Syntheses,characterization,and evaluation of novel non-carboxylic analogues of Gemfibrozil:a bioisosteric approach

• 作者: Anand Gaurav Nidhi Kala Vertika Gautam
• 来源期刊: 中国药学（英文版）
• 学科: 医学
• 年，卷（期）: 2017,（2）
• 所属期刊栏目: 研究论文
• 页码范围: 95-105
• 页数: 11页
• 分类号: R916
• 语种: 英文

摘要

Gernfibrozil is a widely used lipid modifying drug with well-established hypolipidemic and anti-atherosclerotic benefits;however,the presence of a carboxylic acid moiety in its structure is responsible for side effects in the gastrointestinal tract.The principle of bioisosterism was applied to design derivatives replacing the carboxylic acid group.The carboxylic acid group was replaced with bioisoteric groups,such as 1,2,4-triazole-3-thiol and hydroxamic acid.The derivatives were then synthesized,characterized,and evaluated in rats for reduced gastrointestinal irritation and hypolipidemic effects.Gemfibrozil was used as standard for comparison.The derivatives demonstrated less gastric irritation and retained hypolipidemic effects,however the hypolipidemic affects were significantly less than that of Gemfibrozil.The results of this study offers a direction for further research on the application of bioisosterism for the design of new derivatives of Gemfibrozil and other fibric acid derivatives.