Novel tricyclic pyrazolopyrimidines as potent and selective GPR119 agonists

被引：8

作者：

Azimioara, Mihai ^{[1
]}

Alper, Phil ^{[1
]}

Cow, Christopher ^{[1
]}

Mutnick, Daniel ^{[1
]}

Nikulin, Victor ^{[1
]}

Lelais, Gerald ^{[1
]}

Mecom, John ^{[1
]}

McNeill, Matthew ^{[1
]}

Michellys, Pierre-Yves ^{[1
]}

Wang, Zhiliang ^{[1
]}

Reding, Esther ^{[1
]}

Paliotti, Michael ^{[1
]}

Li, Jing ^{[1
]}

Bao, Dingjiu ^{[1
]}

Zoll, Jocelyn ^{[1
]}

Kim, Young ^{[1
]}

Zimmerman, Matthew ^{[1
]}

Groessl, Todd ^{[1
]}

Tuntland, Tove ^{[1
]}

Joseph, Sean B. ^{[1
]}

McNamara, Peter ^{[1
]}

Seidel, H. Martin ^{[1
]}

Epple, Robert ^{[1
]}

机构：

[1] Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 23期

关键词：

GPCR agonists; GPR119; Tricyclic pyrazolopyrimidines; Type; 2; diabetes; PROTEIN-COUPLED RECEPTOR; DISCOVERY; SECRETION; CELLS;

D O I：

10.1016/j.bmcl.2014.10.010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Systematic SAR optimization of the GPR119 agonist lead 1, derived from an internal HTS campaign, led to compound 29. Compound 29 displays significantly improved in vitro activity and oral exposure, leading to GLP1 elevation in acutely dosed mice and reduced glucose excursion in an OGTT study in rats at doses >= 10 mg/kg. (C) 2014 Elsevier Ltd. All rights reserved.

引用

页码：5478 / 5483

页数：6

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