申请人:Syntex (U.S.A.) Inc.
公开号:US05688795A1
公开(公告)日:1997-11-18
The present invention relates to novel .alpha..sub.1 -adrenoceptor antagonists of Formula I: ##STR1## in which: p is 0 or 1; t is 0, 1 or 2; X is O, S or NR.sup.6 (in which R.sup.6 is hydro or (C.sub.1-6)alkyl); Y and Z are independently CH or N; R.sup.1 is hydro, hydroxy, halo, nitro, amino, cyano, (C.sub.1-4)alkylthio, acetylamino, trifluoroacetylamino, methylsulfonylamino, (C.sub.1-6)alkyl, (C.sub.3-6)cycloalkyl, (C.sub.3-6)cycloalkyl (C.sub.1-4)alkyl, oxazol-2-yl, aryl, heteroaryl, aryl (C.sub.1-4)alkyl, heteroaryl (C.sub.1-4)alkyl, (C.sub.1-6)alkyloxy, (C.sub.3-6)cycloalkyloxy, (C.sub.3-6)cycloalkyl (C.sub.1-4)alkyloxy, 2-propynyloxy, aryloxy, heteroaryloxy, aryl (C.sub.1-4)alkyloxy or heteroaryl (C.sub.1-4)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms and aryl or heteroaryl is optionally substituted with one to two substituents independently selected from halo and cyano); R.sup.2 is hydro, hydroxy, halo, cyano, (C.sub.1-6)alkyl or (C.sub.1-6)alkyloxy (wherein alkyl is optionally substituted with one to three halo atoms); R.sup.3 is -C (O)R.sup.7 (wherein R.sup.7 is (C.sub.1-6)alkyl, (C.sub.3-6)cycloalkyl, di(C.sub.1-4)alkylamino, N-(C.sub.1-4)alkyl-N-(C.sub.1-4)alkyloxyamino, (C.sub.1-4)alkyl((C.sub.1-4)alkyloxy)amino, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl or piperazin-1-yl); R.sup.4 is halo, hydroxy, cyano, (C.sub.1-6)alkyl or (C.sub.1-6)alkyloxy; and R.sup.5 is (C.sub.1-6)alkyl; and the pharmaceutically acceptable salts and N-oxides thereof.
本发明涉及以下式I的新型α1-肾上腺素受体拮抗剂:##STR1## 其中:p为0或1;t为0, 1或2;X为O、S或NR.sup.6(其中R.sup.6为羟基或(C.sub.1-6)烷基);Y和Z独立地为CH或N;R.sup.1为羟基、羟基、卤素、硝基、氨基、氰基、(C.sub.1-4)烷基硫基、乙酰氨基、三氟乙酰氨基、甲磺酰氨基、(C.sub.1-6)烷基、(C.sub.3-6)环烷基、(C.sub.3-6)环烷基(C.sub.1-4)烷基、噁唑-2-基、芳基、杂环芳基、芳基(C.sub.1-4)烷基、杂环芳基(C.sub.1-4)烷基、(C.sub.1-6)烷氧基、(C.sub.3-6)环烷氧基、(C.sub.3-6)环烷基(C.sub.1-4)烷氧基、2-丙炔氧基、芳氧基、杂环芳氧基、芳基(C.sub.1-4)烷氧基或杂环芳基(C.sub.1-4)烷氧基(其中烷基可选择性地用1至3个卤原子取代,芳基或杂环芳基可选择性地用1至2个独立选择的卤素和氰基取代);R.sup.2为羟基、羟基、卤素、氰基、(C.sub.1-6)烷基或(C.sub.1-6)烷氧基(其中烷基可选择性地用1至3个卤原子取代);R.sup.3为-C(O)R.sup.7(其中R.sup.7为(C.sub.1-6)烷基、(C.sub.3-6)环烷基、二(C.sub.1-4)烷基氨基、N-(C.sub.1-4)烷基-N-(C.sub.1-4)烷氧基氨基、(C.sub.1-4)烷基((C.sub.1-4)烷氧基)氨基、吡咯烷-1-基、哌啶-1-基、吗啉-4-基或哌嗪-1-基);R.sup.4为卤素、羟基、氰基、(C.sub.1-6)烷基或(C.sub.1-6)烷氧基;R.sup.5为(C.sub.1-6)烷基;以及其药学上可接受的盐和N-氧化物。