3-({5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazol-6-yl}methyl)-1-methylimidazolidine-2,4-dione

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-({5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazol-6-yl}methyl)-1-methylimidazolidine-2,4-dione
• 英文别名: 1-{[5-[4-(ethylsulfonyl)phenoxy]-2-(2-pyridinyl)-1H-benzimidazol-6-yl]methyl}-3-methyl-imidazolidine-2,5-dione；3-[[6-(4-ethylsulfonylphenoxy)-2-pyridin-2-yl-3H-benzimidazol-5-yl]methyl]-1-methylimidazolidine-2,4-dione
• 化学式: C₂₅H₂₃N₅O₅S
• 分子量: 505.554
• InChiKey: XJPUFMSGFDSNKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  134
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  甲酰乙内脲 、 methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole-6-carboxylate 在 2-(三甲基硅烷基)乙氧甲基氯 、 sodium hydride 、 lithium aluminium tetrahydride 作用下， 以 N,N-二甲基甲酰胺 、 paraffin oil 、 四氢呋喃 为溶剂， 反应 0.5h， 生成 3-({5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazol-6-yl}methyl)-1-methylimidazolidine-2,4-dione
  参考文献：
  名称：

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

  摘要：

  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. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2009.05.037

文献信息

• Aryloxy-Substituted Benzimidazole Derivatives
  申请人：Hashimoto Noriaki

  公开号：US20080125429A1

  公开（公告）日：2008-05-29

  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 R 1 and R 2 represent a hydrogen, etc.; R 3 represents a hydrogen atom, a halogen atom, etc.; R 4 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); R 5 and R 6 each represent a hydrogen atom, a lower alkyl group, etc.; X 1 , X 2 , X 3 and X 4 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 X 1 to X 4 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.

  本发明提供了一种葡萄糖激酶激活剂；以及用于糖尿病的治疗和/或预防，或用于糖尿病如视网膜病变、肾病、神经病、缺血性心脏病、动脉硬化等的治疗和/或预防，以及用于肥胖症的治疗和/或预防。本发明涉及一种化合物的公式(I)：[其中R1和R2分别表示氢等；R3表示氢原子、卤原子等；R4各自独立地表示氢原子、低级烷基等；Q表示碳原子、氮原子或硫原子（硫原子可以是单取代或双取代的氧基）；R5和R6各自表示氢原子、低级烷基等；X1、X2、X3和X4各自独立地表示碳原子或氮原子；Z表示氧原子、硫原子或氮原子；Ar表示芳基或杂环芳基，可选择性地单取代至三取代于β取代基；环A表示一个含氮的5-或6成员杂芳基；m表示1至6的整数；n表示0至3的整数；p表示0至2的整数（前提是X1至X4中至少有两个是碳原子）；q表示0或1]或其药学上可接受的盐，具有葡萄糖激酶激活的作用，并且可用作糖尿病的治疗。
• ARYLOXY-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES
  申请人：MSD K.K.

  公开号：EP1810969B1

  公开（公告）日：2013-08-07
• US7932394B2
  申请人：——

  公开号：US7932394B2

  公开（公告）日：2011-04-26
• The design and optimization of a series of 2-(pyridin-2-yl)-1H-benzimidazole compounds as allosteric glucokinase activators
  作者：Keiji Takahashi、Noriaki Hashimoto、Chisato Nakama、Kenji Kamata、Kaori Sasaki、Riki Yoshimoto、Sumika Ohyama、Hideka Hosaka、Hiroko Maruki、Yasufumi Nagata、Jun-ichi Eiki、Teruyuki Nishimura

  DOI：10.1016/j.bmc.2009.05.037

  日期：2009.10

  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. (C) 2009 Published by Elsevier Ltd.