Synthesis and evaluation of human monoamine oxidase inhibitory activities of some 3,5-diaryl-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives.
Sixteen 3-aryl-5-(4-fluorophenyl)-N-substituted-4,5-dihydro-1H-pyrazole-1-carbothioamide derivatives were synthesized and their structure were identified by UV, IR, (1) H NMR, mass spectra, and microanalyses. The compounds were evaluated in vitro for their human monoamine oxidase (hMAO) inhibitory activities and their MAO-A and -B selectivity. All the compounds were found to potently inhibit MAO-A isoforms. 5-(4-Fluorophenyl)-3-(4-methoxyphenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide (1.0 × 10(-3)  µM) was found to inhibit hMAO-A most selectively and potently. The binding mode of 5-(4-fluorophenyl)-3-(4-methoxyphenyl)-N-methyl-4,5-dihydro-1H-pyrazole-1-carbothioamide to hMAO-A was also predicted using docking studies.
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hacettepe University, Ankara, Turkey.
Kerem
K
Sentürk
Oya Unsal
OU
Tan
Samiye Yabanoğlu
SY
Ciftçi
Gülberk
G
Uçar
Erhan
E
Palaska
D015195:Drug Design; D006801:Humans; D007527:Isoenzymes; D008024:Ligands; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013854:Thioamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D007527:Isoenzymes; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D013854:Thioamides