(+/-)-trans-vesamicol hydrochloride | 120447-62-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (+/-)-trans-vesamicol hydrochloride
• 英文别名: (+/-)-vesamicol hydrochloride；(±)-vesamicol hydrochloride；(1R,2R)-2-(4-phenylpiperidin-1-yl)cyclohexan-1-ol;hydrochloride
• CAS: 120447-62-3
• 化学式: C₁₇H₂₅NO*ClH
• 分子量: 295.853
• InChiKey: XJNUHVMJVWOYCW-GBNZRNLASA-N

物化性质

• 溶解度：
  低于pH8的水性缓冲液：1 mM

计算性质

• 辛醇/水分配系数(LogP)：
  3.19
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.647
• 拓扑面积：
  23.5
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• WGK Germany：
  3

制备方法与用途

生物活性

(±)-Vesamicol hydrochloride ((±)-AH5183 hydrochloride) 是一种有效的囊泡乙酰胆碱转运 (vesicular acetylcholine transport) 抑制剂，Ki 为 2 nM。(±)-Vesamicol hydrochloride 也对 σ1 和 σ2 受体具有高亲和力，Ki 值分别为 26 nM 和 34 nM。

靶点

Ki: 2 nM (Vesicular acetylcholine transport), 26 nM (σ1 receptors) and 34 nM (σ2 receptors)

体外研究

The pharmacological actions of (±)-Vesamicol have been attributed to inhibition of acetylcholine transport into synaptic vesicles and the subsequent quantal release of acetylcholine.

体内研究

(±)-Vesamicol (3 mg/kg; intraperitoneal injection; once; male Wistar rats) treatment increases the levels of cytosolic acetylcholine (ACh) in all regions of the brain, while those of vesicular ACh decreased in all regions except for the striatum.

Animal Model:	Male Wistar rats (120-300 g)
Dosage:	3 mg/kg
Administration:	Intraperitoneal injection; once
Result:	The levels of cytosolic acetylcholine (ACh) increased in all regions of the brain, while those of vesicular ACh decreased in all regions except for the striatum.

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-vesamicol hydrochloride 在 platinum(IV) oxide 氢气 作用下， 以 乙醇 为溶剂， 60.0 ℃ 、10.13 MPa 条件下， 反应 3.0h， 以79%的产率得到(+/-)-trans-2-(4-cyclohexylpiperidino)cyclohexanol hydrochloride
  参考文献：
  名称：

  Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogs of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol)

  摘要：

  Eighty-four analogues and derivatives of the acetylcholine-storage-blocking drug trans-2-(4-phenylpiperidino)-cyclohexanol (vesamicol) were synthesized, and their potencies were evaluated with the acetylcholine active-transport assay utilizing purified synaptic vesicles from Torpedo electric organ. The parent drug exhibits enantioselectivity, with (-)-vesamicol being 25-fold more potent than (+)-vesamicol. The atomic structure and absolute configuration of (+)-vesamicol were determined by X-ray crystallography. The absolute configuration of (-)-vesamicol is 1R,2R. Structure-activity evidence indicates that (-)-vesamicol does not act as an acetylcholine analogue. Alterations to all three rings can have large effects on potency. Unexpectedly, analogues locking the alcohol and ammonium groups trans-diequatorial or trans-diaxial both exhibit good potency. A potent benzovesamicol family has been discovered that is suitable for facile elaboration of the sort useful in affinity labeling and affinity chromatography applications. A good correlation was found between potencies as assessed by the acetylcholine transport assay and LD50 values in mouse.

  DOI：

  10.1021/jm00126a013