Document Report Card

ID: ALA1143620

Journal: J Med Chem

Title: Discovery of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective human prostaglandin EP(4) receptor antagonists.

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.

Abstract: Two novel classes of diphenyloxazole and Ndelta-Z-ornithine derivatives as highly potent and selective EP(4) antagonists have been discovered. The optimized diphenyloxzole 8 and Ndelta-Z-ornithine 11 effectively competed with [(3)H]PGE(2) binding to human recombinant EP(4), with K(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(2)-promoted IgE synthesis.

CiteXplore: 15857112

DOI: 10.1021/jm050085k