3,4-二氢-2H-1,5-苯并二氧平-2-羰酰氯 | 77156-62-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 3,4-二氢-2H-1,5-苯并二氧平-2-羰酰氯
• 英文名称: 3,4-Dihydro-2H-benzo[b][1,4]dioxepine-2-carbonyl chloride
• 英文别名: 2H-1,5-Benzodioxepin-2-carbonyl chloride, 3,4-dihydro-；3,4-dihydro-2H-1,5-benzodioxepine-4-carbonyl chloride
• CAS: 77156-62-8
• 化学式: C₁₀H₉ClO₃
• 分子量: 212.633
• InChiKey: OQHRZROPXOWOCD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  3,4-二氢-2H-1,5-苯并二氧平-2-羰酰氯 、 2-哌嗪基-4-氨基-6,7-二甲氧基喹唑啉 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 [4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazin-1-yl]-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-2-yl)-methanone; hydrochloride
  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

• CAMPBELL S. F.; DAVEY M. J.; HARDSTONE J. D.; LEWIS B. N. (IN PART); PALM+, J. MED. CHEM., 30,(1987) N 1, 49-57
  作者：CAMPBELL S. F.、 DAVEY M. J.、 HARDSTONE J. D.、 LEWIS B. N. (IN PART)、 PALM+

  DOI：——

  日期：——
• 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.