{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T14:24:15Z","timestamp":1788272655225,"version":"build-2803163510"},"reference-count":60,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"am","delay-in-days":329,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2022,7]]},"DOI":"10.1016\/j.bioorg.2022.105754","type":"journal-article","created":{"date-parts":[[2022,3,26]],"date-time":"2022-03-26T18:38:50Z","timestamp":1648319930000},"page":"105754","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype"],"prefix":"10.1016","volume":"124","author":[{"given":"Ingridhy O.M.F.","family":"da Silveira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iluska S.B.","family":"Moslaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9ssica A.I.","family":"Muller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiane R.W.","family":"Hortelan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Juliano Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane T.","family":"Okuyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bretton","family":"Badenoch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana","family":"Jana\u00edna de Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro D.","family":"Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyan","family":"Mohammad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allana C.F.","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adilson","family":"Beatriz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eufr\u00e2nio N.","family":"da Silva J\u00fanior","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f4nica","family":"Cristina Toffoli-Kadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"da Silva Gomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.bioorg.2022.105754_h0005","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1002\/1097-4679(200102)57:2<197::AID-JCLP6>3.0.CO;2-O","article-title":"An emotion-focused approach to the overregulation of emotion and emotional pain","volume":"57","author":"Greenberg","year":"2001","journal-title":"Clin. Psychol."},{"issue":"4","key":"10.1016\/j.bioorg.2022.105754_h0010","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.bjp.0707239","article-title":"Inhibition of cyclooxygenases by dipyrone","volume":"151","author":"Pierre","year":"2007","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.bioorg.2022.105754_h0015","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.neubiorev.2014.08.002","article-title":"Emotional consequences of neuropathic pain: insight from preclinical studies","volume":"47","author":"Yalcin","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"issue":"7","key":"10.1016\/j.bioorg.2022.105754_h0020","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1021\/jm0613166","article-title":"Structural and functional basis of cyclooxygenase inhibition","volume":"50","author":"Blobaum","year":"2007","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_h0025","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1111\/j.1526-4637.2010.00983.x","article-title":"Causes and consequences of inadequate management of acute pain","volume":"11","author":"Sinatra","year":"2010","journal-title":"Pain. Med."},{"issue":"11","key":"10.1016\/j.bioorg.2022.105754_h0030","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/nsb1196-927","article-title":"Flexibility of the NSAID binding site in the structure of human cyclooxygenase-2","volume":"3","author":"Luong","year":"1996","journal-title":"Nat. Struct. Biol."},{"key":"10.1016\/j.bioorg.2022.105754_h0035","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.pneurobio.2008.09.018","article-title":"Towards a theory of chronic pain","volume":"87","author":"Apkarian","year":"2009","journal-title":"Prog. Neurobiol."},{"issue":"6610","key":"10.1016\/j.bioorg.2022.105754_h0040","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/384644a0","article-title":"Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents","volume":"384","author":"Kurumbail","year":"1996","journal-title":"Nature"},{"key":"10.1016\/j.bioorg.2022.105754_h0045","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S1734-1140(10)70308-X","article-title":"Vane's discovery of the mechanism of action of aspirin changed our understanding of its clinical pharmacology","volume":"62","author":"Botting","year":"2010","journal-title":"Pharmacol. Rep."},{"issue":"5486","key":"10.1016\/j.bioorg.2022.105754_h0050","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1126\/science.289.5486.1933","article-title":"The productive conformation of arachidonic acid bound to prostaglandin synthase","volume":"289","author":"Malkowski","year":"2000","journal-title":"Science"},{"key":"10.1016\/j.bioorg.2022.105754_h0055","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.2165\/11208240-000000000-00000","article-title":"Celecoxib: a review of its use for symptomatic relief in the treatment of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis","volume":"71","author":"McCormack","year":"2011","journal-title":"Drugs"},{"issue":"33","key":"10.1016\/j.bioorg.2022.105754_h0060","doi-asserted-by":"crossref","first-page":"23305","DOI":"10.1074\/jbc.274.33.23305","article-title":"The binding of arachidonic acid in the cyclooxygenase active site of mouse prostaglandin endoperoxide synthase-2 (COX-2). A putative L-shaped binding conformation utilizing the top channel region","volume":"274","author":"Rowlinson","year":"1999","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_b0035","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1185\/03007995.2010.486301","article-title":"Diclofenac: an update on its mechanism of action and safety profile","volume":"26","author":"Gan","year":"2010","journal-title":"Curr. Med. Res. Opin."},{"key":"10.1016\/j.bioorg.2022.105754_b0040","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1007\/s10787-009-0016-x","article-title":"Ibuprofen: pharmacology, efficacy and safety","volume":"17","author":"Rainsford","year":"2009","journal-title":"Inflammo. Pharmacol."},{"key":"10.1016\/j.bioorg.2022.105754_b0045","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1136\/bmj.320.7241.1058","article-title":"Non-steroidal anti-inflammatory drugs","volume":"320","author":"G\u00f8tzsche","year":"2000","journal-title":"BMJ"},{"key":"10.1016\/j.bioorg.2022.105754_b0050","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.med.53.082901.103952","article-title":"Cyclooxygenase-2: a therapeutic target","volume":"53","author":"Turini","year":"2002","journal-title":"Annu. Rev. Med."},{"key":"10.1016\/j.bioorg.2022.105754_b0055","doi-asserted-by":"crossref","first-page":"27S","DOI":"10.1016\/S0002-9343(99)00365-4","article-title":"Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs)","volume":"107","author":"Rainsford","year":"1999","journal-title":"Am. J. Med."},{"key":"10.1016\/j.bioorg.2022.105754_b0060","first-page":"1319","article-title":"Adjunct dipyrone in association with oral morphine for cancer-related pain: the sooner the better","volume":"15","author":"Duarte Souza","year":"2007","journal-title":"Supp. Care Cancer"},{"key":"10.1016\/j.bioorg.2022.105754_b0065","first-page":"CD003227","article-title":"Single dose dipyrone for acute postoperative pain","volume":"9","author":"Edwards","year":"2010","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.bioorg.2022.105754_b0070","first-page":"CD011421","article-title":"Single dose dipyrone (metamizole) for acute postoperative pain in adults","volume":"4","author":"Hearn","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"10.1016\/j.bioorg.2022.105754_b0075","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1007\/s00482-015-0003-7","article-title":"Pain medication in nursing home residents with and without cancer. Most frequently with metamizole","volume":"29","author":"Schulze","year":"2015","journal-title":"Schmerz."},{"key":"10.1016\/j.bioorg.2022.105754_b0080","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.mrgentox.2016.05.009","article-title":"4-Aminoantipyrine reduces toxic and genotoxic effects of doxorubicin, cisplatin, and cyclophosphamide in male mice, Mut","volume":"805","author":"Berno","year":"2016","journal-title":"Res. Gen. Toxicol. Environm. Mutagen."},{"key":"10.1016\/j.bioorg.2022.105754_b0085","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s002280050511","article-title":"Cerebrospinal fluid and plasma concentrations of dipyrone metabolites after a single oral dose of dipyrone","volume":"54","author":"Cohen","year":"1998","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"10.1016\/j.bioorg.2022.105754_b0090","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/sj.bjp.0707239","article-title":"Inhibition of cyclooxygenases by dipyrone","volume":"151","author":"Pierre","year":"2007","journal-title":"Braz. J. Pharmacol."},{"key":"10.1016\/j.bioorg.2022.105754_b0095","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0014-2999(99)00477-X","article-title":"Regulation of cyclooxygenase activity by metamizole","volume":"378","author":"Campos","year":"1999","journal-title":"Eur. J. Pharmacol."},{"issue":"suppl 5","key":"10.1016\/j.bioorg.2022.105754_b0100","doi-asserted-by":"crossref","first-page":"S202","DOI":"10.1086\/317520","article-title":"Mechanism of action of acetaminophen: is there a cyclooxygenase 3?","volume":"31","author":"Botting","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.bioorg.2022.105754_b0105","doi-asserted-by":"crossref","first-page":"13926","DOI":"10.1073\/pnas.162468699","article-title":"COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic\/antipyretic drugs: cloning, structure, and expression","volume":"99","author":"Chandrasekharan","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"10.1016\/j.bioorg.2022.105754_b0110","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bmc.2011.11.028","article-title":"Novel bioactive metabolites of dipyrone (metamizol)","volume":"20","author":"Rogosch","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_b0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-015-1532-2","article-title":"A novel cytosporone 3-Heptyl-4, 6-dihydroxy-3-H-isobenzofuran-1-one: synthesis; toxicological, apoptotic and immunomodulatory properties; and potentiation of mutagenic damage","volume":"15","author":"Oliveira","year":"2015","journal-title":"BMC cancer"},{"key":"10.1016\/j.bioorg.2022.105754_b0120","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.taap.2018.08.004","article-title":"New Bis copper complex ((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl) oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice","volume":"356","author":"de Oliveira","year":"2018","journal-title":"Toxicol. Appl. Pharm."},{"key":"10.1016\/j.bioorg.2022.105754_b0125","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1590\/1678-4685-gmb-2017-0279","article-title":"Assessment of the toxicogenic effects and cell death potential of the ester (Z)-methyl 4-((1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)amino)-4-oxobut-2-anoate in combination with cisplatin, cyclophosphamide and doxorubicin","volume":"42","author":"Oliveira","year":"2019","journal-title":"Gen. Mol. Biol."},{"key":"10.1016\/j.bioorg.2022.105754_b0130","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1146\/annurev.biophys.36.040306.132550","article-title":"Calculation of protein-ligand binding affinities","volume":"36","author":"Gilson","year":"2007","journal-title":"Annu. Rev. Biophys. Biomol. Struct."},{"key":"10.1016\/j.bioorg.2022.105754_b0135","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1002\/jcc.20013","article-title":"Development and evaluation of a generic evolutionary method for protein-ligand docking","volume":"25","author":"Yang","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_b0140","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.bbrc.2007.06.122","article-title":"Surface plasmon resonance studies and biochemical evaluation of a potent peptide inhibitor against cyclooxygenase-2 as an anti-inflammatory agent","volume":"361","author":"Somvanshi","year":"2007","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.bioorg.2022.105754_b0145","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1194\/jlr.R800042-JLR200","article-title":"Cyclooxygenases: structural and functional insights","volume":"50","author":"Rouzer","year":"2009","journal-title":"J. Lipid. Res."},{"key":"10.1016\/j.bioorg.2022.105754_b0150","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bioorg.2022.105754_b0155","doi-asserted-by":"crossref","first-page":"6752","DOI":"10.1021\/jm901241e","article-title":"Escape from flatland: increasing saturation as an approach to improving clinical success","volume":"52","author":"Lovering","year":"2009","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_b0160","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(00)00129-0","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"46","author":"Lipinski","year":"2001","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"10.1016\/j.bioorg.2022.105754_b0165","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3181\/00379727-111-27849","article-title":"Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs","volume":"111","author":"Winter","year":"1962","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"10.1016\/j.bioorg.2022.105754_b0170","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/path.1711040103","article-title":"Studies on the mediators of the acute inflammatory response induced in rats in different sites by Carrageenan and turpentine","volume":"104","author":"Di Rosa","year":"1971","journal-title":"J. Pathol."},{"key":"10.1016\/j.bioorg.2022.105754_b0175","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0304-3959(87)90088-1","article-title":"The formalin test in mice: dissociation between inflammatory and non-inflammatory pain","volume":"30","author":"Hunskaar","year":"1987","journal-title":"Pain"},{"key":"10.1016\/j.bioorg.2022.105754_b0180","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/j.1742-7843.2010.00648.x","article-title":"A novel COX-2 inhibitor pyrazole derivative proven effective as an anti-inflammatory and analgesic drug, Basic","volume":"108","author":"El-Din","year":"2011","journal-title":"Clin. Pharmacol. Toxicol."},{"key":"10.1016\/j.bioorg.2022.105754_b0185","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nri3908","article-title":"How leukocytes cross the vascular endothelium","volume":"15","author":"Vestweber","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.bioorg.2022.105754_b0190","doi-asserted-by":"crossref","first-page":"5954","DOI":"10.1073\/pnas.0812782106","article-title":"Prostaglandin mediates IL-23\/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFNgamma production","volume":"106","author":"Lemos","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.bioorg.2022.105754_b0195","doi-asserted-by":"crossref","first-page":"60","DOI":"10.2165\/00003495-198600324-00006","article-title":"Pyrazolone derivatives","volume":"32","author":"Brogden","year":"1986","journal-title":"Drugs"},{"key":"10.1016\/j.bioorg.2022.105754_b0200","doi-asserted-by":"crossref","first-page":"10272","DOI":"10.1073\/pnas.180319297","article-title":"Nociception in cyclooxygenase isozyme-deficient mice","volume":"97","author":"Ballou","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.bioorg.2022.105754_b0205","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0014-2999(99)00790-6","article-title":"Involvement of resident macrophages and mast cells in the writhing nociceptive response induced by zymosan and acetic acid in mice","volume":"387","author":"Ribeiro","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.bioorg.2022.105754_b0210","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1073\/pnas.0409225102","article-title":"A cascade of cytokines mediates mechanical inflammatory hypernociception in mice","volume":"102","author":"Cunha","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.bioorg.2022.105754_b0215","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/35093019","article-title":"Molecular mechanisms of nociception","volume":"413","author":"Julius","year":"2001","journal-title":"Nature"},{"key":"10.1016\/j.bioorg.2022.105754_b0220","doi-asserted-by":"crossref","first-page":"4442","DOI":"10.1073\/pnas.0914733107","article-title":"Morphine peripheral analgesia depends on activation of the PI3Kgamma\/AKT\/nNOS\/NO\/KATP signaling pathway","volume":"107","author":"Cunha","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.bioorg.2022.105754_b0225","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1007\/s00424-010-0784-6","article-title":"Understanding inflammatory pain: ion channels contributing to acute and chronic nociception","volume":"459","author":"Linley","year":"2010","journal-title":"Pflugers Arch."},{"key":"10.1016\/j.bioorg.2022.105754_b0230","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/1472-6882-14-181","article-title":"Antioxidant, total phenolic contents and antinociceptive potential of Teucrium stocksianum methanolic extract in different animal models","volume":"14","author":"Shah","year":"2014","journal-title":"BMC Complement. Altern. Med."},{"key":"10.1016\/j.bioorg.2022.105754_b0235","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/ajg.2011.443","article-title":"Double-blind randomized trials of single-tablet ibuprofen\/high-dose famotidine vs. ibuprofen alone for reduction of gastric and duodenal ulcers","volume":"107","author":"Laine","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"10.1016\/j.bioorg.2022.105754_b0240","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1111\/cbdd.12712","article-title":"Synthesis of Novel Substituted Thiourea and Benzimidazole Derivatives Containing a Pyrazolone Ring as Anti-Inflammatory Agents","volume":"87","author":"Moneer","year":"2016","journal-title":"Chem. Biol. Drug. Des."},{"key":"10.1016\/j.bioorg.2022.105754_b0245","doi-asserted-by":"crossref","first-page":"67","DOI":"10.2174\/157016306776637573","article-title":"Anti-inflammatory and anti-oxidant activity of a new class of phenyl-pyrazolone derivatives","volume":"3","author":"Cusan","year":"2006","journal-title":"Curr. Drug. Discov. Technol."},{"key":"10.1016\/j.bioorg.2022.105754_b0250","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/cbdd.12324","article-title":"Synthesis and biologic evaluation of substituted 5-methyl-2-phenyl-1H-pyrazol-3(2H)-one derivatives as selective COX-2 inhibitors: molecular docking study","volume":"84","author":"Dube","year":"2014","journal-title":"Chem. Biol. Drug. Des."},{"key":"10.1016\/j.bioorg.2022.105754_b0255","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.bmcl.2018.01.043","article-title":"Design, synthesis, anti-inflammatory activity and molecular docking of potential novel antipyrine and pyrazolone analogs as cyclooxygenase enzyme (COX) inhibitors","volume":"28","author":"El Sayed","year":"2018","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.bioorg.2022.105754_b0260","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1016\/j.bmc.2014.02.042","article-title":"Synthesis and biological evaluation of new pyrazolone-pyridazine conjugates as anti-inflammatory and analgesic agents","volume":"22","author":"Khalil","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_b0265","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.bioorg.2022.105754_b0270","unstructured":"The PyMOL Molecular Graphics System, Version 1.2r3pre, Schr\u00f6dinger, LLC. http:\/\/pymol.sourceforge.net\/faq.html."}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206822001596?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206822001596?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:36:51Z","timestamp":1758616611000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206822001596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7]]},"references-count":60,"alternative-id":["S0045206822001596"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2022.105754","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2022,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2022.105754","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"105754"}}