2-(6-methyl-4-oxo-3-phenyl-3,4-dihydro-quinazolin-2-ylthio)acetohydrazide | 211562-86-6

• 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-methyl-4-oxo-3-phenyl-3,4-dihydro-quinazolin-2-ylthio)acetohydrazide
• 英文别名: 2-(6-Methyl-4-oxo-3-phenylquinazolin-2-yl)sulfanylacetohydrazide
• CAS: 211562-86-6
• 化学式: C₁₇H₁₆N₄O₂S
• 分子量: 340.406
• InChiKey: QUPMSTJLWONIOS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 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：

  5-氟靛红 、 2-(6-methyl-4-oxo-3-phenyl-3,4-dihydro-quinazolin-2-ylthio)acetohydrazide 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以84%的产率得到N'-(5-fluoro-2-oxoindolin-3-ylidene)-2-((6-methyl-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetohydrazide
  参考文献：
  名称：

  Synthesis and primary cytotoxicity evaluation of 3-[[(3-phenyl-4(3H)-quinazolinone-2-yl)mercaptoacetyl]hydrazono]-1H-2-indolinones

  摘要：

  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.

  DOI：

  10.1016/s0223-5234(03)00085-0
• 作为产物：
  描述：

  2-氨基-5-甲基苯甲酸 在 hydrazine hydrate 、 potassium carbonate 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 2-(6-methyl-4-oxo-3-phenyl-3,4-dihydro-quinazolin-2-ylthio)acetohydrazide
  参考文献：
  名称：

  一些新的6-甲基-3-苯基-4（3H）-喹唑啉酮类似物的合成，抗肿瘤和抗菌活性：计算机研究。

  摘要：

  合成了一些新的取代的4（3H）-喹唑啉酮衍生物，并对其体外抗肿瘤和抗菌活性进行了评估。这项研究的结果表明，化合物5对NSC肺癌EKVX细胞系，结肠癌HCT-15细胞系和乳腺癌MDA-MB-231 / ATCC细胞系具有选择性活性，而NSC肺癌EKVX细胞系和CNS癌症具有选择性活性。 SF-295细胞系对化合物8敏感。此外，化合物12和13对多种属于不同肿瘤亚组的细胞系显示出中等效力。另一方面，抗菌素筛选的结果显示，化合物1、9和14对金黄色葡萄球菌ATCC 29213的活性最高，最小抑菌浓度（MIC）分别为16、32和32μg/ mL，与其他被测化合物相比，化合物14具有对所有被测菌株具有最低MIC的抗菌活性。在计算机研究中，ADME-Tox预测和分子对接方法用于研究抗肿瘤活性并确定抗肿瘤活性所需的结构特征。

  DOI：

  10.3109/14756366.2015.1060482

文献信息

• Synthesis, antitumor and antimicrobial activity of some new 6-methyl-3-phenyl-4(3<i>H</i>)-quinazolinone analogues: <i>in silico</i> studies
  作者：Amer M. Alanazi、Alaa A.-M. Abdel-Aziz、Taghreed Z. Shawer、Rezk R. Ayyad、Abdulrahman M. Al-Obaid、Mohamed H. M. Al-Agamy、Azza R. Maarouf、Adel S. El-Azab

  DOI：10.3109/14756366.2015.1060482

  日期：2016.9.2

  Some new derivatives of substituted-4(3H)-quinazolinones were synthesized and evaluated for their in vitro antitumor and antimicrobial activities. The results of this study demonstrated that compound 5 yielded selective activities toward NSC Lung Cancer EKVX cell line, Colon Cancer HCT-15 cell line and Breast Cancer MDA-MB-231/ATCC cell line, while NSC Lung Cancer EKVX cell line and CNS Cancer SF-295

  合成了一些新的取代的4（3H）-喹唑啉酮衍生物，并对其体外抗肿瘤和抗菌活性进行了评估。这项研究的结果表明，化合物5对NSC肺癌EKVX细胞系，结肠癌HCT-15细胞系和乳腺癌MDA-MB-231 / ATCC细胞系具有选择性活性，而NSC肺癌EKVX细胞系和CNS癌症具有选择性活性。 SF-295细胞系对化合物8敏感。此外，化合物12和13对多种属于不同肿瘤亚组的细胞系显示出中等效力。另一方面，抗菌素筛选的结果显示，化合物1、9和14对金黄色葡萄球菌ATCC 29213的活性最高，最小抑菌浓度（MIC）分别为16、32和32μg/ mL，与其他被测化合物相比，化合物14具有对所有被测菌株具有最低MIC的抗菌活性。在计算机研究中，ADME-Tox预测和分子对接方法用于研究抗肿瘤活性并确定抗肿瘤活性所需的结构特征。
• 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.
• Novel 4(3H)-quinazolinone analogs: synthesis and anticonvulsant activity
  作者：Adel S. El-Azab、Sami G. Abdel-Hamide、Mohamed M. Sayed-Ahmed、Ghada S. Hassan、Tariq M. El-Hadiyah、Othman A. Al-Shabanah、Omar A. Al-Deeb、Hussein I. El-Subbagh

  DOI：10.1007/s00044-012-0280-y

  日期：2013.6

  A new series of quinazoline analogs was designed, synthesized, and evaluated for their anticonvulsant activity. Compounds 6, 12, 21, 36, 37, and 38 showed 70-100 % protection against PTZ-induced seizures acting as GABA(A) receptor agonists. Compound N-(3,4,5,6-tetrachloro-phthalimido)-2-[(3-phenyl-4-oxo-6-methyl-3H-quinazolin-2-yl)-thio]acetamide (12) representing the moderate active compounds and 2-[6-iodo-4-oxo-2-(thiophen-2-yl)-quinazolin-3(4H)-yl]-isoindoline-1,3-dione (38) representing the remarkably active compounds in this stud, showed ED50 values of 457 and 251 mg/kg; TD50 values of 562 and 447 mg/kg; PI values of 1.22 and 1.78, LD50 values of 1,288 and 1,380 mg/kg, and TI values of 2.82 and 5.50, respectively. Compound 38 proved to be almost twofold more active than the standard drug sodium valproate.
• Synthesis, anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies
  作者：Adel S. El-Azab、Abdullah Al-Dhfyan、Alaa A.-M. Abdel-Aziz、Laila A. Abou-Zeid、Hamad M. Alkahtani、Abdulrahman M. Al-Obaid、Manal A. Al-Gendy

  DOI：10.1080/14756366.2017.1344981

  日期：2017.1.1

  A new series of quinazolinone compounds 16-34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC50: 10.38-38.67 mu M and 9.91-15.77 mu M, respectively); the comparative IC50 values for 5-fluorouracil and erlotinib in these cells lines were 70.28 mu M, 22.24 mu M and 15.23 mu M, 25.31 mu M respectively. The EGFR-TK assay and induction of apoptosis for compound 31 were investigated to assess its potential cytotoxic activity as a representative example of the novel synthesized compounds. At a concentration of 10 mu M, compound 31 exhibited efficient inhibitory effect against EGFR-TK and induced apoptosis in MDA-MB-231 cells. Furthermore, a molecular docking study for compound 31 and erlotinib was performed to verify the binding mode toward the EGFR kinase enzyme, and showed a similar interaction as that with erlotinib alone.