4-(furan-2-yl)-6-methyl-N-(3-chloro-4-fluorophenyl)-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine-5-carboxamide | 1258407-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(furan-2-yl)-6-methyl-N-(3-chloro-4-fluorophenyl)-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine-5-carboxamide
• 英文别名: N-(3-chloro-4-fluorophenyl)-4-(furan-2-yl)-6-methyl-4,7-dihydro-1H-pyrazolo[3,4-b]pyridine-5-carboxamide
• CAS: 1258407-69-0
• 化学式: C₁₈H₁₄ClFN₄O₂
• 分子量: 372.786
• InChiKey: ZZTSAHARMUYSDZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  83
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  糠醛 、 3-氨基吡唑 、 N-(3-chloro-4-fluorophenyl)-2-acetylacetamide 在 iron(III) chloride 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以34%的产率得到4-(furan-2-yl)-6-methyl-N-(3-chloro-4-fluorophenyl)-4,7-dihydro-2H-pyrazolo[3,4-b]pyridine-5-carboxamide
  参考文献：
  名称：

  Design, synthesis and bioevaluation of dihydropyrazolo[3,4-b]pyridine and benzo[4,5]imidazo[1,2-a]pyrimidine compounds as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents

  摘要：

  Four series of dihydropyrazolo[3,4-b]pyridines and benzo[4,5]imidazo[1,2-a]pyrimidines were designed and synthesized as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents by introducing some fragments of Aurora-A kinase inhibitors into our KSP inhibitor CPUYL064. A total of 19 target compounds were evaluated by two related enzyme inhibition assays and a cytotoxicity assay in vitro. The results showed that some target compounds could inhibit both enzymes, and several of them showed significant inhibition activity against HCT116 cell line. Despite showing moderate KSP and Aurora-A kinase inhibition, the lead compounds 6a and 6e displayed significant cytotoxic activity in the micromolar range, especially against the HCT116 cell line and HepG2 cell line. The results may be useful for developing a new class of inhibitors having a dual function, KSP inhibition and Aurora-A kinase inhibition, for the treatment of cancer. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.09.020

文献信息

• Design, synthesis and bioevaluation of dihydropyrazolo[3,4-b]pyridine and benzo[4,5]imidazo[1,2-a]pyrimidine compounds as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents
  作者：Rong-geng Fu、Qi-dong You、Lei Yang、Wu-tong Wu、Cheng Jiang、Xiao-li Xu

  DOI：10.1016/j.bmc.2010.09.020

  日期：2010.11.15

  Four series of dihydropyrazolo[3,4-b]pyridines and benzo[4,5]imidazo[1,2-a]pyrimidines were designed and synthesized as dual KSP and Aurora-A kinase inhibitors for anti-cancer agents by introducing some fragments of Aurora-A kinase inhibitors into our KSP inhibitor CPUYL064. A total of 19 target compounds were evaluated by two related enzyme inhibition assays and a cytotoxicity assay in vitro. The results showed that some target compounds could inhibit both enzymes, and several of them showed significant inhibition activity against HCT116 cell line. Despite showing moderate KSP and Aurora-A kinase inhibition, the lead compounds 6a and 6e displayed significant cytotoxic activity in the micromolar range, especially against the HCT116 cell line and HepG2 cell line. The results may be useful for developing a new class of inhibitors having a dual function, KSP inhibition and Aurora-A kinase inhibition, for the treatment of cancer. (C) 2010 Elsevier Ltd. All rights reserved.