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

…, N Hashimoto, C Nakama, K Kamata, K Sasaki…

Index: Takahashi, Keiji; Hashimoto, Noriaki; Nakama, Chisato; Kamata, Kenji; Sasaki, Kaori; Yoshimoto, Riki; Ohyama, Sumika; Hosaka, Hideka; Maruki, Hiroko; Nagata, Yasufumi; Eiki, Jun-ichi; Nishimura, Teruyuki Bioorganic and Medicinal Chemistry, 2009 , vol. 17, # 19 p. 7042 - 7051

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Citation Number: 35

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 1mg/kg po dosing in a rat OGTT ...