申请人:Schering Corporation
公开号:US05476847A1
公开(公告)日:1995-12-19
Phosphinic acid derivatives of the structural formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein R is H, alkyl or alkanoyloxymethylene; R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are H, alkyl, alkenyl, alkenylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, hydroxyalkyl, carboxyalkyl, thioalkyl, alkoxythioalkyl, aminoalkyl, alkylaminoalkyl, cycloalkyl-substituted alkyl or heterocycloalkyl; or R.sub.1 and R.sub.2 form a cycloalkyl ring of 3-8 members and R.sub.3 and R.sub.4 are as defined; or R.sub.3 and R.sub.4 form a cycloalkyl ring of 3-7 members and R.sub.1 and R.sub.2 are as defined; or R.sub.1 and R.sub.2 together, and R.sub.3 and R.sub.4 together, each form a cycloalkyl ring; R.sub.5 is --OR.sub.9 or --NHR.sub.9, wherein R.sub.9 is hydrogen or alkyl; n is 0 or 1; A.sub.1 is p-aminobenzoyl or p-aminobenzenesulfonyl, or A.sub.1 and R.sub.5 together form a radical of an .alpha.-aminoacyl derivative; and R.sub.6 is phenylmethoxycarbonyl, arylcarbonyl, heteroarylcarbonyl or --A.sub.2 --R.sub.7, wherein A.sub.2 is a divalent .alpha.-aminoacyl radical, and R.sub.7 is a substituent on the .alpha.-amino atom selected from H, R.sub.8 OCO--, R.sub.8 SO.sub.2 -- and R.sub.8 NHCO--, wherein R.sub.8 is aryl, arylmethyl or (C.sub.1 -C.sub.8)alkyl; are disclosed for use as endothelin converting enzyme inhibitors; also disclosed are a genus of novel compounds wherein R.sup.3 and R.sup.4 form a cycloalkyl ring, and pharmaceutical compositions comprising said novel compounds.
磷酸衍生物的结构式为##STR1##或其药学上可接受的盐,其中R为H、烷基或烷酰氧亚甲基;R.sub.1、R.sub.2、R.sub.3和R.sub.4为H、烷基、烯基、烯基烷基、芳基、芳基烷基、杂芳基、杂芳基烷基、羟基烷基、羧基烷基、硫代烷基、烷氧硫代烷基、氨基烷基、烷基氨基烷基、环烷基取代烷基或杂环烷基;或R.sub.1和R.sub.2形成3-8个成员的环烷基环,R.sub.3和R.sub.4如定义;或R.sub.3和R.sub.4形成3-7个成员的环烷基环,R.sub.1和R.sub.2如定义;或R.sub.1和R.sub.2一起,R.sub.3和R.sub.4一起,各自形成一个环烷基环;R.sub.5为--OR.sub.9或--NHR.sub.9,其中R.sub.9为氢或烷基;n为0或1;A.sub.1为对氨基苯甲酰基或对氨基苯磺酰基,或A.sub.1和R.sub.5一起形成α-氨基酰衍生物的基团;R.sub.6为苯甲氧羰基、芳基羰基、杂芳基羰基或--A.sub.2--R.sub.7,其中A.sub.2为二价的α-氨基酰基基团,R.sub.7为α-氨基原子上的取代基,选自H、R.sub.8 OCO--、R.sub.8 SO.sub.2--和R.sub.8 NHCO--,其中R.sub.8为芳基、芳基甲基或(C.sub.1-C.sub.8)烷基;用作内皮素转化酶抑制剂;还披露了一类新化合物,其中R.sup.3和R.sup.4形成环烷基环,以及包含所述新化合物的药物组合物。