(rac)-trans-octahydro-2-oxo-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester | 143617-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉类
• 英文名称: (rac)-trans-octahydro-2-oxo-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester
• 英文别名: tert-butyl (3aS,7aR)-2-oxo-3a,4,5,6,7,7a-hexahydro-3H-indole-1-carboxylate
• CAS: 143617-92-9
• 化学式: C₁₃H₂₁NO₃
• 分子量: 239.315
• InChiKey: JHFLUXDFJVKELM-VHSXEESVSA-N

物化性质

• 沸点：
  370.0±11.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (rac)-trans-octahydro-2-oxo-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 以99%的产率得到((1R,2S)-2-tert-Butoxycarbonylamino-cyclohexyl)-acetic acid
  参考文献：
  名称：

  Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29

  摘要：

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.

  DOI：

  10.1021/jm00099a005
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 (rac)-trans-octahydro-2H-indol-2-one 在 4-二甲氨基吡啶 、 sodium hydride 作用下， 生成 (rac)-trans-octahydro-2-oxo-1H-indole-1-carboxylic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Analogs of Ac-CCK-7 incorporating dipeptide mimics in place of Met28-Gly29

  摘要：

  A series of analogs of Ac-CCK-7 [Ac-Tyr(SO3H)-Met28-Gly29-Trp-Met-Asp-Phe-NH2, (1)] Were prepared in which the Met28-Gly29 dipeptide was replaced by omega-aminoalkanoic acids. Compounds were assessed in binding assays using homogenated rat pancreatic membranes and bovine striatum as the source of CCK-A and CCK-B receptors, respectively, and for anorectic activity after intraperitoneal administration to rats. The analog incorporating 4-aminobutanoic acid (5) was only 8 times less potent than 1 in the pancreatic binding assay, was more potent in the striatal binding assay, and was more potent than 1 in reducing food intake in rats. Using a bioactive cyclic analog of Ac-CCK-7 as a template, several rigid spacers were designed and tested as substitutes for the Met28-Gly29 dipeptide. The analogs incorporating 3-aminobenzoic acid (20) and (1S)-trans-2-aminocyclopentanecarboxylic acid (26) proved highly effective in the binding assays and as anorectic agents. We hypothesize that for stimulation of CCK-A receptors, the main function of the N-terminal tripeptide of Ac-CCK-7 is to orient the tyrosine sulfate with respect to Trp30 and that the bioactive arrangement of these elements lies among those which are readily available to both 20 and 26. NOESY and distance-constrained molecular dynamics experiments carried out on 20 and 26 identified conformations in which the relative orientation of the tyrosine hydroxide and the alpha-carbon atom of tryptophan were similar, providing the basis for further drug design efforts.

  DOI：

  10.1021/jm00099a005