Enantiomers of C(5)-chiral 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives: Analytical and semipreparative HPLC separation, chiroptical properties, absolute configuration, and inhibitory activity against monoamine oxidase

Chirality. 2004 Nov;16(9):625-36. doi: 10.1002/chir.20085.

Abstract

The HPLC enantiomer separation of a novel series of C(5)-chiral 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives, with inhibitory activity against monoamine oxidases (MAO) type A and B, was accomplished using polysaccharide-based chiral stationary phases (CSPs: Chiralpak AD, Chiralcel OD, and Chiralcel OJ). Pure alcohols, such as ethanol and 2-propanol, and typical normal-phase binary mixtures, such as n-hexane and alcohol modifier, were used as mobile phases. Single enantiomers of several analytes examined were isolated on a semipreparative scale, and their chiroptical properties were measured. The assignment of the absolute configuration was established for one compound by single-crystal X-ray diffraction method and for the other three by CD spectroscopy. The inhibitory activity against MAO of racemic samples and single enantiomers were evaluated in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / enzymology
  • Cattle
  • Chromatography, High Pressure Liquid
  • Circular Dichroism
  • Computational Biology
  • Crystallography, X-Ray
  • In Vitro Techniques
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Models, Molecular
  • Molecular Conformation
  • Monoamine Oxidase Inhibitors / chemical synthesis*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology*
  • Stereoisomerism

Substances

  • 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole
  • Monoamine Oxidase Inhibitors
  • Pyrazoles