申请人:ZENECA LIMITED
公开号:EP0431856A2
公开(公告)日:1991-06-12
This invention concerns novel compounds of the formula I :
in which P is a group of formula II or a group of formula III; R1 is alkyl, cydoalkyl, cycloalkylalkyl, phenyl or phenylalkyl; R2 is hydrogen, alkyl, amino or alkylamino ; R3 and R4 are independently hydrogen, alkyl, phenyl or benzyl; R6 is alkyl, amino or alkylamino ; C and D are independently ethylene or trimethylene; Z is a direct bond between C and D, or an oxy, thio, carbonyl, methylene, ethylenedioxymethylene, ethylidene, or isopropylidene link, or Z is a group of the formula = N.R5 in which R5 is alkyl, phenyl or benzyl ; R8 is hydrogen, cycloalkylalkyl, alkyl, alkenyl, alkynyl or phenylalkyl; or R8 is a alkylene or alkenylene linked to the nitrogen atom of the group Q.A.N-, either of which linking groups may optionally bear a alkyl, phenyl or phenylalkyl substituent and either of which linking groups thereby completes a ring including two adjacent carbon atoms of ring Q, any carbon atoms in A and the adjacent nitrogen atom of the group ―A.N―; A is a direct bond to the the group ―N(R8)― or is alkylene ; Q is a phenyl or pyridyl moiety; Y is a physiologically acceptable anion ; and wherein any one or more of said phenyl, benzene or pyridyl moieties may optionally be unsubstituted or bear one or more selected substituents.
The invention also indudes certain closely related anhydo-base derivatives which, like the compounds of formula I, possess beneficial effects on the cardiovascular system (and in particular beneficial effects modulated via the sino-atrial node). Also included are pharmaceutical compositions containing compounds of formula I (or a related anhydro-base) as active ingredient, and processes for the manufacrture of the various novel compounds.
本发明涉及式 I 的新型化合物:
其中 P 是式 II 的基团或式 III 的基团;R1 是烷基、环烷基、环烷基烷基、苯基或苯基烷基;R2 是氢、烷基、氨基或烷基氨基;R3 和 R4 独立地是氢、烷基、苯基或苄基;R6 是烷基、氨基或烷基氨基;C 和 D 独立地是亚乙基或三亚甲基;Z 是 C 和 D 之间的直接键,或氧键、硫键、羰基键、亚甲基键、亚乙基二氧亚甲基键、亚乙基键或异亚丙基键,或 Z 是式 = N 的基团。其中 R5 是烷基、苯基或苄基;R8 是氢、环烷基烷基、烷基、烯基、炔基或苯基烷基;或 R8 是与基团 Q.A.N- 的氮原子相连的亚烷基或亚烯基。A.N-,其中任一连接基团可选择性地带有烷基、苯基或苯基烷基取代基,并且其中任一连接基团由此完成一个环,该环包括环 Q 的两个相邻碳原子、A 中的任何碳原子以及基团 -A.N- 的相邻氮原子;A 是直接键。N-;A是与基团-N(R8)-的直接键,或者是亚烷基;Q是苯基或吡啶基;Y是生理上可接受的阴离子;其中所述苯基、苯或吡啶基中的任何一个或多个可任选为未取代的或带有一个或多个选定取代基。
本发明还包括某些密切相关的无水碱衍生物,它们与式 I 化合物一样,对心血管系统具有有益作用(尤其是通过窦房结调节的有益作用)。此外,还包括含有式 I 化合物(或相关酐基)作为活性成分的药物组合物,以及各种新型化合物的制造工艺。