title: Design and synthesis of 1,3-diarylurea derivatives as selective cyclooxygenase (COX-2) inhibitors.
abstract: A group of 1,3-diarylurea derivatives, possessing a methylsulfonyl pharmacophore at the para-position of the N-1 phenyl ring, in conjunction with a N-3 substituted-phenyl ring (4-F, 4-Cl, 4-Me, 4-OMe), were designed and synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 1-(4-methylsulfonylphenyl)-3-(4-methoxyphenyl) urea (4e) as a potent COX-2 inhibitor (IC(50)=0.11 microM) with a high COX-2 selectivity index (SI=203.6) comparable to the reference drug celecoxib (COX-2 IC(50)=0.06 microM; COX-2 SI=405). The structure-activity data acquired indicate that the urea moiety constitutes a suitable scaffold to design new acyclic 1,3-diarylurea derivatives with selective COX-2 inhibitory activity.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, Shaheed Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Afshin
authors.initials: A
authors.lastname: Zarghi
authors.forename: Samaneh
authors.initials: S
authors.lastname: Kakhgi
authors.forename: Atefeh
authors.initials: A
authors.lastname: Hadipoor
authors.forename: Bahram
authors.initials: B
authors.lastname: Daraee
authors.forename: Orkideh G
authors.initials: OG
authors.lastname: Dadrass
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hedayati
mesh_terms: D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D001555:Benzene Derivatives; D052246:Cyclooxygenase 2 Inhibitors; D014508:Urea; D051546:Cyclooxygenase 2