4-溴苯基1,4-二氮杂双环[3.2.2]壬烷-4-羧酸盐酸盐 | 446031-79-4

• 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: 4-溴苯基1,4-二氮杂双环[3.2.2]壬烷-4-羧酸盐酸盐
• 英文名称: SSR180711 hydrochloride
• 英文别名: (4-bromophenyl) 1,4-diazabicyclo(3.2.2)nonane-4-carboxyliate monohydrochloride；SSR180711 monohydrochloride；SSR-180,771；SSR180711；1,4-diaza-bicyclo[3.2.2]nonane-4-carboxylic acid 4-bromo-phenyl ester hydrochloric acid salt；1,4-diaza-bicyclo[3.2.2]nonane-4-carboxylic acid 4-bromo-phenyl ester hydrochloride；SSR 180711 hydrochloride；(4-bromophenyl) 1,4-diazabicyclo[3.2.2]nonane-4-carboxylate;hydrochloride
• CAS: 446031-79-4
• 化学式: C₁₄H₁₇BrN₂O₂*ClH
• 分子量: 361.666
• InChiKey: YNBXNVUZXFMNSJ-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)：
  3.15
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  32.8
• 氢给体数：
  1
• 氢受体数：
  3

制备方法与用途

生物活性

SSR180711 hydrochloride 是具有口服活性，选择性和可逆的 α7 n-AChRs 部分激动剂。SSR180711 hydrochloride 可以作用于大鼠 α7 n-AChRs (Ki=22 nM；IC50=30 nM) 和人 α7 n-AChRs (Ki=14 nM；IC50=18 nM)。SSR180711 hydrochloride 增加海马区的谷氨酸能神经传递，Ach 释放和长时程增强 (LTP)。

靶点

IC50: 30 nM (rat α7 n-AChR) and 18 nM (human α7 n-AChR)
Ki: 22 nM (rat α7 n-AChR) and 14 nM (human α7 n-AChR)

体外研究

SSR180711 hydrochloride is selective for the α7 receptor subtype compared to α4β2, α3β2, α3β4, and α1β1γδ human n-AChR subtypes (IC ₅₀ >5 μM). SSR180711 hydrochloride (10 μM) has no inhibition (lower than 50%) for the ionic channels, neurotransmitter, or peptide receptors.
SSR180711 hydrochloride (0.01-10000 μM) is a potent partial agonist at human α7 n-AChRs expressed in Xenopus oocytes or GH4C1 cells and elicits typical concentration-dependent inward currents with an EC ₅₀ value of 4.4 μM (2.5-7.8 μM).

体内研究

SSR180711 hydrochloride rapidly penetrates into the brain (ID ₅₀ =8 mg/kg; p.o.). SSR180711 hydrochloride dose-dependently inhibits the specific [ ^3H ]α-BTX binding in the mouse brain (ID ₅₀ =8.3 and 7.5 mg/kg for p.o. and i.p., respectively).
SSR180711 hydrochloride (1-10 mg/kg for i.p.; 10-30 mg/kg for p.o.) dose-dependently increases extracellular acetylcholine (ACh) levels in the hippocampus and prefrontal cortex of freely moving rats.
SSR180711 hydrochloride (0.1, 0.3, 1 mg/kg; i.v.) dose-dependently increases firing rate.

反应信息

• 作为产物：
  描述：

  1,4-diazabicyclo[3.2.2]nonane-4-carboxylic acid 4-bromophenyl ester 生成 4-溴苯基1,4-二氮杂双环[3.2.2]壬烷-4-羧酸盐酸盐
  参考文献：
  名称：

  Pharmaceutical compositions for the treatment of disorders of the CNS and other disorders

  摘要：

  公开号：

  EP1231212B1

文献信息

• ANTIPRURITIC AGENT
  申请人：Hayashi Kenichi

  公开号：US20140128606A1

  公开（公告）日：2014-05-08

  An antipruritic which exerts an antipruritic effect based on a novel action mechanism and is effective for pruritus. The antipruritic contains as an effective ingredient a compound which activates a central type nicotinic acetylcholine receptor.

  一种抗瘙痒药物，基于新颖的作用机制发挥抗瘙痒作用，并对瘙痒有效。该抗瘙痒药物含有一种有效成分，该成分可以激活中枢型尼古丁乙酰胆碱受体。
• Novel Diazabicycloalkane Derivatives and Their Medical Use
  申请人：Peters Dan

  公开号：US20090075983A1

  公开（公告）日：2009-03-19

  This invention relates to novel diaza-bicyclo-alkane derivatives, which are found to be cholinergic ligands at the nicotinic acetylcholine receptors and modulators of the monoamine receptors and transporters. 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.

  本发明涉及新型的二氮杂双环烷衍生物，发现它们在尼古丁乙酰胆碱受体上是胆碱能配体，并且是单胺受体和转运体的调节剂。由于它们的药理特性，本发明中的化合物可能对治疗多种疾病或障碍有用，包括与中枢神经系统（CNS）和外周神经系统（PNS）的胆碱能系统相关的疾病或障碍、与平滑肌收缩相关的疾病或障碍、内分泌疾病或障碍、神经退行性疾病或障碍、炎症、以及由于滥用化学物质的终止而引起的戒断症状。
• 2-PHENYL-5-AMINO-1,3,4-OXADIAZOLES AND THEIR USE AS NICOTINIC ACETYLCHOLINE RECEPTOR LIGANDS
  申请人：Coppo Frank Teen

  公开号：US20090105217A1

  公开（公告）日：2009-04-23

  Novel oxadiazole derivatives of formula (I) having pharmacological activity, processes for their preparation, compositions containing them and their use in the treatment of neurological, psychiatric disorders and gastrointestinal disorders through modulation of the nicotinic α7 receptor.

  具有药理活性的式(I)的新型噁二唑衍生物，其制备方法，含有它们的组合物以及它们通过调节尼古丁α7受体在治疗神经、精神障碍和胃肠障碍方面的应用。
• WO2007/93600
  申请人：——

  公开号：——

  公开（公告）日：——
• DIAZABICYCLOALKANE DERIVATIVES AND THEIR MEDICAL USE
  申请人：NeuroSearch A/S

  公开号：EP1987033B1

  公开（公告）日：2010-08-25