(+/-)-2-(4-bromo-2,5-dimethoxyphenyl)morpholin-5-one | 807631-06-7

• 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: (+/-)-2-(4-bromo-2,5-dimethoxyphenyl)morpholin-5-one
• 英文别名: 6-(4-Bromo-2,5-dimethoxyphenyl)morpholin-3-one
• CAS: 807631-06-7
• 化学式: C₁₂H₁₄BrNO₄
• 分子量: 316.151
• InChiKey: VWSNKEFKSUXAPR-UHFFFAOYSA-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：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  56.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-2-(4-bromo-2,5-dimethoxyphenyl)morpholin-5-one 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 2-(4-Bromo-2,5-dimethoxy-phenyl)-morpholine
  参考文献：
  名称：

  β-Oxygenated Analogues of the 5-HT_2A Serotonin Receptor Agonist 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopropane

  摘要：

  Activation of 5-HT2A serotonin receptors represents a novel approach to lowering intraocular pressure. Because 5-HT2A serotonin receptor agonists might also produce undesirable central effects should sufficient quantities enter the brain, attempts were made to identify 5-HT2A serotonin receptor agonists with reduced propensity to penetrate the blood-brain barrier. 1-(4Bromo-2,5-dimethoxyphenyl)-2-aminopropan-1-oI (6), an analogue of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) bearing a benzylic hydroxyl group, was identified as a candidate structure. Of the four optical isomers of 6, the 1R,2R-isomer (6d; K-i = 0.5 nM) was found to bind at 5-HT2A receptors with an affinity similar to that of R(-)DOB (Ki = 0.2 nM). Like R(-)DOB, 6d behaved as a partial agonist (efficacy ca. 50%) in a 5-HT2-mediated calcium mobilization assay. However, in an in vivo test of central action (i.e., stimulus generalization with rats as subjects), 6d was > 15 times less potent than R(-)DOB. O-Methylation of 6d (i.e., 7d; 5-HT2A K-i = 0.3 nM) resulted in an agent that behaved as a full (93% efficacy) agonist. Intraocular administration of 300,mug of 6d and 7d to ocular hypertensive monkeys was shown to reduce intraocular pressure by 20-27%. Given the route of administration (i.e., topical), and concentrations necessary to reduce intraocular pressure, compounds such as 6d should demonstrate minimal central effects at potentially useful therapeutic doses and offer useful leads for further development.

  DOI：

  10.1021/jm040082s
• 作为产物：
  描述：

  4'-溴-2',5'-二甲氧基苯乙酮 在 氢氧化钾 、 sodium hydroxide 、 sodium tetrahydroborate 、 乌洛托品 、 溴 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 为溶剂， 反应 20.0h， 生成 (+/-)-2-(4-bromo-2,5-dimethoxyphenyl)morpholin-5-one
  参考文献：
  名称：

  β-Oxygenated Analogues of the 5-HT_2A Serotonin Receptor Agonist 1-(4-Bromo-2,5-dimethoxyphenyl)-2-aminopropane

  摘要：

  Activation of 5-HT2A serotonin receptors represents a novel approach to lowering intraocular pressure. Because 5-HT2A serotonin receptor agonists might also produce undesirable central effects should sufficient quantities enter the brain, attempts were made to identify 5-HT2A serotonin receptor agonists with reduced propensity to penetrate the blood-brain barrier. 1-(4Bromo-2,5-dimethoxyphenyl)-2-aminopropan-1-oI (6), an analogue of the 5-HT2A serotonin receptor agonist 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; 1a) bearing a benzylic hydroxyl group, was identified as a candidate structure. Of the four optical isomers of 6, the 1R,2R-isomer (6d; K-i = 0.5 nM) was found to bind at 5-HT2A receptors with an affinity similar to that of R(-)DOB (Ki = 0.2 nM). Like R(-)DOB, 6d behaved as a partial agonist (efficacy ca. 50%) in a 5-HT2-mediated calcium mobilization assay. However, in an in vivo test of central action (i.e., stimulus generalization with rats as subjects), 6d was > 15 times less potent than R(-)DOB. O-Methylation of 6d (i.e., 7d; 5-HT2A K-i = 0.3 nM) resulted in an agent that behaved as a full (93% efficacy) agonist. Intraocular administration of 300,mug of 6d and 7d to ocular hypertensive monkeys was shown to reduce intraocular pressure by 20-27%. Given the route of administration (i.e., topical), and concentrations necessary to reduce intraocular pressure, compounds such as 6d should demonstrate minimal central effects at potentially useful therapeutic doses and offer useful leads for further development.

  DOI：

  10.1021/jm040082s