Identification of novel pyrazole acid antagonists for the EP 1 receptor

…, XQ Lewell, RJ Wilson, SH Brown, A Chowdhury…

文献索引：McKeown, Stephen C.; Hall, Adrian; Giblin, Gerard M.P.; Lorthioir, Olivier; Blunt, Richard; Lewell, Xiao Q.; Wilson, Richard J.; Brown, Susan H.; Chowdhury, Anita; Coleman, Tanya; Watson, Stephen P.; Chessell, Iain P.; Pipe, Adrian; Clayton, Nick; Goldsmith, Paul Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 18 p. 4767 - 4771

全文：HTML全文

被引用次数: 27

摘要

The discovery, synthesis and structure–activity relationship (SAR) of a novel series of EP1 receptor antagonists is described. Pyrazole acid 4, identified from a chemical array, had desirable physicochemical properties, an excellent in vitro microsomal inhibition and cytochrome P450 (CYP450) profile and good exposure levels in blood. This compound had an ED50 of 1.3 mg/kg in a rat pain model. A range of more potent analogues in the in vitro ...