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

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Ritter K,Buning C,Halland N,Pöverlein C,Schwink L

doi

10.1021/acs.jmedchem.5b01198

subject

Has Abstract

pub_date

2016-04-28 00:00:00

pages

3579-92

issue

8

eissn

0022-2623

issn

1520-4804

journal_volume

59

pub_type

杂志文章,评审

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