1-(4-甲基-3-戊烯基)-3-甲基-4-(N-丙酰苯胺基)哌啶立体异构体的合成及其镇痛作用

SYNTHESIS AND ANALGESIC ACTIVITY OF 1-(4-METHYL-3-PENTENYL)-3-METHYL-4-(N-PROPIONYLANILINO)-PIPERIDINE AND ITS STEREOISOMERS

合成了具有强效镇痛活性的3-甲基芬太尼衍生物1-(4-甲基-3-戊烯基)-3-甲基-4-(N-丙酰苯胺基)哌啶(1)及其顺(±)反-(±)-和顺-(+)-、顺-(-)-异构体。小白鼠热板试验结果表明,其异构体的构效关系类似于3-甲基芬太尼,但1-乙基的β-苯基被 Me_2C=CH 基取代后降低了分子对阿片受体作用的立体选择性。

1-(4-Methyl-3-pentenyl)-3-methyl-4-(N-propionylanilino)piperidine(1),a 3-methyl fentanyl analog with very strong analgesic activity,and its cis-(±)-,trans-(±)-,cis-(+)-,cis-(-)-isomers were synthesized.Results in mouse hotplate test showed that the structure-analgesic activity relationships of these com-pounds were similar to that of stereoisomers of 3-methyl fentanyl,the resultsmeant that substitution of β-phenyl in 1-ethyl group by Me_2C=CH group reducedstereoselectivity of the molecular at opiate receptor.