4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)homopiperazin-1-yl]-6,7-dimethoxyquinazoline hydrochloride | 70918-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)homopiperazin-1-yl]-6,7-dimethoxyquinazoline hydrochloride
• 英文别名: [4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-1,4-diazepan-1-yl]-(2,3-dihydro-1,4-benzodioxin-3-yl)methanone;hydrochloride
• CAS: 70918-05-7
• 化学式: C₂₄H₂₇N₅O₅*ClH
• 分子量: 501.97
• InChiKey: SKKCFPYPOCODOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(1,4-benzodioxan-2-ylcarbonyl)homopiperazine 、 2-氯-4-氨基-6,7-二甲氧基喹唑啉 在 正丁醇 、 乙醚 、 甲醇 、 乙醇 作用下， 以 正丁醇 为溶剂， 反应 60.0h， 以to give 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)homopiperazin-1-yl]-6,7-dimethoxyquinazoline hydrochloride (0.57 g.), m.p. 250°-251° C.的产率得到4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)homopiperazin-1-yl]-6,7-dimethoxyquinazoline hydrochloride
  参考文献：
  名称：

  Antihypertensive 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)

  摘要：

  具有以下式子##STR1##和其药学上可接受的盐，其中R代表6,7-二(低烷氧基)或6,7,8-三(低烷氧基)；m为1或2，X为--CHR.sup.1 --或--CH.sub.2 CH.sub.2 --；每个R.sup.1和R.sup.0可以相同或不同，且为氢或低烷基；R.sup.2和R.sup.3中的每一个都为氢、低烷氧基、低烷基、卤素、低烷酰基、低烷氧羰基、--CONR.sup.4 R.sup.5或--SO.sub.2 NR.sup.4 R.sup.5，其中每个R.sup.4和R.sup.5为氢或低烷基；它们的制备过程；以及它们作为心血管系统调节剂的用途，特别是用于治疗高血压。

  公开号：

  US04188390A1

文献信息

• Antihypertensive 4-amino-2-[4-(1,4-benzodioxan-2-carbonyl)
  申请人：Pfizer Inc.

  公开号：US04188390A1

  公开（公告）日：1980-02-12

  Compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein R represents 6,7-di(lower alkoxy) or 6,7,8-tri(lower alkoxy); m is 1 or 2, X is --CHR.sup.1 -- or --CH.sub.2 CH.sub.2 --; each R.sup.1 and R.sup.0 may be the same or different and is hydrogen or lower alkyl; each of R.sup.2 and R.sup.3 is hydrogen, lower alkoxy, lower alkyl, halogen, lower alkanoyl, lower alkoxycarbonyl, --CONR.sup.4 R.sup.5 or --SO.sub.2 NR.sup.4 R.sup.5 wherein each of R.sup.4 and R.sup.5 is hydrogen or lower alkyl; processes for their preparation; and their use as regulators of the cardiovascular system, and particularly in the treatment of hypertension.

  具有以下公式的化合物##STR1##及其药用可接受的盐，其中R代表6,7-二(较低烷氧基)或6,7,8-三(较低烷氧基)；m为1或2，X为--CHR.sup.1 --或--CH.sub.2 CH.sub.2 --；每个R.sup.1和R.sup.0可以相同也可以不同，是氢或较低烷基；每个R.sup.2和R.sup.3是氢、较低烷氧基、较低烷基、卤素、较低烷酰基、较低烷氧羰基、--CONR.sup.4 R.sup.5或--SO.sub.2 NR.sup.4 R.sup.5，其中每个R.sup.4和R.sup.5是氢或较低烷基；它们的制备方法；以及它们作为心血管系统调节剂的用途，尤其是在治疗高血压方面。
• 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：——
• 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.