- 作者: 楊憲桂
- 作者服務機構: 成功大學醫學系藥理科
- 中文摘要: Diazepam (1) is a frequently prescribed hypnotic/anxiolytic drug worldwide. 7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-l,4-benzodiazepin-2,2-dioxide(2) is an initial alkaline hydrolysis product of 1. The mechanisms in the conversion of 2 to 2- methylamino-5-chloro-.alpha.-(phenylbenzylidene)glycinate (3) 2-methylamino-5-chlorobenzophenone (4), and 1 in aqueous solutions with pH ranging from 0 to 12.2 is the subject of this report. Results of temperature-dependent hydrolysis kinetics and product identification indicated that: (1) in solutions with pH between 7 and 12.2, 2 underwent a ring-opening reaction to form 3; the rate decreased with increasing pH. (2) In solutions with pH between 2 and 7, 2 was rapidly converted to 3, followed by a pH-dependent conversion to 4; the rate increased with decreasing pH and became less sentitive to pH at pH .ltoreq. 4.5. (3) In solutions with pH between 0 and 2, 2 was rapidly converted to 4 and 1; the percentage of 1 increased with decreasing pH. (4) A 2 containing one oxygen-18 atom lost 50% of its oxygen-18 following conversion to 1 in 1 M HCl. In addition to understanding the mechanism in the transformations of 2 in various pH solutions, this study established a simple and efficient method in the quantitative conversion of 1 to 4 and in the preparation of an oxygen-18-containing 1 at C2 position.
- 英文摘要: --
- 中文關鍵字: Diazepam; Dioxide; Hydrolysis; Benzophenone; Oxygen-18 Labeling; Benzodiazepine
- 英文關鍵字: 二氮平;雙氧化物;水解;二苯甲酮;氧十八標幟;苯并二氮三烯柒圜