| 1457972-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• CAS: 1457972-57-4
• 化学式: C₈H₁₀ClN₃O₂
• 分子量: 215.639
• InChiKey: FQLWHSFAPGCMBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.01
• 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：
  0.5
• 拓扑面积：
  67.15
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  反应 24.0h， 生成 2-hydroxy-2-(hydroxymethyl)-3,4-dihydro-1H-pyrimido[1,2-c]pyrimidin-6-one
  参考文献：
  名称：

  Formation of Fused-Ring 2′-Deoxycytidine Adducts from 1-Chloro-3-buten-2-one, an in Vitro 1,3-Butadiene Metabolite, under in Vitro Physiological Conditions

  摘要：

  1-Chloro-3-buten-2-one (CBO) is a potential metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO is a bifunctional alkylating agent that readily reacts with glutathione (GSH) to form mono-GSH and di-GSH adducts. Recently, CBO and its precursor 1-chloro-2-hydroxy-3-butene (CHB) were found to be cytotoxic and genotoxic in human liver cells in culture with CBO being approximately 100-fold more potent than CHB. In the present study, CBO was shown to react readily with 2'-deoxycytidine (dC) under in vitro physiological conditions (pH 7.4, 37 degrees C) to form four dC adducts with the CBO moieties forming fused rings with the N3 and N-4 atoms of dC. The four products were structurally characterized as 2-hydroxy-2-hydroxymethyl-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-1 and dC-2, a pair of diastereomers), 4-chloromethyl-4-hydroxy-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido [1,6-a]pyrimidin-5-ium (dC-3), and 2-chloromethyl-2-hydroxy-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-4). Interestingly, dC-1 and dC-2 were stable under our experimental conditions (pH 7.4, 37 degrees C, and 6 h) and existed in equilibrium as indicated by HPLC analysis, whereas dC-3 and dC-4 were labile with the half-lives being 3.0 +/- 0.36 and 1.7 +/- 0.06 h, respectively. Decomposition of dC-4 produced both dC-1 and dC-2, whereas acid hydrolysis of dC-1/dC-2 and dC-4 in 1 M HCl at 100 degrees C for 30 min yielded the deribosylated adducts dC-1H/dC-2H and dC-4H, respectively. Because fused-ring dC adducts of other chemicals are mutagenic, the characterized CBO-dC adducts could be mutagenic and play a role in the cytotoxicity and genotoxicity of CBO and its precursors, CHB and BD. The CBO-dC adducts may also be used as standards to characterize CBO DNA adducts and to develop potential biomarkers for CBO formation in vivo.

  DOI：

  10.1021/tx4002435
• 作为产物：
  描述：

  2-chloromethyl-2-hydroxy-7-(2-deoxy-β-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium 在 盐酸 、 水 作用下， 反应 0.5h， 生成
  参考文献：
  名称：

  Formation of Fused-Ring 2′-Deoxycytidine Adducts from 1-Chloro-3-buten-2-one, an in Vitro 1,3-Butadiene Metabolite, under in Vitro Physiological Conditions

  摘要：

  1-Chloro-3-buten-2-one (CBO) is a potential metabolite of 1,3-butadiene (BD), a carcinogenic air pollutant. CBO is a bifunctional alkylating agent that readily reacts with glutathione (GSH) to form mono-GSH and di-GSH adducts. Recently, CBO and its precursor 1-chloro-2-hydroxy-3-butene (CHB) were found to be cytotoxic and genotoxic in human liver cells in culture with CBO being approximately 100-fold more potent than CHB. In the present study, CBO was shown to react readily with 2'-deoxycytidine (dC) under in vitro physiological conditions (pH 7.4, 37 degrees C) to form four dC adducts with the CBO moieties forming fused rings with the N3 and N-4 atoms of dC. The four products were structurally characterized as 2-hydroxy-2-hydroxymethyl-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-1 and dC-2, a pair of diastereomers), 4-chloromethyl-4-hydroxy-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido [1,6-a]pyrimidin-5-ium (dC-3), and 2-chloromethyl-2-hydroxy-7-(2-deoxy-beta-D-erythro-pentofuranosyl)-1,2,3,4-tetrahydro-6-oxo-6H,7H-pyrimido[1,6-a]pyrimidin-5-ium (dC-4). Interestingly, dC-1 and dC-2 were stable under our experimental conditions (pH 7.4, 37 degrees C, and 6 h) and existed in equilibrium as indicated by HPLC analysis, whereas dC-3 and dC-4 were labile with the half-lives being 3.0 +/- 0.36 and 1.7 +/- 0.06 h, respectively. Decomposition of dC-4 produced both dC-1 and dC-2, whereas acid hydrolysis of dC-1/dC-2 and dC-4 in 1 M HCl at 100 degrees C for 30 min yielded the deribosylated adducts dC-1H/dC-2H and dC-4H, respectively. Because fused-ring dC adducts of other chemicals are mutagenic, the characterized CBO-dC adducts could be mutagenic and play a role in the cytotoxicity and genotoxicity of CBO and its precursors, CHB and BD. The CBO-dC adducts may also be used as standards to characterize CBO DNA adducts and to develop potential biomarkers for CBO formation in vivo.

  DOI：

  10.1021/tx4002435