Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-(1 H)-pyrazole-1-carbothioamide derivatives

KOÇ G., Tan O., UÇAR G., YILDIRIM E., Erol K., PALASKA E.

Drug Research, vol.64, no.11, pp.591-598, 2014 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 64 Issue: 11
  • Publication Date: 2014
  • Doi Number: 10.1055/s-0033-1363997
  • Journal Name: Drug Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.591-598
  • Eskisehir Osmangazi University Affiliated: Yes

Abstract

© Georg Thieme Verlag KG Stuttgart New York.28 new 3-(4-fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives were synthesized and evaluated in vitro for their monoamine oxidase (MAO) A and B inhibitory activity and selectivity. The derivatives substituted by halogen on the fifth position of pyrazole ring, inhibited MAO-A enzyme with a high selectivity index. On the other hand, compounds substituted with 2-naphthyl inhibited MAO-B enzyme with a moderate selectivity index. Docking studies were done to highlight the interactions of the most active derivative with the active site of MAO-A. In addition, in vivo antidepressant and anxiolytic activities of the compounds having selective MAO-A inhibitory effects, were investigated by using Porsolt forced swimming and elevated plus-maze tests respectively. 3-(4-Fluorophenyl)-5-(4-chloro-phenyl)-N-allyl-4,5-dihydro-1H-pyrazole-1-carbothio-amide has antidepressant, 3-(4-fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide and 3-(4-fluoro-phenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H-pyrazole-1-carbothioamide have anxiolytic activity.