4-(3'-methoxy-4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine | 90684-19-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 4-(3'-methoxy-4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine
• 英文别名: 4-(4-Hydroxy-3-methoxyphenyl)-1,2,3,6-tetrahydropyridine；2-Methoxy-4-(1,2,3,6-tetrahydropyridin-4-yl)phenol
• CAS: 90684-19-8
• 化学式: C₁₂H₁₅NO₂
• 分子量: 205.257
• InChiKey: WWAKCFYJVOQDNY-UHFFFAOYSA-N

物化性质

• 熔点：
  186-188 °C(Solv: ethanol (64-17-5))
• 沸点：
  363.7±42.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(3'-methoxy-4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine 在 吡啶 、 盐酸 、 potassium carbonate 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 5.0h， 生成 4-(3',4'-dimethoxyphenyl)-1,2,3,6-tetrahydropyridine
  参考文献：
  名称：

  Synthesis and dihydropteridine reductase inhibitory effects of potential metabolites of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

  摘要：

  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a nigrostriatal neurotoxin which can cause irreversible parkinsonism in humans and primates by selective destruction of neurons in the substantia nigra. It is possible that MPTP could be metabolized by hydroxylation of the phenyl ring and/or aromatization of its nitrogen-containing ring. Hydroxylated derivatives of 4-phenyl-1,2,3,6-tetrahydropyridine, 4-phenylpiperidine, and 4-phenylpyridine were synthesized and tested in vitro as inhibitors of dihydropteridine reductase (DHPR) from human liver and rat striatal synaptosomes. It was found that all hydroxy derivatives were about 100-10 000 times more inhibitory than MPTP to DHPR. The inhibitory potency of the hydroxylated derivatives increased with the number of hydroxyl substitutions present on the phenyl ring (catechol greater than phenol) and with oxidation of the nitrogen-containing ring (pyridine greater than tetrahydropyridine greater than piperidine).

  DOI：

  10.1021/jm00381a009
• 作为产物：
  描述：

  4,4-哌啶二醇 、 木榴油 在 盐酸 作用下， 以 溶剂黄146 为溶剂， 反应 48.0h， 以81%的产率得到4-(3'-methoxy-4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine
  参考文献：
  名称：

  Synthesis and dihydropteridine reductase inhibitory effects of potential metabolites of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

  摘要：

  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a nigrostriatal neurotoxin which can cause irreversible parkinsonism in humans and primates by selective destruction of neurons in the substantia nigra. It is possible that MPTP could be metabolized by hydroxylation of the phenyl ring and/or aromatization of its nitrogen-containing ring. Hydroxylated derivatives of 4-phenyl-1,2,3,6-tetrahydropyridine, 4-phenylpiperidine, and 4-phenylpyridine were synthesized and tested in vitro as inhibitors of dihydropteridine reductase (DHPR) from human liver and rat striatal synaptosomes. It was found that all hydroxy derivatives were about 100-10 000 times more inhibitory than MPTP to DHPR. The inhibitory potency of the hydroxylated derivatives increased with the number of hydroxyl substitutions present on the phenyl ring (catechol greater than phenol) and with oxidation of the nitrogen-containing ring (pyridine greater than tetrahydropyridine greater than piperidine).

  DOI：

  10.1021/jm00381a009

文献信息

• Benzopyran derivatives and pharmaceutical compositions containing them
  申请人：Rhone-Poulenc Sante

  公开号：US04977166A1

  公开（公告）日：1990-12-11

  New benzopyran derivatives of formula: ##STR1## in which R.sub.1 is hydrogen, halogen, hydroxy, alkoxy, nitro, amino, alkylsulphonamido, bis(alkylsulphonyl) amino or acylamino, X is nitrogen or a >CH-radical R is a radical of formula: ##STR2## in which A denotes a single bond or methylene or, when X is nitrogen, A may denote carbonyl, and R.sub.2 and R.sub.3, which are identical or different, are hydrogen, halogen, hydroxy, alkyl, alkoxy, nitro, amino, alkylsulphonamido, bis(alkylsulphonyl)amino, acylamino, sulphamoyl or cyano, or, when they are adjacent, together form a methylenedioxy or ethylenedioxy radical, or else R is pyridyl or 2(2H)-benzimidazolonyl if X denotes >CH--, and R' and R" are identical and are hydrogen or alkyl, their isomeric forms and mixtures thereof, and their acid addition salts, can be used as antiarrhythmic and antifibrillation agents.

  新的苯并吡喃衍生物的化学式为：##STR1## 其中 R.sub.1 是氢、卤素、羟基、烷氧基、硝基、氨基、烷基磺酰胺基、双(烷基磺酰基)氨基或酰胺基，X 是氮或一个 >CH-基团，R 是一个化学式的基团：##STR2## 其中 A 表示一个单键或亚甲基，或者当 X 是氮时，A 可表示羰基，R.sub.2 和 R.sub.3，它们相同或不同，是氢、卤素、羟基、烷基、烷氧基、硝基、氨基、烷基磺酰胺基、双(烷基磺酰基)氨基、酰胺基、磺酰胺基或氰基，或者当它们相邻时，一起形成一个亚甲二氧基或乙烯二氧基基团，或者 R 是吡啶基或 2(2H)-苯并咪唑基，如果 X 表示 >CH--，而 R' 和 R" 相同且是氢或烷基，它们的异构体形式和混合物，以及它们的酸盐加合物，可用作抗心律失常和抗纤颤剂。
• BROSSI, A.;GESSNER, W.;RONG-SEN, SHEN;ABELL, C. W., SYMP. CHEM. HETEROCYCL. COMPOUNDS (8TH) AND NUCL. ACID. COMPONENTS (6TH) +
  作者：BROSSI, A.、GESSNER, W.、RONG-SEN, SHEN、ABELL, C. W.

  DOI：——

  日期：——
• GESSNER, W.;BROSSI, A.;SHEN, RONG-SEN;ABELL, C. W., J. MED. CHEM., 1985, 28, N 3, 311-317
  作者：GESSNER, W.、BROSSI, A.、SHEN, RONG-SEN、ABELL, C. W.

  DOI：——

  日期：——
• US4977166A
  申请人：——

  公开号：US4977166A

  公开（公告）日：1990-12-11
• Synthesis and dihydropteridine reductase inhibitory effects of potential metabolites of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  作者：Wieslaw Gessner、Arnold Brossi、Rong Sen Shen、Creed W. Abell

  DOI：10.1021/jm00381a009

  日期：1985.3

  1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a nigrostriatal neurotoxin which can cause irreversible parkinsonism in humans and primates by selective destruction of neurons in the substantia nigra. It is possible that MPTP could be metabolized by hydroxylation of the phenyl ring and/or aromatization of its nitrogen-containing ring. Hydroxylated derivatives of 4-phenyl-1,2,3,6-tetrahydropyridine, 4-phenylpiperidine, and 4-phenylpyridine were synthesized and tested in vitro as inhibitors of dihydropteridine reductase (DHPR) from human liver and rat striatal synaptosomes. It was found that all hydroxy derivatives were about 100-10 000 times more inhibitory than MPTP to DHPR. The inhibitory potency of the hydroxylated derivatives increased with the number of hydroxyl substitutions present on the phenyl ring (catechol greater than phenol) and with oxidation of the nitrogen-containing ring (pyridine greater than tetrahydropyridine greater than piperidine).