2-((6-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide | 174869-10-4

• 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-((6-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide
• 英文别名: 2-(6-Chloro-4-oxo-3-phenylquinazolin-2-yl)sulfanylacetohydrazide；2-(6-chloro-4-oxo-3-phenylquinazolin-2-yl)sulfanylacetohydrazide
• CAS: 174869-10-4
• 化学式: C₁₆H₁₃ClN₄O₂S
• 分子量: 360.824
• InChiKey: HHQOICNYNUKKQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((6-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide 在 sodium acetate 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Gursoy; Karali, Il Farmaco, 1995, vol. 50, # 12, p. 857 - 866

  摘要：

  DOI：
• 作为产物：
  描述：

  2-氨基-5-氯苯甲酸 在 hydrazine hydrate 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 2-((6-chloro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide
  参考文献：
  名称：

  作为 VEGFR-2 抑制剂和凋亡诱导剂的新型喹唑啉衍生物的设计、合成和抗癌活性

  摘要：

  摘要 已经合成了一系列新的硫脲或硫代乙酰胺连接的喹唑啉衍生物，并测试了对 HCT116 和 MCF-7 细胞系的细胞毒性。化合物10b对结肠HCT-116和MCF-7细胞系均表现出强抗增殖作用。化合物10b在 G2/M 期中断 HCT-116 细胞周期。根据DNA流式细胞仪和膜联蛋白测试，杂种10b还能够诱导HCT-116细胞的细胞周期中断和凋亡。它通过激活 caspase-3、增加促凋亡 Bax 和 p53 水平以及降低 Bcl-2 蛋白水平来引起细胞凋亡。因此，新型衍生物10b可被视为抗肿瘤药物开发的有希望的线索。

  DOI：

  10.1134/s107036322210019x

文献信息

• Synthesis, anticonvulsant activity and molecular modeling study of some new hydrazinecarbothioamide, benzenesulfonohydrazide, and phenacylacetohydrazide analogues of 4(3H)-quinazolinone
  作者：Huda S.A. Al-Salem、Gehan H. Hegazy、Kamal E.H. El-Taher、Shahenda M. El-Messery、Abdulrahman M. Al-Obaid、Hussein I. El-Subbagh

  DOI：10.1016/j.bmcl.2015.02.025

  日期：2015.4

  A new series of quinazoline analogues was designed and synthesized to get the target compounds 18–21, 30–41, 46–53, and 57–76. The Obtained compounds were evaluated for their anticonvulsant activity using PTZ and picrotoxin convulsive models. Compounds 47, 63, 68 and 73 proved to be the most active compounds in this study with a remarkable 100% protection against PTZ induced convulsions. Compounds

  一系列新的喹唑啉类似物的设计和合成，以获得目标化合物18 - 21，30 - 41，46 - 53，和57 - 76。使用PTZ和微毒素惊厥模型评估获得的化合物的抗惊厥活性。化合物47，63，68和73被证明是在本研究中最活跃的化合物与对PTZ诱发的惊厥的显着100％的保护。化合物47，63，68和73经证实，它们的活性分别是所用的阳性对照丙戊酸钠的10倍，4倍，4倍和5倍。结构活性相关性得出了有价值的药效学信息，这些信息已通过分子建模研究得到证实。68的分子对接研究表明其对GABA A受体的激动作用。研究的喹唑啉类似物可以被认为是未来开发和进一步衍生化的有用模板。
• New cyclohexylidenehydrazide and 4-aza-1-thiaspiro[4.5]decan-3-one derivatives of 3-phenyl-4(3H)-quinazolinones
  作者：Nilgün Karali、Eser İllhan、Aysel Gürsoy、Muammer Kiraz

  DOI：10.1016/s0014-827x(98)00032-9

  日期：1998.5

  In this study, the synthesis of (3-phenyl-4(3H) -quinazolinon-2-yl) mercaptoacetic acid cyclohexylidenehydrazides and 4-[(3-phenyl-4(3H) -quinazolinon-2-yl) mercaptoacetylamino] -4-aza-1-thiaspiro [4.5] decan-3-ones and the results of the study on their antifungal activity are reported. Most of the tested compounds were found to be active against Microsporum gypseum NCPF-580, Microsporum canis, Tricophyton mentagrophytes NCPF-375 var. erinacei and Tricophyton rubrum at 25 mu g/ml. (C) 1998 Elsevier Science S.A. All rights reserved.
• Synthesis and primary cytotoxicity evaluation of 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones
  作者：A Gürsoy

  DOI：10.1016/s0223-5234(03)00085-0

  日期：2003.6

  New esters (2b and 2c) and hydrazides (3b and 3c) were synthesized from 6-methyl/fluoro-3-phenyl-4(1H, 3H)-quinazolinone-2-thiones (1b and 1c). Subsequent treatment of 3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetic acid hydrazides (3a-e) with 1H- indole-2,3-diones (4a-e) furnished the corresponding 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones (5a-u). The structures of new compounds were determined by analytical and spectral (IR, H-1-NMR, C-13-NMR, EIMS) methods. Previously reported 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-bromo-1H-2-indolinone 5v and compounds 5b, 5d and 5o chosen as prototypes were evaluated against the full panel of 60 human tumour cell lines at a minimum of five concentrations at tenfold dilutions in the National Cancer Institute in vitro primary cytotoxicity assay. Sulforhodamine B protein assay was used to estimate cell stability or growth. 3-[[(6-Chloro-3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-5-fluoro-1H-2-indolinone 5o showed the most favourable cytotoxicity against a renal cancer cell line UO-31 (log(10) GI(50) value -6.68). Compound 5v was also tested against human immunodeficiency virus 1 (HIV-1). Compound 5v was confirmed moderately active against HIV-1. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
• Design, Synthesis, Anticancer Activity, and Cell Cycle Analysis of Novel Quinazoline Derivatives Targeting VEGFR-2 Kinase
  作者：Marwa F. Ahmed、Amany S. Khalifa、Emad M. Eed

  DOI：10.1134/s1070363221120203

  日期：2021.12
• Quinazolin-4(3<i>H</i>)-one based potential multiple tyrosine kinase inhibitors with excellent cytotoxicity
  作者：Tebyan O. Mirgany、Ashraf N. Abdalla、Md Arifuzzaman、A. F. M. Motiur Rahman、Huda S. Al-Salem

  DOI：10.1080/14756366.2021.1972992

  日期：2021.1.1

  A series of quinazolin-4(3H)-one derivatives were synthesised and evaluated for their cytotoxicity against human Caucasian breast adenocarcinoma (MCF-7) and human ovarian carcinoma (A2780) cell lines. Cytotoxicity of the most tested compounds was 2- to 30-fold more than the positive control lapatinib (IC50 of 2j = 3.79 ± 0.96; 3j = 0.20 ± 0.02; and lapatinib = 5.9 ± 0.74) against MCF7 cell lines except two compounds (IC50 of 2 b = 15.72 ± 0.07 and 2e = 14.88 ± 0.99). On the other hand, cytotoxicity was 4 - 87 folds (IC50 of 3a = 3.00 ± 1.20; 3 g = 0.14 ± 0.03) more the positive control lapatinib (IC50 = 12.11 ± 1.03) against A2780 cell lines except compound 2e (IC50 = 16.43 ± 1.80). Among the synthesised quinazolin-4(3H)-one derivatives, potent cytotoxic 2f-j and 3f-j were investigated for molecular mechanism of action. Inhibitory activities of the compounds were tested against multiple tyrosine protein kinases (CDK2, HER2, EGFR and VEGFR2) enzymes. As expected, all the quinazolin-4(3H)-one derivatives were showed comparable inhibitory activity against those kinases tested, especially, compound 2i and 3i showed potent inhibitory activity against CDK2, HER2, EGFR tyrosine kinases. Therefore, molecular docking analysis for quinazolin-4(3H)-one derivatives 2i and 3i were performed, and it was revealed that compounds 2i and 3i act as ATP non-competitive type-II inhibitor against CDK2 kinase enzymes and ATP competitive type-I inhibitor against EGFR kinase enzymes. However, in case of HER2, compounds 2i act as ATP non-competitive type-II inhibitor and 3i act as ATP competitive type-I inhibitor. Docking results of known inhibitors were compared with synthesised compounds and found synthesised 2i and 3i are superior than the known inhibitors in case of interactions. In addition, in silico drug likeness properties of quinazolin-4(3H)-one derivatives showed better predicted ADME values than lapatinib.