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Sci. Pharm. 2008, 76(3), 361-376; doi:10.3797/scipharm.0805-20 (registering DOI)

Design and Synthesis of Some 5-Substituted-2-(4-(azido or methylsulfonyl)phenyl)-1H-indole Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors

1
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University (M.C), P.O. Box: 14155-6153,Tehran, Iran
2
Department of Toxicology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran
3
School of Pharmacy, Azad University, Tehran, Iran
4
Endocrine research center, Shahid Beheshti University (M.C),Tehran, Iran
*
Author to whom correspondence should be addressed.
Received: 27 May 2008 / Accepted: 7 July 2008 / Published: 8 July 2008
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Abstract

A group of 5-substituted-2-(4-azido or (methylsulfonyl)phenyl)-1H-indoles were designed and synthesized as selective cyclooxygenase (COX-2) inhibitors. In vitro COX-1 and COX-2 isozyme inhibition studies were carried out to investigate the effect of different substituents (H, F, Cl, Me, OMe) at C-5 position and different pharmacophore groups (azido or methylsulfonyl) at para position of phenyl ring at C-2 position of the 1H-indole ring on COX-2 selectivity and potency. The structure-activity relationship study of these compounds indicated that the introduction of a methoxy substituent at C-5 position and 4-(methylsulfonyl) phenyl group at C-2 position of the 1H-indole ring (compound 4e) had the best COX-2 selectivity (S.I= 291.2). A molecular modeling study where 4e was docked in the binding site of COX-2 showed that the methylsulfonyl group at para position of phenyl ring is oriented in the vicinity of the COX-2 secondary pocket.
Keywords: 2-Phenyl-1H-indoles; COX-2 inhibitors; SAR 2-Phenyl-1H-indoles; COX-2 inhibitors; 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.; TAHGHIGHI, A.; SOLEIMANI, Z.; DARAIE, B.; DADRASS, O.G.; HEDAYATI, M. Design and Synthesis of Some 5-Substituted-2-(4-(azido or methylsulfonyl)phenyl)-1H-indole Derivatives as Selective Cyclooxygenase (COX-2) Inhibitors. Sci. Pharm. 2008, 76, 361-376.

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