1H), 7.20 (s, 1H), 7.14 (s, 1H), 4.17 (s, 3H), 3.47 (s, 3H), 1.32-1.05 (m, 8H). 412 96% 5-25 [00435] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.82 (s, 1H), 10.92 (s, 1H), 10.86 (s, 1H), 8.96 (s, 1H), 7.98 (t, J = 12.31 Hz, 1H), 7.15 (d, J = 7.60 Hz, 1H), 7.00 (d, J = 8.89 Hz, 2H), 4.44 (s, 1H), 2.67 (s, 3H), 1.28 (s, 2H), 1.12 (s, 2H). 394 98% 5-26 [00436] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 10.94 (s, 1H), 10.87 (s, 1H), 8.86 (s, 1H), 7.97 (d, J = 8.82 Hz, 1H), 7.17 (d, J = 7.41 Hz, 3H), 4.29 (s, 1H), 1.23 (s, 4H). 410 98% 5-27 [00437] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.95 (s, 1H), 7.96 (d, J = 8.75 Hz, 1H), 6.96 (d, J = 10.17 Hz, 1H), 6.92 (d, J = 8.04 Hz, 1H), 6.72 (d, J = 7.83 Hz, 1H), 4.44 (s, 1H), 3.63 (s, 2H), 3.09 (s, 2H), 2.70 (s, 3H), 1.30 (d, J = 5.29 Hz, 2H), 1.10 (s, 2H). 411 98% 5-28 [00438] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 8.89 (s, 1H), 7.94 (d, J = 8.48 Hz, 1H), 7.53 (s, 1H), 7.44 (s, 1H), 7.33 (d, J = 8.57 Hz, 1H), 6.94 (d, J = 8.45 Hz, 1H), 4.39 (s, 1H), 3.80 (s, 2H), 3.48 (s, 2H), 2.64 (s, 3H), 1.23 (s, 2H), 1.06 (s, 2H). 443 98% 5-29 [00439] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 10.84 (s, 1H), 8.83 (s, 1H), 7.86 (d, J = 8.65 Hz, 1H), 6.52 (s, 2H), 4.38 (s, 2H), 4.31 (s, 1H), 3.89 (s, 2H), 2.54 (s, 3H), 1.16 (s, 2H), 1.00 (s, 2H). 436 98% 5-30 [00440] OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 10.91 (s, 1H), 8.79 (s, 1H), 7.88 (d, J = 9.15 Hz, 1H), 6.75 (d, J = 14.51 Hz, 2H), 4.45 (t, J = 4.51 Hz, 2H), 4.27- 4.16 (m, 1H), 3.96 (t, J = 4.53 Hz, 2H), 1.17 (d, J = 7.20 Hz, 4H). 452 99% 5-31 [00441] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 7.95 (d, J = 8.62 Hz, 1H), 6.79 (dd, J = 7.23, 14.68 Hz, 3H), 4.43 (s, 1H), 4.23 (d, J = 10.57 Hz, 1H), 4.06 (d, J = 10.42 Hz, 1H), 3.60-3.41 (m, 3H), 2.70 (s, 3H), 1.30 (d, J = 5.98 Hz, 2H), 1.09 (s, 2H). 425 99% 5-32 [00442] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.95 (s, 1H), 7.98 (d, J = 8.04 Hz, 1H), 7.09 (s, 1H), 6.96 (s, 2H), 4.44 (s, 1H), 4.15 (s, 2H), 3.29 (s, 3H), 2.69 (s, 3H), 2.02 (s, 2H), 1.30 (s, 2H), 1.10 (s, 2H). 409 99% 5-33 [00443] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.76 (s, 1H), 7.77 (d, J = 8.81 Hz, 1H), 6.59 (s, 3H), 4.25 (s, 1H), 4.04 (s, 2H), 3.27 (d, J = 11.94 Hz, 1H), 2.96-2.79 (m, 1H), 2.52 (s, 3H), 1.18 (t, J = 8.54 Hz, 3H), 1.12 (d, J = 5.48 Hz, 2H), 0.91 (s, 2H). 409 98% 5-34 [00444] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.71 (s, 1H), 7.72 (d, J = 8.62 Hz, 1H), 6.54 (s, 3H), 4.20 (s, 2H), 4.03 (d, J = 10.38 Hz, 2H), 3.52 (t, J = 8.97 Hz, 1H), 3.31 (s, 1H), 2.46 (s, 3H), 1.07 (d, J = 5.70 Hz, 2H), 0.96 (d, J = 4.88 Hz, 3H), 0.86 (s, 2H). 409 98% 5-35 [00445] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 10.57 (s, 1H), 8.89 (s, 1H), 7.93 (d, J = 8.73 Hz, 1H), 7.48 (d, J = 52.24 Hz, 1H), 6.96 (d, J = 7.83 Hz, 1H), 6.80 (s, 1H), 6.74 (d, J = 7.83 Hz, 1H), 4.38 (s, 1H), 3.76 (d, J = 12.76 Hz, 1H), 2.63 (s, 3H), 2.07 (s, 1H), 1.85 (s, 1H), 1.66 (s, 1H), 1.58-1.37 (m, 3H), 1.23 (d, J = 6.52 Hz, 2H), 1.06 (s, 2H). 462 98% 5-36 [00446] embedded image Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 10.92 (s, 1H), 10.70 (s, 1H), 8.92 (s, 1H), 8.09 (d, J = 8.43 Hz, 1H), 7.82 (s, 1H), 7.04 (d, J = 22.18 Hz, 1H), 6.64 (d, J = 10.90 Hz, 2H), 4.52-4.28 (m, 3H), 4.01-3.82 (m, 2H), 1.20 (t, J = 10.03 Hz, 2H), 1.12 (d, J = 3.28 Hz, 2H). 456 97% 5-37 [00447] embedded image 8-Me [00448] .sup.1H NMR (400 MHz, DMSO) δ 8.85 (d, J = 3.12 Hz, 1H), 7.90 (d, J = 8.88 Hz, 1H), 6.71 (d, J = 5.48 Hz, 3H), 5.23 (d, J = 3.10 Hz, 1H), 5.07 (d, J = 2.78 Hz, 1H), 4.42-4.27 (m, 1H), 4.22-4.12 (m, 2H), 2.55 (s, 3H), 1.74 (ddd, J = 8.97, 14.93, 17.91 Hz, 1H), 1.62- 1.45 (m, 1H). 413 98% 5-38 [00449] embedded image 8-Me [00450] .sup.1H NMR (400 MHz, DMSO) δ 14.44 (d, J = 137.56 Hz, 2H), 10.82 (d, J = 68.59 Hz, 1H), 8.85 (t, J = 9.38 Hz, 1H), 7.93 (t, J = 10.51 Hz, 1H), 6.56 (t, J = 40.40 Hz, 2H), 4.44 (d, J = 4.54 Hz, 3H), 4.39-4.29 (m, 1H), 4.04-3.90 (m, 3H), 2.54 (s, 3H), 1.64 (m, 2H). 454 98% 5-39 [00451] embedded image Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.10 (d, J = 8.56 Hz, 1H), 7.69 (s, 1H), 7.18 (s, 1H), 4.41 (s, 2H), 4.23-4.19 (m, 3H), 3.51 (s, 2H), 1.22 (d, J = 6.34 Hz, 2H), 1.11 (s, 2H). 416 98% 5-40 [00452] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.68 Hz, 1H), 7.35 (s, 1H), 6.99 (s, 1H), 4.68 (d, J = 4.53 Hz, 2H), 4.58 (d, J = 4.64 Hz, 2H), 4.40 (dd, J = 3.32, 6.77 Hz, 1H), 2.61 (s, 3H), 1.24 (d, J = 6.14 Hz, 2H), 1.10 (s, 2H). 434 98% 5-41 [00453] embedded image 8-OMe [00454] .sup.1H NMR (400 MHz, DMSO) δ 14.59 (s, 1H), 10.91 (s, 1H), 8.82 (s, 1H), 7.89 (d, J = 9.04 Hz, 1H), 6.74 (d, J = 14.28 Hz, 2H), 5.08 (d, J = 64.31 Hz, 1H), 4.45 (s, 2H), 4.19 (s, 1H), 3.96 (s,2H), 1.80 (d, J = 26.47 Hz, 1H), 1.65 (dd, J = 7.14, 16.55 Hz, 1H). 470 98% 5-42 [00455] embedded image 8-OMe [00456] .sup.1H NMR (400 MHz, DMSO) δ 8.80 (s, 1H), 7.86 (d, J = 9.34 Hz, 1H), 6.87 (d, J = 8.16 Hz, 1H), 6.84 (s, 1H), 6.70 (d, J = 8.14 Hz, 1H), 5.18-4.96 (m, 1H), 4.17 (s, 3H), 3.36 (s, 2H), 1.84-1.58 (m, 2H). 429 98% 5-43 [00457] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.75-14.70 (s, 1H), 8.80-8.76 (s, 1H), 7.89-7.83 (d, J = 9.4 Hz, 1H), 6.92-6.86 (d, J = 11.4 Hz, 1H), 6.77-6.73 (s, 1H), 6.16-6.10 (s, 1H), 4.27-4.15 (s, 3H), 3.47-3.41 (s, 3H), 3.40-3.34 (q, J = 3.6 Hz, 2H), 1.20-1.09 (dd, J = 14.4, 5.5 Hz, 4H). 429 90% 5-44 [00458] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.77-14.65 (s, 1H), 8.80-8.76 (s, 1H), 7.89-7.83 (d, J = 9.3 Hz, 1H), 7.09-7.03 (t, J = 1.6 Hz, 1H), 6.90-6.84 (t, J = 1.6 Hz, 1H), 6.19-6.10 (s, 1H), 4.26-4.15 (m, 3H), 3.48-3.39 (s, 5H), 1.20-1.09 (ddd, J = 10.6, 5.5, 3.0 Hz, 4H). 445 100% 5-45 [00459] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.80-8.74 (s, 1H), 7.88-7.80 (d, J = 9.3 Hz, 1H), 6.81-6.71 (dd, J = 17.1, 2.1 Hz, 2H), 4.28-4.18 (tt, J = 7.2, 4.3 Hz, 1H), 4.18-4.12 (t, J = 4.2 Hz, 2H), 3.44-3.35 (m, 5H), 2.16-2.10 (s, 3H), 1.20-1.08 (m, 4H). 425 100% 5-46 [00460] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.79-8.75 (s, 1H), 7.87-7.81 (d, J = 9.3 Hz, 1H), 6.55-6.49 (s, 1H), 6.43-6.39 (s, 1H), 4.27-4.18 (s, 1H), 4.16-4.10 (t, J = 4.3 Hz, 2H), 3.33-3.5 (s, 2H), 2.57-2.52 (s, 3H), 1.20-1.09 (m, 4H). 426 96% 5-47 [00461] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.83-14.56 (s, 1H), 8.81-8.77 (s, 1H), 8.66-8.59 (m, 1H), 7.95-7.89 (d, J = 9.3 Hz, 1H), 7.89-7.84 (t, J = 1.7 Hz, 1H), 7.24- 7.19 (s, 1H), 4.30-4.18 (m, 3H), 3.67-3.60 (q, J = 3.8 Hz, 2H), 3.52-3.44 (s, 3H), 1.20-1.12 (td, J = 6.5, 5.8, 2.7 Hz, 4H). 456 100% 5-48 [00462] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ15.22-14.17 (m, 1H), 8.97-8.90 (s, 1H), 8.84-8.80 (s, 1H), 7.97-7.90 (d, J = 9.0 Hz, 1H), 7.51-7.47 (s, 1H), 7.07-7.02 (s, 1H), 4.69-4.57 (s, 4H), 4.28-4.18 (p, J = 5.7 Hz, 1H), 3.42-3.35 (s, 3H), 1.21-1.12 (d, J = 5.6 Hz, 4H). 436 100% 5-49 [00463] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.70-14.66 (s, 1H), 8.84-8.80 (s, 1H), 7.97-7.92 (d, J = 9.0 Hz, 1H), 7.78-7.74 (s, 1H), 7.08-7.04 (s, 1H), 5.00-4.94 (t, J = 4.9 Hz, 2H), 4.82-4.74 (t, J = 4.8 Hz, 2H), 4.27- 4.18 (p, J = 5.7 Hz, 1H), 3.43-3.38 (s, 3H), 1.21- 1.13 (d, J = 5.6 Hz, 4H). 437 85% 5-50 [00464] embedded image OMe Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.94 (s, 1H), 7.87 (d, J = 9.4 Hz, 1H), 6.89 (d, J = 11.4 Hz, 1H), 6.75 (s, 1H), 6.13 (s, 1H), 4.21 (m, 3H), 3.40 (s, 3H), 1.31-0.94 (m, 4H). 429 90% 5-51 [00465] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.88 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H), 6.91 (s, 1H), 6.72 (s, 1H), 6.07 (s, 1H), 4.48-4.30 (m, 1H), 4.20 (m, 2H), 3.43 (m, 2H), 2.70-2.56 (m, 3H), 1.24 (d, J = 4.0 Hz, 2H), 1.04 (s, 2H). 429 98% 5-52 [00466] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.5 (b, 1H), 8.91 (s, 1H), 8.86 (s, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.34 (s, 1H), 6.90 (s, 1H), 4.63 (s, 4H), 4.39 (mz, 1H), 2.61 (s, 3H), 1.24 (d, J = 4.6 Hz, 2H), 1.09 (s, 2H). 420 98% 5-53 [00467] Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.88 (s, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.22 (s, 1H), 6.76 (s, 1H), 4.44-4.28 (m, 1H), 4.15 (m, 2H), 3.43 (m, 2H), 2.65 (s, 3H), 1.24 (s, 2H), 1.04 (s, 2H). 521 97% 5-54 [00468] embedded image Me Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.89 (s, 1H), 7.91 (d, J = 7.8 Hz, 1H), 6.75 (d, J = 11.3 Hz, 1H), 6.59 (s, 1H), 4.37 (m, 1H), 4.22 (s, 2H), 3.39 (s, 2H), 2.65 (s, 3H), 1.22 (m, 2H), 1.00 (m, 2H). 413 97% 5-55 [00469] Cl Cyclopropyl .sup.1H NMR (400 MHz, DMSO) δ 8.90 (s, 1H), 8.05 (d, J = 8.6 Hz, 1H), 6.91-6.49 (m, 3H), 4.46-4.36 (m, 1H), 4.16 (m, 2H), 3.49 (m, 2H), 2.67 (s, 3H), 1.19 (t, J = 15.1 Hz, 2H), 1.09 (s, 2H). 415 98% 5-56 [00470] embedded image .sup.1H NMR (400 MHz, DMSO) δ 8.77 (s, 1H), 8.15 (d, J = 7.00 Hz, 1H), 7.24-7.02 (m, 2H), 6.78 (d, J = 8.23 Hz, 1H), 4.28-4.13 (m, 2H), 4.05-3.86 (m, 1H), 3.49-3.34 (m, 2H), 2.90 (d, J = 2.66 Hz, 3H), 1.44- 1.32 (m, 2H), 1.28-1.17 (m, 2H). 395 98% 5-57 [00471] .sup.1H NMR (400 MHz, DMSO) δ 15.13 (s, 1H), 8.84 (s, 1H), 8.16 (d, J = 8.2 Hz, 1H), 7.71 (s, 1H), 7.20-7.06 (m, 2H), 6.73 (t, J = 16.6 Hz, 1H), 4.30 (m, 1H), 4.22-4.17 (m, 2H), 3.68 (s, 2H), 3.44 (s, 3H), 1.43- 0.95 (m, 4H). 393 98%

TABLE-US-00006 TABLE 6 [00472] embedded image Com- pound MS No. R.sup.3 = R.sup.2 = NMR (MH.sup.+) HPLC 6-1 [00473] Me .sup.1H NMR (400 MHz, MeOD) δ 7.92 (s, 1H), 7.35 (m, 2H), 6.96 (s, 1H), 6.80 (m, 2H), 4.30-4.19 (m, 1H), 3.75 (s, 3H), 2.59 (s, 3H), 0.96 (m, 2H), 0.79 (m, 2H). 368 98% 6-2 [00474] Me .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 8.89 (s, 1H), 7.92 (d, J = 8.6 Hz, 1H), 7.50 (t, J = 7.7 Hz, 1H), 7.24 (dd, J = 15.3, 7.9 Hz, 2H), 7.14 (d, J = 7.4 Hz, 1H), 4.38 (m, 1H), 3.76 (s, 3H), 2.55 (s, 3H), 1.41-1.15 (m, 2H), 1.12- 0.96 (m, 2H). 482 90% 6-3 [00475] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 8.95 (s, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.57 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.3 Hz, 2H), 7.45-7.36 (m, 3H), 7.26 (d, J = 8.6 Hz, 2H), 5.25 (s, 2H), 4.54-4.32 (m, 1H), 2.67 (s, 3H), 1.30 (d, J = 6.2 Hz, 2H), 1.11 (s, 2H). 444 99% 6-4 [00476] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.90 (s, 1H), 7.94 (d, J = 8.5 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 4.38 (s, 1H), 3.84 (s, 3H), 2.61 (s, 3H), 1.23 (d, J = 6.2 Hz, 2H), 1.05 (s, 2H). 368 96% 6-5 [00477] Me .sup.1H NMR (400 MHz, DMSO) δ 14.63 (s, 1H), 8.88 (s, 1H), 7.92 (d, J = 8.9 Hz, 1H), 7.31 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 4.71 (dt, J = 12.0, 6.0 Hz, 1H), 4.38 (m, 1H), 2.58 (d, J = 26.0 Hz, 3H), 1.32 (d, J = 6.0 Hz, 6H), 1.23 (q, J = 6.9 Hz, 2H), 1.02 (s, 2H). 396 99% 6-6 [00478] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.8 Hz, 1H), 7.58 (s, 4H), 4.52-4.24 (m, 1H), 2.60 (s, 3H), 1.23 (q, J = 7.0 Hz, 2H), 1.15-1.01 (m, 2H). 422 99% 6-7 [00479] Me .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.91 (s, 1H), 7.99 (d, J = 8.8 Hz, 1H), 7.72 (t, J = 7.9 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.52-7.44 (m, 2H), 4.52-4.20 (m, 1H), 2.60 (s, 3H), 1.23 (d, J = 6.8 Hz, 2H), 1.08 (s, 2H). 422 99% 6-8 [00480] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.48 (s, 1H), 8.76 (s, 1H), 7.86 (d, J = 8.7 Hz, 1H), 7.60-7.52 (m, 1H), 7.45 (ddd, J = 10.9, 9.8, 4.6 Hz, 3H), 4.25 (dt, J = 10.7, 3.6 Hz, 1H), 2.43 (s, 3H), 1.06 (dq, J = 9.4, 7.1 Hz, 2H), 0.99-0.71 (m, 3H). 422 99% 6-9 [00481] Me .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 8.83 (s, 1H), 7.87 (d, J = 8.7 Hz, 1H), 6.61 (s, 2H), 4.33 (m, 1H), 3.74 (s, 6H), 3.68 (s, 3H), 2.57 (s, 3H), 1.18 (d, J = 6.4 Hz, 2H), 1.01 (s, 2H). 428 95% 6-10 [00482] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 8.88 (s, 1H), 7.90 (d, J = 8.6 Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 6.76 (d, J = 2.2 Hz, 1H), 6.70 (dd, J = 8.4, 2.3 Hz, 1H), 4.47- 4.28 (m, 1H), 3.85 (s, 3H), 3.75 (s, 3H), 2.55 (s, 3H), 1.21 (dd, J = 6.7, 4.5 Hz, 2H), 1.02 (dd, J = 10.3, 4.5 Hz, 2H). 398 96% 6-11 [00483] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.80 (s, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.32 (m, 2H), 7.16 (d, J = 7.2 Hz, 1H), 4.25 (s, 1H), 3.92 (s, 3H), 2.57 (s, 3H), 1.41-1.10 (m, 2H), 0.89 (m, 2H). 386 96% 6-12 [00484] Me .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 8.90 (s, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 6.97 (s, 1H), 6.93 (dd, J = 8.2, 1.7 Hz, 1H), 4.39 (tt, J = 7.1, 3.8 Hz, 1H), 3.84 (s, 3H), 3.79 (s, 3H), 2.63 (s, 3H), 1.24 (d, J = 6.8 Hz, 2H), 1.07 (s, 2H). 398 99% 6-13 [00485] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.90 (s, 1H), 7.94 (d, J = 8.7 Hz, 1H), 7.54 (s, 1H), 7.35 (dd, J = 18.3, 8.3 Hz, 2H), 4.39 (m, 1H), 3.95 (s, 3H), 2.62 (s, 3H), 1.23 (d, J = 5.8 Hz, 2H), 1.06 (s, 2H). 402 99% 6-14 [00486] Me .sup.1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.6 Hz, 1H), 7.72 (d, J = 8.6 Hz, 1H), 7.67 (s, 1H), 7.47 (d, J = 8.6 Hz, 1H), 4.40 (m, 1H), 3.99 (s, 3H), 2.61 (s, 3H), 1.24 (d, J = 5.6 Hz, 2H), 1.08 (s, 2H). 436 99% 6-15 [00487] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.89 (s, 1H), 7.93 (d, J = 8.5 Hz, 1H), 7.20 (d, J = 12.7 Hz, 2H), 7.11 (d, J = 8.0 Hz, 1H), 4.38 (m, 1H), 3.87 (s, 3H), 2.64 (s, 3H), 2.23 (s, 3H), 1.23 (m, 2H), 1.07 (m, 2H). 382 99% 6-16 [00488] Me .sup.1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 8.88 (s, 1H), 7.91 (d, J = 8.6 Hz, 1H), 6.95 (d, J = 7.4 Hz, 1H), 6.62 (s, 1H), 6.52 (d, J = 6.8 Hz, 1H), 4.94 (s, 2H), 4.39 (s, 1H), 3.84 (s, 3H), 2.63 (s, 3H), 1.23 (s, 2H), 1.03 (s, 2H). 383 95% 6-17 [00489] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 10.16 (s, 1H), 8.91 (s, 1H), 7.96 (d, J = 8.9 Hz, 2H), 7.26 (dd, J = 28.6, 8.1 Hz, 2H), 4.39 (m, 1H), 4.24 (m, 2H), 3.86 (m, 4H), 3.33 (m, 4H), 2.63 (s, 3H), 1.22 (d, J = 6.1 Hz, 2H), 1.05 (s, 2H). 510 90% 6-18 [00490] Me .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 9.12 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 9.0 Hz, 1H), 7.29 (s, 1H), 7.26 (s, 2H), 4.39 (m, 1H), 3.92 (s, 3H), 3.01 (s, 3H), 2.62 (s, 3H), 1.35-1.15 (m, 2H), 1.06 (m, 2H). 461 98% 6-19 [00491] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.76 (s, 1H), 8.89 (s, 1H), 8.14 (d, J = 14.8 Hz, 2H), 7.94 (d, J = 8.9 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H), 6.90 (d, J = 7.9 Hz, 1H), 6.28 (s, 2H), 4.39 (s, 1H), 3.93 (s, 3H), 2.65 (s, 3H), 1.19 (m, 2H), 1.04 (m, 2H). 426 98% 6-20 [00492] Me .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.56 (d, J = 6.9 Hz, 2H), 7.31 (d, J = 8.5 Hz, 1H), 4.39 (m, 1H), 3.91 (s, 3H), 2.62 (s, 3H), 1.52 (s, 9H), 1.24 (m, 2H), 1.07 (m, 2H). 468 98% 6-21 [00493] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.80 (s, 1H), 12.93 (s, 1H), 8.97 (s, 1H), 8.02 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.38 (d, J = 0.8 Hz, 1H), 4.39 (m, 1H), 3.67 (s, 3H), 2.62 (s, 3H), 1.52 (s, 9H), 1.30 (m, 2H), 1.13 (m, 2H). 412 98% 6-22 [00494] Me .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 8.92 (s, 1H), 8.52 (s, 1H), 7.97 (d, J = 8.3 Hz, 1H), 7.81 (s, 3H), 7.57 (d, J = 7.9 Hz, 1H), 7.36 (d, J = 8.4 Hz, 1H), 4.39 (s, 1H), 3.96 (d, J = 24.7 Hz, 3H), 3.54 (s, 2H), 2.99 (s, 2H), 2.69-2.54 (m, 3H), 1.23 (d, J = 5.3 Hz, 2H), 1.07 (s, 2H). 454 95% 6-24 [00495] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 9.40 (s, 1H), 8.92 (s, 1H), 8.60 (s, 1H), 7.99 (s, 1H), 7.81 (s, 1H), 7.57 (s, 1H), 7.38 (s, 1H), 4.40 (s, 1H), 4.00 (s, 3H), 3.66 (s, 2H), 3.28 (s, 2H), 2.85 (s, 6H), 2.61 (s, 3H), 1.24 (s, 2H), 1.07 (s, 2H). 482 99% 6-25 [00496] Me .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.91 (s, 1H), 8.37 (s, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.75 (s, 1H), 7.53 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 6.95 (s, 1H), 4.40 (s, 1H), 3.98 (s, 3H), 3.33 (d, J = 5.1 Hz, 2H), 3.13 (d, J = 5.4 Hz, 2H), 2.61 (s, 3H), 1.36 (s, 9H), 1.24 (d, J = 4.4 Hz, 2H), 1.07 (s, 2H). 554 95% 6-26 [00497] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.72 (s, 1H), 10.43 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.70 (s, 1H), 7.45 (d, J = 8.6 Hz, 1H), 4.39 (m, 1H), 4.02 (s, 3H), 2.61 (s, 3H), 1.23 (m, 2H), 1.07 (m, 2H). 396 98% 6-27 [00498] Me .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.91 (s, 1H), 8.47 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.71 (s, 1H), 7.66 (s, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.38 (d, J = 8.6 Hz, 1H), 4.40 (m, 1H), 4.05 (s, 3H), 2.65 (s, 3H), 1.25 (d, J = 6.7 Hz, 2H), 1.08 (s, 2H). 435 90% 6-28 [00499] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 11.8 Hz, 2H), 7.26 (d, J = 8.0 Hz, 1H), 4.39 (s, 1H), 3.94 (s, 5H), 2.62 (s, 3H), 1.23 (s, 2H), 1.06 (s, 2H). 407 95% 6-29 [00500] Me .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 10.43 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.8 Hz, 1H), 7.86-7.62 (m, 2H), 7.44 (d, J = 8.5 Hz, 1H), 4.39 (s, 1H), 4.02 (s, 2H), 2.64 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H). 396 95% 6-30 [00501] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 2H), 8.93 (s, 1H), 8.33 (s, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.80 (s, 2H), 7.71 (d, J = 8.5 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 7.46 (s, 2H), 4.42 (s, 1H), 4.17 (s, 3H), 2.66 (s, 3H), 1.35- 1.15 (m, 2H), 1.09 (s, 2H). 484 85% 6-31 [00502] Me .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 11.37 (s, 1H), 8.90 (s, 1H), 8.35 (s, 1H), 7.96 (d, J = 8.1 Hz, 1H), 7.64 (s, 1H), 7.43 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 8.5 Hz, 1H), 4.39 (s, 1H), 3.92 (s, 3H), 2.63 (s, 3H), 1.23 (d, J = 5.2 Hz, 2H), 1.06 (s, 2H). 411 95% 6-32 [00503] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.78 (s, 2H), 7.70 (s, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 4.40 (s, 1H), 3.98 (s, 3H), 2.61 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H). 411 94% 6-33 [00504] Me .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.92 (s, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.37 (s, 2H), 7.23 (d, J = 7.3 Hz, 1H), 4.39 (m, 1H), 3.89 (s, 3H), 3.74 (m, 4H), 3.07 (s, 4H), 2.76 (s, 3H), 2.62 (s, 3H), 1.24 (s, 2H), 1.06 (s, 2H). 480 96% 6-34 [00505] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.73 (s, 1H), 8.92 (s, 1H), 8.87 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.48 (s, 2H), 7.29 (d, J = 8.7 Hz, 1H), 4.40 (m, 1H), 4.18 (s, 2H), 3.94 (s, 3H), 2.63 (s, 3H), 2.55 (s, 3H), 1.24 (s, 2H), 1.05 (s, 2H). 411 86% 6-35 [00506] Me .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.6 Hz, 1H), 7.91 (s, 1H), 7.75 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 4.39 (s, 1H), 4.02 (s, 3H), 2.61 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H). 393 95% 6-36 [00507] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.78 (s, 1H), 8.90 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.37 (s, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 5.18 (s, 1H), 4.57 (s, 2H), 4.39 (s, 1H), 3.87 (s, 3H), 2.62 (s, 3H), 1.23 (s, 2H), 1.05 (s, 2H). 398 95% 6-37 [00508] Me .sup.1H NMR (400 MHz, DMSO) δ 14.71 (s, 1H), 9.63 (s, 1H), 8.92 (s, 1H), 8.51 (s, 1H), 7.98 (d, J = 8.5 Hz, 1H), 7.67 (s, 1H), 7.52 (d, J = 8.3 Hz, 1H), 7.32 (d, J = 8.5 Hz, 1H), 4.43 (m, 3H), 3.94 (s, 3H), 3.43 (s, 2H), 2.80 (d, J = 24.7 Hz, 6H), 2.62 (s, 3H), 1.23 (s, 2H), 1.07 (s, 2H). 482 95% 6-38 [00509] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 8.90 (s, 1H), 7.93 (d, J = 9.2 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.02 (s, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.13 (s, 2H), 4.38 (m, 1H), 2.62 (s, 3H), 1.23 (m, 2H), 1.05 (m, 2H). 382 98% 6-39 [00510] Me .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 10.11 (s, 1H), 8.91 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.33 (d, J = 1.6 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H), 6.45-6.21 (s, 2H), 4.41-4.30 (m, 1H), 2.74-2.56 (s, 3H), 1.33-1.17 (d, J = 6.6 Hz, 2H), 1.12-0.96 (t, J = 3.1 Hz, 2H). 410 98% 6-40 [00511] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.09 (s, 1H), 11.53 (s, 1H), 8.90 (s, 1H), 8.16 (s, 1H), 7.95 (d, J = 8.7 Hz, 1H), 7.08 (d, J = 1.7 Hz, 1H), 7.02 (d, J = 1.7 Hz, 1H), 6.21 (s, 2H), 4.48-4.16 (m, 1H), 2.64 (s, 3H), 1.35-1.21 (d, J = 6.8 Hz, 2H), 1.12-1.01 (m, 2H). 425 98% 6-41 [00512] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.64 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.8 Hz, 1H), 7.36 (d, J = 1.6 Hz, 1H), 7.4 (d, J = 1.6 Hz, 1H), 6.36 (s, 2H), 4.52-4.26 (m, 1H), 2.63 (s, 3H), 1.35-1.15 (d, J = 6.6 Hz, 2H), 1.10-0.99 (m, 2H). 407 98% 6-42 [00513] Me .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.89 (s, 1H), 794 (d, J = 8.7 Hz, 1H), 7.06 (d, J = 1.5 Hz, 1H), 6.95 (d, J = 1.5 Hz, 1H), 6.22 (s, 2H), 4.57-4.46 (s, 1H), 4.42-4.30 (m, 1H), 2.63 (s, 3H), 1.33-1.15 (d, J = 6.2 Hz, 2H), 1.12-0.90 (m, 1H). 406 95% 6-43 [00514] embedded image OMe .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.80 (s, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.06 (s, 1H), 7.01 (s, 1H), 6.13 (s, 2H), 5.31 (t, J = 5.6 Hz, 1H), 4.54 (d, J = 5.6 Hz, 2H), 4.34-4.12 (mz, 1H), 3.44 (s, 3H), 1.33-0.69 (m, 4H). 428 97% 6-44 [00515] Me .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.89 (s, 1H), 7.93 (d, J = 8.7 Hz, 1H), 6.97 (s, 1H), 6.93 (s, 1H), 6.73 (dd, J = 17.7, 11.3 Hz, 1H), 6.20 (s, 2H), 6.00 (d, J = 17.6 Hz, 1H), 5.49 (d, J = 11.5 Hz, 1H), 4.53-4.25 (m, 1H), 2.75-2.57 (s, 3H), 1.32-1.17 (d, J = 6.7 Hz, 2H), 1.11-0.89 (s, 2H). 408 95% 6-45 [00516] embedded image OMe .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 8.80 (s, 1H), 7.90 (d, J = 9.1 Hz, 1H), 7.17 (s, 1H), 7.09 (s, 1H), 6.23 (s, 2H), 4.49 (s, 1H), 4.34-4.14 (m, 1H), 3.47-3.42 (s, 3H), 1.31-0.96 (m, 4H). 422 98% 6-46 [00517] OMe .sup.1H NMR (400 MHz, DMSO) δ 14.62 (s, 1H), 8.81 (s, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.45 (s, 1H), 7.44 (s, 1H), 6.36 (s, 2H), 4.39-4.04 (m, 1H), 3.46 (s, 3H), 1.26-1.06 (m, 4H). 423 98% 6-47 [00518] embedded image OMe .sup.1H NMR (400 MHz, DMSO) δ 14.65 (s, 1H), 8.80 (s, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.30 (s, 1H), 7.19 (s, 11H), 7.17 (t, J = 56 Hz, 1H), 6.27 (s, 2H), 4.33-4.17 (m, 1H), 3.45 (s, 3H), 1.29-0.97 (m, 4H). 448 92% 6-48 [00519] OMe .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.80 (s, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.77 (s, 1H), 7.42 (t, J = 1.4 Hz, 1H), 7.28 (t, J = 1.3 Hz, 1H), 7.25 (s, 1H), 6.27 (s, 2H), 4.33-4.13 (m, 1H), 3.449 (s, 3H), 1.37-0.87 (m, 4H). 441 98% 6-49 [00520] embedded image OMe .sup.1H NMR (400 MHz, DMSO) δ 14.66 (s, 1H), 10.12 (d, J = 1.2 Hz, 1H), 8.81 (s, 1H), 7.93 (d, J = 9.5 Hz, 1H), 7.44 (s, 1H), 7.42 (s, 1H), 6.35 (s, 2H), 4.33-4.17 (m, 1H), 3.46 (s, 3H), 1.32-0.97 (m, 4H). 426 98% 6-50 [00521] OMe .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 8.80 (s, 1H), 7.89 (d, J = 9.1 Hz, 1H), 6.83-6.80 (t, J = 1.3 Hz, 1H), 6.80-6.76 (t, J = 1.2 Hz, 1H), 6.11 (s, 2H), 4.34- 4.12 (m, 1H), 3.86 (s, 3H), 3.31 (s, 3H), 1.26-1.02 (m, 4H). 428 98% 6-51 [00522] embedded image OMe .sup.1H NMR (400 MHz, DMSO) δ 14.70-14.61 (s, 1H), 8.84-8.78 (s, 1H), 7.96-7.88 (d, J = 9.0 Hz, 1H), 7.14 (s, 1H), 7.13 (s, 1H), 6.33-6.22 (s, 2H), 4.26- 4.18 (m, 1H), 3.47 (s, 3H), 1.20-1.11 (m, 4H). 432 95% 6-52 [00523] OMe .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 8.80 (s, 1H), 7.92 (d, J = 9.1 Hz, 1H), 7.77 (s, 1H), 7.42 (s, 1H), 7.28 (s, 1H), 7.25 (s, 1H), 6.27 (s, 2H), 4.22 (m, 1H), 3.44 (s, 3H), 1.17 (m, 4H). 441 85% 6-53 [00524] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.49 (s, 1H), 8.83 (s, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 6.36 (s, 2H), 5.10 (m, 1H), 4.18 (m, 1H), 3.47 (s, 3H), 1.82-1.63 (m, 4H). 441 98% 6-54 [00525] .sup.1H NMR (400 MHz, DMSO) δ 14.50 (s, 1H), 11.55 (s, 1H), 8.83 (s, 1H), 8.16 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.27 (s, 1H), 7.10 (s, 1H), 6.22 (s, 1H), 5.10 (m, 1H), 4.18 (m, 1H), 3.47 (s, 3H), 1.82-1.63 (m, 4H). 459 95% 6-55 [00526] embedded image .sup.1H NMR (400 MHz, DMSO) δ 14.47 (s, 1H), 8.82 (s, 1H), 8.10 (d, J = 8.7 Hz, 1H), 8.00-7.87 (m, 1H), 7.68 (t, J = 9.4 Hz, 1H), 7.37 (t, J = 8.3 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.1 Hz, 2H), 3.81 (s, 3H). 440 99% 6-56 [00527] .sup.1H NMR (400 MHz, DMSO) δ 15.44-15.10 (s, 1H), 9.12-8.99 (t, J = 1.7 Hz, 1H), 8.03-7.92 (dt, J = 8.4, 1.8 Hz, 1H), 7.67-7.56 (dd, J = 8.6, 2.5 Hz, 3H), 7.16-6.98 (m, 2H), 5.03-4.89 (d, J = 7.3 Hz, 1H), 4.60-4.47 (d, J = 11.4 Hz, 1H), 4.44-4.33 (d, J = 11.5 Hz, 1H), 3.86-3.75 (t, J = 1.7 Hz, 3H), 1.53-1.42 (d, J = 6.3 Hz, 3H). 352 99%

TABLE-US-00007 TABLE 7 [00528] embedded image Com- pound MS No. R.sup.16 = R.sup.2 = NMR (MH.sup.+) HPLC 7-1 H Me .sup.1H NMR (400 MHz, DMSO) δ 14.74 (s, 1H), 344 100% 8.90 (s, 1H), 7.95 (d, J = 9.3 Hz, 1H), 7.80 (s, 2H), 7.27 (s, 1H), 4.39 (s, 1H), 2.68 (s, 3H), 1.23 (s, 3H), 1.03 (s, 2H). 7-2 [00529] Me .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 9.37 (s, 2H), 8.91 (s, 1H), 7.96 (d, J = 8.9 Hz, 1H), 7.87 (s, 1H), 7.51 (s, 1H), 4.43 (s, 3H), 3.00 (d, J = 6.2 Hz, 2H), 2.71 (s, 3H), 1.24 (d, 401 95% J = 6.4 Hz, 5H), 1.03 (s, 2H). 7-3 [00530] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 13.87 (s, 1H), 8.91 (s, 1H), 7.98 (d, J = 8.1 Hz, 2H), 7.60 (s, 1H), 4.41 (s, 1H), 2.70 (s, 3H), 1.23 (s, 2H), 1.06 (s, 2H). 412 100% 7-4 CH.sub.2CN Me .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 383 97% 8.90 (s, 1H), 7.95 (d, J = 8.8 Hz, 1H), 7.76 (s, 1H), 7.22 (s, 1H), 5.76 (s, 2H), 4.40 (m, 1H), 2.69 (s, 3H), 1.23 (m, 2H), 1.04 (s, 2H). 7-5 CHO Me .sup.1H NMR (400 MHz, DMSO) δ 14.67 (s, 1H), 372 98% 10.03 (s, 1H), 8.92 (s, 1H), 8.39 (s, 1H), 8.23 (s, 1H), 7.99 (d, J = 9.1 Hz, 1H), 4.42 (s, 1H), 2.71 (s, 3H), 1.24 (d, J = 6.4 Hz, 2H), 1.05 (s, 2H). 7-6 [00531] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 11.34 (d, J = 16.3 Hz, 1H), 8.30 (s, 1H), 8.40 (s, 1H), 7.96 (d, J = 8.6 Hz, 1H), 7.78 (s, 1H), 7.42 (d, J = 14.9 Hz, 1H), 4.40 (s, 1H), 2.71 387 96% (s, 3H), 1.24 (d, J = 5.8 Hz, 2H), 1.04 (s, 2H). 7-7 [00532] Me .sup.1H NMR (400 MHz, DMSO) δ 13.57-13.17 (m, 1H), 11.49 (s, 1H), 9.30 (s, 1H), 8.77 (s, 1H), 8.09 (s, 1H), 7.90 (d, J = 9.3 Hz, 1H), 7.83 (s, 1H), 4.33 (s, 1H), 2.66 (s, 3H), 1.22 (d, J = 7.5 Hz, 2H), 0.97 (s, 2H). 403 100% 7-8 CONH.sub.2 Me .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.91 387 100% (s, 1H), 8.12 (s, 1H), 7.98 (m, 2H), 7.89 (s, 1H), 7.57 (s, 1H), 4.41 (s, 1H), 2.71 (s, 3H), 1.25 (d, J = 5.7 Hz, 2H), 1.03 (s, 2H). 7-9 CO.sub.2H Me .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 13.34 388 100% (s, 1H), 8.91 (s, 1H), 8.12 (s, 1H), 7.96 (d, J = 8.7 Hz, 1H), 7.86 (s, 1H), 4.40 (s, 1H), 2.69 (s, 3H), 1.24 (d, J = 6.2 Hz, 2H), 1.05 (s, 2H). 7-10 [00533] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.68 (s, 1H), 12.49 (s, 1H), 8.87 (s, 1H), 7.96 (d, J = 11.9 Hz, 2H), 7.81 (d, J = 15.8 Hz, 1H), 7.69 (s, 1H), 6.30 (d, J = 15.7 Hz, 1H), 4.40 (s, 1H), 2.71 (s, 3H), 1.24 (d, J = 6.4 Hz, 2H), 1.04 (s, 2H). 414 95% 7-11 [00534] Me .sup.1H NMR (400 MHz, DMSO) δ 14.69 (s, 1H), 8.92 (s, 1H), 8.13 (s, 1H), 8.00 (d, J = 8.7 Hz, 1H), 7.91 (s, 1H), 4.42 (s, 1H), 2.74 (s, 3H), 1.24 (s, 2H), 1.06 (s, 2H). 412 100% 7-12 [00535] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.75 (s, 1H), 11.75 (s, 1H), 8.90 (s, 1H), 7.97 (s, 1H), 7.58 (s, 1H), 7.46 (s, 1H), 7.26 (s, 1H), 7.13 (s, 1H), 7.00 (s, 2H), 4.41 (s, 1H), 4.17 (d, J = 6.9 Hz, 2H), 2.75 (s, 3H), 1.99 (s, 2H), 1.23 (s, 3H), 1.04 (s, 2H), 0.85 (s, 2H). 481 100% 7-13 [00536] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 14.70 (s, 1H), 8.91 (s, 1H), 8.49 (s, 1H), 7.97 (d, J = 8.7 Hz, 1H), 7.91 (s, 1H), 7.64 (s, 2H), 4.41 (s, 1H), 2.73 (s, 3H), 1.25 (d, J = 6.5 Hz, 2H), 1.05 (s, 2H). 411 95% 7-14 [00537] Me .sup.1H NMR (400 MHz, DMSO) δ 14.90-14.46 (m, 1H), 8.93 (s, 1H), 8.05 (s, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.63 (s, 2H), 7.28 (s, 2H), 4.44 (s, 1H), 2.78 (s, 3H), 1.27 (d, J = 6.4 Hz, 2H), 1.07 (s, 2H). 460 100% 7-15 [00538] embedded image Me .sup.1H NMR (400 MHz, DMSO) δ 8.92 (s, 1H), 8.07 (d, J = 6.7 Hz, 2H), 7.99 (d, J = 8.8 Hz, 1H), 7.91 (s, 1H), 7.79 (s, 1H), 7.54 (s, 3H), 4.42 (s, 1H), 2.76 (s, 3H), 1.26 (d, J = 6.0 Hz, 3H), 1.07 (m, 2H). 487 95% 7-16 [00539] Me .sup.1H NMR (400 MHz, DMSO) δ 14.68 (b, 1H), 13.75 (s, 1H), 8.90 (s, 1H), 7.96 (d, J = 8.9 Hz, 1H), 7.77 (s, 1H), 7.61 (s, 1H), 4.47-4.32 (m, 1H), 2.73 (s, 3H), 2.41 (s, 3H), 1.25 (t, J = 6.3 Hz, 2H), 1.07 (s, 2H). 425 98% 7-17 CN OMe .sup.1H NMR (400 MHz, DMSO) δ 14.53 (s, 1H), 8.80 385 98% (s, 1H), 8.42 (s, 1H), 7.28 (s, 1H), 7.96 (d, J = 9.2 Hz, 1H), 4.47-4.32 (m, 1H), 3.47 (s, 3H), 1.23-1.15 (m, 4H). 7-18 [00540] embedded image OMe .sup.1H NMR (400 MHz, DMSO) δ 8.57 (s, 1H), 7.72 (s, 2H), 7.58 (s, 1H), 7.43 (d, J = 9.7 Hz, 1H), 4.13 (m, 1H), 3.27 (s, 3H), 2.20 (s, 3H), 1.05- 0.81 (m, 4H). 441 98% 7-19 [00541] Cl .sup.1H NMR (400 MHz, DMSO) δ 8.93 (s, 1H), 8.13 (d, J = 8.0 Hz, 1H), 7.86 (s, 1H), 7.67 (s, 1H), 4.13 (m, 1H), 2.40 (s, 3H), 1.24-1.12 (m, 4H). 445 85%

TABLE-US-00008 TABLE 8-1 [00542] embedded image Com- pound No. R.sup.19 = R.sup.2 = MS (MH.sup.+) 8-1 H Me 352.36 8-2 3-NH2 Me 337.34 8-3 4-F Me 355.33 8-4 4-CO2H Me 381.35 8-5 2-NH2 Me 352.36 8-6 3-Me Me 351.37 8-7 4-Me Me 351.37 8-8 2,3-Dimethyl Me 365.4 8-9 2-Cl Me 371.79 8-10 4-Cl Me 371.79 8-11 3-CO2H Me 381.35 8-12 3-CF3 Me 405.34 8-13 3,4-Dichloro Me 406.23 8-14 3-F Me 355.33 8-15 4-tBu Me 393.45 8-16 4-MeO Cyclopropyl 393.41 8-17 4-Ph Me 413.44 8-18 4-NO2 Me 382.34 8-19 3,4-Dichloro MeO 404.24 8-20 4-MeO Me 365.38 8-21 3,4-Dimethyl Me 365.4 8-22 4-CF3 Me 405.34 8-24 3-CONH2 Me 380.37 8-25 4-NH2 Me 352.36 8-26 4-OH Me 353.34 8-27 4-OMe F 353.34 8-28 4-OMe NO2 398.34 8-29 4-OMe Cl 387.79 8-30 4-OMe NH2 368.36 8-31 4-OMe Br 432.24 8-32 4-OMe H 353.34 8-33 4-OMe CN 378.35 8-34 4-OMe CH2F 385.36 8-35 4-OMe MeO 383.37 8-36 4-OMe CH2Br 446.27 8-37 4-OMe CH2OH 383.37 8-38 4-OMe CHF2 403.35 8-39 4-Amino-3-hydroxy Me 368.36 8-40 4-OMe CHO 381.35 8-41 4-OMe C≡CH 377.37 8-42 4-OMe Et 381.4 8-43 4-OMe CH═CH2 379.38 8-44 3,4-Diamino Me 367.37 8-45 4-Amino-3-nitro Me 397.36 8-46 4-Methylamino-3-nitro Me 411.38 8-47 3-Dimethylamino Me 380.41 8-48 2,4-Dinitro-3- dimethylamino Me 470.41 8-49 4-Nitro-3-dimethylamino Me 425.41 8-50 2-Nitro-3-dimethylamino Me 425.41 8-51 4-Dimethylamino-3-nitro Me 425.41 8-52 4-Ethylamino-3-nitro Me 425.41 8-53 4-Dimethylamino Me 380.41 8-54 3-Formyl-4-nitro Me 410.35 8-55 4-Amino-3-nitro Me 413.36 8-56 3-Fluoro-4-nitro Me 400.33

TABLE-US-00009 TABLE 8-2 [00543] embedded image Com- pound No. R.sup.3 = R.sup.2 = MS(MH.sup.+) 8-57 [00544] Me 451.45 8-58 [00545] Me 465.47 8-59 [00546] Me 480.49 8-60 [00547] Me 495.48 8-61 [00548] Me 508.54 8-62 [00549] Me 452.44 8-63 [00550] Me 466.46 8-64 [00551] Me 467.45 8-65 [00552] Me 411.38 8-66 [00553] Me 415.35 8-67 [00554] embedded image Me 425.41 8-68 [00555] Me 429.37 8-69 [00556] Me 426.35 8-70 [00557] Me 454.45 8-71 [00558] Me 449.39 8-72 [00559] Me 454.45 8-73 [00560] Me 463.42 8-74 [00561] Me 447.46 8-75 [00562] Me 406.45 8-76 [00563] Me 421.46 8-77 [00564] Me 418.42

TABLE-US-00010 TABLE 9 [00565] embedded image Com- pound No. R.sup.3 = R.sup.2 = MS(MH.sup.+) 9-1 [00566] Me 407.19 9-2 [00567] Me 404.39 9-3 [00568] Me 394.35 9-4 [00569] Me 397.4 9-5 [00570] Me 392.38 9-6 [00571] Me 326.32 9-7 [00572] Me 326.32 9-8 [00573] Me 394.4 9-9 [00574] Me 380.41 9-10 [00575] embedded image Me 395.43 9-11 [00576] Me 355.36 9-12 [00577] Me 393.37 9-13 [00578] Me 327.31 9-14 [00579] Me 406.2 9-15 [00580] Me 409.43 9-16 [00581] Me 372.3 9-17 [00582] Me 328.34 9-18 [00583] Me 397.44 9-19 [00584] Me 354.33 9-20 [00585] Me 354.33 9-21 [00586] Me 422.33 9-22 [00587] Me 342.36 9-24 [00588] embedded image Me 411.47

Experimental Example 1

In Vitro Antibacterial Activity

[0838] All compounds were dissolved in dimethyl sulfoxide (DMSO, Merck, purity >99.9%) to achieve final 1 mg/ml desired concentrations.

[0839] MICs (minimum inhibitory concentrations) were determined by the broth microdilution technique with 96-well microdilution plates. The antimicrobials were tested using the following MIC ranges: 0.008 to 8 μg/ml. The plates were filled with 100 μl of reinforced clostridial medium (Oxoid; Unipath Ltd., Basingstoke, United Kingdom) per well containing the final antibiotic concentrations. The plates were thawed and preincubated for 3 hours in an anaerobic chamber (Thermal, USA) containing an atmosphere of 80% N.sub.2, 15% CO.sub.2, and 5% H.sub.2. The bacterial inocula were prepared by suspending growth from 48 hours cultures in reinforced clostridial medium. The final inoculum was approximately 1.0×10.sup.5-6 CFU/well. The plates were incubated for 48 hours at 37° C. in the anaerobic chamber. The MIC was defined as the lowest antibiotic concentration that inhibited visible growth. Ciprofloxacin, vancomycin and metronidazole were used as a positive control. The results are shown in Table 10.

TABLE-US-00011 TABLE 10 MIC of example compounds against C. difficile (μg/mL) Com- pound C. difficile C. difficile C. difficile C. difficile No. ATCC43255 ATCC700057 ATCC70092 IQCC23903 2-18 0.016-0.063 0.016-0.063 ≦0.008-0.063.sup. 0.032-0.063 2-46 0.032-0.125 0.032-0.25 0.063-0.25 0.125-0.25 5-14 0.125-0.25 0.125-0.5 0.125-0.25 0.125-0.5 2-49 0.063-0.25 0.063-0.25 0.063-0.5 0.063-0.25 3-11 ≦0.008-0.032.sup. 0.016-0.032 ≦0.008-0.032.sup. ≦0.008-0.063 2-31 ≦0.008-0.032.sup. 0.016-0.032 0.016-0.032 0.016-0.063 1-2 0.032-0.125 0.032-0.125 0.032-0.125 0.063-0.25 3-21 0.016-0.032 0.016-0.063 0.016-0.063 0.032-0.063 2-38 0.016-0.032 0.016-0.032 0.032-0.063 0.016-0.032 3-30 0.032-0.063 0.063-0.125 0.063-0.125 0.063-0.25

Experimental Example 2

In Vivo Antibacterial Efficacy

[0840] In vivo efficacy was evaluated in a hamster intestinal infection treatment model. Male Golden Syrian hamsters were purchased from Charles River Laboratories (Kingston, N.Y., USA) and were about 6 weeks of age, with weights ranging from 80 to 100 g at the start of the study. The animals were housed individually in filtered polycarbonate shoe-box style cages equipped with water bottles, and Harlan Teklab Global Diet 2016 was available ad libitum via food hoppers. The hamsters were pre-treated with clindamycin (1 mg/kg, p.o.) and vancomycin (50 mg/kg, p.o.), formulated in arabic gum, at Day 0. At Day 7, each hamster was inoculated via oral gavage with 0.5 mL of a suspension of C. difficile ATCC 43255 (10.sup.5 CFU/body, p.o.). To prepare this inoculum, C. difficile was grown in GAM agar (Japan) for 5 days at 37° C., and the bacteria were harvested by centrifugation, rinsed twice with arabic gum, resuspended in arabic gum and the exact bacteria density was determined using the dilution plate count method. Oral dosing of compounds, pulverized and formulated in arabic gum was commenced the following day (Day 8). Treatments were administered once a day for 5 consecutive days at specified doses (10, 2, and 0.4 mg/kg), with five hamsters per group. Controls were included an uninfected group and an infected but untreated group, and vancomycin was used as positive control. The hamsters were observed daily to record clinical signs (duration, time of onset, time of recovery or death), and animals in a lethargic, clearly moribund state were euthanized. A necropsy was performed on animals that were either found dead or were euthanized at the end of the study (37 days). The results are shown in FIG. 1 and FIG. 2.

Preparation Example 1

[0841] An injection preparation is prepared from the following components.

TABLE-US-00012 Components Amount Compound 1-2 200 mg Glucose 250 mg Distilled water for injection q.s. Total 5 ml

[0842] Compound 1-2 and glucose are dissolved in distilled water for injection, and the solution is added to a 5 ml ampoule, which is purged with nitrogen gas and then subjected to sterilization at 121° C. for 15 minutes to give an injection preparation.

Preparation Example 2

[0843] Film coated tablets are prepared from the following components.

TABLE-US-00013 Components Amount Compound 2-18 100 g Avicel (registered trademark) 40 g Corn starch 30 g Magnesium stearate 2 g TC-5 (registered trademark) 10 g Polyethylene glycol 6000 3 g Castor oil 40 g Ethanol 40 g

[0844] Compound 2-18, Avicel (registered trademark of microcrystalline cellulose, manufactured by Asahi Kasei Corporation, Japan), corn starch and magnesium stearate are mixed and kneaded, and the mixture is tabletted using a conventional pounder (R 10 mm) for sugar coating (manufactured by Kikusui Seisakusho Ltd., Japan). The tablets thus obtained are coated with a film coating agent consisting of TC-5 (registered trademark of hydroxypropyl methylcellulose, manufactured by Shin-Etsu Chemical Co., Ltd., Japan), polyethylene glycol 6000, castor oil and ethanol to give film coated tablets.

Preparation Example 3

[0845] An ointment is prepared from the following components.

TABLE-US-00014 Components Amount Compound 3-11 2 g Purified lanolin 5 g Bleached beeswax 5 g White petrolatum 88 g Total 100 g

[0846] Bleached beeswax is made liquid by heating, and thereto are added compound 3-11, purified lanolin and white petrolatum, and the mixture is heated until it becomes liquid. The mixture is stirred until it is solidified to give an ointment.

QUINOLONE COMPOUND

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