title: Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and -2-alkylsulfonyl-1H-imidazole derivatives.
abstract: A series of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and 2-alkylsulfonyl-1H-imidazole derivatives were synthesized. All compounds were tested in human blood assay to determine COX-1 and COX-2 inhibitory potency and selectivity. Among the synthesized compounds, 2-alkylthio series were more potent and selective than 2-sulfonylalkyl derivatives. In molecular modeling, interaction of 2-sulfonylalkyl moiety with Arg120 in COX-1 and an extra hydrogen bond with Tyr341 in COX-2 increased the residence time of ligands in the active site in 2-sulfonylalkyl and 2-alkylthio analogs, respectively.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Assadieskandar
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Amirali
authors.initials: A
authors.lastname: Amirhamzeh
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Salehi
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 2142-L Katz Group Centre for Pharmacy and Health Research, Edmonton, Alberta, Canada T6G 2E9; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Hacettepe, Sihhiye, 06100 Ankara, Turkey.
authors.forename: Keriman
authors.initials: K
authors.lastname: Ozadali
authors.affiliation: Department of Toxicology and Pharmacology, Faculty of Pharmacy and Rational Drug Use Research Center, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Seyed Nasser
authors.initials: SN
authors.lastname: Ostad
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Shafiee
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran. Electronic address: moamini@sina.tums.ac.ir.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
mesh_terms: D051545:Cyclooxygenase 1 / Q000097:blood; D051546:Cyclooxygenase 2 / Q000097:blood; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human