Optimisation of aqueous solubility in a series of G protein coupled receptor 119 (GPR119) agonists

被引：12

作者：

Scott, James S. ^{[1
]}

Birch, Alan M. ^{[1
]}

Brocklehurst, Katy J. ^{[1
]}

Brown, Hayley S. ^{[1
]}

Goldberg, Kristin ^{[1
]}

Groombridge, Sam D. ^{[1
]}

Hudson, Julian A. ^{[1
]}

Leach, Andrew G. ^{[1
]}

MacFaul, Philip A. ^{[1
]}

McKerrecher, Darren ^{[1
]}

Poultney, Ruth ^{[1
]}

Schofield, Paul ^{[1
]}

Svensson, Per H. ^{[2
]}

机构：

[1] AstraZeneca, Cardiovasc & Gastrointestinal Innovat Med Unit, Macclesfield SK10 4TG, Cheshire, England

[2] Royal Inst Technol, Dept Appl Phys Chem, S-10044 Stockholm, Sweden

来源：

MEDCHEMCOMM | 2013年 / 4卷 / 01期

关键词：

INSULIN-SECRETION; GLYCEMIC CONTROL; DISCOVERY; POTENT; AS1535907; AGENT;

D O I：

10.1039/c2md20130e

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Improving aqueous solubility is a challenge frequently faced within drug discovery programs. Herein we describe increases in solubility in two sub-series of GPR119 agonists through reduction of lipophilicity together with hydrogen bond acceptor modulation. Small molecule X-ray crystallography was utilised to investigate effects on solid state interactions.

引用

页码：95 / 100

页数：6

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