1-methyl-3-(4-methoxyphenyl)pyrrole | 37704-41-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 1-methyl-3-(4-methoxyphenyl)pyrrole
• 英文别名: 3-(4-methoxy-phenyl)-1-methyl-pyrrole；3-(4-Methoxyphenyl)-1-methylpyrrole
• CAS: 37704-41-9
• 化学式: C₁₂H₁₃NO
• 分子量: 187.241
• InChiKey: RCZFNTKQFCLMKE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  14.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3-p-methoxyphenyl-1,1,5,5-tetramethyl-1H-1,5-diazapentadienium perchlorate 在 sodium methylate 作用下， 以 吡啶 为溶剂， 生成 1-methyl-3-(4-methoxyphenyl)pyrrole
  参考文献：
  名称：

  Neurotoxicity studies with the monoamine oxidase B substrate 1-methyl-3-phenyl-3-pyrroline

  摘要：

  The neurotoxic properties of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are dependent on its metabolic activation in a reaction catalyzed by centrally located monoamine oxidase B (MAO-13). This reaction ultimately leads to the permanently charged 1-methyl-4-phenylpyridinium species MW, a 4-electron oxidation product of MPTP and a potent mitochondrial toxin. The corresponding 5-membered analogue, 1-methyl-3-phenyt-3-pyrroline, is also a selective MAO-13 substrate. Unlike MPTP, the MAO-B-catalyzed oxidation of 1-methyl-3-phenyl-3-pyrroline is a 2-electron process that leads to the neutral 1-methyl-3-phenylpyrrole. MPP+ is thought to exert its toxic effects only after accumulating in the mitochondria, a process driven by the transmembrane electrochemical gradient. Since this energy-dependent accumulation of MPP+ relies upon its permanent charge, 1-methyl-3-phenyl-3-pyrrolines and their pyrrolyl oxidation products should not be neurotoxic. We have tested this hypothesis by examining the neurotoxic potential of 1-methyl-3-phenyl-3-pyrroline and 1-methyl-3-(4chlorophenyl)-3-pyrroline in the C57BL/6 mouse model. These pyrrolines did not deplete striatal dopamine while analogous treatment with MPTP resulted in 65-73% depletion. Kinetic studies revealed that both 1-methyl-3-phenyl-3-pyrroline and its pyrrolyl oxidation product were present in the brain in relatively high concentrations. Unlike MPP+, however, 1-methyl-3-phenylpyrrole was cleared from the brain quickly. These results suggest that the brain MAO-B-catalyzed oxidation of xenobiotic amines is not, in itself, sufficient to account for the neurodegenerative properties of a compound like MPTP. The rapid clearance of 1-methyl-3-phenylpyrroles from the brain may contribute to their lack of neurotoxicity. (c) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.lfs.2007.06.014

文献信息

• Gallagher, Peter T.; Palmer, Jane L.; Morgan, Sarah E., Journal of the Chemical Society. Perkin transactions I, 1990, # 11, p. 3212 - 3214
  作者：Gallagher, Peter T.、Palmer, Jane L.、Morgan, Sarah E.

  DOI：——

  日期：——
• Neurotoxicity studies with the monoamine oxidase B substrate 1-methyl-3-phenyl-3-pyrroline
  作者：Modupe O. Ogunrombi、Sarel F. Malan、Gisella Terre'Blanche、Kay Castagnoli、Neal Castagnoli、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.lfs.2007.06.014

  日期：2007.7

  The neurotoxic properties of the parkinsonian inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are dependent on its metabolic activation in a reaction catalyzed by centrally located monoamine oxidase B (MAO-13). This reaction ultimately leads to the permanently charged 1-methyl-4-phenylpyridinium species MW, a 4-electron oxidation product of MPTP and a potent mitochondrial toxin. The corresponding 5-membered analogue, 1-methyl-3-phenyt-3-pyrroline, is also a selective MAO-13 substrate. Unlike MPTP, the MAO-B-catalyzed oxidation of 1-methyl-3-phenyl-3-pyrroline is a 2-electron process that leads to the neutral 1-methyl-3-phenylpyrrole. MPP+ is thought to exert its toxic effects only after accumulating in the mitochondria, a process driven by the transmembrane electrochemical gradient. Since this energy-dependent accumulation of MPP+ relies upon its permanent charge, 1-methyl-3-phenyl-3-pyrrolines and their pyrrolyl oxidation products should not be neurotoxic. We have tested this hypothesis by examining the neurotoxic potential of 1-methyl-3-phenyl-3-pyrroline and 1-methyl-3-(4chlorophenyl)-3-pyrroline in the C57BL/6 mouse model. These pyrrolines did not deplete striatal dopamine while analogous treatment with MPTP resulted in 65-73% depletion. Kinetic studies revealed that both 1-methyl-3-phenyl-3-pyrroline and its pyrrolyl oxidation product were present in the brain in relatively high concentrations. Unlike MPP+, however, 1-methyl-3-phenylpyrrole was cleared from the brain quickly. These results suggest that the brain MAO-B-catalyzed oxidation of xenobiotic amines is not, in itself, sufficient to account for the neurodegenerative properties of a compound like MPTP. The rapid clearance of 1-methyl-3-phenylpyrroles from the brain may contribute to their lack of neurotoxicity. (c) 2007 Elsevier Inc. All rights reserved.
• GALLAGHER, PETER T.;PALMER, JANE L.;MORGAN, SARAH E., J. CHEM. SOC. PERKIN TRANS. PT 1,(1990) N1, C. 3212-3214
  作者：GALLAGHER, PETER T.、PALMER, JANE L.、MORGAN, SARAH E.

  DOI：——

  日期：——
• Structure–activity relationships in the inhibition of monoamine oxidase B by 1-methyl-3-phenylpyrroles
  作者：Modupe O. Ogunrombi、Sarel F. Malan、Gisella Terre’Blanche、Neal Castagnoli、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmc.2007.11.059

  日期：2008.3

  Methyl-3-phenyl-3-pyrrolines are structural analogues of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and like MPTP are selective substrates of monoamine oxidase B (MAO-B). As part of an ongoing investigation into the substrate properties of various 1-methyl-3-phenyl-3-pyrrolinyl derivatives, it is shown in the present study that their respective MAO-B catalyzed oxidation products act as reversible competitive inhibitors of the enzyme. The most potent inhibitor among the oxidation products considered was 1-methyl-3-(4-trifluoromethylphenyl)pyrrole with an enzyme-inhibitor dissociation constant (K-i value) of 1.30 mu M. The least potent inhibitor was found to be 1-methyl-3-phenylpyrrole with a K-i value of 118 mu M. The results of an SAR study established that the potency of MAO-B inhibition by the 1-methyl-3-phenylpyrrolyl derivatives examined here is dependent on the Taft steric parameter (E-s) and Swain-Lupton electronic constant (F) of the substituents attached to C-4 of the phenyl ring. Electron-withdrawing substituents with a large degree of steric bulkiness appear to enhance inhibition potency. Potency was also found to vary with the substituents at C-3, again with E-s and F being the principal substituent descriptors. (C) 2007 Elsevier Ltd. All rights reserved.