申请人:A. H. Robins Company, Incorporated
公开号:US04895840A1
公开(公告)日:1990-01-23
Novel N-(Aryl-,aryloxy-,arylthio-,arylsulfinyl-and arylsulfonyl-)alkyl-N,N'-(or N',N')alkylaminoalkyl ureas, thioureas and cyanoguanidines represented by the following formula: ##STR1## wherein Ar is aryl selected from the group consisting of 1- and 2-naphthyl, 2,3-dihydro-1H-inden-4(or 5)-yl,2-furanylmethyl,2-pyridinyl, phenyl and phenyl substituted by 1-3 radicals commonly used in the pharmaceutical art; (X).sub.d is oxygen, thio, sulfinyl, sulfonyl or d is zero; Z and W are each R or-(CH.sub.2).sub.m -NR.sup.1 R.sup.2 wtih the proviso that when Z is R, W is-(CH.sub.2).sub.m -NR.sup.1 R.sup.2 and when Z is-(CH.sub.2).sub.m -NR.sup.1 R.sup.2, W is R; B is carbonyl, thioxomethyl, or cyanoiminomethyl; R, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are selected from the group consisting of hydrogen, loweralkyl, cycloalkyl, phenyl or phenyl-loweralkyl wherein phenyl may be substituted by 1-3 radicals commonly used in the pharmaceutical art; R.sup.1 and R.sup.2, and R.sup.3 and R.sup.4 may together with the adjacent nitrogen form the heterocyclic ring structure 1-homopiperidinyl, 4-morpholinyl, 1-piperazinyl, 4-substituted-1-piperazinyl, 1-pyrrolidinyl or 1-piperidinyl and the pharmaceutically acceptable salts thereof are disclosed. A pharmaceutical method for administering the compounds for their cardiac antiarrhythmic effect and pharmaceutical compositions for the treatment of cardiac arrhythmia are also disclosed.
以下公式所代表的小说N-(芳基,芳氧基,芳硫基,芳基磺酰基和芳基亚磺酰基)-烷基-N,N' -(或N',N')烷基氨基烷基脲,硫脲和氰脲:##STR1##
其中Ar是从1-和2-萘基,2,3-二氢-1H-茚-4(或5)-基,2-呋喃甲基,2-吡啶基,苯基和苯基取代物中选择的芳基;(X).sub.d是氧,硫,亚磺酰基,磺酰基或d为零;Z和W分别为R或-(CH.sub.2).sub.m-NR.sup.1R.sup.2,但是当Z为R时,W为-(CH.sub.2).sub.m-NR.sup.1R.sup.2,当Z为-(CH.sub.2).sub.m-NR.sup.1R.sup.2时,W为R;B是羰基,硫代甲基或氰基亚甲基;R,R.sup.1,R.sup.2,R.sup.3和R.sup.4从氢,低碳基,环烷基,苯基或苯基-低碳基中选择,其中苯基可以被常用于制药的1-3个基团取代;R.sup.1和R.sup.2,R.sup.3和R.sup.4可以与相邻的氮一起形成杂环环结构1-同源哌啶基,4-吗啉基,1-哌嗪基,4-取代-1-哌嗪基,1-吡咯基或1-哌啶基及其制药可接受的盐。还公开了一种用于治疗心脏抗心律失常作用的化合物的药物方法以及用于治疗心脏心律失常的制药组合物。