Discovery of highly selective EP4 receptor agonists that stimulate new bone formation and restore bone mass in ovariectomized rats

被引：24

作者：

Cameron, KO ^{[1
]}

Lefker, BA ^{[1
]}

Chu-Moyer, MY ^{[1
]}

Crawford, DT ^{[1
]}

Jardine, PD ^{[1
]}

DeNinno, SL ^{[1
]}

Gilbert, S ^{[1
]}

Grasser, WA ^{[1
]}

Ke, HZ ^{[1
]}

Lu, BH ^{[1
]}

Owen, TA ^{[1
]}

Paralkar, VM ^{[1
]}

Qi, H ^{[1
]}

Scott, DO ^{[1
]}

Thompson, DD ^{[1
]}

Tjoa, CM ^{[1
]}

Zawistoski, MP ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton Labs, Dept Cardiovasc & Metab Dis, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 07期

关键词：

bone anabolic agent; EP4; EP2; prostaglandin; lactam; osteoporosis;

D O I：

10.1016/j.bmcl.2006.01.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Heptanoic acid lactams. exemplified by 2, were identified as highly selective EP4 agonists via high throughput screening. Lead optimization led to the identification of lactams with a 30-fold increase in EP4 potency in vitro. Compounds demonstrated robust bone anabolic effects when administered in vivo in rat models of osteoporosis. (C) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1799 / 1802

页数：4

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