N-methyl-4-phenylquinazolin-2-amine | 89770-35-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-methyl-4-phenylquinazolin-2-amine
• CAS: 89770-35-4
• 化学式: C₁₅H₁₃N₃
• 分子量: 235.288
• InChiKey: NHFGHJNOUKLRFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-氯-4-苯基喹唑啉 在 氨 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以80%的产率得到N-methyl-4-phenylquinazolin-2-amine
  参考文献：
  名称：

  Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival

  摘要：

  Recent literature has claimed that inhibition of the enzyme MTH1 can eradicate cancer. MTH1 is one of the "housekeeping" enzymes that are responsible for hydrolyzing damaged nucleotides in cells and thus prevent them from being incorporated into DNA. We have developed orthogonal and chemically distinct tool compounds to those published in the literature to allow us to test the hypothesis that inhibition of MTH1 has wide applicability in the treatment of cancer. Here we present the work that led to the discovery of three structurally different series of MTH1 inhibitors with excellent potency, selectivity, and proven target engagement in cells. None of these compounds elicited the reported cellular phenotype, and additional siRNA and CRISPR experiments further support these observations. Critically, the difference between the responses of our highly selective inhibitors and published tool compounds suggests that the effect reported for the latter may be due to off-target cytotoxic effects. As a result, we conclude that the role of MTH1 in carcinogenesis and utility of its inhibition is yet to be established.

  DOI：

  10.1021/acs.jmedchem.5b01760

文献信息

• Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival
  作者：Jason G. Kettle、Husam Alwan、Michal Bista、Jason Breed、Nichola L. Davies、Kay Eckersley、Shaun Fillery、Kevin M. Foote、Louise Goodwin、David R. Jones、Helena Käck、Alan Lau、J. Willem M. Nissink、Jon Read、James S. Scott、Ben Taylor、Graeme Walker、Lisa Wissler、Marta Wylot

  DOI：10.1021/acs.jmedchem.5b01760

  日期：2016.3.24

  Recent literature has claimed that inhibition of the enzyme MTH1 can eradicate cancer. MTH1 is one of the "housekeeping" enzymes that are responsible for hydrolyzing damaged nucleotides in cells and thus prevent them from being incorporated into DNA. We have developed orthogonal and chemically distinct tool compounds to those published in the literature to allow us to test the hypothesis that inhibition of MTH1 has wide applicability in the treatment of cancer. Here we present the work that led to the discovery of three structurally different series of MTH1 inhibitors with excellent potency, selectivity, and proven target engagement in cells. None of these compounds elicited the reported cellular phenotype, and additional siRNA and CRISPR experiments further support these observations. Critically, the difference between the responses of our highly selective inhibitors and published tool compounds suggests that the effect reported for the latter may be due to off-target cytotoxic effects. As a result, we conclude that the role of MTH1 in carcinogenesis and utility of its inhibition is yet to be established.