Ontology highlight
ABSTRACT:
SUBMITTER: Seganish WM
PROVIDER: S-EPMC4538434 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
Seganish W Michael WM Fischmann Thierry O TO Sherborne Brad B Matasi Julius J Lavey Brian B McElroy William T WT Tulshian Deen D Tata James J Sondey Christopher C Garlisi Charles G CG Devito Kristine K Fossetta James J Lundell Daniel D Niu Xiaoda X
ACS medicinal chemistry letters 20150712 8
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 displa ...[more]