6-氨基-2,3-二氢-5-[(苯基亚甲基)氨基]-2-硫代-4(1H)-嘧啶酮 | 64232-83-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-氨基-2,3-二氢-5-[(苯基亚甲基)氨基]-2-硫代-4(1H)-嘧啶酮
• 英文名称: 6-amino-5-(benzylideneamino)-2-sulfanylpyrimidin-4-ol
• 英文别名: 6-Amino-5-(benzylideneamino)-2-sulfanyl-4-pyrimidinol；6-amino-5-(benzylideneamino)-2-sulfanylidene-1H-pyrimidin-4-one
• CAS: 64232-83-3
• 化学式: C₁₁H₁₀N₄OS
• 分子量: 246.293
• InChiKey: SAKOXVNKDMWWLF-UHFFFAOYSA-N

物化性质

• 熔点：
  250 °C (decomp)
• 密度：
  1.45±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO 中≥62.5 mg/mL；不溶于乙醇；不溶于水

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

L 189 是一种新型的人类DNA连接酶抑制剂，其对hLigI、hLigIII和hLigIV的IC50值分别为5μM、9μM和5μM。它能够抑制碱基切除修复（BER）和非同源末端连接（NHEJ），使癌细胞对DNA损伤特别敏感。

靶点

Target	Value
hLigI (Cell-free assay)	5 μM
hLigIV (Cell-free assay)	5 μM
hLigIII (Cell-free assay)	9 μM

反应信息

• 作为反应物：
  描述：

  6-氨基-2,3-二氢-5-[(苯基亚甲基)氨基]-2-硫代-4(1H)-嘧啶酮 在 溶剂黄146 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 sodium 5,6-bis((E)-benzylideneamino)-2-mercaptopyrimidin-4-olate
  参考文献：
  名称：

  COMPOUNDS AS INHIBITOR OF DNA DOUBLE-STRAND BREAK REPAIR, METHODS AND APPLICATIONS THEREOF

  摘要：

  本公开涉及结构式“公式I”的化合物及其制备方法。本公开还涉及利用结构式I化合物抑制DNA双链断裂（DSB）修复的方法。

  公开号：

  US20150158822A1
• 作为产物：
  描述：

  苯甲醛 、 4,5-二氨基-2-硫脲嘧啶 在 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以60%的产率得到6-氨基-2,3-二氢-5-[(苯基亚甲基)氨基]-2-硫代-4(1H)-嘧啶酮
  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

• 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.
• COMPOUNDS AS INHIBITOR OF DNA DOUBLE-STRAND BREAK REPAIR, METHODS AND APPLICATIONS THEREOF
  申请人：INDIAN INSTITUTE OF SCIENCE

  公开号：US20150158822A1

  公开（公告）日：2015-06-11

  The present disclosure relates to compound of structural “formula I” and a method for preparing a compound of structural formula I. The disclosure further relates to a method of arresting DNA double-strand break (DSB) repair by employing the compound of structural formula I.

  本公开涉及结构式“公式I”的化合物及其制备方法。本公开还涉及利用结构式I化合物抑制DNA双链断裂（DSB）修复的方法。