6-[(4-Methyl-phenyl)-hydrazono]-6,7,8,9-tetrahydro-11H-pyrido [2,1-b] quinazoline-11-one | 95610-36-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 6-[(4-Methyl-phenyl)-hydrazono]-6,7,8,9-tetrahydro-11H-pyrido [2,1-b] quinazoline-11-one
• 英文别名: 6-[(4-methylphenyl)hydrazinylidene]-8,9-dihydro-7H-pyrido[2,1-b]quinazolin-11-one
• CAS: 95610-36-9；95631-12-2；80776-68-7
• 化学式: C₁₉H₁₈N₄O
• 分子量: 318.378
• InChiKey: USWOMYFGUHOLLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-[(4-Methyl-phenyl)-hydrazono]-6,7,8,9-tetrahydro-11H-pyrido [2,1-b] quinazoline-11-one 在 PPA 作用下， 反应 1.5h， 生成 10-Methylrutaecarpine
  参考文献：
  名称：

  新型拓扑异构酶抑制剂：芸香碱衍生物的合成及其对拓扑异构酶的抑制活性

  摘要：

  采用先前报道的方法制备了一系列芸香碱衍生物，并评估了它们对拓扑异构酶 I 和 II 的抑制活性。其中，强细胞毒性的 10-bromorutaecarpine 和 3-chlororutaecarpine 对拓扑 I 和 II 显示出强烈的抑制活性。

  DOI：

  10.1007/s12272-012-0504-1
• 作为产物：
  描述：

  8,9-二氢-6H-吡啶并[2,1-b]喹唑啉-11(7h)-酮 、 乙烷,三氯氟- 在 盐酸 、 sodium nitrite 、 溶剂黄146 作用下， 以 水 为溶剂， 生成 6-[(4-Methyl-phenyl)-hydrazono]-6,7,8,9-tetrahydro-11H-pyrido [2,1-b] quinazoline-11-one
  参考文献：
  名称：

  Synthesis and vasodilator effects of rutaecarpine analogues which might be involved transient receptor potential vanilloid subfamily, member 1 (TRPV1)

  摘要：

  Rutaecarpine is the major alkaloid component of Wu-Chu-Yu, a well known Chinese herbal drug. It has been reported that rutaecarpine causes the vasodilator, hypotensive effects by stimulation of CGRP synthesis and release via activation of TRPV1. In present study, 23 rutaecarpine analogues were designed and synthesized. Then, the vasodilator effects of theses compounds were screened by rat aortic ring experiment. The result showed that the 14-N atom of rutaecarpine might be the key site for the activity. The 5-carbonyl might make lower contribution to the effect. And simple substitute in indole-ring or quinazo-line-ring would not enhance the vasodilator effect unless in proper position with proper group. One of these compounds, 10-methylrutaecarpine, exhibited similar effect with rutaecarpine. Further functional experiments showed its vasodilator and hypotensive effect were related to the stimulation of CGRP release via activation of TRPV1. The vasodilator effects of these compounds were evaluated and the structure-activity relationship was elucidated for the first time. The results suggested a new direction of valuable TRPV1 agonist as anti-hypertensive drugs. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.02.015

文献信息

• 6-Hydrazono-pyrido[2,1-b] quinazoline-11 ones
  申请人：Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt.

  公开号：US04395549A1

  公开（公告）日：1983-07-26

  Intermediates useful in the preparation of Rutecarpine and Rutecarpine derivatives are disclosed as well as a process for the preparation of said intermediates having the following formula: ##STR1## wherein R, R.sup.1 and R.sup.2 are the same or different and stand for hydrogen, halogen, nitro, carboxy, nitrile, alkoxy containing 1 to 4 carbon atoms, alkoxycarbonyl containing 1 to 4 carbon atoms in the alkoxy group, alkyl containing 1 to 4 carbon atoms, amino or hydroxy or R and R.sup.1 together stand for methylenedioxy, R.sup.2 stands for hydrogen, R.sup.3 represents hydrogen or alkyl containing 1 to 4 carbon atoms, R.sup.4 stands for phenyl, phenyl substituted by 1 to 3 same or different substituents selected from the group of halogen(s), alkyl, and alkoxy containing 1 to 4 carbon atoms, phenyloxy, hydroxy, nitro, amino, cyano, carboxy, alkoxycarbonyl having 1 to 4 carbon atoms, alkanoyl having 1 to 4 carbon atoms, methylenedioxy, trifluoromethyl, phenyl and dialkylamino having 1 to 4 carbon atoms in the alkyl part or naphthyl and the dotted line indicated an optional double bond. Also pharmaceutically acceptable acid addition and quaternary ammonium salts are disclosed.

  本发明公开了在Rutecarpine和Rutecarpine衍生物制备中有用的中间体，以及制备该中间体的过程，该中间体具有以下结构式：##STR1## 其中R，R.sup.1和R.sup.2相同或不同，代表氢，卤素，硝基，羧基，腈基，含1至4个碳原子的烷氧基，烷氧基中烷氧基组中含有1至4个碳原子的烷氧基，含1至4个碳原子的烷基，氨基或羟基，或R和R.sup.1一起代表亚甲二氧基，R.sup.2代表氢，R.sup.3代表氢或含有1至4个碳原子的烷基，R.sup.4代表苯基，苯基被1至3个相同或不同的取代基所取代，所述取代基从卤素，烷基和含1至4个碳原子的烷氧基，苯氧基，羟基，硝基，氨基，腈基，羧基，含有1至4个碳原子的烷氧基，含有1至4个碳原子的烷酰基，亚甲二氧基，三氟甲基，苯基和在烷基部分含有1至4个碳原子的二烷基氨基中选择，或者是萘基，虚线表示可选的双键。此外，还公开了药学上可接受的酸添加物和季铵盐。
• Koekoesi, Jozsef; Hermecz, Istvan; Podanyi, Benjamin, Journal of Heterocyclic Chemistry, 1985, vol. 22, p. 1373 - 1375
  作者：Koekoesi, Jozsef、Hermecz, Istvan、Podanyi, Benjamin、Szasz, Gyoergy、Meszaros, Zoltan

  DOI：——

  日期：——
• Synthesis and vasodilator effects of rutaecarpine analogues which might be involved transient receptor potential vanilloid subfamily, member 1 (TRPV1)
  作者：Zhuo Chen、Gaoyun Hu、Dai Li、Jun Chen、Yuanjian Li、Huayong Zhou、Ye Xie

  DOI：10.1016/j.bmc.2009.02.015

  日期：2009.3

  Rutaecarpine is the major alkaloid component of Wu-Chu-Yu, a well known Chinese herbal drug. It has been reported that rutaecarpine causes the vasodilator, hypotensive effects by stimulation of CGRP synthesis and release via activation of TRPV1. In present study, 23 rutaecarpine analogues were designed and synthesized. Then, the vasodilator effects of theses compounds were screened by rat aortic ring experiment. The result showed that the 14-N atom of rutaecarpine might be the key site for the activity. The 5-carbonyl might make lower contribution to the effect. And simple substitute in indole-ring or quinazo-line-ring would not enhance the vasodilator effect unless in proper position with proper group. One of these compounds, 10-methylrutaecarpine, exhibited similar effect with rutaecarpine. Further functional experiments showed its vasodilator and hypotensive effect were related to the stimulation of CGRP release via activation of TRPV1. The vasodilator effects of these compounds were evaluated and the structure-activity relationship was elucidated for the first time. The results suggested a new direction of valuable TRPV1 agonist as anti-hypertensive drugs. (C) 2009 Elsevier Ltd. All rights reserved.
• New topoisomerases inhibitors: Synthesis of rutaecarpine derivatives and their inhibitory activity against topoisomerases
  作者：Seung Ill Kim、Seung Ho Lee、Eung-Seok Lee、Chong-Soon Lee、Yurngdong Jahng

  DOI：10.1007/s12272-012-0504-1

  日期：2012.5

  A series of rutaecarpine derivatives were prepared by employing previously reported methods and their inhibitory activities against topoisomerase I and II were evaluated. Among them, strongly cytotoxic 10-bromorutaecarpine and 3-chlororutaecarpine showed strong inhibitory activities against topo I and II.

  采用先前报道的方法制备了一系列芸香碱衍生物，并评估了它们对拓扑异构酶 I 和 II 的抑制活性。其中，强细胞毒性的 10-bromorutaecarpine 和 3-chlororutaecarpine 对拓扑 I 和 II 显示出强烈的抑制活性。