Patent ID: 6372764
Filing Date: 2002-04-16
Classification: C07D

Abstract:
A compound of the formula I: wherein:R1 is â€”X-R8, wherein X is selected from the group consisting of: (1) â€”CH2â€”, (2) â€”COâ€”, (3) â€”CH2CH2â€”, (4) â€”CH2CH2CH2â€”, and (5) â€”CH(C1-6 alkyl)-, and wherein R8 is a selected from: phenyl, naphthyl, biphenyl, fluorenyl, indenyl, indanyl, dihydronaphthyl, tetrahydronaphthyl, octahydronaphthyl, adamantyl, and heterocycle, which may be unsubstituted or substituted, where the substituents are independently selected from: (a) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, wherein the alkyl, alkenyl, or alkynyl is unsubstituted or substituted, wherein the substituents are independently selected from: (i) hydroxy, (ii) halogen, (iii) â€”NR9R10, wherein R9 and R10 are independently selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, wherein the alkyl, alkenyl, or alkynyl is unsubstituted or substituted, wherein the substituents are independently selected from: (A) phenyl, unsubstituted or substituted, wherein the substituents are independently selected from: halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NH(C1-6 alkyl), â€”N(C1-6 alkyl)(C1-6 alkyl), or trifluoromethyl, (B) naphthyl, unsubstituted or substituted, wherein the substituents are independently selected from: halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NH(C1-6 alkyl), â€”N(C1-6 alkyl)(C1-6 alkyl), or trifluoromethyl, (C) heterocycle, unsubstituted or substituted, wherein the substituents are independently selected from: halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NH(C1-6 alkyl), â€”N(C1-6 alkyl)(C1-6 alkyl), or trifluoromethyl, (D) hydroxy, (E) â€”O(C1-6 alkyl), (F) â€”CO2(C1-6 alkyl), (G) â€”S(O)nâ€”(C1-6 alkyl), wherein n is an integer selected from 0, 1 and 2, (H) halogen, (I) â€”NH2, (J) â€”NH(C1-6 alkyl), and (K) â€”N(C1-6 alkyl)(C1-6 alkyl), (iv) â€”NR9-COR10, (v) â€”NR9-CO2R10, (vi) â€”COâ€”NR9R10, (vii) â€”OCOâ€”NR9R10, (viii) â€”NR9COâ€”NR9R10, (ix) â€”S(O)2â€”NR9R10, wherein n is an integer selected from 0, 1 and 2, (x) â€”NR9S(O)2-R10, (xi) â€”NR9S(O)2â€”NR9R10, (xii) â€”S(O)n-R9, (xiii) â€”CF3, (xiv) â€”CHF2, (xv) â€”CH2F, (xvi) â€”O-R9, (xvii) â€”O(C1-6 alkyl)-O-R9, (xviii) phenyl, (xix) naphthyl, (xx) indenyl, (xxi) indanyl, (xxii) heterocycle, (xxiii) â€”CO-phenyl, (xxiv) â€”CO-naphthyl, (xxv) â€”CO-indenyl, (xxvi) â€”CO-indanyl, (xxvii) â€”CO-heterocycle, (xxviii) â€”OCO-R9, (xxix) â€”OCO2-R9, and (xxx) â€”CO-R9, (b) â€”O-C1-6 alkyl, â€”O-C2-6 alkenyl, â€”O-C2-6 alkynyl, wherein the alkyl, alkenyl, or alkynyl is unsubstituted or substituted, wherein the substituents are independently selected from: (i) hydroxy, (ii) halogen, (iii) â€”NR9R10, (iv) â€”NR9-COR10, (v) â€”NR9-CO2R10, (vi) â€”COâ€”NR9R10, (vii) â€”OCOâ€”NR9R10, (viii) â€”NR9COâ€”NR9R10, (ix) â€”S(O)2â€”NR9R10, (x) â€”NR9S(O)2-R10, (xi) â€”NR9S(O)2â€”NR9R10, (xii) â€”S(O)n-R9, (Xiii) â€”CF3, (xiv) â€”CHF2, (xv) â€”CH2F, (xvii) â€”O-R9, (xvii) â€”O(C1-6 alkyl)-O-R9, (xviii) phenyl, (xix) naphthyl, (xx) indenyl, (xxi) indanyl, (xxii) heterocycle, (xxiii) â€”CO-phenyl, (xxiv) â€”CO-naphthyl, (xxv) â€”CO-indenyl, (xxvi) â€”CO-indanyl, (xxvii) â€”CO-heterocycle, (xxviii) â€”OCO-R9, (xxix) â€”OCO2-R9, and (xxx) â€”CO-R9, (c) â€”NO2, (d) hydroxy, (e) halogen, (f) â€”NR9R10, (g) â€”NR9-COR10, (h) â€”NR9-CO2R10, (i) â€”COâ€”NR9R10, (j) â€”OCOâ€”NR9R10, (k) â€”NR9COâ€”NR9R10, (l) â€”S(O)2â€”NR9R10, (m) â€”NR9S(O)2-R10, (n) â€”NR9S(O)2â€”NR9R10, (o) â€”S(O)n-R9, (p) â€”CF3, (q) â€”CHF2, (r) â€”CH2F, (s) â€”OCO-R9, (t) â€”OCO2-R9, and (u) â€”CO-R9; R2 is selected from the group consisting of: â€ƒwherein R5 is a selected from: (1) â€”NR6COâ€”O-R7, wherein R6 is hydrogen, C1-6 alkyl or C1-6 alkyl-C5-6 cycloalkyl, and R7 is C1-6 alkyl, C5-6 cycloalkyl, benzyl or phenyl, wherein the alkyl, cycloalkyl, benzyl or phenyl is unsubstituted or substituted with halogen, C1-3 alkyl, C1-3 alkoxy or trifluoromethyl, (2) phenyl, which is unsubstituted or substituted with halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NHR9, â€”NR9R10, or trifluoromethyl, (3) -pyridyl, (4) -thienyl, (5) -C1-6 alkyl-phenyl, -C1-6 alkyl-naphthyl, -C1-6 alkyl-indenyl, -C1-6 alkyl-indanyl, and -C1-6 alkyl-heterocycle, wherein the phenyl, naphthyl, indenyl, indanyl, or heterocycle is unsubstituted or substituted with: halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NHR9, â€”NR9R10, or trifluoromethyl; and wherein the -C1-6 alkyl is optionally substituted with oxo, hydroxy, C1-6 alkoxy, acetoxy, or halogen, (6) â€”O-C1-6 alkyl-phenyl, â€”O-C1-6 alkyl-naphthyl, â€”O-C1-6 alkyl-indenyl, â€”O-C1-6 alkyl-indanyl, and â€”O-C1-6 alkyl-heterocycle, wherein the phenyl, naphthyl, indenyl, indanyl, or heterocycle is unsubstituted or substituted with: halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NHR9, â€”NR9R10, or trifluoromethyl, (7) C1-4 alkyl-O-C-1-4 alkyl-phenyl, wherein the phenyl is unsubstituted or substituted with halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NHR9, â€”NR9R10, or trifluoromethyl, and (8) -C1-4 alkyl-S(O)n-C1-4 alkyl-phenyl, wherein the phenyl is unsubstituted or substituted with halogen, hydroxy, C1-6 alkyl, C1-6 alkoxy, â€”CO2(C1-6 alkyl), â€”NH2, â€”NHR9, â€”NR9R10, or trifluoromethyl; and wherein R11 is a selected from: (1) -hydrogen, (2) â€”OH, (3) -C1-6 alkyl, and (4) -halogen; R3 is selected from the group consisting of: (1) â€”CHO, (2) â€”CO2(C1-6 alkyl), (3) â€”CO-R9, (4) â€”CONR9R10, (5) â€”CONR9-COR10, (6) â€”CONR9-CO2R10, (7) â€”C(R9)(OR9)(OR10), (8) â€”C(R9)(SR9)(SR10), (9) â€”C(R9)(OR14)(OR15), wherein R14 and R15 are joined together in a C2-3 alkyl group to form a 5- or 6-membered ring which is substituted with R12 and R13 wherein: R12 and R13 are independently selected from: (a) hydrogen, (b) â€”CO2(C1-6 alkyl), (c) hydroxy, (d) halogen, (e) â€”NR9R10, (f) â€”NR9-COR10, (g) â€”NR9-CO2R10, (h) â€”CF3, (i) â€”CHF2, (j) â€”CH2F, (k) â€”O-R9, (l) C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, wherein the alkyl, alkenyl, or alkynyl is unsubstituted or substituted, wherein the substituents are independently selected from: (i) â€”CO2(C1-6 alkyl), (ii) hydroxy, (iii) halogen, (iv) â€”NR9R10, (v) â€”NR9-COR10, (vi) â€”NR9-CO2R10, (vii) phenyl, (viii) â€”CF3, (ix) â€”CHF2, (x) â€”CH2F, and (xi) â€”O-R9, (m) phenyl or heterocycle, wherein the phenyl or heterocycle is unsubstituted or substituted, wherein the substituents are independently selected from: (i) â€”CO2(C1-6 alkyl), (ii) hydroxy, (iii) halogen, (iv) â€”NR9R10, (v) â€”NR9-COR10, (vi) â€”NR9-CO2R10, (vii) phenyl, (viii) â€”CF3, (ix) â€”CHF2, (x) â€”CH2F, and (xi) â€”O-R9, (10) â€”C(R9)(SR14)(SR15), (11) -cyclopentyl, which is substituted with R12 and R13, (12) -cyclohexyl, which is substituted with R12 and R13, (13) -tetrahydrofuranyl, which is substituted with R12 and R13, (14) -tetrahydropyranyl, which is substituted with R12 and R13; R4c, R4d, and R4f are independently selected from the group consisting of: (1) hydrogen, and (2) C1-6 alkyl; and pharmaceutically acceptable salts thereof and individual diastereomers thereof.