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The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators.

Abstract：

:The optimization of a series of benzimidazole glucokinase activators is described. We identified a novel and potent achiral benzimidazole derivative as an allosteric GK activator. This activator was designed and synthesized via removal of the chiral center of the lead compound, 6-(N-acylpyrrolidin-2-yl)benzimidazole. The activator exhibited good PK profiles in rats and dogs, and significant hypoglycemic efficacy at 1 mg/kg po dosing in a rat OGTT model. The binding site and binding mode of the benzimidazole class of GKA with GK protein was confirmed by X-ray crystallographic analysis.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Takahashi K,Hashimoto N,Nakama C,Kamata K,Sasaki K,Yoshimoto R,Ohyama S,Hosaka H,Maruki H,Nagata Y,Eiki J,Nishimura T

doi

10.1016/j.bmc.2009.05.037

subject

Has Abstract

pub_date

2009-10-01 00:00:00

pages

7042-51

issue

19

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(09)00493-3

journal_volume

17

pub_type

杂志文章

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