Synthesis and Monoamine Oxidase Inhibitory Activities of some 3-(4-Fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide Derivatives

G. Ş. Koç; O. U. Tan; G. Uçar; E. Yıldırım; K. Erol; E. Palaska

doi:10.1055/s-0033-1363997

Drug Research, Inhaltsverzeichnis

Drug Res (Stuttg) 2014; 64(11): 591-598
DOI: 10.1055/s-0033-1363997

Original Article

Synthesis and Monoamine Oxidase Inhibitory Activities of some 3-(4-Fluorophenyl)-5-aryl-N-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide Derivatives

G. Ş. Koç

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

,

O. U. Tan

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

,

G. Uçar

²Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

,

E. Yıldırım

³Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir-Turkey

,

K. Erol

³Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir-Turkey

,

E. Palaska

¹Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey

› Institutsangaben

Abstract

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-chlorophenyl)-N-allyl-4,5-dihydro-1H-pyrazole-1-carbothioamide has antidepressant, 3-(4-fluorophenyl)-5-(4-chlorophenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide and 3-(4-fluorophenyl)-5-(4-bromophenyl)-N-ethyl-4,5-dihydro-1H-pyrazole-1-carbothioamide have anxiolytic activity.

Key words

2-pyrazoline - 4,5-dihydropyrazole - monoamine oxidase - antidepressant - docking

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Referenzen

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