773104-00-0Relevant articles and documents
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.
scheme or table, 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.
PYRIMIDINONE DERIVATIVES AS PROTEIN KINASE INHIBITORS
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Page/Page column 23, (2010/11/28)
Pyrimidinone derivatives have enhanced and unexpected drug properties as inhibitors of protein kinases and are useful in treating disorders related to abnormal protein kinase activities such as inflammatory diseases and certain types of cancer.
P-38 inhibitors
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, (2008/06/13)
Provided are 5-membered heterocycle-based p38 kinase, including p38α and p38β kinase, inhibitors. Pharmaceutical compositions containing the compounds are also provided. Methods of use of the compounds and compositions are also provided, including methods of treatment, prevention, or amelioration of one or more symptoms of p38 kinase mediated diseases and disorders, including, but not limited to, inflammatory diseases and disorders.