6,7-diphenyl-2-thioxo-7,8-dihydropteridin-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 6,7-diphenyl-2-thioxo-7,8-dihydropteridin-4-one
• 英文别名: 6,7-diphenyl-2-sulfanylidene-7,8-dihydro-1H-pteridin-4-one
• 化学式: C₁₈H₁₄N₄OS
• 分子量: 334.401
• InChiKey: ANOSXLFFYKJFFC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  97.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6,7-diphenyl-2-thioxo-7,8-dihydropteridin-4-one 以 硝基苯 为溶剂， 反应 0.25h， 以44%的产率得到2,3-二氢-6,7-二苯基-2-硫代-4(1H)-蝶啶酮
  参考文献：
  名称：

  DNA连接酶抑制剂SCR7的合成和结构测定

  摘要：

  与已发表的报告相反，4,5-二氨基-6-羟基-2-巯基嘧啶与2当量的芳族醛的反应产生了6,7-二芳基-2-硫代蝶啶-4-一和6,7-二芳基-2-巯基-7,8-二氢蝶啶-4-一而不是二亚胺。这些化合物代表了SCR7的正确结构，SCR7是一种据报道是DNA修复途径的非同源末端连接抑制剂的物质。可以分离出二氢蝶啶为次要产物，并且可以将其氧化为蝶啶。

  DOI：

  10.1016/j.tetlet.2016.06.037
• 作为产物：
  描述：

  苯甲醛 在 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 6,7-diphenyl-2-thioxo-7,8-dihydropteridin-4-one
  参考文献：
  名称：

  Autocyclized and oxidized forms ofSCR7 induce cancer cell death by inhibiting nonhomologousDNAend joining in a LigaseIVdependent manner

  摘要：

  Nonhomologous DNA end joining (NHEJ) is the major DNA double‐strand break (DSB) repair pathway in mammals. Previously, we have described a small molecule inhibitor, SCR7, which can inhibit NHEJ in a Ligase IV‐dependent manner. Administration of SCR7 within the cells resulted in the accumulation of DNA breaks, cell death, and inhibition of tumor growth in mice. In the present study, we report that parental SCR7, which is unstable, can be autocyclized into a stable form. Both parental SCR7 and cyclized SCR7 possess the same molecular weight (334.09) and molecular formula (C18H14N4OS), whereas its oxidized form, SCR7‐pyrazine, possesses a different molecular formula (C18H12N4OS), molecular weight (332.07), and structure. While cyclized form of SCR7 showed robust inhibition of NHEJ in vitro, both forms exhibited efficient cytotoxicity. Cyclized and oxidized forms of SCR7 inhibited DNA end joining catalyzed by Ligase IV, whereas their impact was minimal on Ligase III, Ligase I, and T4 DNA Ligase‐mediated joining. Importantly, both forms inhibited V(D)J recombination, although the effect was more pronounced for SCR7‐cyclized. Both forms blocked NHEJ in a Ligase IV‐dependent manner leading to the accumulation of DSBs within the cells. Although cytotoxicity due to SCR7‐cyclized was Ligase IV specific, the pyrazine form exhibited nonspecific cytotoxicity at higher concentrations in Ligase IV‐null cells. Finally, we demonstrate that both forms can potentiate the effect of radiation. Thus, we report that cyclized and oxidized forms of SCR7 can inhibit NHEJ in a Ligase IV‐dependent manner, although SCR7‐pyrazine is less specific to Ligase IV inside the cell.

  DOI：

  10.1111/febs.14661

文献信息

• Synthesis and structure determination of SCR7, a DNA ligase inhibitor
  作者：George E. Greco、Zane A. Conrad、Alycia M. Johnston、Qingyao Li、Alan E. Tomkinson

  DOI：10.1016/j.tetlet.2016.06.037

  日期：2016.7

  2 equiv of aromatic aldehydes produces a mixture of 6,7-diaryl-2-thioxopteridine-4-one and 6,7-diaryl-2-thioxo-7,8-dihydropteridine-4-one rather than a diimine. These compounds represent the correct structure for SCR7, a substance reported to be an inhibitor of nonhomologous end-joining, a DNA repair pathway. The dihydropteridine can be isolated as a minor product, and it can be oxidized to the pteridine

  与已发表的报告相反，4,5-二氨基-6-羟基-2-巯基嘧啶与2当量的芳族醛的反应产生了6,7-二芳基-2-硫代蝶啶-4-一和6,7-二芳基-2-巯基-7,8-二氢蝶啶-4-一而不是二亚胺。这些化合物代表了SCR7的正确结构，SCR7是一种据报道是DNA修复途径的非同源末端连接抑制剂的物质。可以分离出二氢蝶啶为次要产物，并且可以将其氧化为蝶啶。
• Autocyclized and oxidized forms of<scp>SCR</scp>7 induce cancer cell death by inhibiting nonhomologous<scp>DNA</scp>end joining in a Ligase<scp>IV</scp>dependent manner
  作者：Supriya V. Vartak、Hassan A. Swarup、Vidya Gopalakrishnan、Vindya K. Gopinatha、Virginie Ropars、Mridula Nambiar、Franklin John、Sharath Kumar S. Kothanahally、Rupa Kumari、Nitu Kumari、Ujjayinee Ray、Gudapureddy Radha、Depina Dinesh、Monica Pandey、Hanumappa Ananda、Subhas S. Karki、Mrinal Srivastava、Jean Baptiste Charbonnier、Bibha Choudhary、Kempegowda Mantelingu、Sathees C. Raghavan

  DOI：10.1111/febs.14661

  日期：2018.11

  Nonhomologous DNA end joining (NHEJ) is the major DNA double‐strand break (DSB) repair pathway in mammals. Previously, we have described a small molecule inhibitor, SCR7, which can inhibit NHEJ in a Ligase IV‐dependent manner. Administration of SCR7 within the cells resulted in the accumulation of DNA breaks, cell death, and inhibition of tumor growth in mice. In the present study, we report that parental SCR7, which is unstable, can be autocyclized into a stable form. Both parental SCR7 and cyclized SCR7 possess the same molecular weight (334.09) and molecular formula (C18H14N4OS), whereas its oxidized form, SCR7‐pyrazine, possesses a different molecular formula (C18H12N4OS), molecular weight (332.07), and structure. While cyclized form of SCR7 showed robust inhibition of NHEJ in vitro, both forms exhibited efficient cytotoxicity. Cyclized and oxidized forms of SCR7 inhibited DNA end joining catalyzed by Ligase IV, whereas their impact was minimal on Ligase III, Ligase I, and T4 DNA Ligase‐mediated joining. Importantly, both forms inhibited V(D)J recombination, although the effect was more pronounced for SCR7‐cyclized. Both forms blocked NHEJ in a Ligase IV‐dependent manner leading to the accumulation of DSBs within the cells. Although cytotoxicity due to SCR7‐cyclized was Ligase IV specific, the pyrazine form exhibited nonspecific cytotoxicity at higher concentrations in Ligase IV‐null cells. Finally, we demonstrate that both forms can potentiate the effect of radiation. Thus, we report that cyclized and oxidized forms of SCR7 can inhibit NHEJ in a Ligase IV‐dependent manner, although SCR7‐pyrazine is less specific to Ligase IV inside the cell.