N-(2-甲基-5-硝基苯基)-4-(3-吡啶基)-2-噻唑胺氢溴酸盐 | 1143459-81-7

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2-甲基-5-硝基苯基)-4-(3-吡啶基)-2-噻唑胺氢溴酸盐
• 英文名称: N-(2-methyl-5-nitrophenyl)-4-(pyridin-3-yl)thiazol-2-amine hydrobromide
• 英文别名: N-(2-Methyl-5-nitrophenyl)-4-(3-pyridinyl)-2-thiazolamine hydrobromide；N-(2-methyl-5-nitrophenyl)-4-pyridin-3-yl-1,3-thiazol-2-amine;hydrobromide
• CAS: 1143459-81-7
• 化学式: BrH*C₁₅H₁₂N₄O₂S
• 分子量: 393.264
• InChiKey: GXSBBIVHFLDEDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.74
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(2-甲基-5-硝基苯基)-4-(3-吡啶基)-2-噻唑胺氢溴酸盐 在 palladium 10% on activated carbon 、 氢气 、 sodium carbonate 、 盐酸 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 50.0 ℃ 、3.04 MPa 条件下， 反应 12.0h， 以99%的产率得到4-methyl-N3-[4-(3-pyridyl)thiazol-2-yl]benzene-1,3-diamine dihydrochloride
  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
• 作为产物：
  描述：

  1-(2-甲基-5-硝基苯基)硫脲 、 3-(2-溴乙酰基)吡啶氢溴酸盐 以 乙醇 为溶剂， 反应 2.0h， 以93%的产率得到N-(2-甲基-5-硝基苯基)-4-(3-吡啶基)-2-噻唑胺氢溴酸盐
  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