2-(RS)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-5-phenylpentanoic acid

• 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-(RS)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-5-phenylpentanoic acid
• 英文别名: 2-[[2-(1H-indole-2-carbonylamino)benzoyl]amino]-5-phenylpentanoic acid
• 化学式: C₂₇H₂₅N₃O₄
• 分子量: 455.513
• InChiKey: MHWJDMSLBDLKCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-碘-3-苯基丙烷 在 吡啶 、 盐酸 、 水 、 sodium ethanolate 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 2-(RS)-{2-[(1H-indole-2-carbonyl)amino]benzoylamino}-5-phenylpentanoic acid
  参考文献：
  名称：

  New Anthranilic Acid Based Antagonists with High Affinity and Selectivity for the Human Cholecystokinin Receptor 1 (hCCK₁-R)

  摘要：

  The anthranilic acid diamides represent the most recent class of nonpeptide CCK1 receptor (CCK1-R) antagonists. Herein we describe the second phase of the anthranilic acid C-terminal optimization using nonproteinogenic amino acids containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797) enhanced 12-fold the affinity for the rat CCK1-R affinity and 15-fold for the human CCK1-R relative to the reference compound 12 (VL-0395). The eutomer of 2 (6) exhibited a nanomolar range affinity toward the human CCK1-R and was at least 400-fold selective for the CCK1-R over the CCK2-R. Molecular docking in the modeled CCK1-R and its validation by site-directed mutagenesis experiments showed that the 6 binding site overlaps that occupied by the C-terminal bioactive region of the natural agonist CCK. Owing to their interesting properties, new compounds provided by this study represent a solid basis for further advances aimed at synthesis of clinically valuable CCK1-R antagonists.

  DOI：

  10.1021/jm200438b

文献信息

• New Anthranilic Acid Based Antagonists with High Affinity and Selectivity for the Human Cholecystokinin Receptor 1 (hCCK₁-R)
  作者：Michela V. Pavan、Lucia Lassiani、Federico Berti、Giorgio Stefancich、Alessia Ciogli、Francesco Gasparrini、Laura Mennuni、Flora Ferrari、Chantal Escrieut、Esther Marco、Francesco Makovec、Daniel Fourmy、Antonio Varnavas

  DOI：10.1021/jm200438b

  日期：2011.8.25

  The anthranilic acid diamides represent the most recent class of nonpeptide CCK1 receptor (CCK1-R) antagonists. Herein we describe the second phase of the anthranilic acid C-terminal optimization using nonproteinogenic amino acids containing a phenyl ring in their side chain. The Homo-Phe derivative 2 (VL-0797) enhanced 12-fold the affinity for the rat CCK1-R affinity and 15-fold for the human CCK1-R relative to the reference compound 12 (VL-0395). The eutomer of 2 (6) exhibited a nanomolar range affinity toward the human CCK1-R and was at least 400-fold selective for the CCK1-R over the CCK2-R. Molecular docking in the modeled CCK1-R and its validation by site-directed mutagenesis experiments showed that the 6 binding site overlaps that occupied by the C-terminal bioactive region of the natural agonist CCK. Owing to their interesting properties, new compounds provided by this study represent a solid basis for further advances aimed at synthesis of clinically valuable CCK1-R antagonists.