Abstract
A novel series of 2-phenyl-5-(1,3-diphenyl-1H-pyrazol-4-yl)-1,3,4-oxadiazoles were designed and synthesized for selective COX-2 inhibition with potent anti-inflammatory activity. Among the compounds tested, 9g (2-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-5-phenyl-1,3,4-oxadiazole) was found to be the most potent inhibitor of COX-2 with IC50 of 0.31 μM showing promising degree of anti-inflammatory activity in the carrageenan-induced rat paw edema model with ED50 of 74.3 mg/kg. The lead compound 9g further showed suppression of acetic acid-induced writhes comparable to that of aspirin and gastro-sparing profile superior to the aspirin. Molecular docking analysis displayed higher binding affinity of ligands towards COX-2 than COX-1.
Keywords:
1,3,4-Oxadiazole; Analgesic; Anti-inflammatory; COX-2; Molecular docking analysis; Pyrazole.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Analgesics / adverse effects
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Analgesics / chemical synthesis
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Analgesics / metabolism
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Analgesics / pharmacology
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / adverse effects
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / metabolism
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Chemistry Techniques, Synthetic
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 / metabolism*
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Cyclooxygenase 2 Inhibitors / adverse effects
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Cyclooxygenase 2 Inhibitors / chemical synthesis*
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Cyclooxygenase 2 Inhibitors / metabolism
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Humans
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Male
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Mice
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Molecular Docking Simulation
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Oxadiazoles / adverse effects
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Oxadiazoles / chemical synthesis*
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Oxadiazoles / metabolism
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Oxadiazoles / pharmacology*
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Protein Conformation
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Rats
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Stomach Ulcer / chemically induced
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Structure-Activity Relationship
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Substrate Specificity
Substances
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Analgesics
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Oxadiazoles
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1,3,4-oxadiazole
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Cyclooxygenase 1
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Cyclooxygenase 2