tert-butyl 4-[(1R,2S)-2-[(2R)-1-[(4-chlorophenyl)methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butan-2-yl]cyclopropyl]imidazole-1-carboxylate | 1226790-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: tert-butyl 4-[(1R,2S)-2-[(2R)-1-[(4-chlorophenyl)methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butan-2-yl]cyclopropyl]imidazole-1-carboxylate
• CAS: 1226790-63-1
• 化学式: C₂₇H₃₈ClN₃O₄
• 分子量: 504.069
• InChiKey: BAPGHVIMGAHSEW-ILWGZMRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(1R,2S)-2-[(2R)-1-[(4-chlorophenyl)methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butan-2-yl]cyclopropyl]imidazole-1-carboxylate 在 盐酸 、 水 作用下， 以 乙醇 为溶剂， 反应 2.0h， 以29%的产率得到(1R,2S)-2-[(1R)-1-ethyl-2-(4-chlorobenzylamino)ethyl]-1-(1H-imidazol-4-yl)cyclopropane
  参考文献：
  名称：

  Investigation of the Bioactive Conformation of Histamine H₃ Receptor Antagonists by the Cyclopropylic Strain-Based Conformational Restriction Strategy

  摘要：

  We previously identified the highly potent histamine H-3 receptor antagonists (1R,2S)-2-[2-(4-chlorobenzylamino)ethyl]-1-(1H-imidazol-4-yl)cyclopropane (1) and its enantiomer ent-1. Although the conformations of 1 and ent-1 are restricted by the central cyclopropane ring, the 2-(4-chlorobenzylamino)ethyl side chain essential for the H3 receptor binding may somewhat freely rotate. To investigate the bioactive conformation, the 1'-ethyl-substituted derivatives 2a and 2b and their enantiomers ent-2a and ent-2b were designed as side chain conformation-restricted analogues of 1 and ent-1, based on the cyclopropylic strain. These compounds were synthesized, and their analysis by NMR and calculations suggested that the side chain moiety was effectively restricted in a syn-form or an anti-form by the cyclopropylic strain as expected. Pharmacological evaluation and docking simulation showed that the bioactive conformations of 1 and ent-1 appear to be the syn-form and the anti-form, respectively. Thus, the cyclopropylic strain can be effectively used for conformational restriction of the side chain moiety of cyclopropane compounds.

  DOI：

  10.1021/jm901848b
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (1R,2S)-2-[1-ethyl-2-(4-chlorobenzylamino)ethyl]-1-(1H-imidazol-4-yl)cyclopropane 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以24 mg的产率得到tert-butyl 4-[(1R,2S)-2-[(2R)-1-[(4-chlorophenyl)methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]butan-2-yl]cyclopropyl]imidazole-1-carboxylate
  参考文献：
  名称：

  Investigation of the Bioactive Conformation of Histamine H₃ Receptor Antagonists by the Cyclopropylic Strain-Based Conformational Restriction Strategy

  摘要：

  We previously identified the highly potent histamine H-3 receptor antagonists (1R,2S)-2-[2-(4-chlorobenzylamino)ethyl]-1-(1H-imidazol-4-yl)cyclopropane (1) and its enantiomer ent-1. Although the conformations of 1 and ent-1 are restricted by the central cyclopropane ring, the 2-(4-chlorobenzylamino)ethyl side chain essential for the H3 receptor binding may somewhat freely rotate. To investigate the bioactive conformation, the 1'-ethyl-substituted derivatives 2a and 2b and their enantiomers ent-2a and ent-2b were designed as side chain conformation-restricted analogues of 1 and ent-1, based on the cyclopropylic strain. These compounds were synthesized, and their analysis by NMR and calculations suggested that the side chain moiety was effectively restricted in a syn-form or an anti-form by the cyclopropylic strain as expected. Pharmacological evaluation and docking simulation showed that the bioactive conformations of 1 and ent-1 appear to be the syn-form and the anti-form, respectively. Thus, the cyclopropylic strain can be effectively used for conformational restriction of the side chain moiety of cyclopropane compounds.

  DOI：

  10.1021/jm901848b