methyl (2R)-2-phenyl-2-[[(2S)-2-[(1S,2S)-2-(1-tritylimidazol-4-yl)cyclopropyl]butanoyl]amino]acetate | 1226790-89-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: methyl (2R)-2-phenyl-2-[[(2S)-2-[(1S,2S)-2-(1-tritylimidazol-4-yl)cyclopropyl]butanoyl]amino]acetate
• CAS: 1226790-89-1
• 化学式: C₃₈H₃₇N₃O₃
• 分子量: 583.73
• InChiKey: FIJBABCWOZRFLM-IZFXIWBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  73.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (1S,2S)-2-((1S)-1-ethyl-2-carboxyethyl)-1-(1-triphenylmethyl-1H-imidazol-4-yl)cyclopropane 、 D-苯甘氨酸甲酯盐酸盐 在 N-甲基吗啉 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以93%的产率得到methyl (2R)-2-phenyl-2-[[(2S)-2-[(1S,2S)-2-(1-tritylimidazol-4-yl)cyclopropyl]butanoyl]amino]acetate
  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

文献信息

• Investigation of the Bioactive Conformation of Histamine H₃ Receptor Antagonists by the Cyclopropylic Strain-Based Conformational Restriction Strategy
  作者：Mizuki Watanabe、Takatsugu Hirokawa、Takaaki Kobayashi、Akira Yoshida、Yoshihiko Ito、Shizuo Yamada、Naoki Orimoto、Yasundo Yamasaki、Mitsuhiro Arisawa、Satoshi Shuto

  DOI：10.1021/jm901848b

  日期：2010.5.13

  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.