1-{2-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carbonyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-ethanone; hydrochloride | 70918-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-{2-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carbonyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-ethanone; hydrochloride
• 英文别名: 1-[2-[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazine-1-carbonyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethanone;hydrochloride
• CAS: 70918-22-8
• 化学式: C₂₅H₂₇N₅O₆*ClH
• 分子量: 529.98
• InChiKey: BOSHGYQSMNLZMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  37.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  129.34
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  6-Acetyl-2,3-dihydro-benzo[1,4]dioxine-2-carbonyl chloride 、 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 1-{2-[4-(4-Amino-6,7-dimethoxy-quinazolin-2-yl)-piperazine-1-carbonyl]-2,3-dihydro-benzo[1,4]dioxin-6-yl}-ethanone; 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：——