Discovery of 5-(2-amino-[1,2,4]triazolo[1,5-a]pyridin-7-yl)-N-(tert-butyl)pyridine-3-sulfonamide (CZC24758), as a potent, orally bioavailable and selective inhibitor of PI3K for the treatment of inflammatory disease
| Autor: | Giovanna Bergamini, Nigel Ramsden, Sunose Mihiro, Gitte Neubauer, Katie Ellard, Kathryn Bell, Thilo Werner |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Models Molecular Pyridines Stereochemistry Clinical Biochemistry Pharmaceutical Science Pharmacology Biochemistry Mice Structure-Activity Relationship In vivo Microsomes Drug Discovery medicine Animals Structure–activity relationship Potency Kinome Molecular Biology Phosphoinositide-3 Kinase Inhibitors Inflammation Sulfonamides Molecular Structure Chemistry Drug discovery Organic Chemistry Sulfonamide (medicine) Hydrogen Bonding Triazoles Rats Microsome Molecular Medicine Triazolopyridine Granulocytes medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 22:4613-4618 |
| ISSN: | 0960-894X |
| Popis: | Herein, we disclose the discovery of a series of 7-substituted triazolopyridines which culminated in the identification of 14 (CZC24758), a potent, orally bioavailable small-molecule inhibitor of PI3Kγ, an attractive drug target for inflammatory and autoimmune disorders. Compound 14 has excellent selectivity across the kinome, demonstrates good potency in cell based assays and furthermore exhibits in vivo efficacy in a collagen induced arthritis model in mouse after oral dosing. |
| Databáze: | OpenAIRE |
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