886976-96-1Relevant articles and documents
The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators
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
experimental part, p. 7042 - 7051 (2010/01/06)
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.