Design and synthesis of a selective EP4-receptor agonist.: Part 3:: 16-phenyl-5-thiaPGE1 and 9-β-halo derivatives with improved stability

被引：25

作者：

Maruyama, T ^{[1
]}

Asada, M ^{[1
]}

Shiraishi, T ^{[1
]}

Yoshida, H ^{[1
]}

Maruyama, T ^{[1
]}

Ohuchida, S ^{[1
]}

Nakai, H ^{[1
]}

Kondo, K ^{[1
]}

Toda, M ^{[1
]}

机构：

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2002年 / 10卷 / 06期

关键词：

D O I：

10.1016/S0968-0896(02)00031-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

To identify a new selective EP4-agonist with improved chemical stability, further chemical modification of those reported previously was continued. We focused our attention on chemical modification of the alpha chain of 3,7-dithiaPGE(1), and selected 5-thiaPGE(1), as a new chemical lead, Introduction of an optimized omega to chain to the 5-thiaPG skeleton afforded in-methoxymethyl derivative 33a, which showed the most potent EP4-receptor agonist activity and good subtype-selectivity both in vitro and in vivo. 9beta-HaloPGF derivatives were also synthesized and biologically evaluated in an attempt to block self-degradation of the beta-hydroxyketone moiety. Among these series, 39a and 39b showed potent agonist activity and good subtype-selectivity. Structure-activity relationships (SARs) are also discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：1743 / 1759

页数：17

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