ethyl 8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate | 173990-13-1

• 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: ethyl 8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
• 英文别名: ethyl 8-ethynyl-5-methyl-6-oxo-5,6-dihydro-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate；[3H]-RY 80；RY 80；ethyl 8-ethynyl-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
• CAS: 173990-13-1
• 化学式: C₁₇H₁₅N₃O₃
• 分子量: 309.324
• InChiKey: WDTNKNNGHGOKBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  64.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate 在 sodium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 XLi-093
  参考文献：
  名称：

  Synthesis, in Vitro Affinity, and Efficacy of a Bis 8-Ethynyl-4H-imidazo[1,5a]- [1,4]benzodiazepine Analogue, the First Bivalent α5 Subtype Selective BzR/GABA_A Antagonist

  摘要：

  The synthesis and in vitro affinity of the alpha5beta3gamma2 (alpha5) subtype selective BzR/GABA(A) antagonist 7 is described. This ligand is selective for alpha5 subtypes in vitro and is a potent antagonist of the effects of diazepam only at alpha5beta3gamma2 subtypes (oocytes). Ligands such as 7 will be important in the determination of which physiological function(s) are subserved by this GABA(A) alpha5 subtype.

  DOI：

  10.1021/jm034164c
• 作为产物：
  描述：

  4-甲基-3,4-二氢-1h-苯并[e][1,4]二氮杂卓-2,5-二酮 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium tert-butylate 、 四丁基氟化铵 、 溴 、 sodium acetate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 41.0h， 生成 ethyl 8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
  参考文献：
  名称：

  The synthesis and anti-inflammatory evaluation of 1,2,3-triazole linked isoflavone benzodiazepine hybrids

  摘要：

  DOI：

  10.24820/ark.5550190.p011.396

文献信息

• GABAERGIC AGENTS TO TREAT MEMORY DEFICITS
  申请人：Cook M. James

  公开号：US20060258643A1

  公开（公告）日：2006-11-16

  The present invention provides molecules and methods for the prevention and/or treatment of memory deficit related conditions and/or enhancement of cognizance. In a preferred embodiment, the invention includes compounds, salts and prodrugs thereof for the prevention and/or treatment of these conditions.

  本发明提供了分子和方法，用于预防和/或治疗与记忆缺陷相关的疾病和/或提高认知能力。在一个首选实施例中，该发明包括化合物、盐和前药，用于预防和/或治疗这些疾病。
• Synthesis and Pharmacological Properties of Novel 8-Substituted Imidazobenzodiazepines:  High-Affinity, Selective Probes for α5-Containing GABA_A Receptors
  作者：Ruiyan Liu、Rona J. Hu、Puwen Zhang、Phil Skolnick、James M. Cook

  DOI：10.1021/jm950887n

  日期：1996.1.1

  zolpidem in blocking convulsions induced by 9 and DMCM, respectively, indicated that occupation of alpha 5-containing GABAA receptors substantially contributed to the convulsant properties of acetylene analog 9. These 8-substituted imidazobenzodiazepines (5, 6, 8 and 9) should prove useful in examining the physiological roles of GABAA receptors bearing an alpha 5 subunit and may also lead to the development

  描述了具有高亲和力和对含α5的GABA A受体具有选择性的咪唑并苯并二氮杂卓的合成和药理特性。这些化合物中的四种（5、6、8和9）抑制[3H]氟硝西m与重组α5β2γ2 GABA A受体的结合，IC50值约为0.4至5 nM。与包含α1，α2或α3亚基的其他“地西p敏感” GABAA受体相比，这些化合物对包含α5亚基的重组受体的选择性高出24-75倍。咪唑并苯二氮卓9（用作原型α5选择性配体）抑制[3H]氟硝西m与具有高亲和力和低亲和力成分（分别为IC50 0.6 +/- 0.2和85.6 +/- 13.1 nM）的海马膜结合，代表受体库的约16％和约84％。用咪唑并苯并二氮杂9 9抑制[3H]氟硝西m与小脑膜的结合最适合单个部位，IC50为79.8 +/- 18.3 nM。这些咪唑并苯并二氮杂as在非洲爪蟾卵母细胞中表达的重组GABAA受体中起GABA负配体的作用，在肠胃外给药后会引起惊
• Gabaergic Agents to Treat Memory Deficits
  申请人：Cook James M.

  公开号：US20100130479A1

  公开（公告）日：2010-05-27

  The present invention provides molecules and methods for the prevention and/or treatment of memory deficit related conditions and/or enhancement of cognition. In a preferred embodiment, the invention includes compounds, salts and prodrugs thereof for the prevention and/or treatment of these conditions.

  本发明提供了预防和/或治疗与记忆缺陷相关疾病和/或增强认知的分子和方法。在一个优选实施例中，本发明包括化合物、盐及其前药，用于预防和/或治疗这些疾病。
• Methods and compositions for treating a subject for central nervous system (CNS) injury
  申请人：Carmichael Stanley T.

  公开号：US10206921B2

  公开（公告）日：2019-02-19

  Methods for treating a central nervous system (CNS) injury in a subject are provided. Aspects of the methods include administering to the subject an effective amount of gamma aminobutyric acid (GABA) receptor signaling inhibitor to treat the subject for the CNS injury. Also provided are compositions finding use in embodiments of the methods. Methods and compositions of the invention find use in the treatment of a variety of different CNS injuries, including but not limited to, treating a subject for CNS injury associated with the occurrence of stroke.

  本文提供了治疗受试者中枢神经系统（CNS）损伤的方法。这些方法的各个方面包括向受试者施用有效量的γ-氨基丁酸（GABA）受体信号转导抑制剂，以治疗受试者的中枢神经系统损伤。此外，还提供了可用于本方法实施方案的组合物。本发明的方法和组合物可用于治疗各种不同的中枢神经系统损伤，包括但不限于治疗与中风发生相关的中枢神经系统损伤。
• A study of the structure–activity relationship of GABAA–benzodiazepine receptor bivalent ligands by conformational analysis with low temperature NMR and X-ray analysis
  作者：Dongmei Han、F. Holger Försterling、Xiaoyan Li、Jeffrey R. Deschamps、Damon Parrish、Hui Cao、Sundari Rallapalli、Terry Clayton、Yun Teng、Samarpan Majumder、Subramaniam Sankar、Bryan L. Roth、Werner Sieghart、Roman Furtmuller、James K. Rowlett、Michael R. Weed、James M. Cook

  DOI：10.1016/j.bmc.2008.08.072

  日期：2008.10

  The stable conformations of GABA(A)- benzodiazepine receptor bivalent ligands were determined by low temperature NMR spectroscopy and confirmed by single crystal X-ray analysis. The stable conformations in solution correlated well with those in the solid state. The linear conformation was important for these dimers to access the binding site and exhibit potent in vitro affinity and was illustrated for alpha 5 subtype selective ligands. Bivalent ligands with an oxygen-containing linker folded back upon themselves both in solution and the solid state. Dimers which are folded do not bind to Bz receptors. (C) 2008 Elsevier Ltd. All rights reserved.