2-[(R)-1-氨基-2-(1H-吲哚-3-基)-乙基]-5-苯基-1H-咪唑-4-羧酸乙酯 | 1027306-94-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-[(R)-1-氨基-2-(1H-吲哚-3-基)-乙基]-5-苯基-1H-咪唑-4-羧酸乙酯
• 英文名称: ethyl 2-[(1R)-1-amino-2-(1H-indol-3-yl)ethyl]-4-phenyl-1H-imidazole-5-carboxylate
• CAS: 1027306-94-0
• 化学式: C₂₂H₂₂N₄O₂
• 分子量: 374.442
• InChiKey: MWQKGUMNGHSDEW-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  96.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-[(R)-1-氨基-2-(1H-吲哚-3-基)-乙基]-5-苯基-1H-咪唑-4-羧酸乙酯 在 N-甲基吗啉 、 lithium hydroxide 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 2-[(R)-1-{(S)-2-[(Azepane-1-carbonyl)-amino]-4-methyl-pentanoylamino}-2-(1H-indol-3-yl)-ethyl]-5-phenyl-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  Azole Endothelin Antagonists. 1. A Receptor Model Explains an Unusual Structure−Activity Profile

  摘要：

  The pseudotetrapeptide FR-139317 is a potent and highly selective antagonist of the endothelin-A (ET(A)) receptor; however, its peptidic nature leads to poor oral absorption characteristics which make it an unlikely drug candidate. In an attempt to improve these properties, we have replaced a portion of the amide bond framework of FR-139317 with a heterocyclic surrogate. The resultant analogs are also ET(A)-selective antagonists, but show a structure-activity profile substantially different from that of the peptidic series, particularly with regard to the requirements for the side chain group that has been incorporated into the heterocycle. The nature of the heterocycle itself also has profound effects on the activity of the compounds. Both of these surprising results can be rationalized through examination of a 3D model of ET ligand-receptor binding that has previously been developed in our laboratories.

  DOI：

  10.1021/jm950591h
• 作为产物：
  描述：

  N-苄氧羰基-D-色氨酸 在 palladium on activated charcoal N-甲基吗啉 、 乙酸铵 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 2-[(R)-1-氨基-2-(1H-吲哚-3-基)-乙基]-5-苯基-1H-咪唑-4-羧酸乙酯
  参考文献：
  名称：

  Azole Endothelin Antagonists. 1. A Receptor Model Explains an Unusual Structure−Activity Profile

  摘要：

  The pseudotetrapeptide FR-139317 is a potent and highly selective antagonist of the endothelin-A (ET(A)) receptor; however, its peptidic nature leads to poor oral absorption characteristics which make it an unlikely drug candidate. In an attempt to improve these properties, we have replaced a portion of the amide bond framework of FR-139317 with a heterocyclic surrogate. The resultant analogs are also ET(A)-selective antagonists, but show a structure-activity profile substantially different from that of the peptidic series, particularly with regard to the requirements for the side chain group that has been incorporated into the heterocycle. The nature of the heterocycle itself also has profound effects on the activity of the compounds. Both of these surprising results can be rationalized through examination of a 3D model of ET ligand-receptor binding that has previously been developed in our laboratories.

  DOI：

  10.1021/jm950591h