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Sci. Pharm. 2011, 79(3), 449-460; doi:10.3797/scipharm.1104-20

Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors

1
Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
Department of Pharmaceutical Chemistry, School of Pharmacy, Azad University, Tehran, Iran
3
Department of Toxicology, Tarbiat Modarres University, Tehran, Iran
4
Research Institute for Endocrine Sciences, Shahid Beheshti University (M.C), Tehran, Iran
*
Author to whom correspondence should be addressed.
Received: 25 April 2011 / Published: 25 July 2011
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Abstract

A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2 pharmacophore at the para position of the C-5 phenyl ring were designed and synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl-hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC50 = 0.077 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC50 = 0.060 μM; selectivity index = 405). A molecular modeling study where 4 was docked in the binding site of COX-2 indicated that the p-MeSO2 COX-2 pharmacophore group on the C-5 phenyl ring is oriented in the vicinity of the COX-2 secondary pocket. The results of this study showed that the type of substituent on the N-3 hydantoin ring substituent is important for COX-2 inhibitory activity.
Keywords: 5,5-Diarylhydantoin derivatives; COX-2 inhibition; Molecular modeling studies; SAR 5,5-Diarylhydantoin derivatives; COX-2 inhibition; Molecular modeling studies; SAR
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

ZARGHI, A.; SATTARY JAVID, F.; GHODSI, R.; DADRASS, O.G.; DARAEI, B.; HEDAYATI, M. Design, Synthesis and Biological Evaluation of New 5,5-Diarylhydantoin Derivatives as Selective Cyclooxygenase-2 Inhibitors. Sci. Pharm. 2011, 79, 449-460.

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