(±)-2-(4-benzyl-piperidin-1-yl)-cyclohexanol | 120446-83-5

• 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: (±)-2-(4-benzyl-piperidin-1-yl)-cyclohexanol
• 英文别名: (+/-)-trans-2-(4-benzylpiperidino)cyclohexanol；Cyclohexanol, 2-(4-(phenylmethyl)-1-piperidinyl)-, trans-(+-)-；(1R,2R)-2-(4-benzylpiperidin-1-yl)cyclohexan-1-ol
• CAS: 120446-83-5
• 化学式: C₁₈H₂₇NO
• 分子量: 273.418
• InChiKey: ZENDJZOIUGRXAX-QZTJIDSGSA-N

物化性质

• 熔点：
  75.5-77.0 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  402.1±38.0 °C(Predicted)
• 密度：
  1.081±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  cyclohexene oxide 、 4-苄基哌啶 以 乙醇 为溶剂， 反应 48.0h， 生成 (±)-2-(4-benzyl-piperidin-1-yl)-cyclohexanol
  参考文献：
  名称：

  New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure

  摘要：

  To verify vesamicol as lead structure in the development of radioligands for imaging of VAChT in the brain by PET, we systematically modified this molecule and investigated four different groups of derivatives. Structural changes were conducted in all three ring systems A, B, and C resulting in a library of different vesamicol analogs. Based on their in vitro binding affinity toward VAChT as well as sigma(1) and sigma(2) receptors, we performed a structure-affinity relationship (SAR) study regarding both affinity and selectivity. The compounds possessed VAChT affinities in the range of 132 nM (benzovesamicol) to >10 mu M and selectivity factors from 0.1 to 73 regarding sigma(1) and sigma(2) receptors, respectively. We could confirm the exceptional position of benzovesamicols as most affine VAChT ligands. However, we also observed that most of the compounds with high VAChT affinity demonstrated considerable affinity in particular to the sigma(1) receptor. Finally, none of the various vesamicol analogs in all four groups showed an in vitro binding profile suitable for specific VAChT imaging in the brain. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.05.033

文献信息

• Synthesis, in vitro acetylcholine-storage-blocking activities, and biological properties of derivatives and analogs of trans-2-(4-phenylpiperidino)cyclohexanol (vesamicol)
  作者：Gary A. Rogers、Stanley M. Parsons、D. C. Anderson、Lena M. Nilsson、Ben A. Bahr、Wayne D. Kornreich、Rose Kaufman、Robert S. Jacobs、Bernard Kirtman

  DOI：10.1021/jm00126a013

  日期：1989.6

  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.
• ROGERS, GARY A.;PARSONS, STANLEY M.;ANDERSON, D. C.;NILSSON, LENA M.;BAHR+, J. MED. CHEM., 32,(1989) N, C. 1217-1230
  作者：ROGERS, GARY A.、PARSONS, STANLEY M.、ANDERSON, D. C.、NILSSON, LENA M.、BAHR+

  DOI：——

  日期：——