ethyl 5-methyl-6-oxo-8-((trimethylsilyl)ethynyl)-5,6-dihydro-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate | 173990-10-8

• 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: ethyl 5-methyl-6-oxo-8-((trimethylsilyl)ethynyl)-5,6-dihydro-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate
• 英文别名: ethyl 5-methyl-6-oxo-8-(2-trimethylsilylethynyl)-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
• CAS: 173990-10-8
• 化学式: C₂₀H₂₃N₃O₃Si
• 分子量: 381.506
• InChiKey: GZGLGVQROXSNSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.86
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 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 5-methyl-6-oxo-8-((trimethylsilyl)ethynyl)-5,6-dihydro-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate 在 sodium hydroxide 、 四丁基氟化铵 、 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 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 (Il) acetate 、 溴 、 sodium acetate 、 氯磷酸二乙酯 、 溶剂黄146 、 三乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 ethyl 5-methyl-6-oxo-8-((trimethylsilyl)ethynyl)-5,6-dihydro-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylate
  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

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
• The synthesis and anti-inflammatory evaluation of 1,2,3-triazole linked isoflavone benzodiazepine hybrids
  作者：Gabriel Menghereş、Olumayokun Olajide、Karl Hemming

  DOI：10.24820/ark.5550190.p011.396

  日期：——
• Liu, Ruiyan; Zhang, Puwen; McKernan, Ruth M., Medicinal Chemistry Research, 1995, vol. 5, # 9, p. 700 - 709
  作者：Liu, Ruiyan、Zhang, Puwen、McKernan, Ruth M.、Wafford, K.、Cook, James M.

  DOI：——

  日期：——
• Synthesis, in Vitro Affinity, and Efficacy of a Bis 8-Ethynyl-4<i>H</i>-imidazo[1,5<i>a</i>]- [1,4]benzodiazepine Analogue, the First Bivalent α5 Subtype Selective BzR/GABA_A Antagonist
  作者：Xiaoyan Li、Hui Cao、Chunchun Zhang、Roman Furtmueller、Karoline Fuchs、Sigismund Huck、Werner Sieghart、Jeffrey Deschamps、James M. Cook

  DOI：10.1021/jm034164c

  日期：2003.12.1

  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.