化学
吡啶
选择性
立体化学
环氧合酶
IC50型
效力
对接(动物)
酶
基因亚型
酶抑制剂
体外
分子模型
生物化学
药物化学
催化作用
基因
护理部
医学
作者
Azami Movahed Mahsa,Bahram Daraei,Afshin Zarghi
出处
期刊:Letters in Drug Design & Discovery
[Bentham Science]
日期:2016-08-26
卷期号:13 (8): 793-799
被引量:8
标识
DOI:10.2174/1570180813666160613090944
摘要
The close structural similarity between cyclooxygenase (COX) isoforms and also the lack of potent selective COX-2 inhibitors with low side effects, stimulate the development of new highly selective COX-2 inhibitors. In this study, a group of imidazo[1,2-a]pyridines was designed, synthesized and investigated to identify potent and selective COX-2 inhibitors. In vitro COX inhibition assay showed that all derivatives were selective COX2 inhibitors with IC50 values in the highly potent 0.07-0.18 µM range and COX-2 selectivity indexes (SI) in 57-217 range. 2-(4- (methylsulfonyl)phenyl)-3-(morpholinomethyl)H-imidazo[1,2-a]pyri-dine (6f) which possessing p-methylsulfonyl phenyl at C-2 of imidazo[1,2-a]pyridine ring, exhibited the highest COX-2 inhibitory selectivity and potency. Molecular modeling and docking studies indicated that synthesized compounds have a binding similar to that of the known inhibitor SC- 558 and also methylsulfonyl group can be inserted into the secondary pocket of COX-2. The ability of synthesized compounds for inhibition of platelet aggregation was also determined. Our results demonstrated that 6f was the most potent platelet aggregation inhibitor as well. Keywords: Cyclooxygenase-2 inhibition, platelet aggregation inhibitor, imidazo[1, 2-a]pyridines, molecular modeling, synthesis.
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