N-(4,6-dimethyl-pyrimidin-2-yl)-N'-(toluene-4-sulfonyl)-urea | 100882-44-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(4,6-dimethyl-pyrimidin-2-yl)-N'-(toluene-4-sulfonyl)-urea
• 英文别名: N-(4,6-Dimethyl-pyrimidin-2-yl)-N'-(toluol-4-sulfonyl)-harnstoff；1-(4,6-Dimethylpyrimidin-2-yl)-3-(4-methylphenyl)sulfonylurea
• CAS: 100882-44-8
• 化学式: C₁₄H₁₆N₄O₃S
• 分子量: 320.372
• InChiKey: QXKKUZWLJSIOFK-UHFFFAOYSA-N

物化性质

• 熔点：
  221 °C (decomp)
• 密度：
  1.355±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基-4,6-二甲基嘧啶 、 对甲基苯磺酰异氰酸酯 以 二氯甲烷 为溶剂， 以48%的产率得到N-(4,6-dimethyl-pyrimidin-2-yl)-N'-(toluene-4-sulfonyl)-urea
  参考文献：
  名称：

  Novel agents effective against solid tumors: the diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships

  摘要：

  A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.

  DOI：

  10.1021/jm00171a013

文献信息

• Logemann et al., Farmaco, Edizione Scientifica, 1957, vol. 12, p. 586,591
  作者：Logemann et al.

  DOI：——

  日期：——
• HOWBERT, J. JEFFRY;GROSSMAN, C. SUE;CROWELL, THOMAS A.;RIEDER, BRENT J.;H+, J. MED. CHEM., 33,(1990) N, C. 2393-2407
  作者：HOWBERT, J. JEFFRY、GROSSMAN, C. SUE、CROWELL, THOMAS A.、RIEDER, BRENT J.、H+

  DOI：——

  日期：——
• Novel agents effective against solid tumors: the diarylsulfonylureas. Synthesis, activities, and analysis of quantitative structure-activity relationships
  作者：J. Jeffry Howbert、C. Sue Grossman、Thomas A. Crowell、Brent J. Rieder、Richard W. Harper、Kenneth E. Kramer、Eddie V. Tao、James Aikins、Gerald A. Poore

  DOI：10.1021/jm00171a013

  日期：1990.9

  A series of diarylsulfonylureas with exceptionally broad-spectrum activity against syngeneic rodent solid tumors in vivo is described. Their discovery resulted from a program dedicated to in vivo screening for novel oncolytics in solid tumor models, rather than traditional ascites leukemia models. The structures, oral efficacy, side-effect profile, and mechanism of action of these sulfonylureas appear to be distinct from previously known classes of oncolytics. An extensive series of analogues was prepared to probe structure-activity relationships (SAR), with particular focus on the substituent patterns of each aryl domain. Quantitative analysis of these substituent SARs, using the method of cluster significance analysis, showed the lipophilicity of the substituents to be the dominant determinant of activity. One compound from the series, LY186641 (104, sulofenur), has progressed to Phase I clinical trials as an antitumor drug.