N-(4-氟-3-硝基苯基)马来酰亚胺 | 67154-40-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 中文名称: N-(4-氟-3-硝基苯基)马来酰亚胺
• 英文名称: 1-(4-fluoro-3-nitrophenyl)-1H-pyrrole-2,5-dione
• 英文别名: 1-(4-fluoro-3-nitrophenyl)pyrrole-2,5-dione
• CAS: 67154-40-9
• 化学式: C₁₀H₅FN₂O₄
• 分子量: 236.159
• InChiKey: FPNVMFULBBEITM-UHFFFAOYSA-N

物化性质

• 熔点：
  127-128
• 沸点：
  424.6±35.0 °C(Predicted)
• 密度：
  1.614±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83.2
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2925190090

反应信息

• 作为反应物：
  描述：

  N-(4-氟-3-硝基苯基)马来酰亚胺 在 铁粉 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 1-(4-(3-amino-6-phenylisoxazolo[3,4-b]pyridine-4-yl)phenyl)-3-(5-(2,5-dioxo-2H-pyrrol-1(5H)-yl)-2-fluorophenyl)urea
  参考文献：
  名称：

  Discovery of 4‐(4‐aminophenyl)‐6‐phenylisoxazolo[3,4‐ b ]pyridine‐3‐amine derivatives as novel FLT3 covalent inhibitors for the intervention of acute myeloid leukemia

  摘要：

  AbstractSmall molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4‐(4‐aminophenyl)‐6‐phenylisoxazolo[3,4‐b]pyridine‐3‐amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3‐internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 μM. Besides, F15 exhibited potent activity against FLT3‐dependent human acute myeloid leukemia (AML) cell lines MOLM‐13 (IC50 = 253 nM) and MV4‐11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.

  DOI：

  10.1002/ddr.22032
• 作为产物：
  描述：

  4-氟-3-硝基苯胺 在 sodium acetate 、 乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 N-(4-氟-3-硝基苯基)马来酰亚胺
  参考文献：
  名称：

  Potent Nematicidal Activity of Maleimide Derivatives on Meloidogyne incognita

  摘要：

  Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N-isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC50/72h values of 2.6 +/- 1.3, 5.1 +/- 3.4, 16.2 +/- 5.4, and 19.0 +/- 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC50 value of 48.6 +/- 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at SO mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts.

  DOI：

  10.1021/acs.jafc.6b02250

文献信息

• Potent Nematicidal Activity of Maleimide Derivatives on <i>Meloidogyne incognita</i>
  作者：Kodjo Eloh、Monica Demurtas、Manuel Giacomo Mura、Alessandro Deplano、Valentina Onnis、Nicola Sasanelli、Andrea Maxia、Pierluigi Caboni

  DOI：10.1021/acs.jafc.6b02250

  日期：2016.6.22

  Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N-isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC50/72h values of 2.6 +/- 1.3, 5.1 +/- 3.4, 16.2 +/- 5.4, and 19.0 +/- 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC50 value of 48.6 +/- 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at SO mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts.
• Discovery of 4‐(4‐aminophenyl)‐6‐phenylisoxazolo[3,4‐ <i>b</i> ]pyridine‐3‐amine derivatives as novel FLT3 covalent inhibitors for the intervention of acute myeloid leukemia
  作者：Qing‐Xin Wang、Yi‐Bo Wang、Jiu‐Kai Sha、Hai Zhou、Jia‐Chuan Liu、Jia‐Zhen Wu、Zhen‐Jiang Tong、Jiao Cai、Zi‐Jun Chen、Chen‐Qian Zhang、Xin‐Rui Zheng、Jing‐Jing Wang、Xiao‐Long Wang、Xin Xue、Yan‐Cheng Yu、Ning Ding、Xue‐Jiao Leng、Wei‐Chen Dai、Shan‐Liang Sun、Liang Chang、Nian‐Guang Li、Zhi‐Hao Shi

  DOI：10.1002/ddr.22032

  日期：——

  AbstractSmall molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4‐(4‐aminophenyl)‐6‐phenylisoxazolo[3,4‐b]pyridine‐3‐amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3‐internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 μM. Besides, F15 exhibited potent activity against FLT3‐dependent human acute myeloid leukemia (AML) cell lines MOLM‐13 (IC50 = 253 nM) and MV4‐11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML.