Synthesis and inhibitory activity against human monoamine oxidase of N1-thiocarbamoyl-3,5-di(hetero)aryl-4,5-dihydro-(1H)-pyrazole derivatives.
A series of N1-thiocarbamoyl-3,5-di(hetero)aryl-4,5-dihydro-(1H)-pyrazole derivatives has been synthesized and assayed for their ability to inhibit the activity of the A and B isoforms of human monoamine oxidase (hMAO). Some of these compounds were endowed with a selective inhibitory activity against hMAO-B in the micromolar range. The most active of the series is the compound 13, N1-thiocarbamoyl-3-(fur-2'-yl)-5-(4'-fluoro-phenyl)-4,5-dihydro-(1H)-pyrazole, with IC(50) 2.75+/-0.81muM value and selectivity ratio of 25, which is the best candidate for further investigations.
Chimenti
Franco
F
Dipartimento di Chimica e Tecnologie del Farmaco, Università di Roma, La Sapienza Ple Aldo Moro 5, 00185 Rome, Italy.
Carradori
Simone
S
Secci
Daniela
D
Bolasco
Adriana
A
Bizzarri
Bruna
B
Chimenti
Paola
P
Granese
Arianna
A
Yáñez
Matilde
M
Orallo
Francisco
F
D006801:Humans; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles; D008995:Monoamine Oxidase