公开(公告)号：US4877779A

公开(公告)日：1989-10-31

申请号：US194903

申请日：1988-05-17

申请人： Waclaw J. Rzeszotarski ,  Maria E. Guzewska ,  John P. Carter ,  Theodore C. Adams ,  Andrea C. Dupont ,  Carl Kaiser

发明人： Waclaw J. Rzeszotarski ,  Maria E. Guzewska ,  John P. Carter ,  Theodore C. Adams ,  Andrea C. Dupont ,  Carl Kaiser

IPC分类号： C07D339/08 ,  C07D409/04

CPC分类号： C07D409/04 ,  C07D339/08

摘要： Novel compounds and their salts are disclosed having the Formulas: ##STR1## wherein: R.sub.1 is hydrogen, phenyl, 9H-fluoren-9-yl, 10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5-yl, 5H-dibenzo[a,d]cyclohepten-5-yl, 1,2,3,4-tetrahydro-1-naphthyl, 9H-xanthen-9-yl, 9H-thioxanthen-9-yl, 2-chloro-9H-thioxanthen-9-yl, 4H-chromanyl, diphenylmethyl, phenylcycloalkylmethyl wherein the bridgehead methylene may optionally be substituted with a hydroxy group and any of the phenyl or benzo-fused rings may be substituted with one or more R.sub.5 groups wherein R.sub.5 is selected from halogen, trifluoromethyl, lower alkyl, hydroxy or lower alkoxy groups; andR.sub.2 and R.sub.3, which may be the same or different, are hydrogen, lower alkyl, phenylalkyl (C.sub.1 -C.sub.5), wherein the phenyl ring may be substituted with one or more R.sub.5 groups or NR.sub.2 R.sub.3 taken together are pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, or 1-piperazinyl (where the 4-position may optionally be substituted with hydrogen, lower alkyl, hydroxy-substituted lower alkyl, amino-substituted lower alkyl, or acetoxy-substituted lower alkyl;R.sub.4 is hydrogen, hydroxyl or trimethylsilyloxy;Ph is an unsubstituted phenyl group or a phenyl group substituted by one or more R.sub.5 groups; andn is 2-4.Pharmaceutical compositions effective as calcium channel blockers and therapeutic methods utilizing such compounds, particularly in the treatment of irritable bowel syndrome, are also disclosed.

摘要翻译： 公开了新的化合物及其盐，其具有下式：其中：R1是氢，苯基，9H-芴-9-基，10,11-二氢-5H-二苯并[a，d]环庚烯-1-酮， 噻吩-5-基，5H-二苯并[a，d]环庚烯-5-基，1,2,3,4-四氢-1-萘基，9H-呫吨-9-基，9H-噻吨-9-基， 氯代-9H-噻吨-9-基，4H-苯并二氢吡喃基，二苯基甲基，苯基环烷基甲基，其中桥头甲基可以任选被羟基取代，任何苯基或苯并稠合环可以被一个或多个R 5基团取代，其中R 5 选自卤素，三氟甲基，低级烷基，羟基或低级烷氧基; 和可以相同或不同的R 2和R 3是氢，低级烷基，苯基烷基（C 1 -C 5），其中苯环可以被一个或多个R 5基团取代，或者NR 2 R 3一起是吡咯烷基，哌啶基，吗啉基， 硫代吗啉基或1-哌嗪基（其中4位可以任选被氢取代，低级烷基，羟基取代的低级烷基，氨基取代的低级烷基或乙酰氧基取代的低级烷基; R 4是氢，羟基或三甲基甲硅烷氧基; Ph 是未被取代的苯基或被一个或多个R 5基取代的苯基; n是2-4。还公开了有效作为钙通道阻断剂的药物组合物和利用这些化合物，特别是治疗肠易激综合征的治疗方法 。