Discovery and Structure Enabled Synthesis of 2,6-Diaminopyrimidin-4-one IRAK4 Inhibitors.
ACS Med Chem Lett
; 6(8): 942-7, 2015 Aug 13.
Article
em En
| MEDLINE
| ID: mdl-26288698
ABSTRACT
We report the identification and synthesis of a series of aminopyrimidin-4-one IRAK4 inhibitors. Through high throughput screening, an aminopyrimidine hit was identified and modified via structure enabled design to generate a new, potent, and kinase selective pyrimidin-4-one chemotype. This chemotype is exemplified by compound 16, which has potent IRAK4 inhibition activity (IC50 = 27 nM) and excellent kinase selectivity (>100-fold against 99% of 111 tested kinases), and compound 31, which displays potent IRAK4 activity (IC50 = 93 nM) and good rat bioavailability (F = 42%).
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
ACS Med Chem Lett
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos