7-acetyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid methyl ester | 70918-51-3

• 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: 7-acetyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid methyl ester
• 英文别名: methyl 7-acetyl-1,4-benzodioxan-2-carboxylate；Methyl 6-acetyl-2,3-dihydro-1,4-benzodioxine-3-carboxylate
• CAS: 70918-51-3
• 化学式: C₁₂H₁₂O₅
• 分子量: 236.224
• InChiKey: SYAQWSQQXZQOFC-UHFFFAOYSA-N

物化性质

• 沸点：
  370.1±42.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,3-二溴丙酸甲酯 、 3,4-二羟基苯乙酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 3.75h， 生成 6-acetyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid methyl ester 、 7-acetyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid methyl ester
  参考文献：
  名称：

  2,4-Diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-Benzodioxan-2-ylcarbonyl)piperazin-1-yl] derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents

  摘要：

  A series of 4-amino-2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1 -yl]-6, 7-dimethoxyquinazoline derivatives was synthesized for evaluation as alpha-antagonists and antihypertensive agents. Most compounds displayed high (nM) binding affinity for alpha 1-adrenoceptors with no significant activity at alpha 2-sites. Selective antagonism of the alpha 1-mediated vasoconstrictor effects of norepinephrine is also characteristic of the series. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented, and structural similarity between the 2,4-diamino-6,7-dimethoxyquinazoline nucleus and norepinephrine is established. An alpha 1-receptor model is presented in which charge-reinforced hydrogen bonding is important for binding of both antagonist and agonist molecules. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and several compounds displayed similar efficacy to prazosin when assessed after 6 h. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compound 1 (doxazosin) was selected for further evaluation and is currently progressing through phase III clinical trials.

  DOI：

  10.1021/jm00384a009

文献信息

• Regioselective Acylation of Benzodioxin Derivatives Employing AlCl₃-DMSO or AlCl₃-DMF Reagent in the Friedel-Crafts Reaction
  作者：Ernesto G. Mata、Alejandra G. Suárez

  DOI：10.1080/00397919708003368

  日期：1997.4

  Abstract A Simple and efficient route to the regioselective acylation of benzodioxin derivatives using AICI3-DMSO or AICI3-DMF as reagent with acyl halides and anhydrides is described.

  摘要 描述了使用 AlCl3-DMSO 或 AlCl3-DMF 作为试剂与酰卤和酸酐区域选择性酰化苯二恶英衍生物的简单有效途径。
• US4188390A
  申请人：——

  公开号：US4188390A

  公开（公告）日：1980-02-12
• 2,4-Diamino-6,7-dimethoxyquinazolines. 1. 2-[4-(1,4-Benzodioxan-2-ylcarbonyl)piperazin-1-yl] derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents
  作者：Simon F. Campbell、Michael J. Davey、J. David Hardstone、Brian N. Lewis、Michael J. Palmer

  DOI：10.1021/jm00384a009

  日期：1987.1

  A series of 4-amino-2-[4-(1,4-benzodioxan-2-ylcarbonyl)piperazin-1 -yl]-6, 7-dimethoxyquinazoline derivatives was synthesized for evaluation as alpha-antagonists and antihypertensive agents. Most compounds displayed high (nM) binding affinity for alpha 1-adrenoceptors with no significant activity at alpha 2-sites. Selective antagonism of the alpha 1-mediated vasoconstrictor effects of norepinephrine is also characteristic of the series. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented, and structural similarity between the 2,4-diamino-6,7-dimethoxyquinazoline nucleus and norepinephrine is established. An alpha 1-receptor model is presented in which charge-reinforced hydrogen bonding is important for binding of both antagonist and agonist molecules. Antihypertensive activity was evaluated after oral administration (5 mg/kg) to spontaneously hypertensive rats, and several compounds displayed similar efficacy to prazosin when assessed after 6 h. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compound 1 (doxazosin) was selected for further evaluation and is currently progressing through phase III clinical trials.