某些氨基酸衍生物的合成与抗惊厥活性。第1部分：丙氨酸衍生物。

Synthesis and anticonvulsant activity of some amino acid derivatives. Part 1: alanine derivatives.

作者信息

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

机构信息

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

出版信息

Pharmazie. 1996 Mar;51(3):145-8.

PMID:8900864

Abstract

Fifteen amides of N-substituted D-Ala, DL-Ala and beta Ala have been designed and synthesized as potential anticonvulsants. All obtained amides as well as one intermediate (8) were evaluated in the maximal electroshock seizure (MES) test, the subcutaneous Metrazol seizure threshold (sc Met) test and the rotorod neurotoxicity (Tox) test in mice. According to the classification of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) eight compounds received class I, three class II and five class III designations. Two of the most active compounds (20, 24) were tested quantitatively. They exhibited, after i.p. administration in mice, a large protective index (PI) 3.2 for 20 and 4.3 for 24 and after oral administration in rat PI > 18 for 20 and > 14 for 24.

摘要

已设计并合成了十五种 N-取代的 D-丙氨酸、DL-丙氨酸和 β-丙氨酸的酰胺，作为潜在的抗惊厥药。在小鼠的最大电休克惊厥（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，对所有得到的酰胺以及一种中间体（8）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，八种化合物被归类为 I 类，三种为 II 类，五种为 III 类。对两种活性最高的化合物（20、24）进行了定量测试。在小鼠腹腔注射给药后，它们表现出较大的保护指数（PI），20 号化合物为 3.2，24 号化合物为 4.3；在大鼠口服给药后，20 号化合物的 PI > 18，24 号化合物的 PI > 14。