ArticleMolecules (Basel, Switzerland)2026
Discovery of Potent PDE4 Inhibitors with 3(2H)-Pyridazinone Scaffold: Synthesis, In Silico Studies and In Vitro/Vivo Evaluation.
Claudia Vergelli, Letizia Crocetti, Gabriella Guerrini, Fabrizio Melani, Jordi Gracia, Maria Antonia Buil, Yolanda Garrido, Lluis Pagès, Joan Taltavull, Amadeu Gavaldà and 2 more
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In one paragraphArticle in Molecules (Basel, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
12 authors.
Claudia VergelliNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.ORCID 0000-0001-9774-8047 Letizia CrocettiNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.ORCID 0000-0003-3473-2683 Gabriella GuerriniNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.ORCID 0000-0001-6711-7965 Fabrizio MelaniNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
Jordi GraciaMedicinal Chemistry Department, Evotec (France) SAS, Campus Curie, 195, Route d'Espagne, 31036 Toulouse CEDEX, France.
Maria Antonia BuilNew Chemical Entities Discovery & Early Development, Almirall R&D, Carrer Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Spain.
Yolanda GarridoNew Chemical Entities Discovery & Early Development, Almirall R&D, Carrer Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Spain.
Lluis PagèsNew Chemical Entities Discovery & Early Development, Almirall R&D, Carrer Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Spain.
Joan TaltavullNew Chemical Entities Discovery & Early Development, Almirall R&D, Carrer Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Spain.
Amadeu GavaldàPharmacology, Almirall R&D, Carrer Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Spain.ORCID 0000-0001-7042-0041 Elena CalamaPharmacology, Almirall R&D, Carrer Laureà Miró 408-410, 08980 Sant Feliu de Llobregat, Spain.
Maria Paola GiovannoniNeurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.ORCID 0000-0003-0310-7850 Funding
No grant is acknowledged in the PubMed record.
6 · The paper itselfAbstract
Phospodiesterase 4 (PDE4) has long been an attractive target not only for the anti-inflammatory therapy in respiratory diseases, but also for other pathologies such as psoriatic arthritis and atopic dermatitis. In this study, we report the synthesis of 5-acetyl-2-ethyl-6-phenyl-3(2H)-pyridazinones differently substituted at position 4 with a variety of aryl/alkylamines, which act as potent PDE4B1 inhibitors in the low nanomolar range. The selectivity toward PDE4A4, PDE4D3 and HARBS, as well as the ability to inhibit TNFα production in human whole blood (hWB), was also evaluated for the most potent products, resulting in a small cluster of compounds with an interesting profile and two selected products (
Indexed as
Cyclic Nucleotide Phosphodiesterases, Type 4Drug DiscoveryPhosphodiesterase 4 InhibitorsPyridazinesAnimalsComputer SimulationHumansMolecular Docking SimulationMolecular StructureStructure-Activity RelationshipTumor Necrosis Factor-alphaCyclic Nucleotide Phosphodiesterases, Type 4Phosphodiesterase 4 InhibitorsPyridazinesTumor Necrosis Factor-alphadockinginhibitionin vivo testphosphodiesterases 4selectivity
Identifiers
PMID41752476
PMCPMC12943719
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