2-[4-(2-isopropoxy-ethoxy)-piperidin-1-yl]-6,7-dimethoxy-quinazolin-4-ylamine | 70978-70-0

• 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: 2-[4-(2-isopropoxy-ethoxy)-piperidin-1-yl]-6,7-dimethoxy-quinazolin-4-ylamine
• 英文别名: 6,7-Dimethoxy-2-[4-(2-propan-2-yloxyethoxy)piperidin-1-yl]quinazolin-4-amine
• CAS: 70978-70-0
• 化学式: C₂₀H₃₀N₄O₄
• 分子量: 390.483
• InChiKey: KOJPQHSSSHQKPH-UHFFFAOYSA-N

物化性质

• 熔点：
  130-134 °C(Solv: ethanol (64-17-5); isopropanol (67-63-0))
• 沸点：
  569.3±60.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  92
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N-乙酰基-4-羟基哌啶 在 sodium hydride 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 paraffin 、 正丁醇 为溶剂， 生成 2-[4-(2-isopropoxy-ethoxy)-piperidin-1-yl]-6,7-dimethoxy-quinazolin-4-ylamine
  参考文献：
  名称：

  2,4-Diamino-6,7-dimethoxyquinazolines. 4. 2-[4-(Substituted oxyethoxy)piperidino] derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents

  摘要：

  A series of 4-amino-6,7-dimethoxy-2-[4-(substituted oxyethoxy)piperidino] quinazoline derivatives (2) was synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. Most compounds showed binding affinities within the nanomolar range for alpha 1-receptors, although 25 and 26 showed enhanced potency (Ki, ca. 1.5 X 10(-10) M), equivalent to that of prazosin. Series 2 also displaced [3H]clonidine from alpha 2-adrenoceptors, but at relatively high doses of 10(-6) M, and selectivity for alpha 1 sites still predominated. In a rabbit pulmonary artery preparation, 12, 16, and 25 were potent antagonists of the alpha 1-mediated, postjunctional vasoconstrictor activity of norepinephrine with no effect at the prejunctional alpha 2 sites which modulate transmitter release. Physicochemical measurements gave a pKa of 7.63 +/- 0.10 for 12, and N-1 protonation will be favored (60%) at physiological pH to provide the alpha 1-adrenoceptor pharmacophore, 28. Antihypertensive activity of series 2 was evaluated following oral administration to spontaneously hypertensive rats, and blood pressure was measured after 1 and 6 h. Compounds 12, 13, 16, 23, and 37 displayed moderate efficacy and duration of action in lowering blood pressure, but the plasma half-life (ca. 2 h) of 16 in dogs was not compatible with potential once-daily administration in humans.

  DOI：

  10.1021/jm00398a006

文献信息

• CAMPBELL, SIMON F.;DANILEWICZ, JOHN C.;GREENGRASS, COLIN W.;PLEWS, RHONA +, J. MED. CHEM., 31,(1988) N 3, 516-520
  作者：CAMPBELL, SIMON F.、DANILEWICZ, JOHN C.、GREENGRASS, COLIN W.、PLEWS, RHONA +

  DOI：——

  日期：——
• 2,4-Diamino-6,7-dimethoxyquinazolines. 4. 2-[4-(Substituted oxyethoxy)piperidino] derivatives as .alpha.1-adrenoceptor antagonists and antihypertensive agents
  作者：Simon F. Campbell、John C. Danilewicz、Colin W. Greengrass、Rhona M. Plews

  DOI：10.1021/jm00398a006

  日期：1988.3

  A series of 4-amino-6,7-dimethoxy-2-[4-(substituted oxyethoxy)piperidino] quinazoline derivatives (2) was synthesized and evaluated for alpha-adrenoceptor affinity and antihypertensive activity. Most compounds showed binding affinities within the nanomolar range for alpha 1-receptors, although 25 and 26 showed enhanced potency (Ki, ca. 1.5 X 10(-10) M), equivalent to that of prazosin. Series 2 also displaced [3H]clonidine from alpha 2-adrenoceptors, but at relatively high doses of 10(-6) M, and selectivity for alpha 1 sites still predominated. In a rabbit pulmonary artery preparation, 12, 16, and 25 were potent antagonists of the alpha 1-mediated, postjunctional vasoconstrictor activity of norepinephrine with no effect at the prejunctional alpha 2 sites which modulate transmitter release. Physicochemical measurements gave a pKa of 7.63 +/- 0.10 for 12, and N-1 protonation will be favored (60%) at physiological pH to provide the alpha 1-adrenoceptor pharmacophore, 28. Antihypertensive activity of series 2 was evaluated following oral administration to spontaneously hypertensive rats, and blood pressure was measured after 1 and 6 h. Compounds 12, 13, 16, 23, and 37 displayed moderate efficacy and duration of action in lowering blood pressure, but the plasma half-life (ca. 2 h) of 16 in dogs was not compatible with potential once-daily administration in humans.