11H-6,7,8,9-tetrahydro-6-(phenylmethylene)pyrido<2,1-b>quinazolin-11-one | 94271-23-5

• 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: 11H-6,7,8,9-tetrahydro-6-(phenylmethylene)pyrido<2,1-b>quinazolin-11-one
• 英文别名: (6E)-6-benzylidene-6,7,8,9-tetrahydropyrido[2,1-b]quinazolin-11-one；(E)-6-benzylidene-6,7,8,9-tetrahydropyrido[2,1-b]quinazolin-11-one；benzylidene-9,10,11,12-tetrahydro-4H-pyrido[2,1-b]quinazolin-4-one；11H-6,7,8,9-tetrahydro-6-(phenylmethylene)pyrido[2,1-b]quinazolin-11-one；(6E)-6-benzylidene-8,9-dihydro-7H-pyrido[2,1-b]quinazolin-11-one
• CAS: 94271-23-5
• 化学式: C₁₉H₁₆N₂O
• 分子量: 288.349
• InChiKey: ZMQDSFDAVQBSRH-FYWRMAATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  11H-6,7,8,9-tetrahydro-6-(phenylmethylene)pyrido<2,1-b>quinazolin-11-one 在 poliyphosphoric acid 、 臭氧 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.5h， 生成 吴茱萸次碱
  参考文献：
  名称：

  Lee, Seung Ho; Kim, Seung Ill; Park, Jae Gyu, Heterocycles, 2001, vol. 55, # 8, p. 1555 - 1567

  摘要：

  DOI：
• 作为产物：
  描述：

  Boc-5-氨基戊酸 在 吡啶 、 亚磷酸三苯酯 作用下， 反应 0.37h， 生成 11H-6,7,8,9-tetrahydro-6-(phenylmethylene)pyrido<2,1-b>quinazolin-11-one
  参考文献：
  名称：

  Privileged structure-based quinazolinone natural product-templated libraries: Identification of novel tubulin polymerization inhibitors

  摘要：

  A focused quinazolinone natural product-templated library was designed and synthesized. Compounds from this privileged structure-based library were identified as antimitotic agents acting through destabilization of tubulin polymerization. The results suggested that 2 could be a privileged substructure. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.022

文献信息

• Design, Synthesis and Evaluation of Arylidene Pyrrolo and Pyrido Fused Quinazolones as Antimicrobial Agents
  作者：Kunal Nepali、Ritu Ojha、Aninder Singh、Abhishek Budhiraja、Preet Mohinder Singh Bedi、Kanaya Lal Dhar

  DOI：10.2174/1570180811310060008

  日期：2013.5.1

  Keeping in view the potential of heterocyclic fused quinazolones and arylidene linked heterocycles , hybrid molecules of these functionalities were designed and synthesised. All the synthesised molecules were characterized by spectroscopic techniques and evaluated for antimicrobial activity against 2 Gram positive bacterial strains; Staphylococcus aureus (MTCC 96) and Bacillus subtilis (MTCC 2451), 3 Gram negative bacterial strains; Escherichia coli (MTCC 82), Pseudomonas aeruginosa (MTCC 2642) and Salmonella typhimurium (MTCC 1251) and 2 fungal strains; Saccharomyces cerevisiae (MTCC 2799) and Candida albicans (MTCC 3018). Among the synthesised molecules, arylidene pyrrolo fused quinazolones displayed significant antimicrobial activity in comparison to arylidene pyrido fused quinazolones. The influence of the electronic factors linked with the arylidene ring was also observed on the antimicrobial potential. Thus the present study highlights the potential of such hybrid molecules as a new class of antimicrobials.

  考虑到杂环融合喹唑啉酮和芳基链杂环的潜力，我们设计并合成了具有这些功能的杂化分子。通过光谱技术对所有合成分子进行了表征，并评估了它们对 2 种革兰氏阳性细菌菌株：金黄色葡萄球菌（MTCC 96）和枯草杆菌（MTCC 2451）以及 3 种革兰氏阴性细菌菌株的抗菌活性；大肠杆菌（MTCC 82）、铜绿假单胞菌（MTCC 2642）和鼠伤寒沙门氏菌（MTCC 1251），以及 2 种真菌菌株：酿酒酵母（MTCC 2799）和白色念珠菌（MTCC 3018）。在合成的分子中，亚芳基吡咯并合喹唑酮与亚芳基吡啶并合喹唑酮相比具有显著的抗菌活性。此外，还观察到与芳基环相关的电子因素对抗菌潜力的影响。因此，本研究强调了这类杂化分子作为一类新型抗菌剂的潜力。
• Structure Activity Relationship of Arylidene Pyrrolo and Pyrido [2,1-b] Quinazolones as Cytotoxic Agents: Synthesis, SAR Studies, Biological Evaluation and Docking Studies
  作者：Veenu Mangla、Kunal Nepali、Gagandip Singh、Jagjeet Singh、Santosh Guru、Manish Gupta、Priya Mahajan、Ajit Saxena、Kanaya Dhar

  DOI：10.2174/1573406411309050003

  日期：2013.6.1

  Tubulin is the one of the most useful and strategic molecular targets for anticancer drugs. Agents that bind in Colchicine-binding site of tubulin include Phenstatin, Combretastatin A-4, Colchicine, Steganacin, Podophyllotoxin and certain other synthetic analogues of these compounds. Arylidene pyrollo and pyrido [2,1- b] quinazolones (isoindigatone and its synthetic analogues) have been earlier reported to be tubulin inhibitors evidenced by tubulin polymerization assay. The present study is an extension of the library of the isoindigatone and its synthetic analogues to generate the structure activity relationship. The study explores the role of the arylidene ring and also provides some intresting observations such as the placement of bicyclic ring such as naphylidene for potential activity. Some of the important interactions of KNH- 3 and KNH-11 with the amino acid residues of active site of Tubulin have also been observed by molecular modeling.

  微管蛋白是抗癌药物最有用、最具战略意义的分子靶点之一。能与微管蛋白的秋水仙碱结合位点结合的药物包括苯司他丁（Phenstatin）、考来替丁 A-4、秋水仙碱（Colchicine）、司替加辛（Steganacin）、鬼臼毒素（Podophyllotoxin）以及这些化合物的某些合成类似物。早先有报告称，亚芳基吡咯并吡啶并[2,1- b]喹唑酮（异茚地加通及其合成类似物）是一种管蛋白抑制剂，这在管蛋白聚合试验中得到了证明。 本研究是对异茚地加通及其合成类似物库的扩展，以生成结构活性关系。该研究探讨了亚芳基环的作用，还提供了一些有趣的观察结果，如将双环（如亚萘基）置于潜在活性中。通过分子建模，还观察到 KNH- 3 和 KNH-11 与 Tubulin 活性位点氨基酸残基的一些重要相互作用。
• Dunn, A. D.; Kinnear, K. I., Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 53 - 57
  作者：Dunn, A. D.、Kinnear, K. I.

  DOI：——

  日期：——
• A facile synthesis of α,α′-bis(substituted-benzylidene)-cycloalkanones and substituted-benzylidene heteroaromatics: utility of NaOAc as a catalyst for aldol-type reaction
  作者：A.F.M. Motiur Rahman、Byeong-Seon Jeong、Dong Hyeon Kim、Jung Ki Park、Eung Seok Lee、Yurngdong Jahng

  DOI：10.1016/j.tet.2007.01.020

  日期：2007.3

  Utility of NaOAc in glacial HOAc as a catalyst for aldol-type condensation reactions was examined. Reactions of cycloalkanones and selected heteroaromatics with various aldehydes in the presence of NaOAc in glacial HOAc provided alpha,alpha-bis(substituted-benzylidene)cycloalkanones and substituted-benzylidene heteroaromatics, respectively, in good yields. (c) 2007 Elsevier Ltd. All rights reserved.
• Privileged structure-based quinazolinone natural product-templated libraries: Identification of novel tubulin polymerization inhibitors
  作者：Ji-Feng Liu、Christopher J. Wilson、Ping Ye、Kevin Sprague、Katie Sargent、Ying Si、Galina Beletsky、Daniel Yohannes、Shi-Chung Ng

  DOI：10.1016/j.bmcl.2005.10.022

  日期：2006.2

  A focused quinazolinone natural product-templated library was designed and synthesized. Compounds from this privileged structure-based library were identified as antimitotic agents acting through destabilization of tubulin polymerization. The results suggested that 2 could be a privileged substructure. (c) 2005 Elsevier Ltd. All rights reserved.