4-N-(2-aminophenyl)-6-methylpyrimidine-2,4-diamine | 500863-61-6

• 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: 4-N-(2-aminophenyl)-6-methylpyrimidine-2,4-diamine
• CAS: 500863-61-6
• 化学式: C₁₁H₁₃N₅
• 分子量: 215.258
• InChiKey: NWXFJGQDPOHJPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  89.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(quinolin-4-ylamino)benzoic acid 、 4-N-(2-aminophenyl)-6-methylpyrimidine-2,4-diamine 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以66%的产率得到N-(2-(2-amino-6-methylpyrimidin-4-ylamino)phenyl)-3-(quinolin-4-ylamino)benzamide
  参考文献：
  名称：

  Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells

  摘要：

  DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound 5 as a potent non-nucleoside DNMTi that is also selective toward other Ado Met-dependent protein methyltransferases. Compound 5 was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, 5 inhibited cell growth, whereas related compound 2 showed high cell differentiation. To the best of our knowledge, 2 and 5 are the first non-nucleoside DNMTi tested in a cancer stem cell line.

  DOI：

  10.1021/jm4012627
• 作为产物：
  描述：

  2-氨基-4-氯-6-甲基嘧啶 在 盐酸 、 stannous chloride dihydrate 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 生成 4-N-(2-aminophenyl)-6-methylpyrimidine-2,4-diamine
  参考文献：
  名称：

  Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells

  摘要：

  DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound 5 as a potent non-nucleoside DNMTi that is also selective toward other Ado Met-dependent protein methyltransferases. Compound 5 was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, 5 inhibited cell growth, whereas related compound 2 showed high cell differentiation. To the best of our knowledge, 2 and 5 are the first non-nucleoside DNMTi tested in a cancer stem cell line.

  DOI：

  10.1021/jm4012627

文献信息

• Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells
  作者：Sergio Valente、Yiwei Liu、Michael Schnekenburger、Clemens Zwergel、Sandro Cosconati、Christina Gros、Maria Tardugno、Donatella Labella、Cristina Florean、Steven Minden、Hideharu Hashimoto、Yanqi Chang、Xing Zhang、Gilbert Kirsch、Ettore Novellino、Paola B. Arimondo、Evelina Miele、Elisabetta Ferretti、Alberto Gulino、Marc Diederich、Xiaodong Cheng、Antonello Mai

  DOI：10.1021/jm4012627

  日期：2014.2.13

  DNA methyltransferases (DNMTs) are important enzymes involved in epigenetic control of gene expression and represent valuable targets in cancer chemotherapy. A number of nucleoside DNMT inhibitors (DNMTi) have been studied in cancer, including in cancer stem cells, and two of them (azacytidine and decitabine) have been approved for treatment of myelodysplastic syndromes. However, only a few non-nucleoside DNMTi have been identified so far, and even fewer have been validated in cancer. Through a process of hit-to-lead optimization, we report here the discovery of compound 5 as a potent non-nucleoside DNMTi that is also selective toward other Ado Met-dependent protein methyltransferases. Compound 5 was potent at single-digit micromolar concentrations against a panel of cancer cells and was less toxic in peripheral blood mononuclear cells than two other compounds tested. In mouse medulloblastoma stem cells, 5 inhibited cell growth, whereas related compound 2 showed high cell differentiation. To the best of our knowledge, 2 and 5 are the first non-nucleoside DNMTi tested in a cancer stem cell line.