1,4-二氮杂双环[3.2.2]壬-4-基[5-[3-(三氟甲基)苯基]-2-呋喃基]甲酮盐酸盐 | 753499-14-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1,4-二氮杂双环[3.2.2]壬-4-基[5-[3-(三氟甲基)苯基]-2-呋喃基]甲酮盐酸盐
• 英文名称: (1,4-diazabicyclo[3.2.2]nonan-4-yl)(5-(3-(trifluoromethyl)phenyl)furan-2-yl)methanone hydrochloride salt
• 英文别名: 1,4-diazabicyclo[3.2.2]nonan-4-yl (5-(3-(trifluoromethyl)-phenyl)-furan-2-yl)methanone hydrochloride；1,4-diazabicyclo[3.2.2]non-4-yl[5-[3-(trifluoromethyl)phenyl]-2-furanyl]methanone hydrochloride；NS6740；(1,4-diaza-bicyclo[3.2.2]non-4-yl)-5-(3-trifluoromethylphenyl)-furan-2-yl-methanone hydrochloric acid salt；1,4-diazabicyclo[3.2.2]nonan-4-yl-[5-[3-(trifluoromethyl)phenyl]furan-2-yl]methanone;hydrochloride
• CAS: 753499-14-8
• 化学式: C₁₉H₁₉F₃N₂O₂*ClH
• 分子量: 400.828
• InChiKey: QHSRBONTAYCFCC-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  36.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (1,4-diazabicyclo[3.2.2]nonan-4-yl)(5-bromofuran-2-yl)methanone 、 3-(三氟甲基)苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 、 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以1.02 g的产率得到1,4-二氮杂双环[3.2.2]壬-4-基[5-[3-(三氟甲基)苯基]-2-呋喃基]甲酮盐酸盐
  参考文献：
  名称：

  Therapeutic efficacy of α7 ligands after acute ischaemic stroke is linked to conductive states of α7 nicotinic ACh receptors

  摘要：

  Background and PurposeTargeting α7 nicotinic ACh receptors (nAChRs) in neuroinflammatory disorders including acute ischaemic stroke holds significant therapeutic promise. However, therapeutically relevant signalling mechanisms remain unidentified. Activation of neuronal α7 nAChRs triggers ionotropic signalling, but there is limited evidence for it in immunoglial tissues. The α7 ligands which are effective in reducing acute ischaemic stroke damage promote α7 ionotropic activity, suggesting a link between their therapeutic effects for treating acute ischaemic stroke and activation of α7 conductive states.Experimental ApproachThis hypothesis was tested using a transient middle cerebral artery occlusion (MCAO) model of acute ischaemic stroke, NS6740, a known selective non‐ionotropic agonist of α7 nAChRs and 4OH‐GTS‐21, a partial α7 agonist. NS6740‐like ligands exhibiting low efficacy/potency for ionotropic activity will be referred to as non‐ionotropic agonists or “metagonists”.Key Results4OH‐GTS‐21, used as a positive control, significantly reduced neurological deficits and brain injury after MCAO as compared to vehicle and NS6740. By contrast, NS6740 was ineffective in identical assays and reversed the effects of 4OH‐GTS‐21 when these compounds were co‐applied. Electrophysiological recordings from acute hippocampal slices obtained from NS6740‐injected animals demonstrated its remarkable brain availability and protracted effects on α7 nAChRs as evidenced by sustained (>8 h) alterations in α7 ionotropic responsiveness.Conclusion and ImplicationsThese results suggest that α7 ionotropic activity may be obligatory for therapeutic efficacy of α7 ligands after acute ischaemic stroke yet, highlight the potential for selective application of α7 ligands to disease states based on their mode of receptor activation.

  DOI：

  10.1111/bph.15392

文献信息

• Novel diazabicyclic aryl derivatives
  申请人：Peters Dan

  公开号：US20060148789A1

  公开（公告）日：2006-07-06

  This invention relates to novel diazabicyclic aryl derivatives which are found to be cholinergic ligands at the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

  本发明涉及新型二氮杂双环芳基衍生物，发现它们是乙酰胆碱受体上的胆碱能配体。由于它们的药理特性，本发明中的化合物可能有用于治疗多种与中枢神经系统（CNS）和外周神经系统（PNS）的胆碱能系统相关的疾病或障碍，与平滑肌收缩有关的疾病或障碍，内分泌疾病或障碍，与神经退行性有关的疾病或障碍，与炎症、疼痛以及化学物质滥用终止引起的戒断症状相关的疾病或障碍。
• NOVEL DIAZABICYCLIC ARYL DERIVATIVES
  申请人：NeuroSearch A/S

  公开号：EP1599476B1

  公开（公告）日：2009-10-14
• US7678788B2
  申请人：——

  公开号：US7678788B2

  公开（公告）日：2010-03-16