R-(+)-N<3-(2,4-dichlorophenoxy)propyl>-N-methyl-3-butyn-2-amine | 141625-61-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: R-(+)-N<3-(2,4-dichlorophenoxy)propyl>-N-methyl-3-butyn-2-amine
• 英文别名: R-(+)-N[3-(2,4-dichlorophenoxy)propyl]-N-methyl-3-butyn-2-amine；(2R)-N-[3-(2,4-dichlorophenoxy)propyl]-N-methylbut-3-yn-2-amine
• CAS: 141625-61-8
• 化学式: C₁₄H₁₇Cl₂NO
• 分子量: 286.201
• InChiKey: XOAYUWJMCMFSCB-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-甲基氨基-1-丁炔 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 R-(+)-N<3-(2,4-dichlorophenoxy)propyl>-N-methyl-3-butyn-2-amine
  参考文献：
  名称：

  Inhibition of monoamine oxidase by the R and S enantiomers of N[3-(2,4-dichlorophenoxy)propyl]-N-methyl-3-butyn-2-amine

  摘要：

  The chemical synthesis of the R-(+)- and S-(-)-enantiomers of N[3-(2,4-dichlorophenoxy)propyl]-N-methyl-3-butyn-2-amine is described. These compounds are derivatives of the mechanism-based irreversible monoamine oxidase inhibitor clorgyline in which a methyl group is substituted for a hydrogen atom on the propargyl methylene carbon. The enantiomeric clorgyline derivatives were both found to be reversible, linearly-competitive inhibitors of monoamine oxidase-A and -B. Thus the methyl-substitution does not prevent non-covalent binding of the inhibitors to the active sites, but it does prevent these compounds from reacting within that complex to form covalent adducts with the enzymes. The substitution of the methyl group resulted in a decreased affinity, as compared to clorgyline, for non-covalent binding to monoamine oxidase-A, with the S-enantiomer having the lower affinity. In contrast, the S-enantiomer showed increased affinity for monoamine oxidase-B. These effects resulted in the high selectivity of the parent compound, clorgyline, towards monoamine oxidase-A being lost. The R-enantiomer showed a small degree of selectivity towards the A-form of the enzyme, whereas the S-enantiomer had a higher affinity for the B-form. These results are discussed in terms of the chemical mechanisms proposed for the interactions of the monoamine oxidases with substrates and inhibitors.

  DOI：

  10.1016/0223-5234(92)90059-a

文献信息

• Inhibition of monoamine oxidase by the R and S enantiomers of N[3-(2,4-dichlorophenoxy)propyl]-N-methyl-3-butyn-2-amine
  作者：P Dostert、EM O'Brien、KF Tipton、M Meroni、P Melloni、M Strolin Benedetti

  DOI：10.1016/0223-5234(92)90059-a

  日期：1992.1

  The chemical synthesis of the R-(+)- and S-(-)-enantiomers of N[3-(2,4-dichlorophenoxy)propyl]-N-methyl-3-butyn-2-amine is described. These compounds are derivatives of the mechanism-based irreversible monoamine oxidase inhibitor clorgyline in which a methyl group is substituted for a hydrogen atom on the propargyl methylene carbon. The enantiomeric clorgyline derivatives were both found to be reversible, linearly-competitive inhibitors of monoamine oxidase-A and -B. Thus the methyl-substitution does not prevent non-covalent binding of the inhibitors to the active sites, but it does prevent these compounds from reacting within that complex to form covalent adducts with the enzymes. The substitution of the methyl group resulted in a decreased affinity, as compared to clorgyline, for non-covalent binding to monoamine oxidase-A, with the S-enantiomer having the lower affinity. In contrast, the S-enantiomer showed increased affinity for monoamine oxidase-B. These effects resulted in the high selectivity of the parent compound, clorgyline, towards monoamine oxidase-A being lost. The R-enantiomer showed a small degree of selectivity towards the A-form of the enzyme, whereas the S-enantiomer had a higher affinity for the B-form. These results are discussed in terms of the chemical mechanisms proposed for the interactions of the monoamine oxidases with substrates and inhibitors.