5-[4-(ethylsulfonyl)phenoxy]-6-[(1-methyl-1H-tetrazol-5-yl)methyl]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole | 1193347-14-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-[4-(ethylsulfonyl)phenoxy]-6-[(1-methyl-1H-tetrazol-5-yl)methyl]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole
• CAS: 1193347-14-6
• 化学式: C₂₉H₃₅N₇O₄SSi
• 分子量: 605.793
• InChiKey: YBWSSOMPTSNIKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  42.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  126.91
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  5-[4-(ethylsulfonyl)phenoxy]-6-[(1-methyl-1H-tetrazol-5-yl)methyl]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.0h， 生成 5-[4-(ethylsulfonyl)phenoxy]-6-[(1-methyl-1H-tetrazol-5-yl)methyl]-2-(pyridin-2-yl)-1H-benzimidazole
  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：

  5-[4-(ethylsulfonyl)phenoxy]-2-(pyridin-2-yl)-6-(2H-tetrazol-5-ylmethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole 、 碘甲烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 paraffin oil 为溶剂， 反应 1.0h， 以24%的产率得到5-[4-(ethylsulfonyl)phenoxy]-6-[(1-methyl-1H-tetrazol-5-yl)methyl]-2-(pyridin-2-yl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-benzimidazole
  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