3-(4-fluorophenyl)-6-hydroxy-2-methylquinazolin-4(3H)-one | 1214739-65-7

• 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: 3-(4-fluorophenyl)-6-hydroxy-2-methylquinazolin-4(3H)-one
• CAS: 1214739-65-7
• 化学式: C₁₅H₁₁FN₂O₂
• 分子量: 270.263
• InChiKey: GRQAXPIAGLZHQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.54
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.12
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-6-hydroxy-2-methylquinazolin-4(3H)-one 在 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 27.5h， 生成 6-((1-((5-(6-amino-9H-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methoxy)-3-(4-fluorophenyl)-2-methylquinazolin-4(3H)-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Activity Evaluation of Novel AZT and Adenosine-Derived 1,2,3-Triazoles

  摘要：

  以 CuSO4/hydrazine hydrate 为催化剂体系，铜（I）催化了 AZT 和 5′-叠氮腺苷与末端炔烃的炔烃-叠氮环加成反应（CuAAC），得到了 30 种新型 1,2,3- 三唑衍生物。对这些衍生物的抗癌、抗炎、血管紧张素转换酶 2（ACE2）和 3C 样蛋白酶（3CLpro）抑制活性的筛选表明，含有 murayafoline A 和 indirubin-3′-oxime 的 AZT 的几种三唑类衍生物可抑制 HepG2 和 LU-1 的生长，其 IC50 值在 11.01 到 19.87 μg/mL 之间。此外，腺苷的一些三唑衍生物对 RAW264.7 细胞具有抗炎活性，IC50 值在 12.00-59.48.00 μg/mL 之间。特别是腺苷的两个三唑类衍生物，在 O 位和 N1 位上含有靛红-3′-肟，具有抑制 ACE2 和 3CLpro 的活性，其中在 N1 位上含有靛红-3′-肟的腺苷三唑类衍生物同时具有抑制 ACE2 和 3CLpro 的活性，IC50 值分别为 135.62 和 142.95 μg/mL。

  DOI：

  10.1155/2023/1605316
• 作为产物：
  描述：

  2-氨基-5-羟基苯甲酸 在 溶剂黄146 作用下， 反应 16.0h， 生成 3-(4-fluorophenyl)-6-hydroxy-2-methylquinazolin-4(3H)-one
  参考文献：
  名称：

  Design, Synthesis and In vitro Cytotoxic Evaluation of Novel Hybrids of Artemisinin and Quinazolinone

  摘要：

  背景：本研究合成了两个新型青蒿素和喹唑啉酮的混合系列，并在体外评估了它们对两种人类癌细胞系（包括肺癌SKLu-1和乳腺癌MCF-7）的细胞毒性。生物测定结果表明，大多数目标化合物对测试的两种人类癌细胞系表现出细胞毒性，并且对于乳腺癌（MCF-7）细胞比肺癌（SKLu-1）细胞更具有细胞毒性。在合成的青蒿素混合物中，含有喹唑啉酮共轭系统的13d化合物对SKLu-1和MCF-7细胞系表现出最强的细胞毒性，IC50值分别为1.62和0.77μM。 目的：本研究旨在开发新型的青蒿素和喹唑啉酮混合物作为抗癌药物。 方法：设计、合成和评估了一系列新型混合物，使用SRB方法对肺癌SKLu-1和乳腺癌MCF-7两种人类癌细胞系的细胞毒性进行了评估。 结果：青蒿素与喹唑啉酮的十三个混合物对测试的两种癌细胞系都表现出细胞毒性，其中13d化合物对SKLu-1和MCF-7细胞系表现出最强的细胞毒性，IC50值分别为1.62和0.77μM。 结论：研究结果表明，一些化合物可以被视为未来混合物设计的引导物，并在抗癌药物开发领域进行进一步研究。

  DOI：

  10.2174/1570178618666211001115131

文献信息

• Quinazolinone linked pyrrolo[2,1-c][1,4]benzodiazepine (PBD) conjugates: Design, synthesis and biological evaluation as potential anticancer agents
  作者：Ahmed Kamal、E. Vijaya Bharathi、M. Janaki Ramaiah、D. Dastagiri、J. Surendranadha Reddy、A. Viswanath、Farheen Sultana、S.N.C.V.L. Pushpavalli、Manika Pal-Bhadra、Hemant Kumar Srivastava、G. Narahari Sastry、Aarti Juvekar、Subrata Sen、Surekha Zingde

  DOI：10.1016/j.bmc.2009.12.015

  日期：2010.1

  series of novel quinazolinone linked pyrrolobenzodiazepine (PBD) conjugates were synthesized. These compounds 4a–f and 5a–f were prepared in good yields by linking C-8 of DC-81 with quinazolinone moiety through different alkane spacers. These conjugates were tested for anticancer activity against 11 human cancer cell lines and found to be very potent anticancer agents with GI50 values in the range of <0

  合成了一系列新型的喹唑啉酮连接的吡咯并苯并二氮杂（PBD）缀合物。这些化合物4a - f和5a - f是通过不同的烷烃间隔基将DC-81的C-8与喹唑啉酮部分连接而制备的，收率很高。测试了这些缀合物对11种人类癌细胞系的抗癌活性，发现它们是非常有效的抗癌剂，GI 50值在<0.1–26.2μM范围内。在所有PBD缀合物中，其中一种缀合物5c已针对一组60个人类癌细胞进行了测试。该化合物对具有GI 50的单个癌细胞系表现出活性值<0.1μM。与DC-81相比，热变性研究显示出有效的DNA结合能力，并且分子模型研究进一步支持了这些结果。研究了这些缀合物在A375细胞系上的详细生物学方面。观察到化合物4b和5c诱导细胞色素c的释放，caspase-3的活化，PARP的切割和随后的细胞死亡。此外，当用A375细胞处理时，这些化合物表现出凋亡的特征，例如细胞周期蛋白依赖性激酶-2（CDK2）的p53
• Design, Synthesis and In vitro Cytotoxic Evaluation of Novel Hybrids of Artemisinin and Quinazolinone
  作者：Tran Khac Vu、Bach Xuan Nguyen、Linh Nguyen Pham Duy、Thuc Bao Nguyen Truong、Anh Tuan Phung、Nguyen Thi Bich Phuong、Tran Thi Hai Van、Thi Xuan Vu

  DOI：10.2174/1570178618666211001115131

  日期：2022.7

  In this study, two novel hybrid series of artemisinin and quinazolinones were synthesized and evaluated in vitro cytotoxicity against two human cancer cell lines, including SKLu-1 (lung cancer), MCF- 7 (breast cancer). The bio-assay results indicated that most of the target compounds exhibited cytotoxic activities against both human cancer cell lines tested and seemed to be more cytotoxic toward the breast (MCF-7) cancer cells than lung (SKLu-1) cancer cells. Among the synthesized artemisinin hybrids, the compound 13d containing a quinazolinone conjugated system exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 μM, respectively.

  This study aims at developing novel hybrids of artemisinin and quinazolinones as anticancer agents.

  A series of novel hybrids were designed, synthesized, and evaluated for cytotoxicity against two human cancer cell lines, including SKLu-1 and MCF-7, using the SRB method.

  All thirteen hybrids of artemisinin with quinazolinone exhibited cytotoxic activity against two tested cancer cell lines, in which the compound 13d exhibited the most potent cytotoxicity against the SKLu-1 and MCF-7 cell lines with IC50 values of 1.62 and 0.77 μM, respectively.

  The research results suggest that some compounds could be considered as leads for future design of hybrids and have the potential for further studies in the field of anti-cancer agent development.

  背景：本研究合成了两个新型青蒿素和喹唑啉酮的混合系列，并在体外评估了它们对两种人类癌细胞系（包括肺癌SKLu-1和乳腺癌MCF-7）的细胞毒性。生物测定结果表明，大多数目标化合物对测试的两种人类癌细胞系表现出细胞毒性，并且对于乳腺癌（MCF-7）细胞比肺癌（SKLu-1）细胞更具有细胞毒性。在合成的青蒿素混合物中，含有喹唑啉酮共轭系统的13d化合物对SKLu-1和MCF-7细胞系表现出最强的细胞毒性，IC50值分别为1.62和0.77μM。 目的：本研究旨在开发新型的青蒿素和喹唑啉酮混合物作为抗癌药物。 方法：设计、合成和评估了一系列新型混合物，使用SRB方法对肺癌SKLu-1和乳腺癌MCF-7两种人类癌细胞系的细胞毒性进行了评估。 结果：青蒿素与喹唑啉酮的十三个混合物对测试的两种癌细胞系都表现出细胞毒性，其中13d化合物对SKLu-1和MCF-7细胞系表现出最强的细胞毒性，IC50值分别为1.62和0.77μM。 结论：研究结果表明，一些化合物可以被视为未来混合物设计的引导物，并在抗癌药物开发领域进行进一步研究。
• Quinazolino linked 4β-amidopodophyllotoxin conjugates regulate angiogenic pathway and control breast cancer cell proliferation
  作者：Ahmed Kamal、Jaki R. Tamboli、M. Janaki Ramaiah、S.F. Adil、S.N.C.V.L. Pushpavalli、Raksha Ganesh、Pranjal Sarma、Utpal Bhadra、Manika Pal-Bhadra

  DOI：10.1016/j.bmc.2013.08.051

  日期：2013.11

  A series of new conjugates of quinazolino linked 4 beta-amidopodophyllotoxins 10aa-af and 10ba-bf were synthesized and evaluated for their anticancer activity against human pancreatic carcinoma (Panc-1) as well as breast cancer cell lines such as MCF-7 and MDA-MB-231 by employing MTT assay. Among these conjugates, some of them like 10bc, 10bd, 10be and 10bf exhibited high potency of cytotoxicity. Flow cytometric analysis showed that these conjugates arrested the cell cycle in the G2/M phase and caused the increase in expression of p53 and cyclin B1 protein with concomitant decrease in Cdk1 thereby suggesting the inhibitory action of these conjugates on mitosis. Interestingly, we observed a decrease in expression of proteins that control the tumor micro environment such as VEGF-A, STAT-3, ERK1/2, ERK-p, AKT-1 ser 473 phosphorylation in compounds treated breast cancer cells. Further, these effective conjugates have exhibited inhibitory action on integrin (alpha V beta III). Furthermore, the MCF-7 cells that were arrested and lost the proliferative capacity undergo mitochondrial mediated apoptosis by activation of caspases-9. Thus these conjugates have the potential to control breast cancer cell growth by effecting tumor angiogenesis and invasion. (C) 2013 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Activity Evaluation of Novel AZT and Adenosine-Derived 1,2,3-Triazoles
  作者：Duc Anh Le、Ngoc Hung Truong、Van Dung Vu、Thanh Huyen Doan、Minh Tri Le、Thi Huong Nguyen、Manh Cuong Nguyen、Huu Nghi Do、Duc Bao Ninh、Phong Le、Thi Phuong Thao Nguyen、Khac Vu Tran、Van Chinh Luu

  DOI：10.1155/2023/1605316

  日期：2023.9.28

  CuSO4/hydrazine hydrate was used as a catalyst system for copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) of AZT and 5′-azido adenosine with terminal alkynes to give 30 novel 1,2,3-triazole derivatives. Screening for their anticancer, anti-inflammatory, angiotensin-converting enzyme 2 (ACE2), and 3C-like protease (3CLpro) inhibitory activities showed that several triazoles of AZT containing murayafoline A and indirubin-3′-oxime inhibited the growth of HepG2 and LU-1 with the IC50 values ranging from 11.01 to 19.87 μg/mL. Besides that, some triazole derivatives of adenosine exhibited anti-inflammatory activity against RAW264.7 cells with the IC50 values within an interval of 12.00–59.48.00 μg/mL. Especially, two triazoles of adenosine with indirubin-3′-oxime at O- and N1 positions expressed the ACE2 and 3CLpro inhibitory activities in which the triazole of adenosine with indirubin-3′-oxime at N1 inhibited both ACE2 and 3CLpro inhibitory activities with IC50 values of 135.62 and 142.95 μg/mL, respectively.

  以 CuSO4/hydrazine hydrate 为催化剂体系，铜（I）催化了 AZT 和 5′-叠氮腺苷与末端炔烃的炔烃-叠氮环加成反应（CuAAC），得到了 30 种新型 1,2,3- 三唑衍生物。对这些衍生物的抗癌、抗炎、血管紧张素转换酶 2（ACE2）和 3C 样蛋白酶（3CLpro）抑制活性的筛选表明，含有 murayafoline A 和 indirubin-3′-oxime 的 AZT 的几种三唑类衍生物可抑制 HepG2 和 LU-1 的生长，其 IC50 值在 11.01 到 19.87 μg/mL 之间。此外，腺苷的一些三唑衍生物对 RAW264.7 细胞具有抗炎活性，IC50 值在 12.00-59.48.00 μg/mL 之间。特别是腺苷的两个三唑类衍生物，在 O 位和 N1 位上含有靛红-3′-肟，具有抑制 ACE2 和 3CLpro 的活性，其中在 N1 位上含有靛红-3′-肟的腺苷三唑类衍生物同时具有抑制 ACE2 和 3CLpro 的活性，IC50 值分别为 135.62 和 142.95 μg/mL。