Synthesis, molecular docking and biological evaluation of some newer 2-substituted-4-(benzo[d][1,3]dioxol-5-yl)-6-phenylpyridazin-3(2H)-ones as potential anti-inflammatory and analgesic agents.

Abstract	A new series of 2-substituted-4-(benzo[d][1,3]dioxol-5-yl)-6-phenylpyridazin-3(2H)-one derivatives has been synthesized and studied. The in vivo anti-inflammatory and analgesic activities of the synthesized compounds were evaluated using carrageen rat paw edema model and acetic acid induced writhing model, respectively. Side effect profile of the newly synthesized pyridazinones was assessed by gastric ulcerogenic and anti-platelet activity. The compounds were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2) by in vitro colorimetric COX (ovine) inhibitor screening assay method. The p-flourophenylpiperazine substituted analogue 14 exhibited most potent anti-inflammatory and analgesic activities with lower ulcer index and extremely good selectivity towards COX-2 versus COX-1 enzyme with a selectivity index of 10. Molecular docking studies showed appreciable binding of new pyridazinone analogues with the amino acids present at the active site of hCOX-2 enzyme.
Authors	Jyoti Singh, Vandana Saini, Ajit Kumar, Ranju Bansal
Journal	Bioorganic chemistry (Bioorg Chem) Vol. 71 Pg. 201-210 (04 2017) ISSN: 1090-2120 [Electronic] United States
PMID	28236449 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2017 Elsevier Inc. All rights reserved.
Chemical References	Analgesics Anti-Inflammatory Agents, Non-Steroidal Cyclooxygenase Inhibitors Pyridazines 5,6-diphenylpyridazin-3-one Carrageenan Cyclooxygenase 1 Cyclooxygenase 2
Topics	Analgesics (adverse effects, chemistry, pharmacology, therapeutic use) Animals Anti-Inflammatory Agents, Non-Steroidal (adverse effects, chemistry, pharmacology, therapeutic use) Blood Platelets (drug effects) Carrageenan Cyclooxygenase 1 (metabolism) Cyclooxygenase 2 (metabolism) Cyclooxygenase Inhibitors (adverse effects, chemistry, pharmacology, therapeutic use) Edema (chemically induced, drug therapy) Humans Male Mice Molecular Docking Simulation Pyridazines (adverse effects, chemistry, pharmacology, therapeutic use) Rats, Wistar Stomach Ulcer (chemically induced)

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