1-cyclopropyl-4-thiophenoxy-1,2,3,6-tetrahydropyridine | 163632-11-9

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1-cyclopropyl-4-thiophenoxy-1,2,3,6-tetrahydropyridine
• 英文别名: 1-cyclopropyl-4-phenylsulfanyl-3,6-dihydro-2H-pyridine
• CAS: 163632-11-9
• 化学式: C₁₄H₁₇NS
• 分子量: 231.362
• InChiKey: JCOOZBUPCXTAHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  28.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-cyclopropyl-4-thiophenoxy-1,2,3,6-tetrahydropyridine 在 MAO-B (monoamine oxidase) from bovine liver 作用下， 以 phosphate buffer 为溶剂， 反应 0.03h， 生成
  参考文献：
  名称：

  Probing the Mechanism of Bioactivation of MPTP Type Analogs by Monoamine Oxidase B: Structure-Activity Studies on Substituted 4-Phenoxy-, 4-Phenyl-, and 4-Thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridines

  摘要：

  Previous studies have shown that 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine is an excellent monoamine oxidase B (MAO-B) substrate (k(cat)/K-M = 1538 min(-1) mM(-1)) although the corresponding 4-phenyl analog displays MAO-B inactivating properties only. This behavior led us to speculate that the pathway for the MAO-B catalyzed oxidation of these tetrahydropyridines may not necessarily proceed via an initial single electron transfer step as proposed by others but rather through an initial alpha-carbon hydrogen atom abstraction step. In the present studies we have examined the interactions of various 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives, some of which bear substituents on the phenyl ring. The 4-thiophenoxy- and all of the 4-phenoxytetrahydropyridine derivatives proved to be substrates but not inactivators of MAO-B, while several of the 4-phenyltetrahydropyridine derivatives were inactivators but not substrates. A case of particular interest was 1-cyclopropyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine, which displayed only substrate properties. The results are discussed in terms of two catalytic pathways, one of which involves partitioning of the proposed cyclopropylaminyl radical cation intermediate between cyclopropyl ring opening and proton loss while the second involves partitioning of the parent amine between an initial single electron transfer step, leading to cyclopropylaminyl radical cation formation and enzyme inactivation, and an initial alpha-carbon hydrogen atom abstraction step, leading to an allylic radical and dihydropyridinium product formation.

  DOI：

  10.1021/tx00047a010
• 作为产物：
  描述：

  吡喃-4-酮 在 sodium tetrahydroborate 、 氯化亚砜 、 三乙胺 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 28.0h， 生成 1-cyclopropyl-4-thiophenoxy-1,2,3,6-tetrahydropyridine
  参考文献：
  名称：

  Probing the Mechanism of Bioactivation of MPTP Type Analogs by Monoamine Oxidase B: Structure-Activity Studies on Substituted 4-Phenoxy-, 4-Phenyl-, and 4-Thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridines

  摘要：

  Previous studies have shown that 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine is an excellent monoamine oxidase B (MAO-B) substrate (k(cat)/K-M = 1538 min(-1) mM(-1)) although the corresponding 4-phenyl analog displays MAO-B inactivating properties only. This behavior led us to speculate that the pathway for the MAO-B catalyzed oxidation of these tetrahydropyridines may not necessarily proceed via an initial single electron transfer step as proposed by others but rather through an initial alpha-carbon hydrogen atom abstraction step. In the present studies we have examined the interactions of various 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives, some of which bear substituents on the phenyl ring. The 4-thiophenoxy- and all of the 4-phenoxytetrahydropyridine derivatives proved to be substrates but not inactivators of MAO-B, while several of the 4-phenyltetrahydropyridine derivatives were inactivators but not substrates. A case of particular interest was 1-cyclopropyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine, which displayed only substrate properties. The results are discussed in terms of two catalytic pathways, one of which involves partitioning of the proposed cyclopropylaminyl radical cation intermediate between cyclopropyl ring opening and proton loss while the second involves partitioning of the parent amine between an initial single electron transfer step, leading to cyclopropylaminyl radical cation formation and enzyme inactivation, and an initial alpha-carbon hydrogen atom abstraction step, leading to an allylic radical and dihydropyridinium product formation.

  DOI：

  10.1021/tx00047a010

文献信息

• Probing the Mechanism of Bioactivation of MPTP Type Analogs by Monoamine Oxidase B: Structure-Activity Studies on Substituted 4-Phenoxy-, 4-Phenyl-, and 4-Thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridines
  作者：John M. Rimoldi、You-Xiong Wang、Sandeep K. Nimkar、Simon H. Kuttab、Andrea H. Anderson、Heidi Burch、Neal Castagnoli

  DOI：10.1021/tx00047a010

  日期：1995.7

  Previous studies have shown that 4-benzyl-1-cyclopropyl-1,2,3,6-tetrahydropyridine is an excellent monoamine oxidase B (MAO-B) substrate (k(cat)/K-M = 1538 min(-1) mM(-1)) although the corresponding 4-phenyl analog displays MAO-B inactivating properties only. This behavior led us to speculate that the pathway for the MAO-B catalyzed oxidation of these tetrahydropyridines may not necessarily proceed via an initial single electron transfer step as proposed by others but rather through an initial alpha-carbon hydrogen atom abstraction step. In the present studies we have examined the interactions of various 4-phenoxy-, 4-phenyl-, and 4-thiophenoxy-1-cyclopropyl-1,2,3,6-tetrahydropyridine derivatives, some of which bear substituents on the phenyl ring. The 4-thiophenoxy- and all of the 4-phenoxytetrahydropyridine derivatives proved to be substrates but not inactivators of MAO-B, while several of the 4-phenyltetrahydropyridine derivatives were inactivators but not substrates. A case of particular interest was 1-cyclopropyl-4-(2-methylphenyl)-1,2,3,6-tetrahydropyridine, which displayed only substrate properties. The results are discussed in terms of two catalytic pathways, one of which involves partitioning of the proposed cyclopropylaminyl radical cation intermediate between cyclopropyl ring opening and proton loss while the second involves partitioning of the parent amine between an initial single electron transfer step, leading to cyclopropylaminyl radical cation formation and enzyme inactivation, and an initial alpha-carbon hydrogen atom abstraction step, leading to an allylic radical and dihydropyridinium product formation.