新型γ-氨基丁酸受体激动剂——Schiff碱型γ-氨基丁酰胺的合成

Synthesis of 4-[(4-Chlorophenyl) (5-Fluoro-2-HydroxYphenyl) Methylene Amino] Butanamide

本文合成了最新的γ-氨基丁酸受体激动剂,4-〔(4-氯苯基)(5-氟-2-羟基苯基)亚甲氨基〕丁酰胺。在合成方法上作了较大的改进。提出并完成了合成对-氟苯酚的新方法;采用催化缩合新法合成Schiff碱。采用美国NIH提出的“抗癲痫药物开发程序”(ADD)进行抗惊厥活性试验,结果证明所合成的目标化合物具有较好的抗癫痫活性。

Progabide, 4-〔 (4-chlorophenyl) (5-fluro-2-hydroxYphenyl) methylene amino〕butanamide, is a lipophilic compound that crosses the blood-brain bar- rier and possesses low toxycity. It is the first specific GABA receptor agonist which has been undergone extensive clinical trials on epilepsy therapeutics. Author has synthesized progabide. In the synthesis of progabide, author used p-methoxyaniline instead of 4-chloronitrobenzene to prepare p-fluorophenol by Schiemann reaction; Schiff base was prepared in 71% yield by refluring (4-chlorophenyl) (5-fluro-2-hydroxyphenyl) methanone with 4-amino- butanamide in xylene which contains a trace of boron trifluoride etherate. The title compound was evaluated as anticonvulsant in mice via the Antiepi- letic Drug Development Program of NIH and showed anticonvulsant activity.