(2S,3S)-2-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol | 1231951-72-6

• 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-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol
• CAS: 1231951-72-6
• 化学式: C₁₃H₁₇F₂NO₂
• 分子量: 257.28
• InChiKey: LHPUYZQFWLLHPT-ISVAXAHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol 、 富马酸 以 甲醇 、 乙醚 为溶剂， 以53%的产率得到(2S,3S)-2-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol hemi-fumarate
  参考文献：
  名称：

  Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation

  摘要：

  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.

  DOI：

  10.1021/jm1003232
• 作为产物：
  描述：

  (3S)-3,5,5-三甲基-2-吗啉酮 、 magnesium,1,2-difluorobenzene-5-ide,bromide 在 水 、 氯化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 以25%的产率得到(2S,3S)-2-(3,4-difluorophenyl)-3,5,5-trimethylmorpholin-2-ol
  参考文献：
  名称：

  Synthesis and Characterization of in Vitro and in Vivo Profiles of Hydroxybupropion Analogues: Aids to Smoking Cessation

  摘要：

  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.

  DOI：

  10.1021/jm1003232

文献信息

• HYDROXYBUPROPION ANALOGUES FOR TREATING DRUG DEPENDENCE
  申请人：Research Triangle Institute

  公开号：US20130150357A1

  公开（公告）日：2013-06-13

  The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

  本发明提供了一种羟基丙酮类似物，能够抑制一个或多个单胺的再吸收和/或作为尼古丁乙酰胆碱受体的拮抗剂。这些化合物可以选择性地结合到一个或多个单胺转运体上，包括多巴胺、去甲肾上腺素和5-羟色胺的转运体，和/或可以选择性地结合到一个或多个尼古丁乙酰胆碱受体亚型上。这些化合物可以用于治疗对单胺水平调节和/或尼古丁乙酰胆碱受体拮抗剂敏感的疾病，包括药物依赖、抑郁症和肥胖症。
• Hydroxybupropion analogues for treating drug dependence
  申请人：Research Triangle Institute

  公开号：US08906908B2

  公开（公告）日：2014-12-09

  The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

  该发明提供了羟基丁酮类似物，能够抑制一个或多个单胺的再摄取，并/或作为尼古丁乙酰胆碱受体的拮抗剂。这些化合物可以选择性地结合到一个或多个单胺转运体，包括多巴胺、去甲肾上腺素和5-羟色胺的转运体，和/或可以选择性地结合到一个或多个尼古丁乙酰胆碱受体亚型。这些化合物可以用于治疗对单胺水平修饰和/或尼古丁乙酰胆碱受体拮抗剂有反应的疾病，包括药物依赖、抑郁症和肥胖症。
• [EN] 1 - PHENYLMORPHOLINE DERIVATIVES AS HYDROXYBUPROPION ANALOGUES FOR TREATING DRUG DEPENDENCE<br/>[FR] ANALOGUES D'HYDROXYBUPROPION POUR LE TRAITEMENT DE LA PHARMACODÉPENDANCE
  申请人：RES TRIANGLE INST

  公开号：WO2011146821A3

  公开（公告）日：2012-01-12
• 1-PHENYLMORPHOLINE DERIVATIVES AS HYDROXYBUPROPION ANALOGUES FOR TREATING DRUG DEPENDENCE
  申请人：Research Triangle Institute

  公开号：EP2571859B1

  公开（公告）日：2015-07-22
• US8906908B2
  申请人：——

  公开号：US8906908B2

  公开（公告）日：2014-12-09