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Discovery and preclinical development of AR453588 as an anti-diabetic glucokinase activator.

Abstract：

:Glucose flux through glucokinase (GK) controls insulin release from the pancreas in response to high levels of glucose. Flux through GK is also responsible for reducing hepatic glucose output. Since many individuals with type 2 diabetes appear to have an inadequacy or defect in one or both of these processes, identifying compounds that can activate GK could provide a therapeutic benefit. Herein we report the further structure activity studies of a novel series of glucokinase activators (GKA). These studies led to the identification of pyridine 72 as a potent GKA that lowered post-prandial glucose in normal C57BL/6J mice, and after 14d dosing in ob/ob mice.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Hinklin RJ,Baer BR,Boyd SA,Chicarelli MD,Condroski KR,DeWolf WE Jr,Fischer J,Frank M,Hingorani GP,Lee PA,Neitzel NA,Pratt SA,Singh A,Sullivan FX,Turner T,Voegtli WC,Wallace EM,Williams L,Aicher TD

doi

10.1016/j.bmc.2019.115232

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

115232

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(19)31029-6

journal_volume

28

pub_type

杂志文章

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