(2R,4S)-2,4-Azetidinedimethanol | 1016232-95-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: (2R,4S)-2,4-Azetidinedimethanol
• 英文别名: [(2R,4S)-4-(hydroxymethyl)azetidin-2-yl]methanol
• CAS: 1016232-95-3
• 化学式: C₅H₁₁NO₂
• 分子量: 117.148
• InChiKey: RVXDNESKZYUPKO-SYDPRGILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  8
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  52.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,4S)-2,4-Azetidinedimethanol 在 草酰氯 、 potassium tert-butylate 、 二甲基亚砜 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 4.0h， 生成 cis-benzyl 2,4-bis(2-(benzo[d][1,3]dioxol-5-yl)vinyl)azetidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake

  摘要：

  Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a-15c and 22a-22c) potently inhibited [H-3]dopamine (DA) uptake into isolated synaptic vesicles (K-i <= 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (K-i = 24 nM), and was twofold more potent that either lobelane (2a, K-i = 45 nM) or norlobelane (2b, K-i = 43 nM). The trans-methylenedioxy analog, 15c (K-i = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis-and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.001
• 作为产物：
  描述：

  ((2R,4S)-1-benzylazetidine-2,4-diyl)dimethanol 在 氢气 、 palladium(II) hydroxide 作用下， 20.0 ℃ 、101.33 kPa 条件下， 生成 (2R,4S)-2,4-Azetidinedimethanol
  参考文献：
  名称：

  Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake

  摘要：

  Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a-15c and 22a-22c) potently inhibited [H-3]dopamine (DA) uptake into isolated synaptic vesicles (K-i <= 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (K-i = 24 nM), and was twofold more potent that either lobelane (2a, K-i = 45 nM) or norlobelane (2b, K-i = 43 nM). The trans-methylenedioxy analog, 15c (K-i = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis-and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.001

文献信息

• Synthesis and evaluation of novel azetidine analogs as potent inhibitors of vesicular [3H]dopamine uptake
  作者：Derong Ding、Justin R. Nickell、Agripina G. Deaciuc、Narsimha Reddy Penthala、Linda P. Dwoskin、Peter A. Crooks

  DOI：10.1016/j.bmc.2013.08.001

  日期：2013.11

  Lobelane analogs that incorporate a central piperidine or pyrrolidine moiety have previously been reported by our group as potent inhibitors of VMAT2 function. Further central ring size reduction of the piperidine moiety in lobelane to a four-membered heterocyclic ring has been carried out in the current study to afford novel cis-and trans-azetidine analogs. These azetidine analogs (15a-15c and 22a-22c) potently inhibited [H-3]dopamine (DA) uptake into isolated synaptic vesicles (K-i <= 66 nM). The cis-4-methoxy analog 22b was the most potent inhibitor (K-i = 24 nM), and was twofold more potent that either lobelane (2a, K-i = 45 nM) or norlobelane (2b, K-i = 43 nM). The trans-methylenedioxy analog, 15c (K-i = 31 nM), was equipotent with the cis-analog, 22b, in this assay. Thus, cis-and trans-azetidine analogs 22b and 15c represent potential leads in the discovery of new clinical candidates for the treatment of methamphetamine abuse. (C) 2013 Elsevier Ltd. All rights reserved.