4-甲氧羰基-4-N-丙酰苯胺基哌啶1位衍生物的合成及其镇痛作用

本文报道了一系列N--1(2-苯乙基-4-甲氧羰基-4-哌啶基]-N-丙酰苯胺(4-甲氧羰基芬太尼)哌啶环1位取代衍生物的合成及其镇痛活性;讨论了结构与镇痛活性之间的关系。药理试验结果表明,大部分化合物具有典型的吗啡样镇痛活性,是一类作用极强的麻醉性镇痛剂。特别是哌啶环1位β-苯环被取代乙烯基替代的化合物具有相当或接近子母体化合物的镇痛活性。其代表物1321的镇痛活性(ED_(50)=0.005mg/kg ip,小鼠,热板法)略强于4-甲氧羰基芬太尼(ED_(50)=0.0063 mg/kg)。

SYNTHESIS AND ANALGESIC ACTIVITY OF 1-SUBSTITUTED DERIVATIVES OF 4-METHOXYCARBONYL-4-N-PROPIONYLANILINEPIPERIDINE

In this paper, the synthesis and analgesic activities of a series of 1-substituted derivatives of N-1-(2-phenylethyl)-4-methoxycarbonyl-4-piperidinyl]-N-propionylanil ine (4-methoxycarbonyl fentanyl) are reported. Preliminary pharmacological results showed that most compounds in this series exhibited typical morphine-like action and that replacement of beta-phenyl group in the 1-position of piperidine ring of 4-methoxycarbonyl fentanyl by some substituents e.g., some substituted vinyl groups, heterocyclic (or alcyclic) radicals, alkyl groups or N-methyl-anilino groups, can keep strong analgesic activity. Especially, some substituted vinyl groups were found to be effective groups which could replace 1-beta-phenyl group of 4-methoxycarbonyl fentanyl. Compounds N-1-(3, 4-dimethyl-3-pentenyl)-4-methoxycarbonyl-4-piperidinyl]-N- propionylaniline(1321) and N-1-(4-methyl-3-pentenyl)-4-methoxycarbonyl-4-piperidinyl]-N- propionylaniline(1302) exhibited higher analgesic activity than that of 4-methoxycarbonyl fentanyl.