源自大麻素的药物。2. 氮的碱性酯类和碳环类似物。

Drugs derived from cannabinoids. 2. Basic esters of nitrogen and carbocyclic analogs.

作者信息

Razdan R K, Terris B Z, Pars H G, Plotnikoff N P, Dodge P W, Dren A T, Kyncl J, Somani P

出版信息

J Med Chem. 1976 Apr;19(4):454-61. doi: 10.1021/jm00226a002.

Abstract

Various basic esters of nitrogen (2) and carbocyclic (3 and 4) analogs of cannabinoids were synthesized using dicyclohexylcarbodiimide in methylene chloride. The compounds in the three series werw studied in selected pharmacological tests in mice, rats, dogs, and cats. It was shown that making the basic ester from the phenol retains biological activity and can lead to a greater selectivity of action, particularly the antinociceptive activity. The most interesting esters were 5, 6, 10, and 14 in the nitrogen analogs series and 19 and 20 in the carbocyclic series. Compound 5 was more potent than codeine in the writhing, hot-plate, and tail-flick tests and is at present undergoing clinical testing. Compound 20 was very potent in the mouse audiogenic seizure test and is of interest as an anticovulsant agent.

摘要

使用二环己基碳二亚胺在二氯甲烷中合成了大麻素的氮（2）和碳环（3和4）类似物的各种碱性酯。在小鼠、大鼠、狗和猫的选定药理试验中研究了这三个系列的化合物。结果表明，由苯酚制备碱性酯可保留生物活性，并可导致更高的作用选择性，特别是抗伤害感受活性。氮类似物系列中最有趣的酯是5、6、10和14，碳环系列中是19和20。化合物5在扭体、热板和甩尾试验中比可待因更有效，目前正在进行临床试验。化合物20在小鼠听源性惊厥试验中非常有效，作为一种抗惊厥剂很受关注。