Discovery of Diphenyloxazole and Nδ-Z-Ornithine Derivatives as Highly Potent and Selective Human Prostaglandin EP4 Receptor Antagonists

Two novel classes of diphenyloxazole and Nδ-Z-ornithine derivatives as highly potent and selective EP4 antagonists have been discovered. The optimized diphenyloxzole 8 and Nδ-Z-ornithine 11 effectively competed with [3H]PGE2 binding to human recombinant EP4, with K i values of 0.30 nM and 0.91 nM, r...

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Published in:Journal of medicinal chemistry 2005-05, Vol.48 (9), p.3103-3106
Main Authors: Hattori, Kouji, Tanaka, Akira, Fujii, Naoaki, Takasugi, Hisashi, Tenda, Yoshiyuki, Tomita, Masayuki, Nakazato, Shoko, Nakano, Keiko, Kato, Yasuko, Kono, Yutaka, Murai, Hidetsugu, Sakane, Kazuo
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Language:English
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Biological and medical sciences
Medical sciences
Miscellaneous
Pharmacology. Drug treatments
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container_end_page 3106
container_issue 9
container_start_page 3103
container_title Journal of medicinal chemistry
container_volume 48
creator Hattori, Kouji
Tanaka, Akira
Fujii, Naoaki
Takasugi, Hisashi
Tenda, Yoshiyuki
Tomita, Masayuki
Nakazato, Shoko
Nakano, Keiko
Kato, Yasuko
Kono, Yutaka
Murai, Hidetsugu
Sakane, Kazuo
description Two novel classes of diphenyloxazole and Nδ-Z-ornithine derivatives as highly potent and selective EP4 antagonists have been discovered. The optimized diphenyloxzole 8 and Nδ-Z-ornithine 11 effectively competed with [3H]PGE2 binding to human recombinant EP4, 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 PGE2-promoted IgE synthesis.
doi_str_mv 10.1021/jm050085k
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source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)
subjects Biological and medical sciences
Medical sciences
Miscellaneous
Pharmacology. Drug treatments
title Discovery of Diphenyloxazole and Nδ-Z-Ornithine Derivatives as Highly Potent and Selective Human Prostaglandin EP4 Receptor Antagonists
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