2-Phenylamino-6-cyano-1H-benzimidazole-based isoform selective casein kinase 1 gamma (CK1γ) inhibitors.
| Autor: | Hua Z; Medicinal Chemistry, Amgen Inc., 360 Binney Street, Cambridge, MA 02142, USA. zihao.hua@amgen.com, Huang X, Bregman H, Chakka N, DiMauro EF, Doherty EM, Goldstein J, Gunaydin H, Huang H, Mercede S, Newcomb J, Patel VF, Turci SM, Yan J, Wilson C, Martin MW |
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| Jazyk: | angličtina |
| Zdroj: | Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2012 Sep 01; Vol. 22 (17), pp. 5392-5. Date of Electronic Publication: 2012 Jul 20. |
| DOI: | 10.1016/j.bmcl.2012.07.046 |
| Abstrakt: | Screening of the Amgen compound library led to the identification of 2-phenylamino-6-cyano-1H-benzimidazole 1a as a potent CK1 gamma inhibitor with excellent kinase selectivity and unprecedented CK1 isoform selectivity. Further structure-based optimization of this series resulted in the discovery of 1h which possessed good enzymatic and cellular potency, excellent CK1 isoform and kinase selectivity, and acceptable pharmacokinetic properties. (Copyright © 2012. Published by Elsevier Ltd.) |
| Databáze: | MEDLINE |
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