title: 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 μM; selectivity index > 1298). It was more selective than the reference drug celecoxib (COX-2 IC(50) = 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-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.
authors: Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors: Afshin
authors: A
authors: Zarghi
authors: Farin Sattary
authors: FS
authors: Javid
authors: Razieh
authors: R
authors: Ghodsi
authors: Orkideh G
authors: OG
authors: Dadrass
authors: Bahram
authors: B
authors: Daraei
authors: Mehdi
authors: M
authors: Hedayati