(2S,3S)-2-(4-chlorophenyl)-3,4,5,5-tetramethylmorpholin-2-ol fumarate | 1231951-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (2S,3S)-2-(4-chlorophenyl)-3,4,5,5-tetramethylmorpholin-2-ol fumarate
• 英文别名: (E)-but-2-enedioic acid;(2S,3S)-2-(4-chlorophenyl)-3,4,5,5-tetramethylmorpholin-2-ol
• CAS: 1231951-96-4
• 化学式: C₄H₄O₄*C₁₄H₂₀ClNO₂
• 分子量: 385.845
• InChiKey: VFZLIBCJSGVIOK-MXQNOICSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.33
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  107
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (3S)-3,5,5-三甲基-2-吗啉酮 在 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 27.0h， 生成 (2S,3S)-2-(4-chlorophenyl)-3,4,5,5-tetramethylmorpholin-2-ol fumarate
  参考文献：
  名称：

  [EN] 1 - PHENYLMORPHOLINE DERIVATIVES AS HYDROXYBUPROPION ANALOGUES FOR TREATING DRUG DEPENDENCE
  [FR] ANALOGUES D'HYDROXYBUPROPION POUR LE TRAITEMENT DE LA PHARMACODÉPENDANCE

  摘要：

  公开号：

  WO2011146821A3

文献信息

• Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation
  作者：Ronald J. Lukas、Ana Z. Muresan、M. Imad Damaj、Bruce E. Blough、Xiaodong Huang、Hernán A. Navarro、S. Wayne Mascarella、J. Brek Eaton、Syndia K. Marxer-Miller、F. Ivy Carroll

  DOI：10.1021/jm1003232

  日期：2010.6.24

  To create potentially superior aids to smoking cessation and/or antidepressants and to elucidate bupropion's possible mechanisms of action(s), 23 analogues based on its active hydroxymetabolite (2S,35)-4a were synthesized and tested for their abilities to inhibit monoamine uptake and nAChR subtype activities in vitro and acute effects of nicotine in vivo. The 3',4'-dichlorophenyl [(+/-)-4n], naphthyl (4r), and 3-chlorophenyl or 3-propyl analogues 4s and 4t, respectively, had higher inhibitory potency and/or absolute selectivity than (2S,3S)-4a for inhibition of DA, NE, or 5HT uptake. The 3'-fluorophenyl, 3'-bromophenyl, and 4-biphenyl analogues 4c, 4d, and 4l, respectively, had higher potency for antagonism of alpha 4 beta 2-nAChR than (2S,3S)-4a. Several analogues also had higher potency than (2S,35)-4a as antagonists of nicotine-mediated antinociception in the tail-flick assay. The results suggest that compounds acting via some combination of DA, NE, or 5HT inhibition and/or antagonism of alpha 4 beta 2-nAChR can potentially be new pharmacotherapeutics for treatment of nicotine dependence.