Synthesis and monoamine oxidase inhibitory activities of some 3-(4-fluorophenyl)-5-aryl-n-substituted-4,5-dihydro-(1H)-pyrazole-1-carbothioamide derivatives.
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.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
G Ş
GŞ
Koç
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
O U
OU
Tan
Department of Biochemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
G
G
Uçar
Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir-Turkey.
E
E
Yildirim
Department of Pharmacology, Faculty of Medicine, Osmangazi University, Eskişehir-Turkey.
K
K
Erol
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
E
E
Palaska
D000818:Animals; D014151:Anti-Anxiety Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles