(6-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-5-yl)methanol | 886976-82-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-5-yl)methanol
• 英文别名: (6-[4-(ethylsulfonyl)phenoxy]-2-(2-pyridinyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-5-yl)methanol；[6-(4-Ethylsulfonylphenoxy)-2-pyridin-2-yl-1-(2-trimethylsilylethoxymethyl)benzimidazol-5-yl]methanol
• CAS: 886976-82-5
• 化学式: C₂₇H₃₃N₃O₅SSi
• 分子量: 539.728
• InChiKey: JTDZESKOIAFKGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.49
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  112
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (6-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-5-yl)methanol 、 甲基磺酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 (6-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-5-yl)methylmethanesulfonate
  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
• 作为产物：
  描述：

  methyl 5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1H-benzimidazole-6-carboxylate 、 2-(三甲基硅烷基)乙氧甲基氯 在 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 (5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-6-yl)methanol 、 (6-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazol-5-yl)methanol
  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：MSD K.K.

  公开号：EP1810969B1

  公开（公告）日：2013-08-07
• 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.