Patent ID: 6162798
Filing Date: 2000-12-19
Classification: A61K,A61P,Y10S

Abstract:
A method for inhibiting re-athenosis after PTCA, cerebrovascular contraction after subarachnoid hemorrhage and obliterating sclerosing arteritis, comprising administering to a patient in need thereof an effective amount of a compound of the formula ##STR58## wherein ring X is phenyl, substituted phenyl or 5- or 6-membered heterocyclic aryl;R.sup.1 and R.sup.2 are, independently, hydrogen, C.sub.1-8 alkyl, C.sub.3-7 cycloalkyl, C.sub.1-3 alkoxy, n-butoxy, i-butoxy, sec-butoxy, tert-butoxy, R.sup.20 R.sup.21 N-, trifluoromethyl, trifluoromethoxy, difluoromethoxy, fluoro, chloro, bromo, phenyl, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-tert-butylsilyloxy, hydroxymethyl or --O(CH.sub.2).sub.l OR.sup.22, where each of R.sup.20 and R.sup.21 is, independently, hydrogen or C.sub.1-3 alkyl, R.sup.22 is hydrogen or C.sub.1-3 alkyl, and l is 1, 2, or 3; or R.sup.1 and R.sup.2 together form --CH.dbd.CH--CH.dbd.CH-- or methylenedioxy, when they are at the o-position to each other;R.sup.3 is hydrogen, C.sub.1-8 alkyl, C.sub.2-6 alkenyl, C.sub.3-7 cycloalkyl, C.sub.5-7 cyloalkenyl or ##STR59## where R.sup.7 is hydrogen, C.sub.1-8 alkyl, C.sub.1-8 alkoxy, C.sub.1-3 alkylthio, chloro, bromo, fluoro, chloromethyl, trichloromethyl, trifluoromethyl, trifluoromethoxy, trichloromethoxy, difluoromethoxy, phenoxy, benzyloxy, hydroxy, trimethylsilyloxy, diphenyl-tert-butylsilyloxy or hydroxymethyl; or C.sub.1-3 alkyl substituted by ##STR60## wherein R.sup.7 is as defined above and zero, one or two C.sub.1-3 alkyl; Y is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, --CH.dbd.CH--CH.sub.2 --, --C(CH.sub.3).dbd.CH-- or --CH.dbd.C(CH.sub.3)--;Z is --Q--CH.sub.2 --W--CH.sub.2 --CO.sub.2 R.sup.12, ##STR61## wherein Q is --C(O)--, --C(OR.sup.13).sub.2 -- or --CH(OH)--, W is --C(O)--, --C(OR.sup.13).sub.2 -- or --C(R.sup.11)(OH)--,R.sup.11 is hydrogen or C.sub.1-3 alkyl,R.sup.12 is hydrogen, alkyl of a chemically or physiologically hydrolyzable alkyl ester moiety, NHR.sup.23 R.sup.24 R.sup.25, sodium, potassium or 1/2 calcium, where each of R.sup.23, R.sup.24 and R.sup.25 is independently hydrogen or C.sub.1-4 alkyl,each R.sup.13 is independently a primary or secondary C.sub.1-6 alkyl, or two R.sup.13 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 --, andeach of R.sup.15 and R.sup.16 is independently a hydrogen atom or C.sub.1-3 alkyl, or R.sup.15 and R.sup.16 together form --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 --.