2-[(R)-1-[(S)-2-(3-Benzyl-ureido)-4-methyl-pentanoylamino]-2-(1H-indol-3-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic acid ethyl ester | 168470-59-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[(R)-1-[(S)-2-(3-Benzyl-ureido)-4-methyl-pentanoylamino]-2-(1H-indol-3-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic acid ethyl ester
• 英文别名: ethyl 2-[(1R)-1-[[(2S)-2-(benzylcarbamoylamino)-4-methylpentanoyl]amino]-2-(1H-indol-3-yl)ethyl]-5-methyl-1H-imidazole-4-carboxylate
• CAS: 168470-59-5
• 化学式: C₃₁H₃₈N₆O₄
• 分子量: 558.681
• InChiKey: VXFBLAPBTJPSHG-FTJBHMTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  41
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  141
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(R)-1-[(S)-2-(3-Benzyl-ureido)-4-methyl-pentanoylamino]-2-(1H-indol-3-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 2-[(R)-1-[(S)-2-(3-Benzyl-ureido)-4-methyl-pentanoylamino]-2-(1H-indol-3-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic acid
  参考文献：
  名称：

  Azole Endothelin Antagonists. 2. Structure−Activity Studies

  摘要：

  Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or arylureas led to substantial improvements in activity. Conformational restriction of these groups provides an additional benefit. N-Methylation of the indole moiety which is part of the heterocyclic dipeptide surrogate also improves potency. The effects of these two modifications appear to be synergistic, with the best of the resultant doubly modified analogs (e.g. 14q, 15y, and 15ff) exhibiting an 80-200-fold improvement over the original leads.

  DOI：

  10.1021/jm950592+
• 作为产物：
  描述：

  ethyl 2-[(1R)-1-amino-2-(1H-indol-3-yl)ethyl]-5-methyl-1H-imidazole-4-carboxylate 在 N-甲基吗啉 、 盐酸 、 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 、 1,4-二氧六环 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 39.0h， 生成 2-[(R)-1-[(S)-2-(3-Benzyl-ureido)-4-methyl-pentanoylamino]-2-(1H-indol-3-yl)-ethyl]-5-methyl-1H-imidazole-4-carboxylic acid ethyl ester
  参考文献：
  名称：

  Azole Endothelin Antagonists. 2. Structure−Activity Studies

  摘要：

  Structure-activity studies have been performed in an attempt to improve the potency of a novel series of azole-based endothelin-A (ET(A)) selective antagonists. Modifications of the hydrophobic group on the terminal urea produced substantial effects on receptor affinity; in particular, the choice of cyclohexyl- or arylureas led to substantial improvements in activity. Conformational restriction of these groups provides an additional benefit. N-Methylation of the indole moiety which is part of the heterocyclic dipeptide surrogate also improves potency. The effects of these two modifications appear to be synergistic, with the best of the resultant doubly modified analogs (e.g. 14q, 15y, and 15ff) exhibiting an 80-200-fold improvement over the original leads.

  DOI：

  10.1021/jm950592+

文献信息

• [EN] ENDOTHELIN ANTAGONISTS<br/>[FR] ANTAGONISTES D'ENDOTHELINE
  申请人：ABBOTT LABORATORIES

  公开号：WO1995008550A1

  公开（公告）日：1995-03-30

  (EN) A compound of formula (I) or a pharmaceutically acceptable salt thereof, as well as processes for and intermediates in the preparation thereof, and methods and compositions of antagonizing endothelin.(FR) Composé représenté par la formule (I), ou un de ses sels pharmaceutiquement acceptable, ainsi que procédés et intermédiaires servant à leur préparation, procédés et compositions antagonistes de l'endothéline.