1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide | 95969-40-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide
• 英文别名: 1-methyl-1-oxido-4-phenyl-3,6-dihydro-2H-pyridin-1-ium
• CAS: 95969-40-7
• 化学式: C₁₂H₁₅NO
• 分子量: 189.257
• InChiKey: FZVSMNOAJGWONA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  18.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide 以 二氯甲烷 、 水 为溶剂， 反应 1.25h， 生成 1,2,5,6-tetrahydro-1-methyl-4-phenyl-2-pyridine carbonitrile
  参考文献：
  名称：

  肝脏匀浆馏分代谢黑质纹状体毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶。

  摘要：

  已在大鼠和兔肝线粒体和兔肝微粒体制剂中检查了黑纹状体毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的代谢命运。线粒体制剂在对Pargyline敏感的反应中将MPTP迅速氧化成极性物质，该物质显示主要成分为1-甲基-4-苯基吡啶鎓。NADPH补充的微粒体制剂将MPTP转换为两种主要产物：4-苯基-1,2,3,6-四氢吡啶和1-甲基-4-苯基-1,2,3,6-四氢吡啶N-氧化物。一氧化碳和SKF 525A选择性抑制MPTP氧化为nor化合物，表明该N-去甲基化反应是细胞色素P-450催化的。试图在与氰化钠的微粒体温育混合物中捕获MPTP可能不稳定的亚氨酸亚胺代谢物，导致分离出单氰基加合物，该单氰基加合物被证明是N-氰基甲基衍生物。因此，肝线粒体和微粒体酶系统通过不同的途径催化MPTP的氧化，前者导致产生可能具有神经毒性的物质。

  DOI：

  10.1021/jm00146a005
• 作为产物：
  描述：

  1-甲基-4-苯基-1,2,3,6-四氢吡啶 在 双氧水 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以94%的产率得到1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide
  参考文献：
  名称：

  将1-甲基-4-苯基-1,2,3,6-四氢吡啶（mptp）及其5-甲基类似物转化为吡啶鎓盐†

  摘要：

  单胺氧化酶B首先将1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP; 1）代谢为1-甲基-4-苯基-2,3-二氢吡啶鎓盐（MPDP + ; 5），然后然后制得1-甲基-4-苯基phr鎓盐（MPP +；7）。MPDP +及其5-甲基类似物6的化学合成分别通过Polonovski反应由MPTP及其5-甲基类似物的N-氧化物3和4完成。用空气将MPDP +氧化为MPPM +，并通过Pt催化剂大大加速了氧化。减少MPDP +用NaBH 4的MPP +提供了MPTP。

  DOI：

  10.1002/hlca.19840670803

文献信息

• Conversion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) and its 5-methyl analog into pyridinium salts
  作者：Wieslaw Gessner、Arnold Brossi、Rong-Sen Shen、Richard R. Fritz、Creed W. Abell

  DOI：10.1002/hlca.19840670803

  日期：1984.12.19

  Monoamine oxidase B metabolizes 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 1) first to 1-methyl-4-phenyl-2,3-dihydropyridinium salt (MPDP+; 5), and then to 1-methyl-4-phenylphridinium salt (MPP+; 7). Chemical synthesis of MPDP+ and its 5-methyl analog 6 was accomplished from the N-oxides 3 and 4 of MPTP and its 5-methyl analog, respectively, by a Polonovski reaction. Oxidation of MPDP+ to

  单胺氧化酶B首先将1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP; 1）代谢为1-甲基-4-苯基-2,3-二氢吡啶鎓盐（MPDP + ; 5），然后然后制得1-甲基-4-苯基phr鎓盐（MPP +；7）。MPDP +及其5-甲基类似物6的化学合成分别通过Polonovski反应由MPTP及其5-甲基类似物的N-氧化物3和4完成。用空气将MPDP +氧化为MPPM +，并通过Pt催化剂大大加速了氧化。减少MPDP +用NaBH 4的MPP +提供了MPTP。
• Preferential Extracellular Generation of the Active Parkinsonian Toxin MPP⁺by Transporter-Independent Export of the Intermediate MPDP⁺
  作者：Stefan Schildknecht、Regina Pape、Johannes Meiser、Christiaan Karreman、Tobias Strittmatter、Meike Odermatt、Erica Cirri、Anke Friemel、Markus Ringwald、Noemi Pasquarelli、Boris Ferger、Thomas Brunner、Andreas Marx、Heiko M. Möller、Karsten Hiller、Marcel Leist

  DOI：10.1089/ars.2015.6297

  日期：2015.11

  Aims: 1-Methyl-4-phenyl-tetrahydropyridine (MPTP) is among the most widely used neurotoxins for inducing experimental parkinsonism. MPTP causes parkinsonian symptoms in mice, primates, and humans by killing a subpopulation of dopaminergic neurons. Extrapolations of data obtained using MPTP-based parkinsonism models to human disease are common; however, the precise mechanism by which MPTP is converted into its active neurotoxic metabolite, 1-methyl-4-phenyl-pyridinium (MPP+), has not been fully elucidated. In this study, we aimed to address two unanswered questions related to MPTP toxicology: (1) Why are MPTP-converting astrocytes largely spared from toxicity? (2) How does MPP+ reach the extracellular space? Results: In MPTP-treated astrocytes, we discovered that the membrane-impermeable MPP+, which is generally assumed to be formed inside astrocytes, is almost exclusively detected outside of these cells. Instead of a transporter-mediated export, we found that the intermediate, 1-methyl-4-phenyl-2,3-dihydropyridinium (MPDP+), and/or its uncharged conjugate base passively diffused across cell membranes and that MPP+ was formed predominately by the extracellular oxidation of MPDP+ into MPP+. This nonenzymatic extracellular conversion of MPDP+ was promoted by O-2, a more alkaline pH, and dopamine autoxidation products. Innovation and Conclusion: Our data indicate that MPTP metabolism is compartmentalized between intracellular and extracellular environments, explain the absence of toxicity in MPTP-converting astrocytes, and provide a rationale for the preferential formation of MPP+ in the extracellular space. The mechanism of transporter-independent extracellular MPP+ formation described here indicates that extracellular genesis of MPP+ from MPDP is a necessary prerequisite for the selective uptake of this toxin by catecholaminergic neurons.
• 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：——
• Metabolism of the nigrostriatal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by liver homogenate fractions
  作者：Jeff Weissman、Anthony Trevor、Kan Chiba、Lisa A. Peterson、Patricia Caldera、Neal Castagnoli、Thomas Baillie

  DOI：10.1021/jm00146a005

  日期：1985.8

  6-tetrahydropyridine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine N-oxide. Carbon monoxide and SKF 525A selectively inhibited the oxidation of MPTP to the nor compound, indicating that this N-demethylation reaction is cytochrome P-450 catalyzed. Attempts to trap possible unstable iminium metabolites of MPTP in microsomal incubation mixtures with sodium cyanide led to the isolation of a monocyano adduct that proved

  已在大鼠和兔肝线粒体和兔肝微粒体制剂中检查了黑纹状体毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的代谢命运。线粒体制剂在对Pargyline敏感的反应中将MPTP迅速氧化成极性物质，该物质显示主要成分为1-甲基-4-苯基吡啶鎓。NADPH补充的微粒体制剂将MPTP转换为两种主要产物：4-苯基-1,2,3,6-四氢吡啶和1-甲基-4-苯基-1,2,3,6-四氢吡啶N-氧化物。一氧化碳和SKF 525A选择性抑制MPTP氧化为nor化合物，表明该N-去甲基化反应是细胞色素P-450催化的。试图在与氰化钠的微粒体温育混合物中捕获MPTP可能不稳定的亚氨酸亚胺代谢物，导致分离出单氰基加合物，该单氰基加合物被证明是N-氰基甲基衍生物。因此，肝线粒体和微粒体酶系统通过不同的途径催化MPTP的氧化，前者导致产生可能具有神经毒性的物质。