| Autor: |
de Dios A; Eli Lilly and Co., Lilly S.A., Avenida de la Industria, 30, 28108 Alcobendas, Madrid, Spain. a.de_dios@lilly.com, Shih C, López de Uralde B, Sánchez C, del Prado M, Martín Cabrejas LM, Pleite S, Blanco-Urgoiti J, Lorite MJ, Nevill CR Jr, Bonjouklian R, York J, Vieth M, Wang Y, Magnus N, Campbell RM, Anderson BD, McCann DJ, Giera DD, Lee PA, Schultz RM, Li LC, Johnson LM, Wolos JA |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 2005 Apr 07; Vol. 48 (7), pp. 2270-3. |
| DOI: |
10.1021/jm048978k |
| Abstrakt: |
We report the design and discovery of a 2-aminobenzimidazole-based series of potent and highly selective p38alphainhibitors. The lead compound 1 had low-nanomolar activity in both ATP competitive enzyme binding and inhibition of TNFalpha release in macrophages. Compound 18 showed excellent pharmacokinetics properties and oral activity in the rat collagen induced arthritis model compared with other p38 reference compounds. A SAR strategy to address CyP3A4 liability is also described. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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