Pyrido pyrimidinones as selective agonists of the high affinity niacin receptor GPR109A: Optimization of in vitro activity

被引：10

作者：

Peters, Jens-Uwe ^{[1
]}

Kuehne, Holger ^{[1
]}

Dehmlow, Henrietta ^{[1
]}

Grether, Uwe ^{[1
]}

Conte, Aurelia ^{[1
]}

Hainzl, Dominik ^{[1
]}

Hertel, Cornelia ^{[1
]}

Kratochwil, Nicole A. ^{[1
]}

Otteneder, Michael ^{[1
]}

Narquizian, Robert ^{[1
]}

Panousis, Constantinos G. ^{[2
]}

Ricklin, Fabienne ^{[1
]}

Roever, Stephan ^{[1
]}

机构：

[1] F Hoffmann La Roche Ltd, Pharma Res, CH-4070 Basel, Switzerland

[2] F Hoffmann La Roche Ltd, Pharma Res, Nutley, NJ 07110 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 18期

关键词：

Flushing; GPR109A; GPR109B; GPCR; Lead identification; Lipolysis; Niacin; Pyrido pyrimidinone; NICOTINIC-ACID RECEPTOR; ESTER TRANSFER PROTEIN; MOLECULAR-IDENTIFICATION; RELEASE NIACIN; EFFICACY; CHOLESTEROL; MECHANISMS; EXPRESSION; DISCOVERY; SAFETY;

D O I：

10.1016/j.bmcl.2010.07.108

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Pyrido pyrimidinones are selective agonists of the human high affinity niacin receptor GPR109A (HM74A). They show no activity on the highly homologous low affinity receptor GPR109B (HM74). Starting from a high throughput screening hit the in vitro activity of the pyrido pyrimidinones was significantly improved providing lead compounds suitable for further optimization. (c) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5426 / 5430

页数：5

共 30 条

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