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Drug Res (Stuttg) 2014; 64(11): 591-598
DOI: 10.1055/s-0033-1363997
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
,
O. U. Tan
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
,
G. Uçar
2   Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
,
E. Yıldırım
3   Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir-Turkey
,
K. Erol
3   Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir-Turkey
,
E. Palaska
1   Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey
› Institutsangaben
Weitere Informationen

Publikationsverlauf

received 05. November 2013

accepted 23. Dezember 2013

Publikationsdatum:
22. Januar 2014 (online)

Auch verfügbar auf
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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

Supporting information

 

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