886979-22-2Relevant academic research and scientific papers
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.
HETEROCYCLE-SUBSTITUTED BENZIMIDAZOLE DERIVATIVE
-
Page/Page column 55, (2010/11/30)
Compounds having glucokinase activating effects and being useful as treatments for diabetes, which are represented by the following formula (I): (wherein X1 to X4 represent a carbon atom, etc., ring A represents a 5- or 6-membered heteroaryl having from 1 to 4 hetero atoms selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom, X5 represent an oxygen atom, etc., X represent a carbon atom, etc., Het represents a 5- or 6-membered aliphatic hetero ring, R1 represents aryl, etc., R2 represents formyl, etc., R3 represents -C1-6 alkyl, etc.), as well as their pharmaceutically acceptable salts.
ARYLOXY-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES
-
Page/Page column 82, (2010/11/28)
A glucokinase activator is provided; and a treatment and/or a preventive for diabetes, or a treatment and/or a preventive for diabetes such as retinopathy, nephropathy, neurosis, ischemic cardiopathy, arteriosclerosis, and further a treatment and/or a preventive for obesity are provided. The invention relates to a compound of a formula (I): [wherein R1 and R2 represent a hydrogen, etc.; R3 represents a hydrogen atom, a halogen atom, etc.; R4 each independently represents a hydrogen atom, a lower alkyl group, etc.; Q represents a carbon atom, a nitrogen atom or a sulfur atom (the sulfur atom may be mono- or di-substituted with an oxo group); R5 and R6 each represent a hydrogen atom, a lower alkyl group, etc.; X1, X2, X3 and X4 each independently represent a carbon atom or a nitrogen atom; Z represents an oxygen atom, a sulfur atom or a nitrogen atom; Ar represents an aryl or heteroaryl group optionally mono to tri-substituted with a group selected from the substituent group β; ring A represents a 5- or 6-membered nitrogen-containing heteroaromatic group; m indicates an integer of from 1 to 6; n indicates an integer of from 0 to 3; p indicates an integer of from 0 to 2 (provided that at least two of X1 to X4 are carbon atoms); q indicates 0 or 1] or its pharmaceutically-acceptable salt, which has an effect of glucokinase activation and is useful as a treatment for diabetes.
