XLi-093 | 646066-59-3

• 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: XLi-093
• 英文别名: bis[8-ethynyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid]1,3-propanediyl ester hydrate；1,3-bis(8-acetyleno-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a][1,4]-benzodiaze-pine-3-carboxy)propyl diester；3-(8-ethynyl-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carbonyl)oxypropyl 8-ethynyl-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate
• CAS: 646066-59-3
• 化学式: C₃₃H₂₆N₆O₆
• 分子量: 602.606
• InChiKey: JYRRJDFICVOODX-UHFFFAOYSA-N

物化性质

• 溶解度：
  二甲基亚砜：~16 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  129
• 氢给体数：
  0
• 氢受体数：
  8

安全信息

• 储存条件：
  将温度存储在2-8°C范围内。

制备方法与用途

Xli 093 是一种α5亚型选择性的苯二氮卓/GABAA受体拮抗剂。它在表达人α5β3γ2受体的Ltk细胞膜上的α5受体处表现出Ki = 5 nM 的亲和力；对其他BDZ/GABAA亚型几乎没有亲和力；在浓度不超过1 μM的情况下，不会触发任何亚型的氯离子电流；并且以剂量依赖性的方式完全抑制地西泮刺激下的α5β3γ2受体中的电流。

反应信息

• 作为反应物：
  描述：

  XLi-093 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以99%的产率得到XLi-356
  参考文献：
  名称：

  GABAERGIC AGENTS TO TREAT MEMORY DEFICITS

  摘要：

  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。

  公开号：

  US20060258643A1
• 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 sodium hydroxide 、 bis(triphenylphosphine) palladium (Il) acetate 、 四丁基氟化铵 、 溴 、 sodium acetate 、 氯磷酸二乙酯 、 溶剂黄146 、 三乙胺 、 N,N'-羰基二咪唑 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 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

文献信息

• 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。
• 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.
• US7595395B2
  申请人：——

  公开号：US7595395B2

  公开（公告）日：2009-09-29
• 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, 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.