DA 3100 | 383907-48-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: DA 3100
• 英文别名: 6-Chloro-7-(indan-1-ylamino)-quinoline-5,8-dione；6-chloro-7-(2,3-dihydro-1H-inden-1-ylamino)quinoline-5,8-dione
• CAS: 383907-48-0
• 化学式: C₁₈H₁₃ClN₂O₂
• 分子量: 324.766
• InChiKey: QNVSFGNOGHOYKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  59.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  6,7-二氯-5,8-喹啉二酮 、 1-氨基茚满 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 以59%的产率得到DA 3100
  参考文献：
  名称：

  Discovery and Biological Evaluation of a New Family of Potent Inhibitors of the Dual Specificity Protein Phosphatase Cdc25

  摘要：

  The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signaling processes and cell proliferation, but potent and selective inhibitors are lacking. We experimentally examined the 1990 compound National Cancer Institute Diversity Set and then computationally selected from their 140 000 compound repository 30 quinolinediones of which 8 had in vitro mean inhibitory concentrations < 1 muM. The most potent was 6-chloro-7-(2-morpholin-4-ylethylamino)quinoline-5,8-dione (NSC 663284), which was 20- and 450-fold more selective against Cdc25B(2) as compared with VHR or PTP1B phosphatases, respectively. NSC 663284 exhibited mixed competitive kinetics against Cdc25A, Cdc25B(2), and Cdc25C with K-i values of 29, 95, and 89 nM, respectively. As compared with NSC 663284, the regioisomer 7-chloro-6-(2-morpholin-4-ylethylamino)quinoline-5,8-dione was 3-fold less active against Cdc25B(2) in vitro and less potent as a growth inhibitor of human breast cancer cells. Computational electrostatic potential mapping suggested the need for an electron-deficient 7-position for maximal inhibitor activity. Using a chemical complementation assay, we found that NSC 663284 blocked cellular Erk dephosphorylation caused by ectopic Cdc25A expression.

  DOI：

  10.1021/jm0102046

文献信息

• Structural Modification and Pharmacological Evaluation of Substituted Quinoline-5,8-diones as Potent NSD2 Inhibitors
  作者：Hairong Tang、Aisong Yu、Li Xing、Xiaoyu Chen、Huaqian Ding、Hong Yang、Zilan Song、Qiongyu Shi、Meiyu Geng、Xun Huang、Ao Zhang

  DOI：10.1021/acs.jmedchem.2c01920

  日期：2023.1.26