(3-aminophenyl)-1H-pyrrole-2,5-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: (3-aminophenyl)-1H-pyrrole-2,5-dione
• 英文别名: 1-(3-Aminophenyl)pyrrole-2,5-dione
• 化学式: C₁₀H₈N₂O₂
• 分子量: 188.186
• InChiKey: TZRNBHFCAHXUFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 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：
  63.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3-aminophenyl)-1H-pyrrole-2,5-dione 在 三乙胺 作用下， 以 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-(3-(2,5-dioxo-2H-pyrrol-1(5H)-yl)phenyl)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：

  马来酸酐 以52%的产率得到
  参考文献：
  名称：

  MAKSUDOVA F.; SEJTKASYMOV ZH.; SULTANOV K. S., TASHKENT. IN-T INZH. IRRIGATSII I MEXANIZ. S. X. TASHKENT, 1977. 4 S., BI+

  摘要：

  DOI：

文献信息

• Pyrrole-2,5-dione analogs as a promising antioxidant agents: microwave-assisted synthesis, bio-evaluation, SAR analysis and DFT studies/interpretation
  作者：Guda Mallikarjuna Reddy、Alexandre Camilo、Jarem Raul Garcia

  DOI：10.1016/j.bioorg.2020.104465

  日期：2021.1

  antioxidant activity, compounds DFT studies were performed. Noteworthy results have been attained and the structure activity relationship (SAR) was discussed with the support of this results. It was found that highly biological active compounds exhibited a low HOMO-LUMO energy gap (Eg) and the high Eg value compounds show very low/negligible or inactive antioxidant activities. In other cases, compounds containing

  通过微波辐射合成开发了一系列新的吡咯类似物。因此，得到了高产率的产品。由于吡咯类具有多种生物学特性，因此对所有获得的化合物的抗氧化特性进行了筛选，大多数化合物显示出显着的活性。事实上，图案5e、5g、5h和5m表现出优异的抗氧化性能。此外，为了启发抗氧化活性背后的生物能量行为，进行了化合物 DFT 研究。已经获得了值得注意的结果，并在此结果的支持下讨论了结构活性关系 (SAR)。发现高生物活性化合物表现出低 HOMO-LUMO 能隙 (Eg)，而高 Eg 值化合物表现出非常低/可忽略或无活性的抗氧化活性。在其他情况下，含有高 HOMO 能级的化合物也提供高抗氧化活性。我们的结果发人深省的一点是，HOMO-LUMO 能隙和最高占据分子轨道能量的理论描述是生物有机研究中支持生物实验的重要描述。
• MAKSUDOVA F.; SEJTKASYMOV ZH.; SULTANOV K. S., TASHKENT. IN-T INZH. IRRIGATSII I MEXANIZ. S. X. TASHKENT, 1977. 4 S., BI+
  作者：MAKSUDOVA F.、 SEJTKASYMOV ZH.、 SULTANOV K. S.

  DOI：——

  日期：——
• METHOD OF CONJUGATING A POLYPEPTIDE
  申请人：MedImmune, LLC

  公开号：US20220160882A1

  公开（公告）日：2022-05-26

  The present disclosure relates to a method of conjugating a compound of formula (I) O 5 R1-Q (ZL-COn-X—N O (I) with a polypeptide comprising at least one thiol group and molecules obtained from said method.
• 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.