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

Bioorganic & Medicinal Chemistry Letters
Zacharia S CheruvallathCharles E Grimshaw

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.

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Jan 26, 2005·Biochemical Society Transactions·D ZelentF M Matschinsky
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May 14, 2009·Bioorganic & Medicinal Chemistry Letters·Jeffrey A PfefferkornPeter J Oates
May 6, 2011·Diabetes Care·Franz M MatschinskyJoseph Grimsby
Feb 26, 2013·Bioorganic & Medicinal Chemistry Letters·Zacharia S CheruvallathYiqin Wu

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Citations

Dec 14, 2018·Current Medicinal Chemistry·Sara N GarciaM Matilde Marques
Nov 2, 2019·Current Drug Targets·Ping WuHao Fang
Oct 30, 2021·Chemical Biology & Drug Design·Ramasamy ThilagavathiChelliah Selvam

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