8-((3-(dimethylamino)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 8-((3-(dimethylamino)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
• 英文别名: 8-[3-(Dimethylamino)anilino]-1-methyl-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide；8-[3-(dimethylamino)anilino]-1-methyl-4,5-dihydropyrazolo[4,3-h]quinazoline-3-carboxamide
• 化学式: C₁₉H₂₁N₇O
• 分子量: 363.422
• InChiKey: AJNLDWXAVGGEHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N,N-二甲基间苯二胺 在 盐酸 、 氨 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 8-((3-(dimethylamino)phenyl)amino)-1-methyl-4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline-3-carboxamide
  参考文献：
  名称：

  Synthesis and SAR of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent and selective CDK4/6 inhibitors

  摘要：

  CDK4/6 pathway is an attractive target for development of anti-cancer drugs. Herein, we reported the design and synthesis of a series of 4,5-dihydro-1H-pyrazolo [4,3-h]guinazoline derivatives as selective CDK4/6 inhibitors. Applied with the optimizing strategy to the initial scaffold, it is found that compound 13n is able to selectively inhibit CDK4 and CDK6 with IC50 values 0.01 and 0.026 mu M, respectively. The compound showed good anti-proliferative activity when tested in a panel of tumor cell lines with CDK4/6 related mechanism of action, the results clearly suggest that compound 13n works much better than Ly2385219 which is a selective CDK4/6 inhibitor. This compound was also found to have favorable pharmacokinetic parameters. Taken together, compound 13n could be selected for further preclinical evaluation. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.08.043

文献信息

• Synthesis and SAR of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazoline derivatives as potent and selective CDK4/6 inhibitors
  作者：Hui Zhao、Xiaoxia Hu、Kai Cao、Yue Zhang、Kuantao Zhao、Chunlei Tang、Bainian Feng

  DOI：10.1016/j.ejmech.2018.08.043

  日期：2018.9

  CDK4/6 pathway is an attractive target for development of anti-cancer drugs. Herein, we reported the design and synthesis of a series of 4,5-dihydro-1H-pyrazolo [4,3-h]guinazoline derivatives as selective CDK4/6 inhibitors. Applied with the optimizing strategy to the initial scaffold, it is found that compound 13n is able to selectively inhibit CDK4 and CDK6 with IC50 values 0.01 and 0.026 mu M, respectively. The compound showed good anti-proliferative activity when tested in a panel of tumor cell lines with CDK4/6 related mechanism of action, the results clearly suggest that compound 13n works much better than Ly2385219 which is a selective CDK4/6 inhibitor. This compound was also found to have favorable pharmacokinetic parameters. Taken together, compound 13n could be selected for further preclinical evaluation. (C) 2018 Elsevier Masson SAS. All rights reserved.