cis-2,6-di-(2-quinolylpiperidine) | 1451077-56-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: cis-2,6-di-(2-quinolylpiperidine)
• 英文别名: 2-[2-[(2R,6S)-6-(2-quinolin-2-ylethyl)piperidin-2-yl]ethyl]quinoline
• CAS: 1451077-56-7
• 化学式: C₂₇H₂₉N₃
• 分子量: 395.547
• InChiKey: FPLLJKIKTBZION-ZRZAMGCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-2,6-di-(2-quinolylpiperidine) 、 (S)-缩水甘油 以 乙醇 为溶剂， 以66%的产率得到
  参考文献：
  名称：

  Quinolyl analogues of norlobelane: Novel potent inhibitors of [3H]dihydrotetrabenazine binding and [3H]dopamine uptake at the vesicular monoamine transporter-2

  摘要：

  We have previously shown that quinolyl moieties are attractive structural replacements for the phenyl groups in lobelane. These quinolyl analogues had improved water-solubility over lobelane and retained the potent vesicular monoamine transporter-2 (VMAT-2) inhibitory properties of the parent compound, with quinlobelane (4) exhibiting potent inhibition of uptake at VMAT-2 (K-i = 51 nM). However, the VMAT-2 inhibitory properties of quinolyl analogues of norlobelane, which is equipotent with lobeline as an inhibitor of [H-3] dopamine (DA) uptake at VMAT-2, have not been reported. In the current communication, we describe the synthesis of some novel des-methyl quinolyl analogues of lobelane that exhibit greater affinity (K-i = 178-647 nM) for the dihydrotetrabenazine binding site located on VMAT-2 compared with lobelane (K-i = 970 nM), norlobelane (K-i = 2310 nM) and quinlobelane (K-i = 2640 nM). The most potent compounds, 14 and 15, also exhibited inhibition of [H-3] DA uptake at VMAT-2 (K-i = 42 nM) which was comparable to both lobelane (K-i = 45 nM) and norlobelane (K-i = 43 nM). Results reveal that binding affinity at VMAT-2 serves as an accurate predictor of inhibition of the function of VMAT-2 for the majority of these analogues. These novel analogues are under consideration for further development as treatments for methamphetamine abuse. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.04.105
• 作为产物：
  描述：

  N-carbobenzoxy-cis-2,6-bis(hydroxymethyl)piperidine 在 盐酸 、 palladium 10% on activated carbon 、 potassium tert-butylate 、 氢气 、 戴斯-马丁氧化剂 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 cis-2,6-di-(2-quinolylpiperidine)
  参考文献：
  名称：

  Efficient synthesis of cis-2,6-di-(2-quinolylpiperidine)

  摘要：

  An efficient synthesis of cis-2,6-di-(2-quinolylpiperidine) has been developed. The key steps involve Wittig reaction of N-Cbz-protected cis-piperidine-2,6-dicarboxaldehyde (3) with 2-(triphenylphosphinylmethyl)quinoline bromide (4) and sequential removal of the N-Cbz group and double bond reduction. This synthetic procedure provides an efficient preparation for this useful norlobelane analogue. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.07.067

文献信息

• Efficient synthesis of cis-2,6-di-(2-quinolylpiperidine)
  作者：Derong Ding、Linda P. Dwoskin、Peter A. Crooks

  DOI：10.1016/j.tetlet.2013.07.067

  日期：2013.9

  An efficient synthesis of cis-2,6-di-(2-quinolylpiperidine) has been developed. The key steps involve Wittig reaction of N-Cbz-protected cis-piperidine-2,6-dicarboxaldehyde (3) with 2-(triphenylphosphinylmethyl)quinoline bromide (4) and sequential removal of the N-Cbz group and double bond reduction. This synthetic procedure provides an efficient preparation for this useful norlobelane analogue. (C) 2013 Elsevier Ltd. All rights reserved.
• Quinolyl analogues of norlobelane: Novel potent inhibitors of [3H]dihydrotetrabenazine binding and [3H]dopamine uptake at the vesicular monoamine transporter-2
  作者：Derong Ding、Justin R. Nickell、Linda P. Dwoskin、Peter A. Crooks

  DOI：10.1016/j.bmcl.2015.04.105

  日期：2015.7

  We have previously shown that quinolyl moieties are attractive structural replacements for the phenyl groups in lobelane. These quinolyl analogues had improved water-solubility over lobelane and retained the potent vesicular monoamine transporter-2 (VMAT-2) inhibitory properties of the parent compound, with quinlobelane (4) exhibiting potent inhibition of uptake at VMAT-2 (K-i = 51 nM). However, the VMAT-2 inhibitory properties of quinolyl analogues of norlobelane, which is equipotent with lobeline as an inhibitor of [H-3] dopamine (DA) uptake at VMAT-2, have not been reported. In the current communication, we describe the synthesis of some novel des-methyl quinolyl analogues of lobelane that exhibit greater affinity (K-i = 178-647 nM) for the dihydrotetrabenazine binding site located on VMAT-2 compared with lobelane (K-i = 970 nM), norlobelane (K-i = 2310 nM) and quinlobelane (K-i = 2640 nM). The most potent compounds, 14 and 15, also exhibited inhibition of [H-3] DA uptake at VMAT-2 (K-i = 42 nM) which was comparable to both lobelane (K-i = 45 nM) and norlobelane (K-i = 43 nM). Results reveal that binding affinity at VMAT-2 serves as an accurate predictor of inhibition of the function of VMAT-2 for the majority of these analogues. These novel analogues are under consideration for further development as treatments for methamphetamine abuse. (C) 2015 Elsevier Ltd. All rights reserved.