1-methyl-2-(1H-indol-3-yl)methylcarbonylaminomethyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine | 123903-81-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1-methyl-2-(1H-indol-3-yl)methylcarbonylaminomethyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine
• 英文别名: N-[5-(2-Fluoro-phenyl)-1-methyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-2-ylmethyl]-2-(1H-indol-3-yl)-acetamide；N-[[5-(2-fluorophenyl)-1-methyl-2,3-dihydro-1,4-benzodiazepin-2-yl]methyl]-2-(1H-indol-3-yl)acetamide
• CAS: 123903-81-1
• 化学式: C₂₇H₂₅FN₄O
• 分子量: 440.52
• InChiKey: BAYFEFXAUQUWCZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  60.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-吲哚乙酸 、 1-methyl-2-(aminomethyl)-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine 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26%的产率得到1-methyl-2-(1H-indol-3-yl)methylcarbonylaminomethyl-5-(2'-fluorophenyl)-2,3-dihydro-1H-1,4-benzodiazepine
  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

文献信息

• 2-Substituted-aminomethyl-1,4-benzodiazepines, process for their preparation and pharmaceutical compositions containing them
  申请人：Merck & Co., Inc.

  公开号：EP0166356A2

  公开（公告）日：1986-01-02

  Novel 2-substituted-aminomethyl-1,4-benzodiazepines which have been found to be antagonists of the function of cholecystokinins (CCK), to the preparation of these compounds, and to the use of these compounds to antagonize the function of CCK, which antagonism is useful, e.g., for the treatment and prevention of disorders of the gastrointestinal, central nervous and appetite regulatory systems of mammals, especially of humans.

  新型 2-取代-氨甲基-1,4-苯并二氮杂卓，已被发现是胆囊收缩素（CCK）功能的拮抗剂，制备这些化合物，以及使用这些化合物来拮抗 CCK 的功能，这种拮抗作用可用于治疗和预防哺乳动物，特别是人类的胃肠道、中枢神经和食欲调节系统紊乱等疾病。
• US4724237A
  申请人：——

  公开号：US4724237A

  公开（公告）日：1988-02-09
• Cholecystokinin-A receptor ligands based on the .kappa.-opioid agonist tifluadom
  作者：Mark G. Bock、Robert M. DiPardo、Ben E. Evans、Kenneth E. Rittle、Willie L. Whitter、Daniel F. Veber、Roger M. Freidinger、Raymond S. L. Chang、T. B. Chen、Victor J. Lotti

  DOI：10.1021/jm00163a069

  日期：1990.1

  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.