XE991双盐酸盐 | 122955-42-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: XE991双盐酸盐
• 中文别名: 10,10二(4-吡啶甲基)-9(10H)-蒽酮
• 英文名称: 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone
• 英文别名: XE 991；(10,10-bis(4-pyrindylmethyl)-9(10H)-anthracenone)；10,10-bis(4Pyridinylmethyl)-9(10H)-anthracenone；10,10-bis(pyridin-4-ylmethyl)anthracen-9-one；XE991；XE-991
• CAS: 122955-42-4
• 化学式: C₂₆H₂₀N₂O
• 分子量: 376.458
• InChiKey: KHJFBUUFMUBONL-UHFFFAOYSA-N

物化性质

• 熔点：
  231-232 °C
• 沸点：
  585.0±38.0 °C(Predicted)
• 密度：
  1.238±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  蒽酮 、 4-氯甲基吡啶盐酸盐 在 sodium hydroxide 、 苄基三乙基氯化铵 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以33%的产率得到XE991双盐酸盐
  参考文献：
  名称：

  2-Fluoro-4-pyridinylmethyl Analogues of Linopirdine as Orally Active Acetylcholine Release-Enhancing Agents with Good Efficacy and Duration of Action

  摘要：

  In an effort to improve the pharmacokinetic and pharmacodynamic properties of the cognition-enhancer linopirdine (DuP 996), a number of core structure analogues were prepared in which the 4-pyridyl pendant group was systematically replaced with 2-fluoro-4-pyridyl. This strategy resulted in the discovery of several compounds with improved activity in acetylcholine (ACh) release-enhancing assays, in vitro and in vivo. The most effective compound resulting from these studies, 10,10-bis[(2-fluoro-4-pyridinyl)methyl]-9(10H)-anthracenone (9), is between 10 and 20 times more potent than linopirdine in increasing extracellular hippocampal ACh levels in the rat with a minimum effective dose of 1 mg/kg. In addition to superior potency, 9 possesses an improved pharmacokinetic profile compared to that of linopirdine. The half-life of 9 (2 h) in rats is 4-fold greater than that of linopirdine (0.5 h), and it showed a g-fold improvement in brain-plasma distribution over linopirdine. On the basis of its pharmacologic, pharmacokinetic, absorption, and distribution properties, 9 (DMP543) has been advanced for clinical evaluation as a potential palliative therapeutic for treatment of Alzheimer's disease.

  DOI：

  10.1021/jm9803424
• 作为试剂：
  描述：

  地西泮 、 N，N'-'二苯甲酰基乙烷-1，2-二胺二盐酸盐 、 D-蛋氨酸 、 更昔洛韦 、 白藜芦醇 、 新霉素标液 在 XE991双盐酸盐 作用下， 生成 XE991双盐酸盐
  参考文献：
  名称：

  Auris Formulations for Treating Otic Diseases and Conditions

  摘要：

  本文揭示了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过将免疫调节和/或耳压调节组合物和配方直接应用于耳媒体和/或耳内靶区或通过灌注到耳媒体和/或耳内结构，局部给患有耳部疾病的个体治疗。

  公开号：

  US20160095902A1

文献信息

• BENZOFURANS AS POTASSIUM ION CHANNEL MODULATORS
  申请人：WELMAKER Gregory S.

  公开号：US20080027049A1

  公开（公告）日：2008-01-31

  The present invention is directed to compounds of Formula I: that are potassium channel modulators and pharmaceutical compositions thereof. The present invention is further directed to methods of treatment using the compounds and pharmaceutical compositions of the invention. The present invention is still further directed to synthetic processes for producing the compounds of the invention.

  本发明涉及以下化合物的化学式I：这些化合物是钾通道调节剂及其药物组合物。本发明进一步涉及使用这些化合物和本发明的药物组合物进行治疗的方法。本发明还进一步涉及用于生产本发明化合物的合成过程。
• KCNQ Potentiators
  申请人：Eli Lilly and Company

  公开号：US20200247752A1

  公开（公告）日：2020-08-06

  Small molecule potentiatiors to potassium channels (such as Kv7 potentiators—which are also called KCNQ potentiators), compositions including such compounds, and methods of using such compounds for the treatment of Amyotrophic Lateral Sclerosis and other neurological diseases caused by changes in motor neuron excitability, including, but not limited to, primary lateral sclerosis, pseudobulbar palsy, progressive bulbar palsy, progressive muscular atrophy and epilepsy.

  针对钾通道的小分子增效剂（例如Kv7增效剂，也称为KCNQ增效剂），包括这类化合物的组合物，以及利用这类化合物治疗由运动神经元兴奋性变化引起的肌萎缩侧索硬化症和其他神经系统疾病的方法，包括但不限于原发性侧索硬化症、假性延髓麻痹、进行性延髓麻痹、进行性肌萎缩和癫痫。
• TETRACYCLIC INDOLES AS POTASSIUM CHANNEL MODULATORS
  申请人：WILSON Matthew A.

  公开号：US20080027090A1

  公开（公告）日：2008-01-31

  The present invention is directed to compounds of Formula I: that are potassium channel modulators and pharmaceutical compositions thereof. The present invention is further directed to methods of treatment using the compounds and pharmaceutical compositions of the invention. The present invention is still further directed to synthetic processes for producing the compounds of the invention.

  本发明涉及以下的化合物：Formula I，它们是钾通道调节剂及其药物组合物。本发明还涉及使用这些化合物和药物组合物进行治疗的方法。本发明还涉及用于生产本发明化合物的合成过程。
• AURIS FORMULATIONS FOR TREATING OTIC DISEASES AND CONDITIONS
  申请人：LICHTER Jay

  公开号：US20090306225A1

  公开（公告）日：2009-12-10

  Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

  本文公开了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过将免疫调节剂和/或耳压调节剂组合物和配方直接应用于耳媒介和/或耳内靶区，或通过灌注进入耳媒介和/或耳内结构，局部给患有耳部疾病的个体进行治疗。
• Auris formulations for treating otic diseases and conditions
  申请人：Lichter Jay

  公开号：US09132087B2

  公开（公告）日：2015-09-15

  Disclosed herein are compositions and methods for the treatment of otic disorders with immunomodulating agents and auris pressure modulators. In these methods, the auris compositions and formulations are administered locally to an individual afflicted with an otic disorder, through direct application of the immunomodulating and/or auris pressure modulating compositions and formulations onto the auris media and/or auris interna target areas, or via perfusion into the auris media and/or auris interna structures.

  本文公开了使用免疫调节剂和耳压调节剂治疗耳部疾病的组合物和方法。在这些方法中，通过直接将免疫调节和/或耳压调节组合物和制剂应用于耳部介质和/或耳内靶区，或通过灌注到耳部介质和/或耳内结构中，局部给予患有耳部疾病的个体。