(11aS)-7-bromo-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]-diazepine-5,11-(10H,11aH)-dione | 84378-77-8

• 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: (11aS)-7-bromo-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]-diazepine-5,11-(10H,11aH)-dione
• 英文别名: (6aS)-2-bromo-6a,7,8,9-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-6,11-dione
• CAS: 84378-77-8
• 化学式: C₁₂H₁₁BrN₂O₂
• 分子量: 295.136
• InChiKey: RDVLVQKLHHZHAK-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (11aS)-7-bromo-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]-diazepine-5,11-(10H,11aH)-dione 在 四(三苯基膦)钯 sodium hydroxide 、 sodium formate 、 sodium hydride 、 氯磷酸二乙酯 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 2,2,2-trifluoroethyl (S)-9-oxo-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c]benzodiazepine-1-carboxylate
  参考文献：
  名称：

  Development of Selective Ligands for Benzodiazepine Receptor Subtypes by Manipulating the Substituents at Positions 3- and 7- of Optically Active BzR Ligands

  摘要：

  Two series of analogs of the optically active alpha5 subtype selective imidazobenzodiazepine 20 have been prepared. The framework constrained analogs were synthesized by variation of the C (3) ethyl ester function 20 to either t-butyl 7 or 2, 2, 2-trifluoroethyl 14. In both cases receptor binding was decreased; as well as alpha5 selectivity. In the second series the 7-acetylenyl function in 14 was varied over the range vinyl, 2-furyl, 2-thienyl and 2-phenyl. Again receptor binding was maintained in most cases; however, alpha5 selectivity was not increased. The significance of this in regard to occupation of lipophilic regions L-Di vs L-2 in the pharmacophore/receptor model of the BzR is discussed.

  DOI：

  10.1007/s00044-004-0033-7
• 作为产物：
  描述：

  (S)-(+)-2,3-二氢-1H-吡咯并[2,1-c][1,4]苯并二氮卓-5,11(10H,11aH)-二酮 在 溴 、 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 以70%的产率得到(11aS)-7-bromo-2,3-dihydro-1H-benzo[e]pyrrolo[1,2-a][1,4]-diazepine-5,11-(10H,11aH)-dione
  参考文献：
  名称：

  Syntheses of N10-substituted 7-Arylpyrrolo[2,1-c]-[1,4]benzodiazepine-5,11-diones

  摘要：

  Pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione and its 7‐bromo derivative were alkylated at the N10 atom applying various methods. The resulting products were subjected to Suzuki–Miyaura reactions using a catalyst system consisting of Pd(Cl)2(PPh3)2 and sodium tert‐butanolate in toluene. Results of an X‐ray single crystal analysis are presented.

  DOI：

  10.1002/jhet.1775

文献信息

• An Improved Process for the Synthesis of 4<i>H</i>-Imidazo[1,5-<i>a</i>][1,4]benzo­diazepines
  作者：Jie Yang、Yun Teng、Shamim Ara、Sundari Rallapalli、James Cook

  DOI：10.1055/s-0028-1083358

  日期：——

  The construction of CNS active imidazo[1,5-a][1,4]benzodiazepines has been improved in a one-pot annulation process. GABAA/Bz receptors - imidazo[1,5-a][1,4]benzodiazepines - ethyl isocyanoacetate - annulation

  CNS活性咪唑并[1,5- a ] [1,4]苯并二氮杂卓的结构已通过一锅法制得。 GABA A / Bz受体-咪唑并[1,5- a ] [1,4]苯并二氮杂卓-异氰基乙酸乙酯-环化
• Identification of an Orally Bioavailable, Brain-Penetrant Compound with Selectivity for the Cannabinoid Type 2 Receptor
  作者：Meirambek Ospanov、Suresh P. Sulochana、Jason J. Paris、John M. Rimoldi、Nicole Ashpole、Larry Walker、Samir A. Ross、Abbas G. Shilabin、Mohamed A. Ibrahim

  DOI：10.3390/molecules27020509

  日期：——

  endocannabinoid system (ECS) is of great interest for its therapeutic relevance in several pathophysiological processes. The CB2 subtype is largely localized to immune effectors, including microglia within the central nervous system, where it promotes anti-inflammation. Recently, a rational drug design toward precise modulation of the CB2 active site revealed the novelty of Pyrrolo[2,1-c][1,4]benzodiazepines

  内源性大麻素系统 (ECS) 的调节因其在多种病理生理过程中的治疗相关性而备受关注。CB2 亚型主要定位于免疫效应器，包括中枢神经系统内的小胶质细胞，在那里它促进抗炎。最近，针对精确调节 CB2 活性位点的合理药物设计揭示了 Pyrrolo[2,1-c][1,4]苯二氮卓类三环化学型的新颖性，与现有线索相比具有高度的构象相似性。这些化合物在结构上是独特的，证实了它们的化学型新颖性。在我们继续寻找新的化学型作为选择性 CB2 调节分子的过程中，遵循 SAR 方法，总共选择了 17 个（S，E)-11-[2-(芳基亚甲基)肼基]-PBD 类似物被合成并测试它们与 CB1 和 CB2 受体正构位点结合的能力。竞争性 [3H]CP-55,940 结合筛选显示五种化合物在 10 μM 浓度下表现出 >60% 的置换。进一步的浓度反应分析揭示了两种化合物 4k 和 4q，它们是具有亚微摩尔活性的有效和选择性
• Liu, Ruiyan; Zhang, Puwen; Gan, Tong, Medicinal Chemistry Research, 1997, vol. 7, # 1, p. 25 - 35
  作者：Liu, Ruiyan、Zhang, Puwen、Gan, Tong、McKernan, Ruth M.、Cook, James M.

  DOI：——

  日期：——
• Syntheses of N10-substituted 7-Arylpyrrolo[2,1-<i>c</i>]-[1,4]benzodiazepine-5,11-diones
  作者：Anika Sabine Lindner、Egor Geist、Mimoza Gjikaj、Andreas Schmidt

  DOI：10.1002/jhet.1775

  日期：2014.3

  Pyrrolo[2,1‐c][1,4]benzodiazepine‐5,11‐dione and its 7‐bromo derivative were alkylated at the N10 atom applying various methods. The resulting products were subjected to Suzuki–Miyaura reactions using a catalyst system consisting of Pd(Cl)2(PPh3)2 and sodium tert‐butanolate in toluene. Results of an X‐ray single crystal analysis are presented.
• Development of Selective Ligands for Benzodiazepine Receptor Subtypes by Manipulating the Substituents at Positions 3- and 7- of Optically Active BzR Ligands
  作者：Xiaoyan Li、Jianming Yu、John R. Atack、James M. Cook

  DOI：10.1007/s00044-004-0033-7

  日期：2004.6

  Two series of analogs of the optically active alpha5 subtype selective imidazobenzodiazepine 20 have been prepared. The framework constrained analogs were synthesized by variation of the C (3) ethyl ester function 20 to either t-butyl 7 or 2, 2, 2-trifluoroethyl 14. In both cases receptor binding was decreased; as well as alpha5 selectivity. In the second series the 7-acetylenyl function in 14 was varied over the range vinyl, 2-furyl, 2-thienyl and 2-phenyl. Again receptor binding was maintained in most cases; however, alpha5 selectivity was not increased. The significance of this in regard to occupation of lipophilic regions L-Di vs L-2 in the pharmacophore/receptor model of the BzR is discussed.