(4-fluorophenyl)(3'-hydroxy-1'-(pyridin-3-ylmethyl)-[1,4'-bipiperidin]-4-yl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-fluorophenyl)(3'-hydroxy-1'-(pyridin-3-ylmethyl)-[1,4'-bipiperidin]-4-yl)methanone
• 英文别名: (4-fluorophenyl)-[1-[(3S,4S)-3-hydroxy-1-(pyridin-3-ylmethyl)piperidin-4-yl]piperidin-4-yl]methanone
• 化学式: C₂₃H₂₈FN₃O₂
• 分子量: 397.493
• InChiKey: QPXCZQCUAHMROY-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  56.7
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4-fluorophenyl)(3'-hydroxy-1'-(pyridin-3-ylmethyl)-[1,4'-bipiperidin]-4-yl)methanone 、 草酸 以 丙酮 为溶剂， 生成 (4-fluorophenyl)(3'-hydroxy-1'-(pyridin-3-ylmethyl)-[1,4'-bipiperidin]-4-yl)methanone oxalic acid
  参考文献：
  名称：

  Synthesis and in Vitro Biological Evaluation of Carbonyl Group-Containing Analogues for σ₁ Receptors

  摘要：

  To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1)(K-i = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K-i > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K-i = 44.2 nM). The compound [1'-(4-fluorobenzy1)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanone (14a) displayed very high affinity and selectivity for sigma(1) receptor (K-i = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo.

  DOI：

  10.1021/jm200203f
• 作为产物：
  描述：

  1,2,3,6-四氢吡啶 在 盐酸 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 38.0h， 生成 (4-fluorophenyl)(3'-hydroxy-1'-(pyridin-3-ylmethyl)-[1,4'-bipiperidin]-4-yl)methanone
  参考文献：
  名称：

  Synthesis and in Vitro Biological Evaluation of Carbonyl Group-Containing Analogues for σ₁ Receptors

  摘要：

  To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1)(K-i = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K-i > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K-i = 44.2 nM). The compound [1'-(4-fluorobenzy1)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanone (14a) displayed very high affinity and selectivity for sigma(1) receptor (K-i = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo.

  DOI：

  10.1021/jm200203f

文献信息

• Synthesis and in Vitro Biological Evaluation of Carbonyl Group-Containing Analogues for σ₁ Receptors
  作者：Wei Wang、Jinquan Cui、Xiaoxia Lu、Prashanth K. Padakanti、Jinbin Xu、Stanley M. Parsons、Robert R. Luedtke、Nigam P. Rath、Zhude Tu

  DOI：10.1021/jm200203f

  日期：2011.8.11

  To identify the ligands for sigma(1) receptors that are potent and selective, analogues of prezamicol and trozamicol scaffolds of carbonyl-containing vesicular acetylcholine transporter (VAChT) inhibitors were explored. Of the 23 analogues synthesized and tested, 5 displayed very high affinity for sigma(1)(K-i = 0.48-4.05 nM) and high selectivity for sigma(1) relative to sigma(2) receptors (sigma(1)/sigma(2) selectivity of >749-fold). Four of the five compounds (14a, 14b, 14c, and 14e) showed very low affinity for VAChT (K-i > 290 nM), and the fifth compound (14g) showed moderate affinity for VAChT (K-i = 44.2 nM). The compound [1'-(4-fluorobenzy1)-3'-hydroxy[1,4']bipiperidinyl-4-yl]-(4-fluorophenyl)methanone (14a) displayed very high affinity and selectivity for sigma(1) receptor (K-i = 0.48 nM, sigma(1)/sigma(2) > 3600). All four of these most promising compounds (14a, 14b, 14c, and 14e) can be radiosynthesized with fluorine-18 or carbon-11, which will allow further evaluation of their properties as PET probes for imaging sigma(1) receptor in vivo.