G Protein-Coupled Receptor 119 (GPR119) Agonists for the Treatment of Diabetes: Recent Progress and Prevailing Challenges

被引：98

作者：

Ritter, Kurt ^{[1
]}

Buning, Christian ^{[1
]}

Halland, Nis ^{[1
]}

Poverlein, Christoph ^{[1
]}

Schwink, Lothar ^{[1
]}

机构：

[1] Sanofi Aventis Deutschland GmbH, Bldg G838,Ind Pk Hoechst, D-65926 Frankfurt, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 08期

关键词：

GLUCAGON-LIKE PEPTIDE-1; BIOLOGICAL EVALUATION; INSULIN-SECRETION; 4-AMINO-2-PHENYLPYRIMIDINE DERIVATIVES; GLYCEMIC CONTROL; IN-VITRO; DISCOVERY; POTENT; SERIES; OPTIMIZATION;

D O I：

10.1021/acs.jmedchem.5b01198

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In this Perspective, recent advances and challenges in the development of GPR119 agonists as new oral antidiabetic drugs will be discussed. Such agonists are expected to exhibit a low risk to induce hypoglycemia as well as to have a beneficial impact on body weight. Many pharmaceutical companies have been active in the search for GPR119 agonists, making it a highly competitive area in the industrial environment. Several GPR119 agonists have been entered into clinical studies, but many have failed either in phase I or II and none has progressed beyond phase II. Herein we describe the strategies chosen by the different medicinal chemistry teams in academia and the pharmaceutical industry to improve potency, physicochemical properties, pharmacokinetics, and the safety profile of GPR119 agonists in the discovery phase in order to improve the odds for successful development.

引用

页码：3579 / 3592

页数：14

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