Patent ID: 6121325
Filing Date: 2000-09-19
Classification: A61K,A61P,C07D,C07K

Abstract:
A compound of the formula: ##STR185## wherein: R.sub.1 is aryl, aryl(C.sub.1 -C.sub.6 alkyl)-, or aryl(C.sub.0 -C.sub.5 alkyl)-K--(C.sub.1 -C.sub.5 alkyl)- wherein aryl is naphthyl,K is O, S(O).sub.m, N(R.sub.2)C(O), C(O)N(R.sub.2), OC(O), C(O)O, --CR.sub.2 .dbd.CR.sub.2 --, or --C.tbd.C--, where R.sub.2 and the alkyl groups may be further substituted by 1 to 9 halogen, S(O).sub.m R.sub.2a, 1 to 3 of OR.sub.2a or C(O)OR.sub.2a, and the aryl groups may be further substituted by 1 to 3 of C.sub.1 -C.sub.6 alkyl, 1 to 3 of halogen, 1 to 2 of OR.sub.2, methylenedioxy, S(O).sub.m R.sub.2, 1 to 2 of CF.sub.3, OCF.sub.3, nitro, N(R.sub.2)(R.sub.2), N(R.sub.2)C(O)(R.sub.2), C(O)OR.sub.2, C(O)N(R.sub.2)(R.sub.2), SO.sub.2 N(R.sub.2)(R.sub.2), or --N(R.sub.2)SO.sub.2 R.sub.2 ;each R.sub.1a is independently hydrogen or C.sub.1 -C.sub.4 alkyl;R.sub.2 is hydrogen, C.sub.1 -C.sub.6 alkyl, or C.sub.3 -C.sub.7 cycloalkyl, and where two C.sub.1 -C.sub.6 alkyl groups are present on one atom, they may be optionally joined to form a C.sub.3 -C.sub.8 cyclic ring, optionally including oxygen, sulfur, SO.sub.2 or NR.sub.2a,R.sub.2a is hydrogen or C.sub.1 -C.sub.6 alkyl;R.sub.3 and R.sub.3a are independently hydrogen, --C.sub.1 -C.sub.6 alkyl, --(CH.sub.2).sub.r (C.sub.3 -C.sub.7 cycloalkyl), (CH.sub.2).sub.r aryl, or C(O)aryl, where aryl is phenyl or naphthyl, and where the aryl can be substituted by 1 to 2 halogen, 1 to 2 OR.sub.2, 1 to 2 (C.sub.1 -C.sub.4 alkyl), (CH.sub.2).sub.r (OR.sub.2), (CH.sub.2).sub.r C(O)OR.sub.2, C(O)O(CH.sub.2).sub.r aryl, (CH.sub.2).sub.r C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.r C(O)N(R.sub.2)(CH.sub.2).sub.v aryl, (CH.sub.2).sub.r S(O).sub.m R.sub.2, (CH.sub.2).sub.r SO.sub.2 N(R.sub.2)(R.sub.2), (CH.sub.2).sub.r SO.sub.2 N(R.sub.2)(CH.sub.2).sub.v aryl,(CH.sub.2).sub.r 1H-tetrazol-5-yl, or (CH.sub.2).sub.r C(O)NH SO.sub.2 R.sub.2, where aryl is phenyl or naphthyl;R.sub.4 and R.sub.5 are independently hydrogen, C.sub.1 -C.sub.6 alkyl, substituted C.sub.1 -C.sub.6 alkyl where the substituents may be 1 to 5 halogen, 1 to 3 hydroxy, 1 to 3 C.sub.1 -C.sub.10 alkanoyloxy, 1 to 3 C.sub.1 -C.sub.6 alkoxy, phenyl, phenoxy, 2-furyl, C.sub.1 -C.sub.6 alkoxycarbonyl, S(O).sub.m (C.sub.1 -C.sub.6 alkyl); or R.sub.4 and R.sub.5 can be taken together to form --(CH.sub.2).sub.d L.sub.a (CH.sub.2).sub.e -- where L.sub.a is C(R.sub.2).sub.2, O, S(O).sub.m or N(R.sub.2a), and d and e are independently 1 to 3;R.sub.6 is hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl C.sub.1 -C.sub.6 alkyl or naphthyl C.sub.1 -C.sub.6 alkyl;A is: ##STR186## where x and y are independently 0, 1, 2 or 3; R.sub.7 and R.sub.7a are independently hydrogen, C.sub.1 -C.sub.6 alkyl, trifluoromethyl, phenyl, substituted C.sub.1 -C.sub.6 alkyl where the substituents are imidazolyl, phenyl, indolyl, p-hydroxyphenyl, OR.sub.2, S(O).sub.m R.sub.2, C(O)OR.sub.2, C.sub.3 -C.sub.7 cycloalkyl, N(R.sub.2)(R.sub.2), C(O)N(R.sub.2)(R.sub.2); or R.sub.7 and R.sub.7a can independently be joined to one or both of R.sub.4 and R.sub.5 groups to form an alkylene bridge between the terminal nitrogen and the alkyl portion of the R.sub.7 or R.sub.7a groups, wherein the bridge contains 1 to 5 carbons atoms;W is hydrogen, (CH.sub.2).sub.r C(O)OR.sub.2, (CH.sub.2).sub.r C(O)O(CH.sub.2).sub.v aryl, (CH.sub.2).sub.r C(O)N(R.sub.2)(R.sub.2), (CH.sub.2).sub.r C(O)N(R.sub.2)(CH.sub.2).sub.r aryl, (CH.sub.2).sub.r OR.sub.2, (CH.sub.2).sub.r O(CH.sub.2).sub.v aryl, (CH.sub.2).sub.r CN, (CH.sub.2).sub.r 1H-tetrazol-5-yl, (CH.sub.2).sub.r S(O).sub.m R.sub.2, (CH.sub.2).sub.r S(O).sub.m (CH.sub.2).sub.r aryl, (CH.sub.2).sub.r SO.sub.2 N(R.sub.2)(R.sub.2), (CH.sub.2).sub.r SO.sub.2 N(R.sub.2)(CH.sub.2).sub.r aryl, (CH.sub.2).sub.r N(R.sub.2)C(O)R.sub.2, (CH.sub.2).sub.r N(R.sub.2)C(O)(CH.sub.2).sub.r aryl, (CH.sub.2).sub.r N(R.sub.2)SO.sub.2 R.sub.2, or (CH.sub.2).sub.r N(R.sub.2)SO.sub.2 (CH.sub.2).sub.r aryl, where aryl is phenyl or naphthyl, and wherein the aryl groups may be substituted by 1-3 halogens, 1-3 R.sub.2, 1-3 OR.sub.2, S(O).sub.m R.sub.2, CF.sub.3, or C(O)OR.sub.2, and R.sub.2 may be substituted by 1-3 halogens, 1 to 2 OR.sub.2a, S(O).sub.m R.sub.2a, or C(O)OR.sub.2a ;m is 0, 1, or 2;n is 0 or 1;r is 0, 1, 2, or 3;v is 0, 1, or 2;and pharmaceutically acceptable salts and individual diastereomers thereof.