Synthesis,cyclooxygenase inhibitory effects,and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and -2-alkylsulfonyl-1H-imidazole derivatives |
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| Authors: | Amir Assadieskandar Amirali Amirhamzeh Marjan Salehi Keriman Ozadali Seyed Nasser Ostad Abbas Shafiee Mohsen Amini |
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| Institution: | 1. Department of Medicinal Chemistry, Faculty of Pharmacy and Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran;2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 2142-L Katz Group Centre for Pharmacy and Health Research, Edmonton, Alberta, Canada T6G 2E9;3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Hacettepe, Sihhiye, 06100 Ankara, Turkey;4. Department of Toxicology and Pharmacology, Faculty of Pharmacy and Rational Drug Use Research Center, Tehran University of Medical Sciences, Tehran, Iran;5. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran 14176, Iran |
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| 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. |
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