1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)naphthalen-1-yl)-3-(5-methylisoxazol-3-yl)urea

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)naphthalen-1-yl)-3-(5-methylisoxazol-3-yl)urea
• 英文别名: 1-[4-(6,7-Dimethoxyquinazolin-4-yl)oxynaphthalen-1-yl]-3-(5-methyl-1,2-oxazol-3-yl)urea；1-[4-(6,7-dimethoxyquinazolin-4-yl)oxynaphthalen-1-yl]-3-(5-methyl-1,2-oxazol-3-yl)urea
• 化学式: C₂₅H₂₁N₅O₅
• 分子量: 471.472
• InChiKey: UNIUFCSHAQZREL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-硝基-1-萘酚 在 铁粉 、 sodium hydride 、 氯化铵 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 、 mineral oil 为溶剂， 反应 55.5h， 生成 1-(4-((6,7-dimethoxyquinazolin-4-yl)oxy)naphthalen-1-yl)-3-(5-methylisoxazol-3-yl)urea
  参考文献：
  名称：

  Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant Antiproliferative Activity against Cancer Cell Lines

  摘要：

  Computational and experimental studies were applied to the discovery of a series of novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. Eight compounds exhibited nanomolar IC50 values against VEGFR-2, and compounds 6, 19, 22, and 23 showed potent antiproliferative effects against several cell lines. Particularly, compound 23 behaved better than FDA approved drugs, sorafenib and sunitinib, in antiproliferative activity against cell lines related to all nine tumor types tested (GI(50) values), and it was better or comparable in safety (LC50 values). Compound 23 even demonstrated a high potency on one of the drug-resistant cell lines (NCl/ADR-RES) responsible for ovarian cancer and cell lines contributing to prostate cancer, regarded as one of the VEGF/VEGFR pathway drug-resistant tumors. This compound is likely a promising candidate for the treatment of leukemia, non-small cell lung cancer (NSCLC), colon cancer, ovarian cancer, and breast cancer with a suitable balance of both efficacy and safety.

  DOI：

  10.1021/acs.jmedchem.7b01091

文献信息

• Discovery of Novel Potent VEGFR-2 Inhibitors Exerting Significant Antiproliferative Activity against Cancer Cell Lines
  作者：Yanmin Zhang、Yadong Chen、Danfeng Zhang、Lu Wang、Tao Lu、Yu Jiao

  DOI：10.1021/acs.jmedchem.7b01091

  日期：2018.1.11

  Computational and experimental studies were applied to the discovery of a series of novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitors. Eight compounds exhibited nanomolar IC50 values against VEGFR-2, and compounds 6, 19, 22, and 23 showed potent antiproliferative effects against several cell lines. Particularly, compound 23 behaved better than FDA approved drugs, sorafenib and sunitinib, in antiproliferative activity against cell lines related to all nine tumor types tested (GI(50) values), and it was better or comparable in safety (LC50 values). Compound 23 even demonstrated a high potency on one of the drug-resistant cell lines (NCl/ADR-RES) responsible for ovarian cancer and cell lines contributing to prostate cancer, regarded as one of the VEGF/VEGFR pathway drug-resistant tumors. This compound is likely a promising candidate for the treatment of leukemia, non-small cell lung cancer (NSCLC), colon cancer, ovarian cancer, and breast cancer with a suitable balance of both efficacy and safety.