Patent ID: 6117909
Filing Date: 2000-09-12
Classification: A61K,A61P,Y10S

Abstract:
A method for lowering the serum or plasma level of Lp(a) in a mammal in need thereof, comprising administering to said mammal an amount effective for lowering the serum or plasma level of said Lp(a) of a compound of formula: ##STR5## or a pharmaceutically acceptable salt thereof wherein: X and Y are selected from oxygen, sulfur and (CR'R"").sub.n wherein n is an integer of from 1 to 4 and R' and R"" are each independently hydrogen, alkyl, alkoxy, halogen, hydroxy, acyloxy, cycloalkyl, phenyl optionally substituted or R' and R"" together form a spirocycloalkyl or a carbonyl; with the proviso at least one of X and Y is (CR'R"").sub.n and with the further proviso when X and Y are both (CR'R"").sub.n and R' and R"" are hydrogen and n is one, R.sub.1 and R.sub.2 are aryl;R is hydrogen, a straight or branched alkyl of from 1 to 8 carbon atoms or benzyl;R.sub.1 and R.sub.2 are each independently selected from(a) phenyl or phenoxy each of which is unsubstituted or is substituted with 1 to 5 substituents selected fromphenyl,an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;phenoxy,hydroxy,fluorine,chlorine,bromine,nitro,trifluoromethyl,--COOH,--COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,--(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p is zero or one, and each of R.sub.3 and R.sub.4 is selected from hydrogen or a straight or branched alkyl group having 1 to 4 carbon atoms;(b) 1- or 2-naphthyl unsubstituted or substituted with from 1 to 3 substituents selected fromphenyl,an alkyl group having from 1 to 6 carbon atoms and which is straight or branched,an alkoxy group having from 1 to 6 carbon atoms and which is straight or branched;hydroxy,phenoxy,fluorine,chlorine,bromine,nitro,trifluoromethyl,--COOH,--COOalkyl wherein alkyl has from 1 to 4 carbon atoms and is straight or branched,--(CH.sub.2).sub.p NR.sub.3 R.sub.4 wherein p, R.sub.3 and R.sub.4 have the meanings defined above;(c) arylalkyl;(d) a straight or branched alkyl chain having from 1 to 20 carbon atoms and which is saturated or contains from 1 to 3 double bonds; or(e) adamantyl or a cycloalkyl group wherein the cycloalkyl moiety has from 3 to 6 carbon atoms;with the provisos:(i) where X is (CH.sub.2).sub.n, Y is oxygen, and R.sub.1 is a substituted phenyl, then R.sub.2 is a substituted phenyl;(ii) where Y is oxygen, X is (CH.sub.2).sub.n, R.sub.2 is phenyl or naphthyl; then R.sub.1 is not a straight or branched alkyl chain; and(iii) the following compounds are excluded: X Y R R.sub.1 R.sub.2  CH.sub.2 O H (CH.sub.2).sub.2 CH.sub.3 Ph CH.sub.2 O H CH.sub.3 Ph - CH.sub.2 O H Pr. iSTR6##