Design, synthesis and biological evaluation of new (E)- and (Z)-1,2,3-triaryl-2-propen-1-ones as selective COX-2 inhibitors

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• 作者：Sara Arfaie ; Afshin Zarghi
• 关键词：Cyclooxygenase-2 inhibition ; 1 ; 2 ; 3-Triaryl-2-propen-1-ones ; Synthesis ; Selectivity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：September 2010
• 年：2010
• 卷：45
• 期：9
• 页码：4013-4017
• 全文大小：220 K

文摘

A group of (E)-and (Z)-1,2,3-triaryl-2-propen-1-one derivatives possessing a methylsulfonyl COX-2 pharmacophore at the para position of the C-1 phenyl ring were synthesized and evaluated as selective COX-2 inhibitors. In vitro COX-1/COX-2 structure–activity relationships were determined by varying the substituents on the C-3 propenone moiety. Among the 1,2,3-triaryl-2-propen-1-ones, (Z)-1-(4-(methylsulfonyl)phenyl)-2,3-diphenylprop-2-en-1-one (3b) showed the most potency and selectivity on COX-2 inhibition (COX-2 IC₅₀ = 0.07 μM; selectivity index = 201). The Z-propenones were also found to be more potent and selective than their E-isomers for COX-2 inhibitory activity. The structure–activity data acquired indicate that the geometry of propenone and also the type of substituents on the C-3 propenone are important for COX-2 inhibitory activity.