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Design, synthesis and biological evaluation of new 5,5-diarylhydantoin derivatives as selective cyclooxygenase-2 inhibitors.


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 IC(50) = 0.077 ?M; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC(50) = 0.060 ?M; selectivity index = 405). A molecular modeling study where 4 was docked in the binding site of COX-2 indicated that the p-MeSO(2) 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.

SUBMITTER: Zarghi A 

PROVIDER: S-EPMC3163375 | biostudies-literature | 2011 Jul-Sep

REPOSITORIES: biostudies-literature

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Design, synthesis and biological evaluation of new 5,5-diarylhydantoin derivatives as selective cyclooxygenase-2 inhibitors.

Zarghi Afshin A   Javid Farin Sattary FS   Ghodsi Razieh R   Dadrass Orkideh G OG   Daraei Bahram B   Hedayati Mehdi M  

Scientia pharmaceutica 20110725 3


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 IC(50) = 0.077 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC(50) = 0  ...[more]

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