Identification of piperazine-bisamide GHSR antagonists for the treatment of obesity

被引：29

作者：

Yu, Ming ^{[1
]}

Lizarzaburu, Mike ^{[1
]}

Beckmann, Holger ^{[1
]}

Connors, Richard ^{[1
]}

Dai, Kang ^{[1
]}

Haller, Katrin ^{[2
]}

Li, Cong ^{[1
]}

Liang, Lingming ^{[1
]}

Lindstrom, Michelle ^{[1
]}

Ma, Ji ^{[1
]}

Motani, Alykhan ^{[1
]}

Wanska, Malgorzata ^{[1
]}

Zhang, Alex ^{[1
]}

Li, Leping ^{[3
]}

Medina, Julio C. ^{[1
]}

机构：

[1] Amgen Inc, San Francisco, CA 94080 USA

[2] Syntacoll Gmbh, D-93342 Saal Donau, Germany

[3] Presidio Pharmaceut Inc, San Francisco, CA 94158 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 05期

关键词：

Piperazine-bisamide; Ghrelin; Growth hormone secretagogue receptor (GHSR); Agonist; Antagonist; Inositol phosphate (IP) assay; Pituitary assay; HORMONE SECRETAGOGUE RECEPTOR; GHRELIN RECEPTOR; LYSOPHOSPHATIDIC ACID; ENERGY HOMEOSTASIS; UNITED-STATES; FOOD-INTAKE; HUMANS; DERIVATIVES; PREVALENCE; EXPRESSION;

D O I：

10.1016/j.bmcl.2010.01.043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Piperazine-bisamide analogs were discovered as partial agonists of human growth hormone secretagogue receptor (GHSR) in a high throughput screen. The partial agonists were optimized for potency and converted into antagonists through structure-activity relationship (SAR) studies. The efforts also led to the identification of potent antagonist with favorable PK profile suitable as a tool compound for in vivo studies. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：1758 / 1762

页数：5

共 35 条

[1] Recombinant human G protein-coupled lysophosphatidic acid receptors mediate intracellular calcium mobilization [J].