PCM-0102255

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: PCM-0102255
• 英文别名: Ethyl 4-[(chloroacetyl)amino]piperidine-1-carboxylate；ethyl 4-[(2-chloroacetyl)amino]piperidine-1-carboxylate
• 化学式: C₁₀H₁₇ClN₂O₃
• mdl: MFCD07838315
• 分子量: 248.71
• InChiKey: QHXPNDBRFVFWIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  PCM-0102255 、 4-[2-thioxo-1,2,3,4-tetrahydroquinazolin-4-on-3-yl]benzenesulfonamide 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 12.0h， 以75%的产率得到ethyl 4-(2-[(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydroquinazolin-2-yl)thio] acetamido)piperidine-1-carboxylate
  参考文献：
  名称：

  Antioxidant activity of novel quinazolinones bearing sulfonamide: Potential radiomodulatory effects on liver tissues via NF-κB/ PON1 pathway

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2020.112333

文献信息

• Dual EGFR/HER2 inhibitors and apoptosis inducers: New benzo[g]quinazoline derivatives bearing benzenesulfonamide as anticancer and radiosensitizers
  作者：Mostafa M. Ghorab、Mansour S. Alsaid、Aiten M. Soliman

  DOI：10.1016/j.bioorg.2018.07.015

  日期：2018.10

  Dual targeting of EGFR and HER2 is a proven anticancer strategy for the treatment of solid tumors. An array of new N-substituted-2-(4-oxo-3-(4-sulfamoylphenyl)-3,4-dihydrobenzo[g]quinazolin-2-ylthio) acetamides 5–18 were designed and synthesized from the starting compound 4-(2-mercapto-4-oxobenzo[g]quinazolin-3(4H)-yl) benzenesulfonamide 4. The targeted compounds were screened for their cytotoxic activity

  EGFR和HER2的双重靶向是一种公认​​的治疗实体瘤的抗癌策略。的新的数组Ñ取代的-2-（4-氧代-3-（4-氨磺酰苯基）-3,4-二氢苯并[克]喹唑啉-2-基硫基）乙酰胺5 - 18设计并从起始化合物4合成-（2-巯基-4-氧代苯并[ g ]喹唑啉-3（4 H）-基）苯磺酰胺4。筛选目标化合物对MDA-MB-231乳腺癌细胞系的细胞毒活性。IC 50所有化合物的含量范围为0.36–40.90 µM。测量对EGFR的抑制百分比，发现在63.00–16.90％的范围内。最有效的化合物5，9，15，17和18进一步筛选它们对EGFR和HER2两者受体的活性。与参考药物埃洛替尼相比，该化合物对EGFR的IC 50范围为0.64–1.81 µM，对HER2的IC 50范围为1.13–2.21 µM。在该系列中对EGFR最有效的化合物17经历了细胞周期分析，并发现其在G2 / M期停滞。化合物17
• 10.1016/j.molstruc.2024.139060
  作者：Ghorab, Walid M.、Ghorab, Mostafa M.

  DOI：10.1016/j.molstruc.2024.139060

  日期：——

  Two novel sets of quinazoline-thioacetamides – and quinazoline-thioacetamides constituting sulfonamide tail (, were synthesized as anti-proliferative agents targeting cancer through VEGFR-2 inhibition. The cytotoxicity of the newly constructed candidates was evaluated against MCF-7 cell line. Ten compounds and (IC range= 36.41–76.05 µM) displayed better cytotoxic activity comparable to Doxorubicin

  合成了两组新型喹唑啉-硫代乙酰胺和构成磺酰胺尾的喹唑啉-硫代乙酰胺，作为通过抑制 VEGFR-2 靶向癌症的抗增殖剂。针对 MCF-7 细胞系评估了新构建的候选物的细胞毒性。十种化合物(IC50范围 = 36.41–76.05 µM) 与多柔比星 (IC50 = 32.02 µM) 相比，显示出更好的细胞毒活性，并且显示出有希望的生物活性，并被选择进行 VEGFR-2 抑制活性测试，并显示 IC 值为 0.176 和 0.618 µg。分别与索拉非尼的 IC 0.042 μg 相比。此外， 、 、 、 、 、 、 、 、 、 、 、 分别接受γ射线剂量（8 Gy）照射，其细胞毒性在照射后增强，验证了化合物 、 的增强作用。作为该系列的一个有影响力的证明，通过检查对 caspase-3 的影响来估计细胞凋亡诱导剂的影响，观察到与阳性相比，诱导其水平的化合物提高了 Bax 水平并降低了 BCl2
• Computational, in vitro and radiation-based in vivo studies on acetamide quinazolinone derivatives as new proposed purine nucleoside phosphorylase inhibitors for breast cancer
  作者：Mostafa G.M. El-Gazzar、Mostafa M. Ghorab、Mohamed A. Amin、Mohamed Korany、Mohammed A. Khedr、Marwa G. El-Gazzar、Tamer M. sakr

  DOI：10.1016/j.ejmech.2023.115087

  日期：2023.2
• 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.