(R)-6-(2-fluorophenyl)-4-(1H-indol-3-ylmethyl)-1-methyl-4H-<1,2,4>triazolo<4,3-a><1,4>benzodiazepine | 103195-57-9

• 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: (R)-6-(2-fluorophenyl)-4-(1H-indol-3-ylmethyl)-1-methyl-4H-<1,2,4>triazolo<4,3-a><1,4>benzodiazepine
• 英文别名: (4R)-6-(2-fluorophenyl)-4-(1H-indol-3-ylmethyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine
• CAS: 103195-57-9
• 化学式: C₂₆H₂₀FN₅
• 分子量: 421.477
• InChiKey: VKMJGKFQKLVODR-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  58.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2H-1,4-苯并二氮卓-2-酮,5-(2-氟苯基)-1,3-二氢-3-(1H-吲哚-3-基甲基)-,(3R)- 在 劳森试剂 、 硫酸 、 肼 作用下， 以 甲醇 、 乙醇 、 甲苯 为溶剂， 反应 14.0h， 生成 (R)-6-(2-fluorophenyl)-4-(1H-indol-3-ylmethyl)-1-methyl-4H-<1,2,4>triazolo<4,3-a><1,4>benzodiazepine
  参考文献：
  名称：

  Cholecystokinin antagonists. Synthesis and biological evaluation of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines

  摘要：

  A series of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared by standard methodology. These compounds were tested in vitro as antagonists of the binding of [125I]cholecystokinin (CCK) to rat pancreas and guinea pig brain receptors and of the binding of [125I]gastrin to guinea pig gastric glands. All compounds proved to have greater affinity for the peripheral CCK receptor with some analogues having IC50's in the subnanomolar range. In vivo activity of selected compounds in mice is presented and the structure/activity profile of this class of benzodiazepines as CCK antagonists is discussed.

  DOI：

  10.1021/jm00396a028

文献信息

• Design of nonpeptidal ligands for a peptide receptor: cholecystokinin antagonists
  作者：B. E. Evans、K. E. Rittle、M. G. Bock、R. M. DiPardo、R. M. Freidinger、W. L. Whitter、N. P. Gould、G. F. Lundell、C. F. Homnick

  DOI：10.1021/jm00390a019

  日期：1987.7

  3-substituted 5-phenyl-1,4-benzodiazepines, nonpeptidal antagonists of the peptide hormone cholecystokinin (CCK), have been synthesized. Designed on the basis of facts regarding CCK, its natural-product antagonist asperlicin (3), and the antianxiety agent diazepam (4), these compounds represent a significant departure from existing CCK antagonists. They also constitute perhaps the first examples of simple

  已经合成了一系列3-取代的5-苯基-1,4-苯并二氮杂卓，它们是肽激素胆囊收缩素（CCK）的非肽拮抗剂。根据有关CCK，其天然产物拮抗剂Asperlicin（3）和抗焦虑药地西epa（4）的事实进行设计，这些化合物与现有的CCK拮抗剂有很大的不同。它们也可能构成通过设计而不是通过筛选产生的肽受体的简单，非肽配体的第一个实例。这些化合物用于阐明中枢和外周CCK受体之间的区别，并提供具有潜在药理或治疗用途的口服有效CCK拮抗剂。他们的受体亲和力的一个基本原理可能会在设计其他受体的非肽配体时应用，
• BOCK, MARK G.;DIPARDO, ROBERT M.;EVANS, BEN E.;RITTLE, KENNETH E.;VEBER, +, J. MED. CHEM., 31,(1988) N 1, 176-181
  作者：BOCK, MARK G.、DIPARDO, ROBERT M.、EVANS, BEN E.、RITTLE, KENNETH E.、VEBER, +

  DOI：——

  日期：——
• BOCK, M. G.;EVANS, B. E.;FREIDINGER, R. M.
  作者：BOCK, M. G.、EVANS, B. E.、FREIDINGER, R. M.

  DOI：——

  日期：——
• Cholecystokinin antagonists. Synthesis and biological evaluation of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines
  作者：Mark G. Bock、Robert M. DiPardo、Ben E. Evans、Kenneth E. Rittle、Daniel F. Veber、Roger M. Freidinger、Raymond S. L. Chang、Victor J. Lotti

  DOI：10.1021/jm00396a028

  日期：1988.1

  A series of 4-substituted 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepines was prepared by standard methodology. These compounds were tested in vitro as antagonists of the binding of [125I]cholecystokinin (CCK) to rat pancreas and guinea pig brain receptors and of the binding of [125I]gastrin to guinea pig gastric glands. All compounds proved to have greater affinity for the peripheral CCK receptor with some analogues having IC50's in the subnanomolar range. In vivo activity of selected compounds in mice is presented and the structure/activity profile of this class of benzodiazepines as CCK antagonists is discussed.