| Literature DB >> 12482439 |
John E Stelmach1, Luping Liu, Sangita B Patel, James V Pivnichny, Giovanna Scapin, Suresh Singh, Cornelis E C A Hop, Zhen Wang, John R Strauss, Patricia M Cameron, Elizabeth A Nichols, Stephen J O'Keefe, Edward A O'Neill, Dennis M Schmatz, Cheryl D Schwartz, Chris M Thompson, Dennis M Zaller, James B Doherty.
Abstract
The development of potent, orally bioavailable (in rat) and selective dihydroquinazolinone inhibitors of p38alpha MAP kinase is described. These analogues are hybrids of a pyridinylimidazole p38alpha inhibitor reported by Merck Research Laboratories and VX-745. Optimization of the C-5 phenyl and the C-7 piperidinyl substituents led to the identification of 15i which gave excellent suppression of TNF-alpha production in LPS-stimulated whole blood (IC(50)=10nM) and good oral exposure in rats (F=68%, AUCn PO=0.58 microM h).Entities:
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Year: 2003 PMID： 12482439 DOI： 10.1016/s0960-894x(02)00752-7
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823