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1,5-二烷基-1,5-苯并二氮杂卓-2,4-二硫酮的合成与药理研究

[Synthesis and pharmacologic study of 1,5-dialkyl-1,5-benzodiazepine-2,4-dithiones].

作者信息

Zellou A, Keita A, Cherrah Y, Essassi E M, Hassar M

机构信息

Laboratoire de Pharmacologie et de Toxicologie, Faculté de Médecine et de Pharmacie, Rabat-Instituts, Maroc.

出版信息

Therapie. 1999 Sep-Oct;54(5):645-9.

Abstract

The synthesis and psychotropic activity of 1,5-diakyl-1,5-benzodiazepine-2,4-dithiones (alkyl = methyl, ethyl and benzyl radicals) were studied. Alkylation reactions were performed in catalytic conditions by phase transfer. These reactions allowed us to isolate only one kind of product N-alkyl. Acute toxicity studies were conducted according to European protocols in two species of appropriate mammals in order to discover the lethal doses. The activity of the compounds on the CNS was then studied, using a battery of compartmental tests used in psychopharmacology. No toxicity was demonstrated at therapeutic doses. Each product had a sedative effect more or less pronounced and different from the reference substance clobazam (Urbanyl). They also had myorelaxant and anxiolytic effects, even lengthening the hypnotic effect of thiopental (synergic action).

摘要

研究了1,5 - 二烷基 - 1,5 - 苯并二氮杂卓 - 2,4 - 二硫酮(烷基 = 甲基、乙基和苄基)的合成及其精神活性。烷基化反应在相转移催化条件下进行。这些反应使我们仅分离出一种产物N - 烷基。根据欧洲协议,在两种合适的哺乳动物中进行急性毒性研究,以确定致死剂量。然后,使用精神药理学中一系列分区试验研究这些化合物对中枢神经系统的活性。在治疗剂量下未显示出毒性。每种产物都有或多或少明显的镇静作用,且与参比物质氯巴占(乌班尼)不同。它们还具有肌松和抗焦虑作用,甚至延长了硫喷妥钠的催眠作用(协同作用)。

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