ethyl 2-{[4-(6-chloroimidazo[1,2-a]pyridin-3-yl)-1,3-thiazol-2-yl]thio}-4-nitrobenzoate | 917926-26-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: ethyl 2-{[4-(6-chloroimidazo[1,2-a]pyridin-3-yl)-1,3-thiazol-2-yl]thio}-4-nitrobenzoate
• CAS: 917926-26-2
• 化学式: C₁₉H₁₃ClN₄O₄S₂
• 分子量: 460.922
• InChiKey: DRYQFPHJICZUQP-UHFFFAOYSA-N

物化性质

• 密度：
  1.58±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.35
• 重原子数：
  30.0
• 可旋转键数：
  6.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  99.63
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  ethyl 2-{[4-(6-chloroimidazo[1,2-a]pyridin-3-yl)-1,3-thiazol-2-yl]thio}-4-nitrobenzoate 在 sodium tetrahydroborate 、 二异丁基氢化铝 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 3.0h， 生成 6-chloro-3-{2-[(2-methyl-5-nitrophenyl)sulfinyl]-1,3-thiazol-4-yl}imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors

  摘要：

  3-{1-[(4-Fluorophenyl)sulfonyl]-1H-pyrazol-3-yl}-2-methylimidazo[1,2-a]pyridine, 2a, was discovered in our chemical library as a novel p110 alpha inhibitor with an IC50 of 0.67 mu M, through screening in a scintillation proximity assay. Optimization of the substituents of 2a increased the p110 alpha inhibitory activity by more than 300-fold (2g: IC50 = 0.0018 mu M). Further structural modification of 2g afforded thiazole derivative 12, which has potent p110 alpha inhibitory activity (IC50 of 0.0028 mu M) and is highly selective for p110 alpha over other PI3K isoforms. Compound 12 also inhibited serum-induced cell proliferation of A375 and HeLa cells in vitro with IC50 values of 0.14 mu M and 0.21 mu M, respectively, and suppressed tumor growth by 37% in a mouse HeLa xenograft model when dosed intraperitoneally at 25 mg/kg. These results suggest that selective p110 alpha inhibitors may have potential as cancer therapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.047
• 作为产物：
  描述：

  2-bromo-1-(6-chloroimidazo[1,2-a]pyridin-3-yl)ethanone hydrobromide 在 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.25h， 生成 ethyl 2-{[4-(6-chloroimidazo[1,2-a]pyridin-3-yl)-1,3-thiazol-2-yl]thio}-4-nitrobenzoate
  参考文献：
  名称：

  Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110α inhibitors

  摘要：

  3-{1-[(4-Fluorophenyl)sulfonyl]-1H-pyrazol-3-yl}-2-methylimidazo[1,2-a]pyridine, 2a, was discovered in our chemical library as a novel p110 alpha inhibitor with an IC50 of 0.67 mu M, through screening in a scintillation proximity assay. Optimization of the substituents of 2a increased the p110 alpha inhibitory activity by more than 300-fold (2g: IC50 = 0.0018 mu M). Further structural modification of 2g afforded thiazole derivative 12, which has potent p110 alpha inhibitory activity (IC50 of 0.0028 mu M) and is highly selective for p110 alpha over other PI3K isoforms. Compound 12 also inhibited serum-induced cell proliferation of A375 and HeLa cells in vitro with IC50 values of 0.14 mu M and 0.21 mu M, respectively, and suppressed tumor growth by 37% in a mouse HeLa xenograft model when dosed intraperitoneally at 25 mg/kg. These results suggest that selective p110 alpha inhibitors may have potential as cancer therapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.09.047