Discovery of Diphenyloxazole and N delta -Z-Ornithine Derivatives as Highly Potent and Selective Human Prostaglandin EP sub(4) Receptor Antagonists

Two novel classes of diphenyloxazole and N delta -Z-ornithine derivatives as highly potent and selective EP sub(4) antagonists have been discovered. The optimized diphenyloxzole 8 and N delta -Z-ornithine 11 effectively competed with [ super(3)H]PGE sub(2) binding to human recombinant EP sub(4), wit...

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Published in:Journal of medicinal chemistry 2005-05, Vol.48 (9), p.3103-3106
Main Authors: Hattori, K, Tanaka, A, Fujii, N, Takasugi, H, Tenda, Y, Tomita, M, Nakazato, S, Nakano, K, Kato, Y, Kono, Y, Murai, H, Sakane, K
Format: Article
Language:English
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Summary:Two novel classes of diphenyloxazole and N delta -Z-ornithine derivatives as highly potent and selective EP sub(4) antagonists have been discovered. The optimized diphenyloxzole 8 and N delta -Z-ornithine 11 effectively competed with [ super(3)H]PGE sub(2) binding to human recombinant EP sub(4), with K sub(i) values of 0.30 nM and 0.91 nM, respectively, and were selective for all members of the human prostanoid receptor family. 8 was shown to exhibit good pharmacokinetic properties in rats and dogs and potent inhibitory activity toward in vitro PGE sub(2)-promoted IgE synthesis.
ISSN:0022-2623
DOI:10.1021/jm050085k