Pyrazoline based MAO inhibitors: synthesis, biological evaluation and SAR studies

Bioorg Med Chem Lett. 2011 Jul 15;21(14):4296-300. doi: 10.1016/j.bmcl.2011.05.057. Epub 2011 May 25.

Abstract

Twenty-two pyrazoline derivatives were synthesized and tested for their human MAO (hMAO) inhibitory activity. Twelve molecules with unsubstituted ring A and substituted ring C (5-16) were found to be potent inhibitors of hMAO-A isoform with SI(MAO-A) in the order 10(3) and 10(4). Ten molecules with unsubstituted ring A and without ring C (21-30), in which eight molecules (21, 23-26, and 28-30) were selective for hMAO-A, one for hMAO-B (22) and the other one non-selective (27). Presence of ring C increases potency as well as SI towards hMAO-A; however its absence decreases both potency and SI towards hMAO-A and hMAO-B.

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Humans
  • Monoamine Oxidase / chemistry
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / chemical synthesis
  • Monoamine Oxidase Inhibitors / chemistry*
  • Monoamine Oxidase Inhibitors / pharmacology
  • Protein Isoforms / antagonists & inhibitors
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship

Substances

  • Monoamine Oxidase Inhibitors
  • Protein Isoforms
  • Pyrazoles
  • Monoamine Oxidase