α-Acetoxy-N-desmethyltamoxifen | 288617-60-7

• 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: α-Acetoxy-N-desmethyltamoxifen
• 英文别名: (E)-2-Acetoxy-4-{4-[2-(methylamino)ethoxy]phenyl}-3,4-diphenyl-3-butene
• CAS: 288617-60-7
• 化学式: C₂₇H₂₉NO₃
• 分子量: 415.532
• InChiKey: FEMBRPZDTPXUNG-RQZHXJHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  31.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  47.56
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  α-Acetoxy-N-desmethyltamoxifen 、 2'-Deoxyguanosine 3'-monophosphate 在 Tris-HCl buffer 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 、
  参考文献：
  名称：

  Identification of Tamoxifen−DNA Adducts Induced by α-Acetoxy-N-desmethyltamoxifen

  摘要：

  Treatment with tamoxifen increased the risk of endometrial cancers in breast cancer patients and women participating in the chemoprevention study. In our laboratory, tamoxifen-DNA adducts, including alpha-(N-2-deoxyguanosinyl)tamoxifen (dG-N-2-TAM), were detected in the endometrium of women taking tamoxifen [Shibutani, S., et al. (1999) Chem. Res. Toxicol. 12, 646-653]. On the basis of recent animal studies, deoxyguanosinyl-N-desmethyltamoxifen (dG-N-desmethylTAM) adducts are also suspected to be formed in the liver. In the study presented here, we synthesized alpha-acetoxy-N-desmethyltamoxifen as a model activated metabolite of N-desmethyltamoxifen. The overall yield of alpha-acetoxy-N-desmethyltamoxifen from alpha-hydroxytamoxifen was approximately 42%. alpha-Acetoxy-N-desmethyltamoxifen was highly reactive to 2'-deoxyguanosine, as was similarly observed for tamoxifen alpha-sulfate. The two reaction products were identified as a mixture of epimers of the trans form or cis form of alpha-(N-2-deoxyguanosinyl)N-desmethyltamoxifen (dG-N-2-N-desmethylTAM) by mass and proton magnetic resonance spectres copy. In addition, the trans and cis forms of dG 3'-monophosphate-N-2-N-desmethylTAM were prepared as standard markers for P-32-postlabeling/HPLC analysis. Using this technique, dG-N-2-N-desmethylTAM adducts were detected in calf thymus DNA reacted with alpha-acetoxy-N-desmethyltamoxifen.

  DOI：

  10.1021/tx000074o
• 作为产物：
  描述：

  (E)-4-{4-[2-(N-Ethoxycarbonyl-N-methylamino)ethoxy]phenyl}-3,4-diphenyl-3-buten-2-ol 在 palladium on activated charcoal 吡啶 、 氢氧化钾 、 氢气 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 乙二醇 、 乙酸乙酯 为溶剂， 反应 22.0h， 生成 α-Acetoxy-N-desmethyltamoxifen
  参考文献：
  名称：

  Identification of Tamoxifen−DNA Adducts Induced by α-Acetoxy-N-desmethyltamoxifen

  摘要：

  Treatment with tamoxifen increased the risk of endometrial cancers in breast cancer patients and women participating in the chemoprevention study. In our laboratory, tamoxifen-DNA adducts, including alpha-(N-2-deoxyguanosinyl)tamoxifen (dG-N-2-TAM), were detected in the endometrium of women taking tamoxifen [Shibutani, S., et al. (1999) Chem. Res. Toxicol. 12, 646-653]. On the basis of recent animal studies, deoxyguanosinyl-N-desmethyltamoxifen (dG-N-desmethylTAM) adducts are also suspected to be formed in the liver. In the study presented here, we synthesized alpha-acetoxy-N-desmethyltamoxifen as a model activated metabolite of N-desmethyltamoxifen. The overall yield of alpha-acetoxy-N-desmethyltamoxifen from alpha-hydroxytamoxifen was approximately 42%. alpha-Acetoxy-N-desmethyltamoxifen was highly reactive to 2'-deoxyguanosine, as was similarly observed for tamoxifen alpha-sulfate. The two reaction products were identified as a mixture of epimers of the trans form or cis form of alpha-(N-2-deoxyguanosinyl)N-desmethyltamoxifen (dG-N-2-N-desmethylTAM) by mass and proton magnetic resonance spectres copy. In addition, the trans and cis forms of dG 3'-monophosphate-N-2-N-desmethylTAM were prepared as standard markers for P-32-postlabeling/HPLC analysis. Using this technique, dG-N-2-N-desmethylTAM adducts were detected in calf thymus DNA reacted with alpha-acetoxy-N-desmethyltamoxifen.

  DOI：

  10.1021/tx000074o