强效镇痛剂研究——Ⅴ.N-[1-(β-羟基-β-苯乙基)-3-甲基-4-哌啶基]-N-丙酰苯胺(7302)酯类衍生物的合成及镇痛活性

本文报道了一系列N-[1-(β-酰氧基-β-苯乙基)-3-甲基-4-哌啶基]-N-丙酰苯胺类衍生物及其化学结构与镇痛强度之间的关系,并测定了几个代表化合物的镇痛作用时间及与阿片受体亲和力。实验结果表明,7302的β-羟基酯化后,均能维持一定的镇痛强度,其镇痛作用时间与母体化合物7302相近。从受体结合试验来看,酯化后与受体亲和的能力显著下降。

Studies on potent analgesics. V. Synthesis and analgesic activity of the ester derivatives of N-(1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl)-N-phenylpropan amide (7302)

In this paper, thestructure and activity relationship of a series of ester derivatives of N-[1-(2-hydroxy-2-phenylethyl)-3-methyl-4-piperidyl]-N-phenylpropanamide(7302) is reported. It was found that after esterification of the β-hydroxy group of 7302, the analgesic activity could be maintained at a rather high level. The duration of analgesic action of some compounds could not be prolonged. In the binding test in vitro, it was found that the derivatives of esterification of 7302 decreased the affinity for receptor markedly.