1,2-二苯基-1-(4-羟基苯基)乙醇 | 355803-76-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 1,2-二苯基-1-(4-羟基苯基)乙醇
• 中文别名: 1-乙基-5-吡啶-3-基吡咯烷-2-酮
• 英文名称: (+/-)-[1-(4-hydroxyphenyl)]-1,2-diphenylethanol
• 英文别名: 4-(1-hydroxy-1,2-diphenylethyl)phenol；(+/-)-1-Hydroxy-1.2-diphenyl-1-(4-hydroxy-phenyl)-aethan；1-(4-Hydroxy-phenyl)-1,2-diphenyl-aethanol；1,2-Diphenyl-1-(4-hydroxyphenyl)ethanol
• CAS: 355803-76-8
• 化学式: C₂₀H₁₈O₂
• 分子量: 290.362
• InChiKey: LQDKHIMEMDNRPO-UHFFFAOYSA-N

物化性质

• 熔点：
  135-137°C
• 沸点：
  452.5±40.0 °C(Predicted)
• 密度：
  1.195±0.06 g/cm3(Predicted)
• 溶解度：
  溶于乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2907299090

反应信息

• 作为反应物：
  描述：

  1,2-二苯基-1-(4-羟基苯基)乙醇 在 氢氧化钾 、 溴 作用下， 以 1,4-二氧六环 、 四氯化碳 、 甲苯 为溶剂， 反应 1.08h， 生成 (E,Z)-1-bromo-2-[4-(2-aminoethoxy)phenyl]-1,2-diphenylethene
  参考文献：
  名称：

  Quantification of Tamoxifen DNA Adducts Using On-Line Sample Preparation and HPLC-Electrospray Ionization Tandem Mass Spectrometry

  摘要：

  The nonsteroidal antiestrogen tamoxifen is used as an adjuvant chemotherapeutic agent for the treatment of all stages of hormone-dependent breast cancer and more recently as a chemopreventive agent in women with elevated risk of developing the disease. While clearly beneficial for the treatment of breast cancer, tamoxifen has been reported to increase the risk of endometrial cancer in women. Furthermore, it has been shown to be hepatocarcinogenic in rats. Tamoxifen is clearly genotoxic in rat liver, as indicated by the formation of DNA adducts; the occurrence of tamoxifen DNA adducts in human endometrial tissue is more controversial. The detection and quantitation of tamoxifen DNA adducts have relied primarily upon P-32-postlabeling, with other techniques, such as immunoassays and accelerator mass spectrometry, being used to a much lesser extent. To expand the range of available analytical methodologies for quantifying tamoxifen DNA adducts, we have developed an assay using on-line sample preparation, coupled with HPLC and electrospray ionization tandem mass spectrometry (ES-MS/MS). alpha-Acetoxytamoxifen was reacted with salmon testis DNA at ratios between 0.1 ng and 1 mg alpha-acetoxytamoxifen per mg DNA. After enzymatic hydrolysis to nucleosides, the most highly modified DNA samples were analyzed by HPLC-UV, which indicated the presence of two adduct peaks in approximately a 1:4 ratio. The major adduct was isolated, rigorously characterized as (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen, and quantified on the basis of its molar extinction coefficient. A similar reaction was conducted with [N(CD3)(2)]-alpha-acetoxytamoxifen to prepare a deuterated adduct that could serve as an internal standard for ES-MS/MS. The limit of detection for the HPLC-ES-MS/MS method was approximately 5 adducts/10(9) nucleotides, with an intra- and interassay precision of 3% relative standard deviation. The method was validated over the range of 8-1 520 000 adducts/10(8) nucleotides using 100 mug samples of DNA modified in vitro. Analysis of liver DNA from female Sprague-Dawley rats treated by gavage with seven daily doses of 20 mg tamoxifen/kg body weight gave a value of 496 +/- 16 adducts/10(8) nucleotides for (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen and 626 +/- 18 adducts/10(8) nucleotides for (E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen. These data indicate that the HPLC-ES-MS/MS methodology has sufficient sensitivity and precision to be useful in the analysis of tamoxifen DNA adducts formed in vivo in experimental models and may be able to detect tamoxifen DNA adduct formation in human tissue samples.

  DOI：

  10.1021/tx020090g
• 作为产物：
  描述：

  4-羟基-二苯甲酮 、 苄基氯化镁 在 氯化铵 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以86%的产率得到1,2-二苯基-1-(4-羟基苯基)乙醇
  参考文献：
  名称：

  Doing the methylene shuffle – Further insights into the inhibition of mitotic kinesin Eg5 with S-trityl l-cysteine

  摘要：

  S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on these data, we have explored the SAR of the trityl head group using the methylene shuffle strategy to expand the occupation of one of the hydrophobic pockets. The most potent compounds exhibit strong (<100 nM) inhibition of Eg5 in the basal ATPase assay and inhibit growth in a variety of tumour-derived cell lines. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.034

文献信息

• Hydroxy substituted triphenyl vinyl halides
  申请人：G W CARNRICK COMPANY

  公开号：US02429556A1

  公开（公告）日：1947-10-21
• Doing the methylene shuffle – Further insights into the inhibition of mitotic kinesin Eg5 with S-trityl l-cysteine
  作者：Murad N. Abualhasan、James A.D. Good、Kitiyaporn Wittayanarakul、Nahoum G. Anthony、Giacomo Berretta、Oliver Rath、Frank Kozielski、Oliver B. Sutcliffe、Simon P. Mackay

  DOI：10.1016/j.ejmech.2012.05.034

  日期：2012.8

  S-Trityl L-cysteine (STLC) is an inhibitor of the mitotic kinesin Eg5 with potential as an antimitotic chemotherapeutic agent. We previously reported the crystal structure of the ligand protein complex, and now for the first time, have quantified the interactions using a molecular dynamics based approach. Based on these data, we have explored the SAR of the trityl head group using the methylene shuffle strategy to expand the occupation of one of the hydrophobic pockets. The most potent compounds exhibit strong (<100 nM) inhibition of Eg5 in the basal ATPase assay and inhibit growth in a variety of tumour-derived cell lines. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Quantification of Tamoxifen DNA Adducts Using On-Line Sample Preparation and HPLC-Electrospray Ionization Tandem Mass Spectrometry
  作者：Gonçalo Gamboa da Costa、M. Matilde Marques、Frederick A. Beland、James P. Freeman、Mona I. Churchwell、Daniel R. Doerge

  DOI：10.1021/tx020090g

  日期：2003.3.1

  The nonsteroidal antiestrogen tamoxifen is used as an adjuvant chemotherapeutic agent for the treatment of all stages of hormone-dependent breast cancer and more recently as a chemopreventive agent in women with elevated risk of developing the disease. While clearly beneficial for the treatment of breast cancer, tamoxifen has been reported to increase the risk of endometrial cancer in women. Furthermore, it has been shown to be hepatocarcinogenic in rats. Tamoxifen is clearly genotoxic in rat liver, as indicated by the formation of DNA adducts; the occurrence of tamoxifen DNA adducts in human endometrial tissue is more controversial. The detection and quantitation of tamoxifen DNA adducts have relied primarily upon P-32-postlabeling, with other techniques, such as immunoassays and accelerator mass spectrometry, being used to a much lesser extent. To expand the range of available analytical methodologies for quantifying tamoxifen DNA adducts, we have developed an assay using on-line sample preparation, coupled with HPLC and electrospray ionization tandem mass spectrometry (ES-MS/MS). alpha-Acetoxytamoxifen was reacted with salmon testis DNA at ratios between 0.1 ng and 1 mg alpha-acetoxytamoxifen per mg DNA. After enzymatic hydrolysis to nucleosides, the most highly modified DNA samples were analyzed by HPLC-UV, which indicated the presence of two adduct peaks in approximately a 1:4 ratio. The major adduct was isolated, rigorously characterized as (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen, and quantified on the basis of its molar extinction coefficient. A similar reaction was conducted with [N(CD3)(2)]-alpha-acetoxytamoxifen to prepare a deuterated adduct that could serve as an internal standard for ES-MS/MS. The limit of detection for the HPLC-ES-MS/MS method was approximately 5 adducts/10(9) nucleotides, with an intra- and interassay precision of 3% relative standard deviation. The method was validated over the range of 8-1 520 000 adducts/10(8) nucleotides using 100 mug samples of DNA modified in vitro. Analysis of liver DNA from female Sprague-Dawley rats treated by gavage with seven daily doses of 20 mg tamoxifen/kg body weight gave a value of 496 +/- 16 adducts/10(8) nucleotides for (E)-alpha-(deoxyguanosin-N-2-yl)tamoxifen and 626 +/- 18 adducts/10(8) nucleotides for (E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen. These data indicate that the HPLC-ES-MS/MS methodology has sufficient sensitivity and precision to be useful in the analysis of tamoxifen DNA adducts formed in vivo in experimental models and may be able to detect tamoxifen DNA adduct formation in human tissue samples.