tert-butyl 4-[(2-ethyl-3H-benzimidazol-5-yl)oxy]piperidine-1-carboxylate | 470715-71-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: tert-butyl 4-[(2-ethyl-3H-benzimidazol-5-yl)oxy]piperidine-1-carboxylate
• CAS: 470715-71-0
• 化学式: C₁₉H₂₇N₃O₃
• 分子量: 345.442
• InChiKey: KVQOZPVXTOMADQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(2-ethyl-3H-benzimidazol-5-yl)oxy]piperidine-1-carboxylate 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-[2-Ethyl-5-(piperidin-4-yloxy)-benzoimidazol-1-ylmethyl]-naphthalene-2-carboximidic acid methyl ester
  参考文献：
  名称：

  Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors

  摘要：

  Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00139-6
• 作为产物：
  描述：

  3,4-二氨基苯酚 在 氨 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 为溶剂， 生成 tert-butyl 4-[(2-ethyl-3H-benzimidazol-5-yl)oxy]piperidine-1-carboxylate
  参考文献：
  名称：

  Design, synthesis, and in vitro biological activity of benzimidazole based factor Xa inhibitors

  摘要：

  Inhibitors based on the benzimidazole scaffold showed subnanomolar potency against Factor Xa with 500-1000-fold selectivity against thrombin and 50-100-fold selectivity against trypsin. The 2-substituent on the benzimidazole ring had a strong impact on the FXa inhibitory activity. Crystallography studies suggest that the 2-substituent may have a conformational effect favoring the extended binding conformation. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00139-6

文献信息

• Benzimidazole-Based fXa inhibitors with improved thrombin and trypsin selectivity
  作者：Kenneth J. Shaw、William J. Guilford、Brian D. Griedel、Steve Sakata、Lan Trinh、Shung Wu、Wei Xu、Zuchun Zhao、Michael M. Morrissey

  DOI：10.1016/s0960-894x(02)00145-2

  日期：2002.5

  Optimization of the benzimidazole-based fXa inhibitors for selectivity versus thrombin and trypsin was achieved by substitution on the benzimidazole ring and replacement of the naphthylamidine group. Substitution of a nitro group at the 4-position on the benzimidazole improves both potency against fXa and selectivity versus thrombin. Alternatively, replacement of the naphthylamidine with either a biphenylamidine or propenylbenzamidine not only improves fXa potency and selectivity versus thrombin, but selectivity versus trypsin as well. (C) 2002 Elsevier Science Ltd. All rights reserved.