Patent ID: 6380249
Filing Date: 2002-04-30
Classification: C07C,C07D

Abstract:
A compound of structural formula (I): and tautomers and pharmaceutically acceptable salts thereof, wherein:A is a six-membered aromatic ring substituted on carbon by R1, R2, R8, and R9, optionally fused with another ring system, and is selected from: (1) phenyl, (2) naphthyl, R1 is selected from: (1) â€”H, (2) â€”C1-5 alkyl, (3) â€”C1-6 alkyl-OR7; (4) â€”Oâ€”C1-6 alkyl-OR7, (5) â€”Oâ€”C1-6 alkyl-SR7, (6) â€”CF3 or â€”CH2CF3, (7) â€”F, Cl, or Br, (8) â€”NO2, (9) â€”C0-3 alkyl â€”N(R4)(R5), (10) -phenyl, (11) substituted phenyl substituted with 1 or 2 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) phenyl, (e) â€”CF3, (f) â€”OCF3, (g) â€”CN, (h) hydroxy, (i) phenyloxy, and (j) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (12) phenyl C1-3 alkyl-, wherein the phenyl group may be unsubstituted or substituted with 1 to four substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”CF3, (f) â€”SCH3, (g) â€”CN, (h) hydroxy, (i) phenyloxy, (j) â€”C0-6 alkyl-N(R7)2, (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (13) â€”Oâ€”R6, (14) â€”Oâ€”C1-6 alkyl, unsubstituted or substituted with one to three fluorine atoms, (15) â€”Oâ€”C1-6 alkyl-NHâ€”C(O)â€”OR7; (16) â€”Oâ€”C2-6 alkyl-N(R4)(R5); (17) â€”Sâ€”C1-3 alkyl; (18) â€”C(O)CH2C(O)C(O)OR7; (19) â€”CH2â€”CH(OH)â€”CH2â€”Oâ€”R7; and (20) â€”C(OH)(CH3)â€”CH2N(R4)(R5); R2 is selected from: (1) â€”R3, (2) â€”C1-6 alkyl substituted with R3, wherein one or more of the hydrogen atoms on C1-6 alkyl may be replaced with a fluorine atom, (3) â€”Oâ€”C1-6 alkyl-SR6; (4) â€”C1-6 alkyl (OR6)(R4), (5) â€”C0-6 alkyl-N(R4)(R6), (6) â€”C1-6 alkyl Sâ€”R6, (7) â€”C0-6 alkyl C(O)â€”R6, (8) â€”C0-6 alkyl C(O)CH2â€”C(O)â€”OH, (9) â€”C1-6 alkyl NR4C(O)â€”R6, (10) â€”C1-6 alkyl-C(O)N(R4)(R5), and (11) â€”CH2(OR7)â€”R6; each R3 is independently selected from: (1) phenyl; (2) substituted phenyl with 1, 2, 3 or 4 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”CN, (f) hydroxy, (g) phenyloxy, (h) â€”C0-6 alkyl-N(R7)2, (j) oxo, and (k) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (3) thienyl, (4) substituted thienyl substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (5) pyridyl, (6) substituted pyridyl substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (7) substituted imidazolyl substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (8) pyrrolyl, (9) substituted pyrrolyl substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (10) pyrazolyl, (11) substituted pyrazolyl substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (12) piperidinyl, (13) substituted piperidinyl substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, (g) &boxH;O, (h) benzyl, and (i) hydroxy; (14) substituted morpholinyl substituted at a carbon or nitrogen atom with 1 or 2 substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, (g) &boxH;O, (h) benzyl, and (i) hydroxy; (15) hexahydrothieno[3,4-d]imidazolyl, (16) substituted hexahydrothieno[3,4-d]substituted hexahydrothieno[3,4-d]imidazolyl with one or two substituents independently selected from: (a) oxo, (b) halogen, (c) C1-6 alkyl, (d) C1-6 alkyloxy-, (e) â€”CF3, (f) â€”OCF3, (g) â€”CN, and (h) hydroxy, (17) naphthyl, (18) substituted naphthyl with 1, 2, or 3 substituents independently selected from: (a) -halogen, (b) â€”C1-6 alkyl, (c) â€”C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, and (g) -hydroxy, (19) indolyl, (20) substituted indolyl substituted on a carbon atom with one or two substituents independently selected from: (a) -halogen, (b) â€”C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, and (g) -hydroxy; (21) C3-5 cycloalkyl fused with a phenyl ring, (22) substituted C3-6 cycloalkyl fused with a phenyl ring substituted on carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, (g) &boxH;O, and (h) hydroxy; (23) pyrazinyl; (24) substituted pyrazinyl substituted on nitrogen or carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (25) pyrimidinyl; (26) substituted pyrimidinyl substituted on nitrogen or carbon with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (27) triazolyl; (28) substituted triazolyl with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (29) tetrazolyl; (30) substituted tetrazolyl with a substituent selected from: (a) halogen, (b) C1-6 alkyl, wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (c) C1-6 alkyloxy- wherein one or more of the hydrogen atoms may be replaced with a fluorine atom, (d) phenyl, (e) â€”Sâ€”C1-6 alkyl, (f) â€”CN, (g) hydroxy, (h) phenyloxy, (i) â€”C0-6 alkyl-N(R7)2, (k) oxo, and (l) substituted phenyloxy with 1, 2, or 3 substituents selected from: (i) halogen, (ii) C1-6 alkyl, (iii) â€”CF3, and (iv) hydroxy; (31) C3-6 cycloalkyl; (32) substituted C3-6 cycloalkyl substituted with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, (g) &boxH;O, (h) benzyl, and (i) hydroxy; (33) tetrahydrofuran; (34) substituted tetrahydrofuran substituted with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, (g) &boxH;O, (h) benzyl, and (i) hydroxy; (35) piperazinyl; (36) substituted piperazinyl substituted with one or two substituents independently selected from: (a) halogen, (b) C1-6 alkyl, (c) C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, (g) &boxH;O, (h) benzyl, and (i) hydroxy; (37) benzotriazolyl, (38) substituted benzotriazolyl substituted on a carbon atom with one or two substituents independently selected from: (a) -halogen, (b) â€”C1-6 alkyl, (c) â€”C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, and (g) -hydroxy; (39) benzoimidazolyl, (40) substituted benzoimidazolyl substituted on a carbon atom with one or two substituents independently selected from: (a) -halogen, (b) â€”C1-6 alkyl, (c) â€”C1-6 alkyloxy-, (d) â€”CF3, (e) â€”OCF3, (f) â€”CN, and (g) -hydroxy; each R4 is independently selected from: (1) â€”H, (2) â€”C1-4 alkyl, (3) â€”CF3, (4) â€”R3, (5) â€”C2-3 alkenyl, (6) â€”C1-3 alkyl-R3, (7) â€”C2-3 alkenyl-R3, and (8) â€”C(O)â€”R3; each R5 is independently selected from: (1) â€”H, (2) â€”C1-3 alkyl, (3) â€”CF3, (4) â€”R3, (5) â€”C2-3 alkenyl, (6) â€”C1-3 alkyl-R3, (7) â€”S(O)nâ€”R3, (8) â€”C(O)â€”R3, (9) â€”C(O)OR4, and (10) â€”C(O)C(O)OH; each R6 is independently selected from: (1) â€”C1-3 alkyl-R3, and (2) â€”R3; each R7 is independently selected from: (1) â€”H, and (2) â€”C1-6 alkyl; R8 is selected from hydrogen, methyl and â€”Oâ€”C1-6 alkyl; R9 is selected from: (1) â€”H, (2) â€”Oâ€”C1-3 alkyl, (3) â€”OH, and (4) oxo; and each n is independently selected from 0, 1 and 2; andPROVIDED THAT when A is phenyl: (1) R1 is not: (a) phenyl para to the dioxobutyric acid moiety, (b) substituted phenyl para to the dioxobutyric acid moiety, (c) â€”C1-3 alkyl phenyl para to the dioxobutyric acid moiety, or (d) substituted â€”C1-3 alkyl phenyl para to the dioxobutyric acid moiety; and (2) R2 is not selected from: (a) phenyl para to the dioxobutyric acid moiety, (b) substituted phenyl para to the dioxobutyric acid moiety, (c) â€”C1-6 alkyl phenyl para to the dioxobutyric acid moiety, and (d) substituted â€”C1-6 alkyl phenyl para to the dioxobutyric acid moiety; and (3) at least one of R1, R2, and R8 is not: (a) â€”H, (b) C1-6 alkyl, or (c) R3 wherein R3 is cycloalkyl.