trans-2-(hydroxymethyl)-3-methyl-2,3-dihydro-1,4-benzodioxin | 16163-44-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: trans-2-(hydroxymethyl)-3-methyl-2,3-dihydro-1,4-benzodioxin
• 英文别名: (+/-)-(trans-3-Methyl-2,3-dihydro-benzo[1,4]dioxin-2-yl)-methanol；[(2R,3R)-2-methyl-2,3-dihydro-1,4-benzodioxin-3-yl]methanol
• CAS: 16163-44-3；16163-85-2；58908-98-8
• 化学式: C₁₀H₁₂O₃
• 分子量: 180.203
• InChiKey: VVPVIOBUOZOYRP-GMSGAONNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trans-2-(hydroxymethyl)-3-methyl-2,3-dihydro-1,4-benzodioxin 在 吡啶 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 72.0h， 生成 ((2R,3R)-3-Methyl-2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-(1-pyrimidin-2-yl-piperidin-4-ylmethyl)-amine
  参考文献：
  名称：

  N-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents

  摘要：

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.

  DOI：

  10.1021/jm9910122
• 作为产物：
  描述：

  3-Methyl-1,4-benzodioxan-2-carbonsaeureethylester 在 lithium aluminium tetrahydride 、 乙醚 作用下， 生成 trans-2-(hydroxymethyl)-3-methyl-2,3-dihydro-1,4-benzodioxin
  参考文献：
  名称：

  Derivatives of 1,4-Benzodioxan. II.^1,2 3-Methyl-1,4-benzodioxan-2-carboxamides and Corresponding Amines

  摘要：

  DOI：

  10.1021/jo01061a017

文献信息

• Derivatives of 1,4-Benzodioxan. II.^1,2 3-Methyl-1,4-benzodioxan-2-carboxamides and Corresponding Amines
  作者：JOHN KOO

  DOI：10.1021/jo01061a017

  日期：1961.2
• Koo et al., Chemistry and industry, 1958, p. 832
  作者：Koo et al.

  DOI：——

  日期：——
• Structure-activity relationships in 1,4-benzodioxan-related compounds. 4. Effect of aryl and alkyl substituents at position 3 on .alpha.-adrenoreceptor blocking activity
  作者：Wilma Quaglia、Maria Pigini、Seyed K. Tayebati、Alessandro Piergentili、Mario Giannella、Gabriella Marucci、Carlo Melchiorre

  DOI：10.1021/jm00063a002

  日期：1993.5

  The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha1-adrenoreceptor antagonist, phendioxan (2), prompted us to further investigate that position of the 2,3-dihydro-1,4-benzodioxin moiety. Thus the 3-phenyl of 2 was replaced by methyl, isopropyl, cyclohexyl, or para-substituted phenyl groups either in a cis or a trans relationships affording compounds 3-17 and 58. The structure of these new derivatives was assigned on the basis of the coupling constant of hydrogens at positions 2 and 3 and confirmed by a crystallographic study. The blocking activity and relative selectivity of 3-17 on alpha1- and alpha2-adrenoreceptors were evaluated in the isolated rat vas deferens. The results were compared with those obtained for 1 and 2. All the compounds, with the exception of isopropyl and cyclohexyl derivatives 5-8, were effective al-adrenoreceptor antagonists with a significant alpha1/alpha2-selectivity. The lipophilic and/or electronic character of para substituents of the 3-phenyl ring does not alter markedly the affinity toward alpha1-adrenoreceptors. However, the 3-p-tolyl derivative 10 was slightly more potent and even more selective than 2.
• <i>N</i>-Substituted (2,3-Dihydro-1,4-benzodioxin-2-yl)methylamine Derivatives as D₂ Antagonists/5-HT_1A Partial Agonists with Potential as Atypical Antipsychotic Agents
  作者：Alan M. Birch、Paul A. Bradley、Julie C. Gill、Frank Kerrigan、Pat L. Needham

  DOI：10.1021/jm9910122

  日期：1999.8.1

  A series of N-substituted 1-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamine derivatives with D-2 antagonist/5-HT1A partial agonist activity has been prepared as potential atypical antipsychotic agents. Optimization of in vitro receptor binding activity and in vivo activity in rodent models of psychosis has led to compound 24, which showed good affinities for human D-2, D-3, and 5-HT1A receptors but significantly less affinity for human alpha(1) adrenoceptors and rat H-1 and muscarinic receptors. In rodents, 24 showed functional D-2-like antagonism and 5-HT1A partial agonism. After oral dosing, 24 showed good activity in rodent antipsychotic tests and very little potential to cause extrapyramidal side effects (EPS), as measured by its ability to induce catalepsy in rats only at very high doses. In the light of this promising profile of activity, 24 has been selected for clinical investigation as a novel antipsychotic agent with a predicted low propensity to cause EPS.
• Adrenergic Neurone Blocking Agents. II.¹ Some Dioxane-Substituted Derivatives of Guanoxan
  作者：A. M. Monro、G. W. H. Potter、M. J. Sewell

  DOI：10.1021/jm00317a027

  日期：1967.9