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

doi:10.5246/jcps.2017.02.008

中国药学(英文版) ›› 2017, Vol. 26 ›› Issue (2): 95-105.DOI: 10.5246/jcps.2017.02.008

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

Nidhi Kala¹, Anand Gaurav^2*, Vertika Gautam³

1. School of Pharmaceutical Sciences, Shobhit University, Modipuram, Meerut 250110, India
2. Faculty of Pharmaceutical Sciences, UCSI University, No. 1, UCSI Heights, Jalan Menara Gading, Taman Connaught, Kuala Lumpur 56000, Federal Territory of Kuala Lumpur
3. Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

收稿日期:2016-11-15 修回日期:2016-12-15 出版日期:2017-02-28 发布日期:2016-12-26
通讯作者: Tel.: +60176894547, E-mail: anand.pharma@gmail.com, anand@ucsiuniversity.edu.my

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

Nidhi Kala¹, Anand Gaurav^2*, Vertika Gautam³

1. School of Pharmaceutical Sciences, Shobhit University, Modipuram, Meerut 250110, India
2. Faculty of Pharmaceutical Sciences, UCSI University, No. 1, UCSI Heights, Jalan Menara Gading, Taman Connaught, Kuala Lumpur 56000, Federal Territory of Kuala Lumpur
3. Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur 50603, Malaysia

Received:2016-11-15 Revised:2016-12-15 Online:2017-02-28 Published:2016-12-26
Contact: Tel.: +60176894547, E-mail: anand.pharma@gmail.com, anand@ucsiuniversity.edu.my

摘要/Abstract

摘要：

Gemfibrozil 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.

关键词: Atherosclerosis, Coronary heart disease, Fibrates, Bioisosterism, Hypolipidemic effect, Gemfibrozil

Abstract: Gemfibrozil 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.

Key words: Atherosclerosis, Coronary heart disease, Fibrates, Bioisosterism, Hypolipidemic effect, Gemfibrozil

中图分类号:

R916

Supporting:

Nidhi Kala, Anand Gaurav, Vertika Gautam. Syntheses, characterization, and evaluation of novel non-carboxylic analogues of Gemfibrozil: a bioisosteric approach[J]. 中国药学(英文版), 2017, 26(2): 95-105.

Nidhi Kala, Anand Gaurav, Vertika Gautam. Syntheses, characterization, and evaluation of novel non-carboxylic analogues of Gemfibrozil: a bioisosteric approach[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(2): 95-105.

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

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

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