1314804-48-2Relevant academic research and scientific papers
Substituted N-aryl-6-pyrimidinones: A new class of potent, selective, and orally active p38 MAP kinase inhibitors
Devadas, Balekudru,Selness, Shaun R.,Xing, Li,Madsen, Heather M.,Marrufo, Laura D.,Shieh, Huey,Messing, Dean M.,Yang, Jerry Z.,Morgan, Heidi M.,Anderson, Gary D.,Webb, Elizabeth G.,Zhang, Jian,Devraj, Rajesh V.,Monahan, Joseph B.
, p. 3856 - 3860 (2011/08/06)
A novel series of highly potent and selective p38 MAP kinase inhibitors was developed originating from a substituted N-aryl-6-pyrimidinone scaffold. SAR studies coupled with in vivo evaluations in rat arthritis model culminated in the identification of 10 with excellent oral efficacy. Compound 10 exhibited a significantly enhanced dissolution rate compared to 1, translating to a high oral bioavailability (>90%) in rat. In animal studies 10 inhibited LPS-stimulated production of tumor necrosis factor-α in a dose-dependent manner and demonstrated robust efficacy comparable to dexamethasone in a rat streptococcal cell wall-induced arthritis model.
