2(R)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-4-methylsulfanylbutyric acid ethyl ester | 1155261-62-3

• 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: 2(R)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-4-methylsulfanylbutyric acid ethyl ester
• CAS: 1155261-62-3
• 化学式: C₂₃H₂₅N₃O₄S
• 分子量: 439.535
• InChiKey: QLEUCYICLUJAIN-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.83
• 重原子数：
  31.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  100.29
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2(R)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-4-methylsulfanylbutyric acid ethyl ester 在 lithium hydroxide monohydrate 、 水 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 以61%的产率得到2-(R)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-4-methylsulfanylbutyric acid
  参考文献：
  名称：

  Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same ‘words’ of the endogenous ligand

  摘要：

  The anthranilic acid diamides represent the more recent class of nonpeptide CCK1 receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK1 receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively. Herein we describe the first step of the anthranilic acid C- terminal optimization using, instead of Phe, aminoacids belonging to the primary structure of CCK-8 and other not coded residues. Thus we demonstrate that the CCK1 receptor affinity depends on the nature of the aminoacidic side chain as well as that the free carboxy group of the alpha-aminoacids is crucial for the binding. The R enantiomers of the most active compounds represent the eutomers of this class of antagonists confirming thus the stereo preference of the receptor. Moreover this SAR study demonstrates that the receptor binding pocket, that host the aminoacidic side chain, results much more tolerant respect to that accommodating the indole ring. As a result, an appropriate variation of the aminoacidic side chain could provide a better CCK1 receptor affinity diorthosis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.02.012
• 作为产物：
  描述：

  吲哚-2-羧酸 、 2-(R)-(2-aminobenzoylamino)-4-methylsulfanylbutyric acid ethyl ester 在 五氯化磷 、 乙酰氯 、 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 以80%的产率得到2(R)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-4-methylsulfanylbutyric acid ethyl ester
  参考文献：
  名称：

  Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same ‘words’ of the endogenous ligand

  摘要：

  The anthranilic acid diamides represent the more recent class of nonpeptide CCK1 receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK1 receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively. Herein we describe the first step of the anthranilic acid C- terminal optimization using, instead of Phe, aminoacids belonging to the primary structure of CCK-8 and other not coded residues. Thus we demonstrate that the CCK1 receptor affinity depends on the nature of the aminoacidic side chain as well as that the free carboxy group of the alpha-aminoacids is crucial for the binding. The R enantiomers of the most active compounds represent the eutomers of this class of antagonists confirming thus the stereo preference of the receptor. Moreover this SAR study demonstrates that the receptor binding pocket, that host the aminoacidic side chain, results much more tolerant respect to that accommodating the indole ring. As a result, an appropriate variation of the aminoacidic side chain could provide a better CCK1 receptor affinity diorthosis. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.02.012