6-phenylhydrazono-6,7,8,9-tetrahydro-11H-pyrido<2,1-b>quinazolin-11-one

• 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-phenylhydrazono-6,7,8,9-tetrahydro-11H-pyrido<2,1-b>quinazolin-11-one
• 英文别名: 6-phenylhydrazono-6,7,8,9-tetrahydro-11-oxo-11H-pyrido[2,1-b]quinazoline；6-(phenylhydrazinylidene)-8,9-dihydro-7H-pyrido[2,1-b]quinazolin-11-one
• 化学式: C₁₈H₁₆N₄O
• 分子量: 304.351
• InChiKey: YZFHQWNGLJSWLT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 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-phenylhydrazono-6,7,8,9-tetrahydro-11H-pyrido<2,1-b>quinazolin-11-one 在 PPA 作用下， 反应 0.5h， 以92%的产率得到吴茱萸次碱
  参考文献：
  名称：

  氮桥头化合物第16部分。轻松进行7,8-二氢-13H-吲哚并[2'，3'：3,4]吡啶并[2,1-b]喹唑啉-5-酮（卢卡品平）的全合成。

  摘要：

  Rutecarpine已从腙synthetised ，在通过Fischer吲哚合成高收率，腙已从制备与重氮苯酰氯或与苯肼。显示出溶剂依赖性的EZ异构现象。

  DOI：

  10.1016/s0040-4039(01)92365-2
• 作为产物：
  描述：

  5-氯代戊酰氯 在 盐酸 、 potassium tert-butylate 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 12.25h， 生成 6-phenylhydrazono-6,7,8,9-tetrahydro-11H-pyrido<2,1-b>quinazolin-11-one
  参考文献：
  名称：

  源自芸苔芸香碱的新型PDE5抑制剂可用于治疗阿尔茨海默氏病

  摘要：

  合成了一系列新的芸苔芸香碱衍生物，并作为PDE5抑制剂进行了药理学评估。讨论了结构与活性之间的关系，并通过分子对接研究进一步阐明了它们的结合构象和同时相互作用方式。在25个类似物中，化合物8i表现出最有效的PDE5抑制作用，IC 50值为约0.086μM。而且，它在体内对抗东pol碱引起的认知障碍也产生了良好的效果。这些结果可能为进一步开发潜在的源自芸苔芸香碱的PDE5抑制剂提供指导，这是治疗阿尔茨海默氏病的良好候选药物。

  DOI：

  10.1016/j.bmcl.2020.127097

文献信息

• 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。
• Indolo[2',3';3,4]pyrido[2,1-b]quinazoline-5-ones, a process for the
  申请人：Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Rt.

  公开号：US04472399A1

  公开（公告）日：1984-09-18

  New Rutecarpine analogs are disclosed having Rutecarpine-like activity, especially diuretic activity. Also a novel process for the preparation of the Rutecarpine analogs is disclosed.

  揭示了具有类似于Rutecarpine活性的新Rutecarpine类似物，特别是利尿活性。还揭示了一种用于制备这些Rutecarpine类似物的新型工艺。
• Nitrogen bridgehead compounds part 16. Facile total synthesis of 7,8-dihydro-13H-indolo[2′,3′:3,4]pyrido[2,1-b]quinazolin-5-one (Rutecarpine).
  作者：József Kökösi、Istvan Hermecz、György Szász、Zoltán Mészáros

  DOI：10.1016/s0040-4039(01)92365-2

  日期：1981.1

  Rutecarpine has been synthetised from hydrazone , in high yield by Fischer indole synthesis, Hydrazone has been prepared from with benzenediazonium chloride or with phenylhydrazine. Shows a solvent dependent E-Z isomerism.

  Rutecarpine已从腙synthetised ，在通过Fischer吲哚合成高收率，腙已从制备与重氮苯酰氯或与苯肼。显示出溶剂依赖性的EZ异构现象。
• 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.

  本文公开了在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，烷氧羰基，在烷氧基中含有1至4个碳原子的烷基，氨基或羟基，或者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个相同或不同的卤素、烷基和在烷氧基中含有1至4个碳原子、苯氧基、羟基、硝基、氨基、腈基、羧基、含有1至4个碳原子的烷氧羰基、含有1至4个碳原子的脂肪酰基、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取代的苯基取代，或者萘基，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。
• 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.