title: 4-substituted 1,5-diarylpyrazole, analogues of celecoxib: synthesis and preliminary evaluation of biological properties.
abstract: A number of 5-aryl-1-[4-(methylsulfonyl)-phenyl]-1H-pyrazoles and 4-(5-aryl-1H-pyrazol-1-yl)benzenesulfonamides 3, 4, 5, 6, analogues of the COX-2 selective inhibitor celecoxib (celebrex), were synthesized. In order to verify the effects on the biological properties of certain substituents put on position 4 of the pyrazole nucleus, some of these compounds were screened in vivo for their anti-inflammatory and analgesic activities. Moreover, sodium salts of carboxylic acids 4 were tested in vitro for their platelet anti-aggregating properties. The results of these preliminary biological assays showed that new derivatives are not endowed with improved anti-inflammatory and analgesic properties, in comparison with celecoxib. In addition, docking studies were carried out on the most significative compounds to evaluate their interaction mode at the active site of both COX-1 and COX-2. Some remarks about the SAR of this class of COX-inhibitors are drown out.
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008565:Membrane Proteins; D051379:Mice; D008958:Models, Molecular; D010147:Pain Measurement; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D010975:Platelet Aggregation Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; C496513:Ptgs1 protein, rat; D000068579:Celecoxib