SR-II-54 | 1140968-15-5

• 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: SR-II-54
• 英文别名: 8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepine-3-carboxylic acid；8-ethynyl-6-pyridin-2-yl-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylic acid
• CAS: 1140968-15-5
• 化学式: C₁₉H₁₂N₄O₂
• 分子量: 328.33
• InChiKey: LNWKMCTYBSXUHQ-UHFFFAOYSA-N

物化性质

• 沸点：
  598.1±50.0 °C(predicted)
• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  80.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  SR-II-54 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 C₁₉H₁₁ClN₄O
  参考文献：
  名称：

  GABAERGIC RECEPTOR SUBTYPE SELECTIVE LIGANDS AND THEIR USES

  摘要：

  本文描述了α3或α2或α2/α3 GABA能受体亚型选择性配体、药物组合物以及使用这些配体和组合物治疗焦虑症、癫痫和精神分裂症的方法，具有减少镇静和共济失调副作用。在某些实施例中，例如α3或α2或α2/α3 GABA能受体亚型选择性配体不含酯键，因此相对不容易被酯酶水解。

  公开号：

  US20120295892A1
• 作为产物：
  描述：

  8-乙炔基-6-吡啶-2-基-4H-咪唑[1,5-a] [1,4]苯并二氮杂-3-羧酸乙酯 在 lithium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以35.5%的产率得到SR-II-54
  参考文献：
  名称：

  Carboxamide GABAa ALPHA2 Modulators

  摘要：

  这项发明涵盖了Formula I的化合物，包括药用盐、它们的药物组合物以及它们在治疗中枢神经系统疾病中的应用。

  公开号：

  US20090093466A1

文献信息

• Selective Agents for Pain Suppression
  申请人：Cook James

  公开号：US20100317619A1

  公开（公告）日：2010-12-16

  In preferred embodiments, the present invention provides methods of treatment and pharmaceutical compositions for the suppression, alleviation and prevention of the often chronic, severe and debilitating pain that can accompany inflammatory diseases and neuropathic insults, pain that is often unresponsive to conventional analgesic treatment. The preferred embodiments of the present invention further relate to methods of treatment and pharmaceutical compositions using benzodiazepine derivatives that provide suppression, alleviation and prevention of neuropathic pain, migraine-related pain and inflammatory pain with reduced sedative and ataxic side effects.

  在首选实施例中，本发明提供了治疗方法和药物组合物，用于抑制、缓解和预防伴随炎症性疾病和神经病变的常见、严重和令人痛苦的慢性疼痛，这种疼痛通常对常规镇痛治疗无效。本发明的首选实施例还涉及使用苯二氮平衍生物的治疗方法和药物组合物，其提供了抑制、缓解和预防神经病理性疼痛、偏头痛相关疼痛和炎症性疼痛的效果，并减少了镇静和共济失调的副作用。
• Synthesis and Characterization of a Novel γ-Aminobutyric Acid Type A (GABA_A) Receptor Ligand That Combines Outstanding Metabolic Stability, Pharmacokinetics, and Anxiolytic Efficacy
  作者：Michael M. Poe、Kashi Reddy Methuku、Guanguan Li、Ashwini R. Verma、Kelly A. Teske、Douglas C. Stafford、Leggy A. Arnold、Jeffrey W. Cramer、Timothy M. Jones、Rok Cerne、Michael J. Krambis、Jeffrey M. Witkin、Enrique Jambrina、Sabah Rehman、Margot Ernst、James M. Cook、Jeffrey M. Schkeryantz

  DOI：10.1021/acs.jmedchem.6b01332

  日期：2016.12.8

  1,4-Benzodiazepines are used in the treatment of anxiety disorders but have limited long-term use due to adverse effects. HZ-166 (2) has been shown to have anxiolytic-like effects with reduced sedative/ataxic liabilities. A 1,3-oxazole KRM-II-81 (9) was discovered from a series of six bioisosteres with significantly improved pharmacokinetic and pharmacodynamic properties as compared to 2. Oxazole 9 was further characterized and exhibited improved anxiolytic-like effects in a mouse marble burying assay and a rat Vogel conflict test.
• Search for α3β2/3γ2 subtype selective ligands that are stable on human liver microsomes
  作者：Ojas A. Namjoshi、Zhi-jian Wang、Sundari K. Rallapalli、Edward Merle Johnson、Yun-Teng Johnson、Hanna Ng、Joachim Ramerstorfer、Zdravko Varagic、Werner Sieghart、Samarpan Majumder、Bryan L. Roth、James K. Rowlett、James M. Cook

  DOI：10.1016/j.bmc.2012.10.057

  日期：2013.1

  Selective modulation of specific benzodiazepine receptor (BzR) gamma amino butyric acid-A (GABA(A)) receptor ion channels has been identified as an important method for separating out the variety of pharmacological effects elicited by BzR-related drugs. Importantly, it has been demonstrated that both alpha 2 beta((2/3))gamma 2 (alpha 2BzR) and alpha 3BzR (and/or alpha 2/alpha 3) BzR subtype selective ligands exhibit anxiolytic effects with little or no sedation. Previously we have identified several such ligands; however, three of our parent ligands exhibited significant metabolic liability in rodents in the form of a labile ester group. Here eight analogs are reported which were designed to circumvent this liability by utilizing a rational replacement of the ester moiety based on medicinal chemistry precedents. In a metabolic stability study using human liver microsomes, four compounds were found to undergo slower metabolic transformation, as compared to their corresponding ester analogs. These compounds were also evaluated in in vitro efficacy assays. Additionally, bioisostere 11 was evaluated in a rodent model of anxiety. It exhibited anxiolytic activity at doses of 10 and 100 mg/kg and was devoid of sedative properties. (C) 2012 Elsevier Ltd. All rights reserved.
• US8835424B2
  申请人：——

  公开号：US8835424B2

  公开（公告）日：2014-09-16
• US9006233B2
  申请人：——

  公开号：US9006233B2

  公开（公告）日：2015-04-14