methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole-6-carboxylate | 886976-80-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole-6-carboxylate
• 英文别名: methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(2-pyridinyl)-1H-benzimidazole-6-carboxylate；Methyl 6-(4-(ethylsulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-5-carboxylate；methyl 6-(4-ethylsulfonylphenoxy)-2-pyridin-2-yl-3H-benzimidazole-5-carboxylate
• CAS: 886976-80-3
• 化学式: C₂₂H₁₉N₃O₅S
• 分子量: 437.476
• InChiKey: NHZOJGZREPLRIV-UHFFFAOYSA-N

物化性质

• 沸点：
  688.2±65.0 °C(Predicted)
• 密度：
  1.365±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole-6-carboxylate 在 sodium hydroxide 、 水 、 盐酸 作用下， 生成 6-(4-(Ethylsulfonyl)phenoxy)-2-pyridin-2-yl-1H-benzimidazole-5-carboxylic acid
  参考文献：
  名称：

  HETEROCYCLE-SUBSTITUTED BENZIMIDAZOLE DERIVATIVE

  摘要：

  公开号：

  EP1905769B1
• 作为产物：
  描述：

  methyl 2-[4-(ethylsulfonyl)phenoxy]-5-nitro-4-[(pyridin-2-ylcarbonyl)amino]benzoate 在 盐酸 、 tin(II) chloride dihydrate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.67h， 以6.9 g的产率得到methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole-6-carboxylate
  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。
• Heterocycle-substituted benzimidazole derivative
  申请人：Ogino Yoshio

  公开号：US20100087360A1

  公开（公告）日：2010-04-08

  A compound represented by the formula (I) or a pharmaceutically acceptable salt thereof: (I) wherein X 1 to X 4 independently represent a carbon atom or the like; the ring A represents a 5- to 6-membered heteroaryl having 1 to 4 heteroatoms independently selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom; X 5 represents an oxygen atom or the like; X represents a carbon atom or the like; Het represents a 5- or 6-membered aliphatic heterocycle; R 1 represents an aryl or the like; R 2 represents a formyl group or the like; and R 3 represents a —C 1-6 alkyl or the like. The compound or salt has a glucokinase activation effect and is useful as a therapeutic agent for diabetes.

  化合物的化学式为(I)或其药学上可接受的盐：(I)其中X1至X4分别代表碳原子或类似物；环A代表具有1至4个杂原子的5-至6成员杂芳基，所述杂原子独立地选自氮原子、硫原子和氧原子的群；X5代表氧原子或类似物；X代表碳原子或类似物；Het代表5-或6成员脂肪族杂环；R1代表芳基或类似物；R2代表甲酰基或类似物；R3代表—C1-6烷基或类似物。该化合物或盐具有葡萄糖激酶激活作用，并可用作糖尿病治疗剂。
• Aryloxy-substituted benzimidazole derivatives
  申请人：MSD K.K.

  公开号：US07932394B2

  公开（公告）日：2011-04-26

  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.

  本发明提供了一种葡萄糖激酶激活剂；以及一种治疗和/或预防糖尿病，或一种治疗和/或预防糖尿病如视网膜病变、肾病、神经病、缺血性心脏病、动脉硬化，以及进一步治疗和/或预防肥胖症的药物。本发明涉及公式(I)的化合物：[其中R1和R2代表氢等；R3代表氢原子、卤原子等；R4各自独立地代表氢原子、较低的烷基等；Q代表碳原子、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各自代表氢原子、较低的烷基等；X1、X2、X3和X4各自独立地代表碳原子或氮原子；Z代表氧原子、硫原子或氮原子；Ar代表芳基或杂环芳基，可选择性地单取代至三取代于从取代基β选择的基团；环A代表一含有5-或6-成员的含氮杂环芳基；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（但至少X1至X4中的两个为碳原子）；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，可用于治疗糖尿病。
• ARYLOXY-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES
  申请人：MSD K.K.

  公开号：EP1810969B1

  公开（公告）日：2013-08-07
• US7994331B2
  申请人：——

  公开号：US7994331B2

  公开（公告）日：2011-08-09