Patent ID: 6248755
Filing Date: 2001-06-19
Classification: A61P,C07D

Abstract:
A compound of the formula I: ##STR822##wherein:R.sup.1 is selected from:(1) --CO.sub.2 H,(2) --NO.sub.2,(3) -tetrazolyl,(4) -hydroxyisoxazole,(5) --SO.sub.2 NH--(CO.sub.0-3 alkyl)--R.sup.9, wherein R.sup.9 is independently selected from: hydrogen, C.sub.1-6 alkyl, C.sub.5-6 cycloalkyl, benzyl or phenyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from: halo, C.sub.1-3 alkyl, C.sub.1-3 alkoxy and trifluoromethyl,(6) --SO.sub.2 NHCO--(CO.sub.0-3 alkyl)-R.sup.9, wherein R.sup.9 is independently selected from: hydrogen, C.sub.1-6 alkyl, C.sub.5-6 cycloalkyl, benzyl or phenyl, which is unsubstituted or substituted with 1-3 substituents where the substituents are independently selected from: halo, C.sub.1-3 alkyl, C.sub.1-3 alkoxy and trifluoromethyl, and(7) --P(O)(OH).sub.2 ;R.sup.2 is selected from the group consisting of: ##STR823##wherein R.sup.7 is selected from:(1) hydrogen,(2) C.sub.1-6 alkyl, which is unsubstituted or substituted with 1-4 substituents where the substituents are independently selected from: hydroxy, cyano, and halo,(3) cyano,(4) hydroxy, and(5) halo,and wherein R.sup.8 is selected from:phenyl, naphthyl, biphenyl, and heterocycle, which is unsubstituted or substituted with 1-7 of R.sup.11 where R.sup.11 is independently selected from:(a) halo,(b) cyano,(c) hydroxy,(d) C.sub.1-6 alkyl, which is unsubstituted or substituted with 1-5 of R.sup.12 where R.sup.12 is independently selected from: halo, cyano, hydroxy, C.sub.1-6 alkoxy, --CO.sub.2 H, --CO.sub.2 (C.sub.1-6 alkyl), trifluoromethyl, --NR.sup.9 R.sup.1 O (where R.sup.9 is defined above and R.sup.10 is independently selected from the definitions of R.sup.9), phenyl, naphthyl, biphenyl, and heterocycle,wherein phenyl, naphthyl, biphenyl, or heterocycle is unsubstituted or substituted with 1-7 of R.sup.13 where R.sup.13 is independently selected from: halo, cyano, hydroxy, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, --CO.sub.2 H, --CO.sub.2 (C.sub.1-6 alkyl), trifluoromethyl, --NR.sup.9 R.sup.10, --(C.sub.1-6 alkyl)--NR.sup.9 R.sup.10, --SO.sub.2 R.sup.9, C.sub.1-6 fluoroalkoxy, --(C.sub.1-6 alkyl)hydroxy, C.sub.3-6 cycloalkyloxy, benzyloxy, phenoxy, and --NO.sub.2,(e) --O--C.sub.1-6 alkyl, which is unsubstituted or substituted with 1-5 of R.sup.12,(f) --O-phenyl, which is unsubstituted or substituted with 1-5 of R.sup.13,(g) --O-heterocycle, which is unsubstituted or substituted with 1-5 of R.sup.13,(h) --CF.sub.3,(i) --CHF.sub.2,(j) --CH.sub.2 F,(k) --NO.sub.2,(j) phenyl,(m) --CO.sub.2 R.sup.9,(n) tetrazolyl,(o) --NR.sup.9 R.sup.10,(p) --NR.sup.9 --COR.sup.10,(q) --NR.sup.9 --CO.sub.2 R.sup.10,(r) --CO--NR.sup.9 R.sup.10,(s) --OCO--NR.sup.9 R.sup.10,(t) --NR.sup.9 CO--NR.sup.9 R.sup.10,(u) --S(O).sub.m --R.sup.9, wherein m is an integer selected from 0, 1 and 2,(v) --S(O).sub.2 --NR.sup.9 R.sup.10,(w) --NR.sup.9 S(O).sub.2 --R.sup.10,(x) --NR.sup.9 S(O).sub.2 --NR.sup.9 R.sup.10,(y) C.sub.2-6 alkenyl,(z) furanyl, which is unsubstituted or substituted with benzyl which is unsubstituted or substituted with 1-7 of R.sup.13 wherein R.sup.13 is independently as defined above, and(aa) R.sup.9, and(bb) --O--C.sub.3-6 cycloalkyl;R.sup.3 is selected from the group consisting of:phenyl, naphthyl, and heterocycle, which is unsubstituted or substituted with 1-7 substituents where the substituents are independently selected from:(a) halo,(b) trifluoromethyl,(c) hydroxy,(d) C.sub.1-3 alkyl,(e) --O--C.sub.1-3 alkyl,(f) --CO.sub.2 R.sup.9,(g) --NR.sup.9 R.sup.10, and(h) --CONR.sup.9 R.sup.10 ;R.sup.4 is selected from:C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl, --(C.sub.1-3 alkyl)-C.sub.3-8 cycloalkyl, --(C.sub.0-2 alkyl)-(C.sub.3-8 cycloalkylidenyl)-(C.sub.1-2 alkyl), C.sub.2-10 alkenyl, C.sub.2-10 alkynyl, phenyl, --(C.sub.1-6 alkyl)-phenyl, naphthyl, biphenyl, heterocycle, hydrogen, cyclohexenyl, dihydronaphthyl, tetrahydronaphthyl, and octahydronaphthyl, which is unsubstituted or substituted with 1-7 of R.sup.11 where R.sup.11 is independently as defined above;R.sup.5 is selected from:hydrogen or C.sub.1-6 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) C.sub.1-3 alkyl,(e) --O--C.sub.1-3 alkyl,(f) --CO.sub.2 R.sup.9,(g) --NR.sup.9 R.sup.10, and(h) --CONR.sup.9 R.sup.10,or where R.sup.4 and R.sup.5 may be joined together to form a C.sub.3-8 cycloalkyl ring which may be unsubstituted or substituted with 1-7 of R.sup.11 ;R.sup.6 is independently selected from:hydrogen or C.sub.1-6 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) C.sub.1-3 alkyl,(e) --O--C.sub.1-3 alkyl,(f) --CO.sub.2 R.sup.9,(g) --NR.sup.9 R.sup.10, and(h) --CONR.sup.9 R.sup.10 ;R.sup.14 is hydrogen or C.sub.1-6 alkyl;n is an integer selected from 0, 1, 2 and 3;or a pharmaceutically acceptable salt thereof or an individual diastereomer thereof.