1-(4-methylphenyl)sulfonyl-3-(pyrazin-2-yl)urea | 128924-84-5

• 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: 1-(4-methylphenyl)sulfonyl-3-(pyrazin-2-yl)urea
• 英文别名: 1-(4-methylphenyl)sulfonyl-3-pyrazin-2-ylurea
• CAS: 128924-84-5
• 化学式: C₁₂H₁₂N₄O₃S
• 分子量: 292.318
• InChiKey: QWXHGCDNGSILSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-methylphenyl)sulfonyl-3-(pyrazin-2-yl)urea 、 对硝基溴化苄 以 异丙醇 为溶剂， 反应 2.0h， 以27%的产率得到2-(4-methylphenyl)sulfonylcarbamido-1-(4-nitrobenzyl)pyrazinium bromide
  参考文献：
  名称：

  N-tosylcarbamide derivatives of 2-pyrazinium and 9-acridinium salts as inhibitors of acetylcholine potassium channels in cardiomyocytes

  摘要：

  DOI：

  10.1007/s10593-009-0234-6
• 作为产物：
  描述：

  氨基吡嗪 、 对甲基苯磺酰异氰酸酯 以 二氯甲烷 、 乙腈 为溶剂， 以94%的产率得到1-(4-methylphenyl)sulfonyl-3-(pyrazin-2-yl)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

• Design and development of sulfonylurea derivatives as zinc metalloenzyme modulators
  作者：Murtuza Hadianawala、Bhaskar Datta

  DOI：10.1039/c5ra27341b

  日期：——

  Sulfonamide derivatives are an important class of zinc metalloenzyme inhibitors. While the sulfonylurea group is a bioisoster of sulfonamide, their effect on the modulation of metalloenzymes has never been studied. In the present work we synthesize and screen new sulfonylurea derivatives towards the zinc metalloenzymes, human Carbonic Anhydrase II (hCA II) and histone deacetylase 1 (HDAC 1). Specific

  磺酰胺衍生物是一类重要的锌金属酶抑制剂。尽管磺酰脲基是磺酰胺的生物等排体，但从未研究它们对金属酶的调节的作用。在目前的工作中，我们合成和筛选了针对锌金属酶，人碳酸酐酶II（hCA II）和组蛋白脱乙酰基酶1（HDAC 1）的新磺酰脲衍生物。发现特定的磺酰脲衍生物可通过IC 50抑制hCA II在纳米摩尔至微摩尔范围内。对接研究表明抑制剂与活性位点腔口的结合，从而阻止了酶的进入。令人惊讶地，磺酰脲衍生物表现出HDAC 1的活化而不是抑制。HDAC 1的活化在所测试的衍生物之间并不均匀，这表明取决于化合物结构特征的特定模式。由于HDAC抑制剂具有潜在的抗癌作用，因此已经进行了广泛的研究，但是关于HDAC活化的报道相对较少。在这项工作中，我们提出了关于hCA II和HDAC 1的同一类分子，即磺酰脲衍生物的明显不同的行为，并试图提供对它们的理解。
• 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.
• N-tosylcarbamide derivatives of 2-pyrazinium and 9-acridinium salts as inhibitors of acetylcholine potassium channels in cardiomyocytes
  作者：A. P. Stankevicius、L. N. Janusiene、V. I. Gendviliene、D. P. Zablockaite

  DOI：10.1007/s10593-009-0234-6

  日期：2009.1