Patent ID: 6211184
Filing Date: 2001-04-03
Classification: A61K,C07D

Abstract:
A method of eliciting a vitronectin receptor antagonizing effect in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of a compound of the formula ##STR100##wherein X is selected from a 9- to 10-membered polycyclic ring system, wherein one or more of the rings is aromatic, and wherein the polycyclic ring system contains 0, 1, 2, 3 or 4 heteroatoms selected from N, O or S, and wherein the polycyclic ring system is either unsubstituted or substituted with R.sup.1 and R.sup.2 ;Y is selected from --(CH.sub.2).sub.r -- or --(CH.sub.2).sub.m --NR.sup.3 --(CH.sub.2).sub.t--;Z is ##STR101##R.sup.1, R.sup.2 and R.sup.4 are each independently selected from hydrogen, halogen, C.sub.1-10 alkyl, C.sub.3-8 cycloalkyl, C.sub.3-8 cycloheteroalkyl, C.sub.3-8 cycloalkyl C.sub.1-6 alkyl, C.sub.3-8 cycloheteroalkyl C.sub.1-6 alkyl, aryl, aryl C.sub.1-8 alkyl, amino, amino C.sub.1-8 alkyl, C.sub.1-3 acylamino, C.sub.1-3 acylamino C.sub.1-8 alkyl, (C.sub.1-6 alkyl).sub.q amino, (C.sub.1-6 alkyl).sub.q amino C.sub.1-8 alkyl, C.sub.1-4 alkoxy, C.sub.1-4 alkoxy C.sub.1-6 alkyl, hydroxycarbonyl, hydroxycarbonyl C.sub.1-6 alkyl, C.sub.1-3 alkoxycarbonyl, C.sub.1-3 alkoxycarbonyl C.sub.1-6 alkyl, hydroxycarbonyl-C.sub.1-6 alkyloxy, hydroxy, hydroxy C.sub.1-6 alkyl, C.sub.1-6 alkyloxy-C.sub.1-6 alkyl, nitro, cyano, trifluoromethyl, trifluoromethoxy, trifluoroethoxy, C.sub.1-8 alkyl-S(O).sub.q, (C.sub.1-8 alkyl).sub.q aminocarbonyl, C.sub.1-8 alkyloxycarbonylamino, (C.sub.1-8 alkyl).sub.q aminocarbonyloxy, oxo, (aryl C.sub.1-8 alkyl).sub.q amino, (aryl).sub.q amino, aryl C.sub.1-8 alkylsulfonylamino, or C.sub.1-8 alkylsulfonylamino;R.sup.3 is selected fromhydrogen,aryl-(CH.sub.2).sub.p --C.sub.1-5 alkoxycarbonyl,C.sub.3-8 cycloalkyl,(aryl).sub.q aminocarbonyl,(aryl C.sub.1-5 alkyl).sub.q aminocarbonyl,C.sub.1-8 alkyl,aryl C.sub.1-6 alkyl,C.sub.1-8 alkylsulfonyl,arylsulfonyl,aryl C.sub.1-6 alkylsulfonyl,C.sub.1-8 alkoxycarbonyl,aryloxycarbonyl,aryl C.sub.1-8 alkoxycarbonyl,C.sub.1-8 alkylcarbonyl,arylcarbonyl,aryl C.sub.1-6 alkylcarbonyl, or(C.sub.1-8 alkyl).sub.q aminocarbonyl,wherein any of the alkyl groups may be unsubstituted or substituted with R.sup.1 and R.sup.2 ;R.sup.8 is selected fromhydrogen,aryl,aryl-(CH.sub.2).sub.p --,HC.tbd.C--(CH.sub.2).sub.s --,C.sub.1-6 alkyl-C.tbd.C--(CH.sub.2).sub.s --,C.sub.3-7 cycloalkyl-C.tbd.C--(CH.sub.2).sub.s --,aryl-C.tbd.C--(CH.sub.2).sub.s --,C.sub.1-6 alkylaryl-C.tbd.C--(CH.sub.2).sub.s --,CH.sub.2.dbd.CH--(CH.sub.2).sub.s --,C.sub.1-6 alkyl-CH.dbd.CH--(CH.sub.2).sub.s --,C.sub.3-7 cycloalkyl-CH.dbd.CH--(CH.sub.2).sub.s --,aryl-CH.dbd.CH--(CH.sub.2).sub.s --,C.sub.1-6 alkylaryl-CH.dbd.CH--(CH.sub.2).sub.s --,C.sub.1-6 alkyl-SO.sub.2 -(CH.sub.2).sub.s --, orC.sub.1-6 alkylaryl-SO.sub.2 -(CH.sub.2).sub.s --; andR.sup.12 is selected fromhydrogen,C.sub.1-8 alkyl,aryl,aryl C.sub.1-8 alkyl,C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyl,aryl C.sub.1-8 alkylcarbonyloxy C.sub.1-4 alkyl,C.sub.1-8 alkylaminocarbonylmethylene, orC.sub.1-8 dialkylaminocarbonylmethylene;m, s and t are each independently an integer from 0 to 3;p is an integer from 0 to 4;q is an integer from 0 to 2;r is an integer from 0 to 6;and the pharmaceutically acceptable salts thereof.