反-2-(3,4-二氯苯基)-N-甲基-N-〔2-(1-吡咯烷基)环己基〕乙酰胺盐酸盐的合成

反-2-(3,4-二氯苯基)-N-甲基-N-〔2-(1-吡咯烷基)环己基〕乙酰胺盐酸盐(U-50488H,1)是近年国外报道的一个高选择性K-型阿片受体激动剂。动物实验结果表明1     

3,4-二氯-N-甲基-N-[反式-2-(1-△3-吡咯啉基)环己基]-苯乙酰胺盐酸盐的合成及其镇痛活性的研究

3, 4-Dichloro-N-methyl-N-[trans-2- (1-△³-pyrrolinyl)-cyclohexyl]-benzenacetamide hydrochloride (K-Ⅱ) was synthesized from N-methyl-7-azabicyclo [4.1.0] heptane by treatment with 2,5-dihydropyrrole to give N-[trans-2(1-△³-pyrrolinyl)-cyclohexyl]-N-methylamine which was amidated with 3,4-dichlorophenyl-acetic acid. K-Ⅱ is an analogue of U-50488 H(K-Ⅰ), a known kappa receptor agonist.The results of animal tests showed that K-Ⅱ is 3 times as potent as K-Ⅰ as an analgesic in the mouse hot plate test and 5 times in the mouse writhing test and that the affinity of K-Ⅱ for kappa receptor may be higher than that of K-Ⅰ. The general behavioural effects of these two agents are similar in mice.     

3,4-二氯-N-甲基-N-[反式-2-(1-△~3-吡咯啉基)环己基]-苯乙酰胺盐酸盐的合成及其镇痛活性的研究

U-50488H(K-Ⅰ)是国外近年来报道的一个高选择性的K-阿片受体激动剂,动物实验结果表明:该化谷物有较强的镇痛活性,且成瘾性较低、呼吸抑制较弱、无吗啡样毒副作用的新型麻醉镇痛剂。为了寻找一个对K-受体亲和性比U-50488H更大,而选择性与其相当的K-阿片受体激动剂,我们合成了3,4-二氯-N-甲基-N-[反式-2-(1-△-吡咯啉基)环己基]-苯乙酰胺盐酸盐(K-Ⅱ),取得了较好的结果。