2-[(14)C]-5-fluoro-6-nitro-1H-benzimidazol-2-amine | 1353869-02-9

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-[(14)C]-5-fluoro-6-nitro-1H-benzimidazol-2-amine
• CAS: 1353869-02-9
• 化学式: C₇H₅FN₄O₂
• 分子量: 198.13
• InChiKey: MIQSFSZUPRFTII-WGGUOBTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.19
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.84
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-[(14)C]-5-fluoro-6-nitro-1H-benzimidazol-2-amine 、 丙酮醛 、 碘甲烷 在 ammonium hydroxide 、 sodium tetrahydroborate 作用下， 生成 2-[(14)C]-2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline 、 2-[(14)C]-2-amino-1,6-dimethylimidazo[4,5-g]quinoxaline
  参考文献：
  名称：

  Cytochrome P450-Mediated Metabolism and DNA Binding of 2-Amino-1,7-dimethylimidazo[4,5-g]quinoxaline and Its Carcinogenic Isomer 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Mice

  摘要：

  2-Amino-1,7-dimethylimidazo[4,5-g]quinoxaline (MeIgQx) is a recently discovered heterocyclic aromatic amine (HAA) that is formed during the cooking of meats. MeIgQx is an isomer of 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx), a rodent carcinogen and possible human carcinogen that also occurs in cooked meats. MeIgQx is a bacterial mutagen, but knowledge about its metabolism and carcinogenic potential is lacking. Metabolism studies on MeIgQx and MeIQx were conducted with human and mouse liver microsomes, and recombinant human P450s. DNA binding studies were also investigated in mice to ascertain the genotoxic potential of MeIgQx in comparison to MeIQx. Both HAAs underwent comparable rates of N-oxidation to form genotoxic N-hydroxylated metabolites with mouse liver microsomes (0.2-0.3 nmol/min/mg protein). The rate of N-oxidation of MeIQx was 4-fold greater than the rate of N-oxidation of MeIgQx with human liver microsomes (1.7 vs 0.4 nmol/min/mg protein). The rate of N-oxidation, by recombinant human P450 1A2, was comparable for both substrates (6 pmol/min/pmol P450 1A2). MeIgQx also underwent N-oxidation by human P450s 1A1 and 1B1 at appreciable rates, whereas MeIQx was poorly metabolized by these P450s. The potential of MeIgQx and MeIQx to form DNA adducts was assessed in female C57BL/6 mice given [C-14]-MeIgQx (10 mu Ci, 9.68 mg/kg body wt) or [C-14]-MeIQx (10 mu Ci, 2.13 mg/kg body wt). DNA adduct formation in the liver, pancreas, and colorectum was measured by accelerator mass spectrometry at 4, 24, or 48 h post-treatment Variable levels of adducts were detected in all organs. The adduct levels were similar for both HAAs, when adjusted for dose, and ranged from 1 to 600 adducts per 10(7) nudeotides per mg/kg dose. Thus, MeIgQx undergoes metabolic activation and binds to DNA at levels that are comparable to MeIQx. Given the high amounts of MeIgQx formed in cooked meats, further investigations are warranted to assess the carcinogenic potential of this HAA.

  DOI：

  10.1021/tx2004536
• 作为产物：
  描述：

  potassium [14C]cyanide 、 4-氟-5-硝基-1,2-苯二胺 在 溴 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 0.33h， 生成 2-[(14)C]-5-fluoro-6-nitro-1H-benzimidazol-2-amine
  参考文献：
  名称：

  Cytochrome P450-Mediated Metabolism and DNA Binding of 2-Amino-1,7-dimethylimidazo[4,5-g]quinoxaline and Its Carcinogenic Isomer 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline in Mice

  摘要：

  2-Amino-1,7-dimethylimidazo[4,5-g]quinoxaline (MeIgQx) is a recently discovered heterocyclic aromatic amine (HAA) that is formed during the cooking of meats. MeIgQx is an isomer of 2-amino-3,8-dimethylmidazo[4,5-f]quinoxaline (MeIQx), a rodent carcinogen and possible human carcinogen that also occurs in cooked meats. MeIgQx is a bacterial mutagen, but knowledge about its metabolism and carcinogenic potential is lacking. Metabolism studies on MeIgQx and MeIQx were conducted with human and mouse liver microsomes, and recombinant human P450s. DNA binding studies were also investigated in mice to ascertain the genotoxic potential of MeIgQx in comparison to MeIQx. Both HAAs underwent comparable rates of N-oxidation to form genotoxic N-hydroxylated metabolites with mouse liver microsomes (0.2-0.3 nmol/min/mg protein). The rate of N-oxidation of MeIQx was 4-fold greater than the rate of N-oxidation of MeIgQx with human liver microsomes (1.7 vs 0.4 nmol/min/mg protein). The rate of N-oxidation, by recombinant human P450 1A2, was comparable for both substrates (6 pmol/min/pmol P450 1A2). MeIgQx also underwent N-oxidation by human P450s 1A1 and 1B1 at appreciable rates, whereas MeIQx was poorly metabolized by these P450s. The potential of MeIgQx and MeIQx to form DNA adducts was assessed in female C57BL/6 mice given [C-14]-MeIgQx (10 mu Ci, 9.68 mg/kg body wt) or [C-14]-MeIQx (10 mu Ci, 2.13 mg/kg body wt). DNA adduct formation in the liver, pancreas, and colorectum was measured by accelerator mass spectrometry at 4, 24, or 48 h post-treatment Variable levels of adducts were detected in all organs. The adduct levels were similar for both HAAs, when adjusted for dose, and ranged from 1 to 600 adducts per 10(7) nudeotides per mg/kg dose. Thus, MeIgQx undergoes metabolic activation and binds to DNA at levels that are comparable to MeIQx. Given the high amounts of MeIgQx formed in cooked meats, further investigations are warranted to assess the carcinogenic potential of this HAA.

  DOI：

  10.1021/tx2004536