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Solubility-driven optimization of phosphodiesterase-4 inhibitors leading to a clinical candidate

التفاصيل البيبلوغرافية
العنوان: Solubility-driven optimization of phosphodiesterase-4 inhibitors leading to a clinical candidate
المؤلفون: Sandra Haberthuer, Trixie Wagner, Lyndon Nigel Brown, Julia Hatto, Nicola Arnold, Clive Mccarthy, Julie Christie, John R. Fozard, Helene Sahri, Helen Oakman, Thomas H. Keller, Roger J. Taylor, Robert Cheung, Mark Keenan, Neil John Press, Joseph D. Fullerton, Andrew R. Tuffnell, Alexandre Trifilieff, John W. Tyler, David Beer, Alastair Denholm, Morris Tweed, Mark Mercer, Pamela Tranter
المصدر: Journal of medicinal chemistry. 55(17)
سنة النشر: 2012
مصطلحات موضوعية: Models, Molecular, Magnetic Resonance Spectroscopy, Chemistry, Vomiting, Drug Evaluation, Preclinical, Pharmacology, Bioavailability, Rats, Disease Models, Animal, Mice, Phosphodiesterase-4, Pharmacokinetics, Solubility, In vivo, Drug Design, Drug Discovery, Aqueous solubility, Molecular Medicine, Animals, Humans, Phosphodiesterase 4 Inhibitors, Cells, Cultured
الوصف: The solubility-driven optimization of a series of 1,7-napthyridine phosphodiesterase-4 inhibitors is described. Directed structural changes resulted in increased aqueous solubility, enabling superior pharmacokinetic properties with retention of PDE4 inhibition. A range of potent and orally bioavailable compounds with good in vivo efficacy in animal models of inflammation and reduced emetic potential compared to previously described drugs were synthesized. Compound 2d was taken forward as a clinical candidate for the treatment of COPD.
تدمد: 1520-4804
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::817ed3d0e78a77ec4c0cc42ee5087e6b
https://pubmed.ncbi.nlm.nih.gov/22889281
رقم الأكسشن: edsair.doi.dedup.....817ed3d0e78a77ec4c0cc42ee5087e6b
قاعدة البيانات: OpenAIRE
الوصف
تدمد:15204804