{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Rosa FA"],"funding":["Fundação Araucária","Conselho Nacional de Desenvolvimento Científico e Tecnológico","Coordenação de Aperfeiçoamento de Pessoal de Nível Superior"],"pagination":["1038-1045"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10953476"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(3)"],"pubmed_abstract":["In this paper, we present the design and synthesis of a novel series of pyrido[2,3-<i>d</i>]pyridazine-2,8-dione derivatives <i>via</i> the annulation of the 2-pyridone pattern. The synthesized derivatives were evaluated for <i>in vivo</i> anti-inflammatory activity using an ear edema model. Compound 7c, which showed a greater inhibition of ear edema (82%), was further tested for its <i>in vitro</i> COX-1/COX-2 inhibitory activity. Compound 7c showed similar inhibitory activities against COX-1 and COX-2 isoenzymes. The structural features that ensure the dual inhibition of COX-1 and COX-2 were elucidated using molecular docking studies. Overall, the ring closing of 2-pyridone pattern I transformed this highly selective COX-2 inhibitor into a dual COX inhibitor (7c), which could serve as a "],"journal":["RSC medicinal chemistry"],"pubmed_title":["Discovery of a new pyrido[2,3-<i>d</i>]pyridazine-2,8-dione derivative as a potential anti-inflammatory agent through COX-1/COX-2 dual inhibition."],"pmcid":["PMC10953476"],"funding_grant_id":["311457/2022-3"],"pubmed_authors":["Nakamura CV","Goncalves DS","Lazarin-Bidoia D","Bersani-Amado CA","Ames FQ","Pianoski KE","Aguiar RP","Rosa FA","Volpato H","da Silva MJV"],"additional_accession":[]},"is_claimable":false,"name":"Discovery of a new pyrido[2,3-<i>d</i>]pyridazine-2,8-dione derivative as a potential anti-inflammatory agent through COX-1/COX-2 dual inhibition.","description":"In this paper, we present the design and synthesis of a novel series of pyrido[2,3-<i>d</i>]pyridazine-2,8-dione derivatives <i>via</i> the annulation of the 2-pyridone pattern. The synthesized derivatives were evaluated for <i>in vivo</i> anti-inflammatory activity using an ear edema model. Compound 7c, which showed a greater inhibition of ear edema (82%), was further tested for its <i>in vitro</i> COX-1/COX-2 inhibitory activity. Compound 7c showed similar inhibitory activities against COX-1 and COX-2 isoenzymes. The structural features that ensure the dual inhibition of COX-1 and COX-2 were elucidated using molecular docking studies. Overall, the ring closing of 2-pyridone pattern I transformed this highly selective COX-2 inhibitor into a dual COX inhibitor (7c), which could serve as a ","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-06-02T00:14:44.81Z","creation":"2025-04-04T02:23:00.428Z"},"accession":"S-EPMC10953476","cross_references":{"pubmed":["38516591"],"doi":["10.1039/d3md00604b"]}}