N2-(2-aminophenyl)-N5-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)thiophene-2,5-dicarboxamide | 1295580-75-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N2-(2-aminophenyl)-N5-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)thiophene-2,5-dicarboxamide
• 英文别名: 2-N-(2-aminophenyl)-5-N-[4-methyl-3-[(5-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]thiophene-2,5-dicarboxamide
• CAS: 1295580-75-4
• 化学式: C₂₈H₂₃N₇O₂S
• 分子量: 521.602
• InChiKey: WSOUPZRFRJNSQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  163
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  tert-butyl 2-(5-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenylcarbamoyl)thiophene-2-carboxamido)phenylcarbamate 在 三氟乙酸 作用下， 反应 2.0h， 以98%的产率得到N2-(2-aminophenyl)-N5-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)thiophene-2,5-dicarboxamide
  参考文献：
  名称：

  Design of Chimeric Histone Deacetylase- and Tyrosine Kinase-Inhibitors: A Series of Imatinib Hybrides as Potent Inhibitors of Wild-Type and Mutant BCR-ABL, PDGF-Rβ, and Histone Deacetylases

  摘要：

  Inhibitors of histone deacetylases are a new class of cancer therapeutics with possibly broad applicability. Combinations of HDAC inhibitors with the kinase inhibitor 1 (Imatimb) in recent studies showed additive and synergistic effects. Here we present a new concept by combining inhibition of protein kinases and HDACs, two independent pharmacological activities, in one synthetic small molecule. In general, the HDAC inhibition profile, the potencies, and the probable binding modes to HDAC1 and HDAC6 were similar as for 6 (SAHA). Inhibition of AN kinase in biochemical assays was maintained for Most compounds, but in general the kinase selectivity profile differed from that of I with nearly equipotent inhibition of the wildtype and the Imatimb resistant Abl (TI)-I-315 mutant. A potent cellular inhibition of PDGFR and cytotoxicity toward EOL-1 cells, a model for idiopathic hypereosinophilic syndrome (HES), are restored or enhanced for selected analogues (12b, 14b, and 18b). Cytotoxicity was evaluated by using a broad panel Of tumor cell lines, with selected analogues displaying mean IC50 values between 3.6 and 7.1 mu M.

  DOI：

  10.1021/jm800988r