Design, Synthesis, Docking Studies and Monoamine Oxidase Inhibition of a Small Library of 1-acetyl- and 1-thiocarbamoyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazoles

Paolo Guglielmi, Simone Carradori, Giulio Poli, Daniela Secci, Roberto Cirilli, Giulia Rotondi, Paola Chimenti, Anél Petzer, Jacobus P Petzer

Research output: Contribution to journalArticlepeer-review

Abstract

New N-acetyl/N-thiocarbamoylpyrazoline derivatives were designed and synthesized in high yields to assess their inhibitory activity and selectivity against human monoamine oxidase A and B. The most important chiral compounds were separated into their single enantiomers and tested. The impact of the substituents at N1, C3 and C5 positions as well the influence of the configuration of the C5 on the biological activity were analyzed. Bulky aromatic groups at C5 were not tolerated. p-Prenyloxyaryl moiety at C3 oriented the selectivity toward the B isoform. The results were also corroborated by molecular modelling studies providing new suggestions for the synthesis of privileged structures to serve as lead compounds for the treatment of mood disorders and neurodegenerative diseases.

Original languageEnglish
JournalMolecules (Basel, Switzerland)
Volume24
Issue number3
DOIs
Publication statusPublished - Jan 29 2019

Keywords

  • Enzyme Activation/drug effects
  • Models, Molecular
  • Monoamine Oxidase/metabolism
  • Monoamine Oxidase Inhibitors/chemical synthesis
  • Pyrazoles/chemical synthesis
  • Stereoisomerism
  • Structure-Activity Relationship

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