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

作者：Arfaie Sara; Zarghi Afshin^*

来源：European Journal of Medicinal Chemistry, 2010, 45(9): 4013-4017.

DOI：10.1016/j.ejmech.2010.05.058

• Cyclooxygenase-2 inhibition
• 1,2,3-Triaryl-2-propen-1-ones
• Synthesis
• Selectivity

A group of (E)-and (Z)-1,2,3-triaryl-2-propen-l-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 IC(50) = 0.07 mu M; 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.

• 出版日期2010-9