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Synthesis and evaluation of novel modified γ-lactam prostanoids as EP4 subtype-selective agonists.

Abstract：

:To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified γ-lactam prostanoids has been continued. Prostanoids bearing 2-oxo-1,3-oxazolidine, 2-oxo-1,3-thiazolidine and 5-thioxopyrrolidine as a surrogate for the γ-hydroxycyclopentanone without a troublesome 11-hydroxy group were identified as highly subtype-selective EP4 agonists. Among the tested, several representative compounds demonstrated in vivo efficacy after oral dosing in rats. Their pharmacokinetic and structure-activity relationship studies are presented.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Kambe T,Maruyama T,Nagase T,Ogawa S,Minamoto C,Sakata K,Maruyama T,Nakai H,Toda M

doi

10.1016/j.bmc.2011.12.009

subject

Has Abstract

pub_date

2012-01-15 00:00:00

pages

702-13

issue

2

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)01015-7

journal_volume

20

pub_type

杂志文章

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