Monoamine oxidase inhibitory activity of 3,5-biaryl-4,5-dihydro-1H-pyrazole-1-carboxylate derivatives

Eur J Med Chem. 2013 Nov;69:762-7. doi: 10.1016/j.ejmech.2013.09.010. Epub 2013 Sep 18.

Abstract

Ethyl and phenyl carbamate derivatives of pyrazoline (3a-3h) were synthesized and tested for their MAO inhibitory activity. All the compounds were found to be selective towards MAO-A. Phenyl carbamates (3e-3h) were better than ethyl carbamates (3a-3d) and displayed the best selectivity index. Compound 3f (KiMAO-A; 4.96 ± 0.21 nM) was found to be equally potent as that of standard drug, Moclobemide (KiMAO-A; 5.01 ± 0.13 nM) but with best selectivity index (8.86 × 10(-5)). Molecular docking studies with R &S conformer of 3f revealed S-enantiomer is better than R-enantiomer as reported earlier by other groups. It is proposed that VdW's radii of the substitution (bulkiness) in ring B determine the potency of phenyl carbamates.

Keywords: Carbamates; Human monoamine oxidase; Inhibitors; MAO; Molecular docking; Pyrazolines; SAR; back-bone; bb; hMAO; human MAO; monoamine oxidase; rMAO; rat MAO; sc; side-chain; structure–activity-relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Pyrazoles
  • Monoamine Oxidase