Patent ID: 6531484
Filing Date: 2003-03-11
Classification: A61K,C07D

Abstract:
A compound of the formula I: wherein:R1 is selected from: (1) â€”CO2H, (2) â€”NO2, (3) -tetrazolyl, (4) -hydroxyisoxazole, (5) â€”SO2NHCOâ€”(C0-3 alkyl)-R9, wherein R9 is independently selected from hydrogen, C1-6 alkyl, C5-6 cycloalkyl, benzyl or phenyl, wherein alkyl, cycloalkyl, benzyl or phenyl is unsubstituted or substituted with 1-3 substituents independently selected from halo, C1-3 alkyl, â€”Oâ€”C1-3 alkyl and trifluoromethyl, and (6) â€”P(O)(OH)2; j is an integer which is 0, 1, 2 or 3; R2 is hydrogen or C1-6 alkyl; Q is â€”(CH2)1-3â€”, â€”CH2OCH2â€”, â€”CH2SCH2â€”, â€”CH2S(O)CH2â€”, â€”CH2S(O2)CH2â€”, or â€”CH2N(Rd)CH2â€”; k, l, m and n are each independently integers from zero to 3; R3 is phenyl, naphthyl, or heterocycle, wherein any one of which is optionally substituted with from 1 to 7 of R11 where R11 is independently selected from: (a) halo, (b) cyano, (c) hydroxy, (d) C1-6 alkyl, which is unsubstituted or substituted with 1-5 of R12 where R12 is independently selected from halo, cyano, hydroxy, â€”Oâ€”C1-6 alkyl, â€”C3-6 cycloalkyl, â€”CO2H, â€”CO2â€”(C1-6 alkyl), â€”CF3, â€”SO2R9, â€”NR9R10 (where R9 is independently as defined above and R10 is independently selected from the definitions of R9), phenyl, naphthyl, biphenyl, and heterocycle; wherein phenyl, naphthyl, biphenyl, or heterocycle is unsubstituted or substituted with 1-7 of R13 where R13 is independently selected from halo, cyano, hydroxy, C1-6 alkyl, C1-6 haloalkyl, â€”Oâ€”C1-6 alkyl, â€”Oâ€”C1-6 haloalkyl, â€”CO2H, â€”CO2(C1-6 alkyl), â€”NR9R10, â€”(C1-6 alkyl)-NR9R10, â€”SO2R9, â€”(C1-6 alkyl)hydroxy, â€”Oâ€”C3-6 cycloalkyl, benzyloxy, phenoxy, and â€”NO2, (e) â€”Oâ€”C1-6 alkyl, which is unsubstituted or substituted with 1-5 of R12, (f) â€”O-phenyl, which is unsubstituted or substituted with 1-5 of R13, (g) â€”O-heterocycle, which is unsubstituted or substituted with 1-5 of R13, (h) â€”NO2, (i) phenyl, (j) â€”CO2R9, (k) tetrazolyl, (l) â€”NR9R10, (m) â€”NR9â€”COR10, (n) â€”NR9â€”CO2R10, (o) â€”COâ€”NR9R10, (p) â€”OCOâ€”NR9R10, (q) â€”NR9COâ€”NR9R10, (r) â€”S(O)mâ€”R9, wherein m is an integer selected from 0, 1 and 2, (s) â€”S(O)2â€”NR9R10, (t) â€”NR9S(O)2â€”R10, (u) â€”NR9S(O)2â€”NR9R10, (v) â€”C2-6 alkenyl, (w) furanyl, which is unsubstituted or substituted with benzyl which is unsubstituted or substituted with 1-7 of R13 wherein R13 is independently as defined above, (x) â€”C3-6 cycloalkyl, (y) â€”Oâ€”C3-6 cycloalkyl, and (y) oxo; R4 is hydrogen or C1-6 alkyl; R5 is phenyl, naphthyl, or heterocycle, wherein any one of which is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from: (a) halo, (b) trifluoromethyl, (c) hydroxy, (d) C1-3 alkyl, (e) â€”Oâ€”C1-3 alkyl, (f) â€”CO2R9, (g) â€”NR9R10, and (h) â€”CONR9R10; R6 is hydrogen, C1-10 alkyl, C3-8 cycloalkyl, â€”(C1-3 alkyl)-C3-8 cycloalkyl, â€”(C0-2 alkyl)-(C3-8 cycloalkylidenyl)-(C1-2 alkyl), C2-10 alkenyl, C2-10 alkynyl, cyclohexenyl, phenyl, â€”(C1-6 alkyl)-phenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, octahydronaphthyl, biphenyl, or heterocycle; wherein any of which except for hydrogen is unsubstituted or substituted with 1-7 of R11 where R11 is independently as defined above; R7 is hydrogen or C1-6 alkyl, wherein the alkyl is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from: (a) halo, (b) trifluoromethyl, (c) hydroxy, (d) C1-3 alkyl, (e) â€”Oâ€”C1-3 alkyl, (f) â€”CO2R9, (g) â€”NR9R10, and (h) â€”CONR9R10; or alternatively R6 and R7 together with the carbon atom to which they are attached form a C3-8 cycloalkyl ring which may be unsubstituted or substituted with 1-7 of R11; R8a and R8b are each independently hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, phenyl, naphthyl, or heterocycle; wherein any one of which except hydrogen is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from: (a) halo, (b) C1-4 haloalkyl, (c) hydroxy, (d) C1-4 alkyl, (e) â€”Oâ€”C1-4 alkyl, (f) â€”Oâ€”C1-4 haloalkyl, (g) C3-8 cycloalkyl, (h) â€”CO2Ra, (i) â€”NRaRb, and (i) â€”CONRaRb; alternatively R8a and R8b together with the carbon atom to which they are attached form: (a) a 3- to 8-membered saturated carbocyclic ring, (b) a 4- to 8-membered monocyclic heterocycle containing from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, (c) a 5- to 8-membered saturated carbocyclic ring to which is fused a C3-8 cycloalkyl, or (d) a 5- to 8-membered heterocyclic ring containing from 1 to 3 heteroatoms selected from nitrogen, oxygen and sulfur, to which is fused a C3-8 cycloalkyl, wherein the ring system of (a), (b), (c) or (d) is optionally substituted with from 1 to 3 substituents selected from halo, C1-4 alkyl, C1-4 haloalkyl, â€”Oâ€”C1-4 alkyl, â€”Oâ€”C1-4 haloalkyl, and hydroxy; or a pharmaceutically acceptable salt thereof.