2-Benzimidazolyl-9-(chroman-4-yl)-purinone derivatives as JAK3 inhibitors

Autor:	Celia Kingsbury, Irina Neagu, Ming You, Haengsoon Park, Tsung H. Lin, Koc-Kan Ho, Elizabeth Quadros, Maria L. Webb, Michael Ohlmeyer, Yuefei Shao, Matthew Sills, Jeffrey J. Letourneau, Andrew G. Cole, Yingchun Lu, Earl F. Kimble, Jorge Quintero, Riviello Christopher, Ray Anthony James, Bojing Wang, Vidyadhar M. Paradkar, Adolph Bohnstedt, Kenneth C. Appell, David J. Diller
Rok vydání:	2009
Předmět:	Models Molecular Benzimidazole Stereochemistry Clinical Biochemistry Substituent Pharmaceutical Science Biochemistry Chemical synthesis Interferon-gamma Mice Structure-Activity Relationship chemistry.chemical_compound Interferon Drug Discovery medicine Animals Moiety Enzyme Inhibitors Kinase activity Molecular Biology Dose-Response Relationship Drug Molecular Structure Organic Chemistry Janus Kinase 3 Stereoisomerism Biological activity chemistry Purines Drug Design Models Animal Interleukin-2 Molecular Medicine Benzimidazoles Janus kinase medicine.drug
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 19:6788-6792
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2009.09.080
Popis:	A novel class of Janus tyrosine kinase 3 (JAK3) inhibitors based on a 2-benzimidazoylpurinone core structure is described. Through substitution of the benzimidazoyl moiety and optimization of the N-9 substituent of the purinone, compound 24 was identified incorporating a chroman-based functional group. Compound 24 shows excellent kinase activity, good oral bioavailability and demonstrates efficacy in an acute mechanistic mouse model through inhibition of interleukin-2 (IL-2) induced interferon-gamma (INF-gamma) production.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3dd21d26420d59e8a1c379ce66894ef1 https://doi.org/10.1016/j.bmcl.2009.09.080 Zobrazit plný text záznamu Full Text from ScienceDirect