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Discovery of potent and orally active 1,4-disubstituted indazoles as novel allosteric glucokinase activators.

Abstract：

:Guided by co-crystal structural information obtained from a different series we were exploring, a scaffold morphing and SBDD approach led to the discovery of the 1,4-disubstituted indazole series as a novel class of GKAs that potently activate GK in enzyme and cell assays. anti-diabetic OGTT efficacy was demonstrated with 29 in a rodent models of type 2 diabetes.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Cheruvallath ZS,Gwaltney SL 2nd,Sabat M,Tang M,Wang H,Jennings A,Hosfield D,Lee B,Wu Y,Halkowycz P,Grimshaw CE

doi

10.1016/j.bmcl.2017.04.041

subject

Has Abstract

pub_date

2017-06-15 00:00:00

pages

2678-2682

issue

12

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(17)30416-X

journal_volume

27

pub_type

杂志文章

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