[(S)-1-{[5-(2-Fluoro-phenyl)-1-methyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-2-ylmethyl]-carbamoyl}-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester | 102428-92-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: [(S)-1-{[5-(2-Fluoro-phenyl)-1-methyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-2-ylmethyl]-carbamoyl}-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester
• CAS: 102428-92-2
• 化学式: C₃₃H₃₆FN₅O₃
• 分子量: 569.679
• InChiKey: POQAFSKCCQVOAP-WNWQKLGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  42.0
• 可旋转键数：
  7.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  98.82
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  [(S)-1-{[5-(2-Fluoro-phenyl)-1-methyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-2-ylmethyl]-carbamoyl}-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 以99%的产率得到1-methyl-2-<<<2(S)-amino-3-(1H-indol-3-yl)propanoyl>amino>methyl>-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine dihydrochloride
  参考文献：
  名称：

  Cholecystokinin-A receptor ligands based on the .kappa.-opioid agonist tifluadom

  摘要：

  Tifluadom, a kappa-opioid agonist and cholecystokinin-A (CCK-A) receptor antagonist, was utilized as a model to prepare a series of 2-(aminomethyl)- and 3-(aminomethyl)-1,4-benzodiazepines. These compounds were tested in vitro as inhibitors of the binding of [125I]CCK to rat pancreas and guinea pig brain receptors. All compounds with IC50's less than 100 microM proved to have greater affinity for the CCK-A receptor, with the most potent analogue, 6e, having an IC50 of 0.16 microM. The benzodiazepines described in this study are simultaneously CCK-A and opioid receptor ligands. The ramification of this dichotomy on current concepts of peptide hormone action are discussed. These results further demonstrate the versatility of the benzodiazepine core structure for designing nonpeptide ligands for peptide receptors and the ability to fine-tune the receptor interactions of these benzodiazepines by appropriate structure modifications.

  DOI：

  10.1021/jm00163a069
• 作为产物：
  描述：

  1-methyl-2-(aminomethyl)-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine 、 N-叔丁氧羰基-L-色氨酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以54%的产率得到[(S)-1-{[5-(2-Fluoro-phenyl)-1-methyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-2-ylmethyl]-carbamoyl}-2-(1H-indol-3-yl)-ethyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Cholecystokinin-A receptor ligands based on the .kappa.-opioid agonist tifluadom

  摘要：

  Tifluadom, a kappa-opioid agonist and cholecystokinin-A (CCK-A) receptor antagonist, was utilized as a model to prepare a series of 2-(aminomethyl)- and 3-(aminomethyl)-1,4-benzodiazepines. These compounds were tested in vitro as inhibitors of the binding of [125I]CCK to rat pancreas and guinea pig brain receptors. All compounds with IC50's less than 100 microM proved to have greater affinity for the CCK-A receptor, with the most potent analogue, 6e, having an IC50 of 0.16 microM. The benzodiazepines described in this study are simultaneously CCK-A and opioid receptor ligands. The ramification of this dichotomy on current concepts of peptide hormone action are discussed. These results further demonstrate the versatility of the benzodiazepine core structure for designing nonpeptide ligands for peptide receptors and the ability to fine-tune the receptor interactions of these benzodiazepines by appropriate structure modifications.

  DOI：

  10.1021/jm00163a069