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

被引：8

作者：

Kambe, Tohru ^{[1
]}

Maruyama, Toru ^{[1
]}

Nagase, Toshihiko ^{[1
]}

Ogawa, Seiji ^{[1
]}

Minamoto, Chiaki ^{[1
]}

Sakata, Kiyoto ^{[1
]}

Maruyama, Takayuki ^{[1
]}

Nakai, Hisao ^{[1
]}

Toda, Masaaki ^{[1
]}

机构：

[1] Ono Pharmaceut Co Ltd, Minase Res Inst, Mishima, Osaka 6188585, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 02期

关键词：

Prostaglandin; EP4; receptor; Agonist; TNF-alpha; RECEPTOR AGONISTS; DISCOVERY;

D O I：

10.1016/j.bmc.2011.12.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

To identify chemically and metabolically stable subtype-selective EP4 agonists, design and synthesis of a series of modified gamma-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 gamma-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. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：702 / 713

页数：12

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