3-[(4'-benzyloxyphenyl)amino]propane-1,2-diol | 70133-06-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-[(4'-benzyloxyphenyl)amino]propane-1,2-diol
• 英文别名: 3-(4-benzyloxy-anilino)-propane-1,2-diol；1,2-Propanediol, 3-[[4-(phenylmethoxy)phenyl]amino]-；3-(4-phenylmethoxyanilino)propane-1,2-diol
• CAS: 70133-06-1
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: PTVDPONOUBBLRI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  61.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[(4'-benzyloxyphenyl)amino]propane-1,2-diol 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 3-[(4'-hydroxyphenyl)amino]propane-1,2-diol
  参考文献：
  名称：

  Biotransformation and Clearance of 3-(Phenylamino)propane-1,2-diol, a Compound Present in Samples Related to Toxic Oil Syndrome, in C57BL/6 and A/J Mice

  摘要：

  In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were detected in oils and implicated as potential toxic agents and markers of toxic oil batches. Epidemiological evidence points to 3-(phenylamino)propane-1,2-diol derivatives as the putative toxic agents, which were generated during the refining process at the ITH refinery. Here we present the biotransformation and clearance of 3-(phenylamino)propane-1,2-diol (PAP) administered intraperitoneally to A/J and C57BL/6 mice that have been proposed as a murine model for the immunological features of TOS. Mice eliminated 6 mu Ci of [U-C-14]PAP during a 24 h period, mostly in urine. Animals exhibited urine elimination rates of 70 and 36% in A/J and C57BL/6 strains, respectively. A/J mice exhibited no increase in the elimination rate when induced with P-naphthoflavone, whereas C57BL/6 did increase the rate of elimination to 57%. Feces contributed to a lesser extent to the elimination rate (0.6 and 3.3% in A/J and C57BL/6 mice, respectively). Radioactivity remaining in organ tissues was lower than 1% (liver, lung, kidney, spleen, heart, and muscle). Metabolic species in urine were identified by HPLC coupled to UV and radioisotope detectors and further GC/MS analyses. 2-Hydroxy-3-(phenylamino)propanoic acid metabolite was the major chemical species excreted in urine in both strains, in both control and induced animal groups. This compound was the main urinary metabolite of PAP, and unmetabolized PAP excreted in urine constituted less than 1% of the total administered dose. Two additional highly polar metabolites also detected in urine were identified as 3- [(4'-hydroxyphenyl)amino] propane-1,2-diol and 2-hydroxy-3-[(4'-hydroxyphenyl) amino] propanoic acid. These findings are the first reported on PAP metabolism and clearance in mice strains and suggest that PAP can be extensively metabolized in vivo and potential reactive species can be generated.

  DOI：

  10.1021/tx990105j
• 作为产物：
  描述：

  4-苄氧基苯胺 、 缩水甘油 在 lithium trifluoromethanesulfonate 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 4.0h， 以45%的产率得到3-[(4'-benzyloxyphenyl)amino]propane-1,2-diol
  参考文献：
  名称：

  Biotransformation and Clearance of 3-(Phenylamino)propane-1,2-diol, a Compound Present in Samples Related to Toxic Oil Syndrome, in C57BL/6 and A/J Mice

  摘要：

  In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were detected in oils and implicated as potential toxic agents and markers of toxic oil batches. Epidemiological evidence points to 3-(phenylamino)propane-1,2-diol derivatives as the putative toxic agents, which were generated during the refining process at the ITH refinery. Here we present the biotransformation and clearance of 3-(phenylamino)propane-1,2-diol (PAP) administered intraperitoneally to A/J and C57BL/6 mice that have been proposed as a murine model for the immunological features of TOS. Mice eliminated 6 mu Ci of [U-C-14]PAP during a 24 h period, mostly in urine. Animals exhibited urine elimination rates of 70 and 36% in A/J and C57BL/6 strains, respectively. A/J mice exhibited no increase in the elimination rate when induced with P-naphthoflavone, whereas C57BL/6 did increase the rate of elimination to 57%. Feces contributed to a lesser extent to the elimination rate (0.6 and 3.3% in A/J and C57BL/6 mice, respectively). Radioactivity remaining in organ tissues was lower than 1% (liver, lung, kidney, spleen, heart, and muscle). Metabolic species in urine were identified by HPLC coupled to UV and radioisotope detectors and further GC/MS analyses. 2-Hydroxy-3-(phenylamino)propanoic acid metabolite was the major chemical species excreted in urine in both strains, in both control and induced animal groups. This compound was the main urinary metabolite of PAP, and unmetabolized PAP excreted in urine constituted less than 1% of the total administered dose. Two additional highly polar metabolites also detected in urine were identified as 3- [(4'-hydroxyphenyl)amino] propane-1,2-diol and 2-hydroxy-3-[(4'-hydroxyphenyl) amino] propanoic acid. These findings are the first reported on PAP metabolism and clearance in mice strains and suggest that PAP can be extensively metabolized in vivo and potential reactive species can be generated.

  DOI：

  10.1021/tx990105j

文献信息

• Process of preparing by condensation certain
  申请人：Delalande S.A.

  公开号：US05235063A1

  公开（公告）日：1993-08-10

  The derivatives of the formula: ##STR1## wherein: R.sub.1 is H or C.sub.1 -C.sub.4 alkyl; X is an oxygen atom, a methylene group or a --CH.dbd.CH-- group; n is 1 or 2 when X is an oxygen atom or a methylene group and is 0 or 1 when X is a --CH.dbd.CH-- group; R.sub.3 is a C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.7 cycloalkyl, phenyl, benzyl, CHF.sub.2, CF.sub.3 or CF.sub.3 CF.sub.2 group; each of R.sub.2 and R'.sub.2 independently is a hydrogen atom or a C.sub.1 -C.sub.4 alkyl, C.sub.4 -C.sub.7 cycloalkyl, phenyl or benzyl group; R'.sub.2 and R.sub.3 may further form together a --(CH.sub.2).sub.3 -- or --(CH.sub.2).sub.4 -- chain; and each of R.sub.4 and R'.sub.4 independently is a C.sub.1 -C.sub.4 alkyl group or R.sub.4 and R'.sub.4 form together either a --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 -- chain, a --(CH.sub.2).sub.2 -- or --(CH.sub.2).sub.3 -- chain substituted by one or two C.sub.1 -C.sub.4 alkyl groups, or a --(CH.sub.2).sub.2 -- chain substituted by one or two --CH.sub.2 --NH.sub.2 groups or by one or two --CH.sub.2 --NH.sub.2 groups N-substituted by one or two C.sub.1 -C.sub.4 alkyl groups, useful as drugs.

  该公式的衍生物：##STR1## 其中：R.sub.1为H或C.sub.1-C.sub.4烷基；X为氧原子，亚甲基或--CH.dbd.CH--基团；当X为氧原子或亚甲基时，n为1或2，当X为--CH.dbd.CH--基团时，n为0或1；R.sub.3为C.sub.1-C.sub.4烷基，C.sub.3-C.sub.7环烷基，苯基，苄基，CHF.sub.2，CF.sub.3或CF.sub.3 CF.sub.2基团；R.sub.2和R'.sub.2各自独立地为氢原子或C.sub.1-C.sub.4烷基，C.sub.4-C.sub.7环烷基，苯基或苄基；R'.sub.2和R.sub.3还可以共同形成一个--(CH.sub.2).sub.3--或--(CH.sub.2).sub.4--链；R.sub.4和R'.sub.4各自独立地为C.sub.1-C.sub.4烷基，或者R.sub.4和R'.sub.4共同形成一个--(CH.sub.2).sub.2--或--(CH.sub.2).sub.3--链，一个被一个或两个C.sub.1-C.sub.4烷基取代的--(CH.sub.2).sub.2--或--(CH.sub.2).sub.3--链，或一个被一个或两个--CH.sub.2--NH.sub.2基团或被一个或两个C.sub.1-C.sub.4烷基取代的--CH.sub.2--NH.sub.2基团取代的--(CH.sub.2).sub.2--链，可用作药物。
• Fauran; Douzon, Chimica therapeutica, 1973, vol. 8, # 3, p. 324 - 327
  作者：Fauran、Douzon

  DOI：——

  日期：——
• GATES, KENT S.;SILVERMAN, RICHARD B., J. AMER. CHEM. SOC., 112,(1990) N5, C. 9364-9372
  作者：GATES, KENT S.、SILVERMAN, RICHARD B.

  DOI：——

  日期：——
• Metabolism of (<i>R</i>)- and (<i>S</i>)-3-(Phenylamino)propane-1,2-diol in C57BL/6- and A/J-Strain Mice. Identification of New Metabolites with Potential Toxicological Significance to the Toxic Oil Syndrome
  作者：Jordi Bujons、Margarita G. Ladona、Angel Messeguer、Anna Morató、Coral Ampurdanés

  DOI：10.1021/tx010001k

  日期：2001.8.1

  The Toxic Oil Syndrome was a massive food-borne intoxication that occurred in Spain in 1981. Epidemiological studies point to 3-(phenylamino)propane-1,2-diol (PAP) derivatives as the putative toxic agents. We report further identification of metabolites cleared in urine of A/J and C57BL/6 mice in which (R)- and (S)-3-(phenylamino)propane-1,2-diol were administered intraperitoneally. This investigation is an extension of previous studies carried out with the racemic compound [Ladona, M. G., Bujons, J., Messeguer, A., Ampurdanes, C., Morato, A., and Corbella, J. (1999) Chem. Res. Toxicol. 12, 1127-1137]. Both PAP enantiomers were extensively metabolized, and several metabolites were eliminated in urine. The HPLC profiles of the urine samples of both mouse strains treated with each enantiomer were qualitatively similar, but differences were found in a relatively higher proportion of several detected metabolites in mice treated with (R)-PAP compared with those treated with (S)-PAP. The main urine metabolite continues to be 2-hydroxy-3-(phenylamino)propanoic acid (1), which confirms our previous results obtained with rac-PAP. In addition to the detection of other metabolites already reported in our previous paper, interesting evidence is provided on the presence of 4-aminophenol and paracetamol conjugates in the urine samples from both mouse strains. The detection of these metabolites suggests the in vivo formation of quinoneimine PAP derivatives. Indeed, some quinoneimine species (11 and 12), as well as other PAP metabolites (13) that bear modifications in the alkyl chain, have been tentatively identified in mouse urine. These metabolic findings might imply a potential toxicological significance for the Toxic Oil Syndrome.
• Biotransformation and Clearance of 3-(Phenylamino)propane-1,2-diol, a Compound Present in Samples Related to Toxic Oil Syndrome, in C57BL/6 and A/J Mice
  作者：Margarita G. Ladona、Jordi Bujons、Angel Messeguer、Coral Ampurdanés、Anna Morató、Jacint Corbella

  DOI：10.1021/tx990105j

  日期：1999.12.1

  In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were detected in oils and implicated as potential toxic agents and markers of toxic oil batches. Epidemiological evidence points to 3-(phenylamino)propane-1,2-diol derivatives as the putative toxic agents, which were generated during the refining process at the ITH refinery. Here we present the biotransformation and clearance of 3-(phenylamino)propane-1,2-diol (PAP) administered intraperitoneally to A/J and C57BL/6 mice that have been proposed as a murine model for the immunological features of TOS. Mice eliminated 6 mu Ci of [U-C-14]PAP during a 24 h period, mostly in urine. Animals exhibited urine elimination rates of 70 and 36% in A/J and C57BL/6 strains, respectively. A/J mice exhibited no increase in the elimination rate when induced with P-naphthoflavone, whereas C57BL/6 did increase the rate of elimination to 57%. Feces contributed to a lesser extent to the elimination rate (0.6 and 3.3% in A/J and C57BL/6 mice, respectively). Radioactivity remaining in organ tissues was lower than 1% (liver, lung, kidney, spleen, heart, and muscle). Metabolic species in urine were identified by HPLC coupled to UV and radioisotope detectors and further GC/MS analyses. 2-Hydroxy-3-(phenylamino)propanoic acid metabolite was the major chemical species excreted in urine in both strains, in both control and induced animal groups. This compound was the main urinary metabolite of PAP, and unmetabolized PAP excreted in urine constituted less than 1% of the total administered dose. Two additional highly polar metabolites also detected in urine were identified as 3- [(4'-hydroxyphenyl)amino] propane-1,2-diol and 2-hydroxy-3-[(4'-hydroxyphenyl) amino] propanoic acid. These findings are the first reported on PAP metabolism and clearance in mice strains and suggest that PAP can be extensively metabolized in vivo and potential reactive species can be generated.