SAR of a Series of 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridines as Potent Inhibitors of Human Eosinophil Phosphodiesterase
| العنوان: | SAR of a Series of 5,6-Dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-α]pyridines as Potent Inhibitors of Human Eosinophil Phosphodiesterase |
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| المؤلفون: | Allen J. Duplantier, T. H. Jenkinson, Michael William Mckechney, Kenneth G. Kraus, Elizabeth L Bachert, Cohan Victoria L, John B. Cheng, Joann D. Pillar, John W. Watson |
| المصدر: | Journal of Medicinal Chemistry. 50:344-349 |
| بيانات النشر: | American Chemical Society (ACS), 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Male, Phosphodiesterase Inhibitors, Pyridines, Vomiting, Stereochemistry, Biological Availability, In Vitro Techniques, Chemical synthesis, Structure-Activity Relationship, chemistry.chemical_compound, Dogs, Drug Discovery, Pyridine, Animals, Humans, Structure–activity relationship, Moiety, biology, Chemistry, Ferrets, Phosphodiesterase, Triazoles, Recombinant Proteins, Cyclic Nucleotide Phosphodiesterases, Type 4, Rats, Bioavailability, Eosinophils, Isoenzymes, 3',5'-Cyclic-AMP Phosphodiesterases, Enzyme inhibitor, biology.protein, Lactam, Pyrazoles, Molecular Medicine, Female, Heterocyclic Compounds, 3-Ring |
| الوصف: | The potency and physical properties of a previously reported 7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine series of human eosinophil phosphodiesterase inhibitors were improved by tying the lactam moiety into a triazolo ring. The resulting 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine series provided nonionizable analogs with melting point properties suitable for micronization. Substitution at the 3-position of the 5,6-dihydro-(9H)-pyrazolo[3,4-c]-1,2,4-triazolo[4,3-alpha]pyridine tricycle led to a 2-thienyl analog, 19 (tofimilast), a potent PDE4 inhibitor with low oral bioavailability and no emesis-associated behaviors in ferrets at plasma concentrations up to 152 ng/mL. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9a463db61959becd7dabc5d6243e6d31 https://doi.org/10.1021/jm060904g |
| رقم الأكسشن: | edsair.doi.dedup.....9a463db61959becd7dabc5d6243e6d31 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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