某些氨基酸衍生物的合成及其抗惊厥活性。第2部分：甘氨酸、丙氨酸、亮氨酸、脯氨酸、色氨酸、对氯苯丙氨酸、α-甲基丙氨酸的衍生物

Synthesis and anticonvulsant activity of some amino acid derivatives. Part 2: Derivatives of Gly, Ala, Leu, Pro, Trp, Phe(4 Cl), Ala(alpha-Me).

作者信息

Paruszewski R, Rostafinska-Suchar G, Strupinska M, Jaworski P, Winiecka I, Stables J P

机构信息

Department of Pharmaceutical Chemistry, Medical University, Warszawa, Poland.

出版信息

Pharmazie. 1996 Apr;51(4):212-5.

PMID:8628738

Abstract

Fourteen amides of N-substituted natural and anatural amino acids have been designed and synthesized as potential anticonvulsants. They were evaluated in the maximal electroshock seizure (MES) test, the subcutaneous Metrazol seizure threshold (sc Met) test and the rotorod neurotoxicity (Tox) test. According to the classification of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) eight of synthesized compounds received class I, two class II and four class III. One of the compounds classified in class I (18) was tested quantitatively after i.p. administration in mice. It showed MES ED50 = 67.41 mg/kg and protective index (PI) = 4.5. Conformational models of the synthesized compounds were compared to one another, as well as to models of some standard compounds.

摘要

已设计并合成了十四种N-取代天然和非天然氨基酸的酰胺，作为潜在的抗惊厥剂。它们在最大电休克惊厥（MES）试验、皮下戊四氮惊厥阈值（sc Met）试验和转棒神经毒性（Tox）试验中进行了评估。根据抗癫痫药物开发计划（ADDP）的抗惊厥筛选项目（ASP）的分类，八种合成化合物被归为I类，两种为II类，四种为III类。对I类（18号）中的一种化合物进行了小鼠腹腔注射后的定量测试。它的MES ED50 = 67.41 mg/kg，保护指数（PI） = 4.5。将合成化合物的构象模型相互比较，也与一些标准化合物的模型进行了比较。