Angiotensin converting enzyme inhibitors and their production and use as pharmaceuticals
申请人:FISONS plc
公开号:EP0183398A1
公开(公告)日:1986-06-04
There are described compounds of formula I,
in which Z is R2CH(COOH)NH-, R1SCH2- or Ph(CH2)PPO(OH)-,
Ph is phenyl,
p is an integer from 1 to 6,
R, is hydrogen or RBCO-,
R8 is alkyl C1 to 10 or phenyl,
R is hydrogen or alkyl C1 to 10,
R2 is alkyl C1 to 10 or phenylalkyl C7 to 12,
R4 andR5, which may be the same or different, are each hydrogen, phenyl, naphthyl; a 5 or 6 membered alicyclic or heterocyclic ring each of which is optionally fused to a benzene ring; cycloalkyl containing 3 to 7 carbon atoms; or alkyl C1 to 10 optionally substituted by phenyl, napthyl or a 5 or 6 membered heterocyclic ring which latter is optionally fused to a benzene ring,
the phenyl, naphthyl or 5 or 6 membered alicyclic or heterocyclic ring (which latter two are optionally fused to a benzene ring (are all optionally substituted by one or more alkyl C1 to 10, alkoxy C1 to 10, halogen, phenylalkyl C7 to 12, phenylalkoxy C7 to 12, phenyl, hydroxy, =0, fluoroalkyl C1 to 10, cyano, nitro, phenylsulphonamido, dialkyl (C1 to 10) -amino-alkoxy (C1 to 10), alkylthio C1 to 10, or dialkyl (C1 to 10)-amino,
or R4 and R5 together form a - (CH2)4-, -(CH2)5-,
chain
R6 is hydrogen or alkyl C1 to 10,
q is 2 or 3,
n is 0 or 1,
Y is hydroxy or -NHS02R9, and
R9 is alkyl C1 to 10,
and pharmaceutically acceptable salts, esters and amides thereof.
There are also described methods for making the compounds, formulations containing them and their use, eg as antihypertensives.
所述化合物为式 I、
其中 Z 是 R2CH(COOH)NH-、R1SCH2- 或 Ph(CH2)PPO(OH)-、
Ph 是苯基、
p 是 1 至 6 的整数、
R 是氢或 RBCO-、
R8 是 C1-10 烷基或苯基、
R 是氢或 C1 至 10 的烷基、
R2 是 C1 至 10 的烷基或 C7 至 12 的苯基烷基、
R4 和 R5 可以相同或不同,各自为氢、苯基、萘基;5 或 6 个成员的脂环或杂环,其中每个环可选择与苯环融合;含 3 至 7 个碳原子的环烷基;或 C1 至 10 的烷基,可选择被苯基、萘基或 5 或 6 个成员的杂环取代,后者可选择与苯环融合、
苯基、萘基或 5 或 6 分子脂环或杂环(后两者可选择与苯环融合)均可选择被一个或多个 C1 至 10 烷基、C1 至 10 烷氧基、卤素取代、苯基烷基 C7 至 12、苯基烷氧基 C7 至 12、苯基、羟基、=0、氟烷基 C1 至 10、氰基、硝基、苯磺酰胺基、二烷基(C1 至 10)-氨基-烷氧基(C1 至 10)、烷硫基 C1 至 10 或二烷基(C1 至 10)-氨基、
或 R4 和 R5 共同形成-(CH2)4-、-(CH2)5-、
链
R6 是氢或 C1-10 烷基、
q 是 2 或 3
n 为 0 或 1、
Y 是羟基或-NHS02R9,以及
R9 是 C1 至 10 的烷基、
及其药学上可接受的盐、酯和酰胺。
此外,还介绍了制造这些化合物的方法、含有这些化合物的制剂及其用途,例如用作抗高血压药。