2-chloro-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide | 98142-25-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-chloro-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide
• 英文别名: 5-(chloroacetylamino)uracil；chloro-acetic acid-(2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylamide)；Chlor-essigsaeure-(2,4-dioxo-1,2,3,4-tetrahydro-pyrimidin-5-ylamid)；2-chloro-N-(2,4-dioxo-1H-pyrimidin-5-yl)acetamide
• CAS: 98142-25-7
• 化学式: C₆H₆ClN₃O₃
• mdl: MFCD01797525
• 分子量: 203.585
• InChiKey: HPHUJFLDBKOWSX-UHFFFAOYSA-N

物化性质

• 密度：
  1.57±0.1 g/cm3(Predicted)
• 溶解度：
  >30.5 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  87.3
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide 在 ammonium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 以81%的产率得到5-(aminoacetylamino)uracil
  参考文献：
  名称：

  修饰的嘧啶碱基的合成以及化学反应性取代基对其体外抗增殖活性的积极影响

  摘要：

  一系列修饰的尿嘧啶和胞嘧啶碱基以及一些相应的无环核苷在人肿瘤细胞系中的抗增殖活性筛选，以及结构-活性关系的比较表明，尿嘧啶C5位上取代基的化学反应活性对于研究化合物的活性。即，对于活性最高的化合物5-（氯乙酰氨基）尿嘧啶（2）及其无环糖类似物18所获得的结果表明，反应性取代基与胸苷酸合酶机制内若干可能的靶标之间形成了共价键（半胱氨酸残基，酶的基本部分，N，N-亚甲基四氢叶酸或其反应性亚胺形式）是最可能的作用方式。另外，新型的C 5-取代的尿嘧啶衍生物6（5- [双-（2-对-甲氧基苄基硫乙基）胺]乙酰氨基尿嘧啶）通过未知的机制对HeLa和MiaPaCa-2细胞系表现出高的抗增殖活性。

  DOI：

  10.1016/j.ejmech.2008.06.002
• 作为产物：
  描述：

  5-氨基尿嘧啶 、 氯乙酰氯 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 2.0h， 以62%的产率得到2-chloro-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide
  参考文献：
  名称：

  修饰的嘧啶碱基的合成以及化学反应性取代基对其体外抗增殖活性的积极影响

  摘要：

  一系列修饰的尿嘧啶和胞嘧啶碱基以及一些相应的无环核苷在人肿瘤细胞系中的抗增殖活性筛选，以及结构-活性关系的比较表明，尿嘧啶C5位上取代基的化学反应活性对于研究化合物的活性。即，对于活性最高的化合物5-（氯乙酰氨基）尿嘧啶（2）及其无环糖类似物18所获得的结果表明，反应性取代基与胸苷酸合酶机制内若干可能的靶标之间形成了共价键（半胱氨酸残基，酶的基本部分，N，N-亚甲基四氢叶酸或其反应性亚胺形式）是最可能的作用方式。另外，新型的C 5-取代的尿嘧啶衍生物6（5- [双-（2-对-甲氧基苄基硫乙基）胺]乙酰氨基尿嘧啶）通过未知的机制对HeLa和MiaPaCa-2细胞系表现出高的抗增殖活性。

  DOI：

  10.1016/j.ejmech.2008.06.002

文献信息

• Design, synthesis and molecular modeling study of certain quinazolinone derivatives targeting poly (ADP-ribose) polymerase 1 (PARP-1) enzyme as anti-breast cancer and radio-sensitizers
  作者：Walid M. Ghorab、Samiha A. El-Sebaey、Mostafa M. Ghorab

  DOI：10.1016/j.molstruc.2022.134358

  日期：2023.2

  06 µM). Additionally, the capability of γ-radiation to augment the in vitro cytotoxic activity of 10 and 15 was studied and exhibited an increase in the cell-killing effect at lower concentrations after combining with γ-radiation. A molecular modeling study was performed to investigate the possible binding mode of compounds 10 and 15 in the active site of the PARP-1 enzyme.

  设计并合成了两个系列的新型S-烷基化喹唑啉酮4-10和N-烷基化喹唑啉酮11-17作为潜在的 PARP-1 抑制剂。喹唑啉酮支架被用作奥拉帕尼（参考药物）酞嗪酮核心的生物等排体。评估了所有新合成的化合物对人乳腺癌 MCF-7 细胞系的体外细胞毒性。活性最强的化合物10和15分别具有 11.4 µM 和 10.6 µM 的 IC 50值，分别是多柔比星 (IC 50 32.02 µM) 的 2.8 倍和 3 倍，测试了 PARP-1 抑制活性并显示 IC与奥拉帕尼 (IC 50 0.06 µM)相比， 50分别为 0.17 µM 和 0.14 µM 。此外，研究了 γ 射线增强10和15的体外细胞毒活性的能力，并在与 γ 射线结合后在较低浓度下表现出细胞杀伤作用的增加。进行分子建模研究以研究化合物10和15在 PARP-1 酶的活性位点中可能的结合模式。
• Antioxidant activity of novel quinazolinones bearing sulfonamide: Potential radiomodulatory effects on liver tissues via NF-κB/ PON1 pathway
  作者：Aiten M. Soliman、Heba M. Karam、Mai H. Mekkawy、Mostafa M. Ghorab

  DOI：10.1016/j.ejmech.2020.112333

  日期：2020.7

  In order to discover new antioxidants, fifteen novel quinazolinone derivatives bearing benzenesulfonamide moiety with variable heterocyclic tail, were synthesized and their structures were established on the basis of spectral data. All the synthesized compounds were screened for their antioxidant potential using DPPH assay in comparison to ascorbic acid. The N-(pyrazin-2-yl)-2-[(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-yl)thio]acetamide 16 was the most active scaffold in this series with greater scavenging activity than that of ascorbic acid. In vivo acute toxicity study of compound 16 indicates its relative safety with a median lethal dose of 200 mg/kg. The possible antioxidant and hepatoprotective activities of compound 16 were evaluated in irradiated mice. Compound 16 caused mitigation of gamma radiation-induced oxidative stress verified by the decline in MDA, ROS and NF-kappa B levels. Moreover, SOD and PON1 activities, as well as Zn2+ levels, were improved in liver tissues. Furthermore, molecular docking of compound 16 inside the active site of SOD and PON1 demonstrated the same binding interactions as that of the co-crystallized ligands considering the binding possibilities and energy scores. These findings support that compound 16 may represent a structural lead for developing new antioxidants and hepatoprotective agents. (C) 2020 Elsevier Masson SAS. All rights reserved.
• Weng, Yaoxue Xuebao/Acta pharmaceutica Sinica, 1959, vol. 7, p. 253,255
  作者：Weng

  DOI：——

  日期：——
• US2494125
  申请人：——

  公开号：——

  公开（公告）日：——
• Novel sulfonamide benzoquinazolinones as dual EGFR/HER2 inhibitors, apoptosis inducers and radiosensitizers
  作者：Aiten M. Soliman、Ali S. Alqahtani、Mostafa M. Ghorab

  DOI：10.1080/14756366.2019.1609469

  日期：2019.1.1

  A series of sulphonamide benzoquinazolinones 5-18 was synthesized and evaluated for cytotoxic activity against MDA-MB-231 cell line. The compounds showed IC50 ranging from 0.26 to 161.49 mu M. The promising compounds were evaluated for their inhibitory profile against epidermal growth factor (EGFR) and HER2 enzymes. Compound 10 showed more potent activity on both EGFR and HER2 than erlotinib (IC50 3.90 and 5.40 mu M versus 6.21 and 9.42 mu M). The pro-apoptotic activity of 10 was evaluated against caspase-3, Bax, B-cell lymphoma protein 2 (Bcl-2) expression levels, and cell cycle analysis. Compound 10 increased the level of caspase-3 by 10 folds, Bax level by 9 folds, decreased the level of the Bcl-2 by 0.14 and arrested the cell cycle in the G2/M phase. The radio-sensitizing activity of 10 was measured using a single dose of 8 Gy gamma radiation (IC50 decreased from 0.31 to 0.22 mu M). Molecular docking was performed on EGFR and HER2 receptors.