Design, synthesis, and in vitro hMAO-B inhibitory evaluation of some 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles.
A series of 1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (3a-k and 4a-u) were designed, synthesized, and evaluated for their inhibitory efficacy towards the two hMAO isoforms. Most of the derivatives were found to be potent and selective hMAO-B inhibitors. In particular, derivative 3g showed greater hMAO-B affinity than selective inhibitor selegiline coupled with high selectivity index (SI=145). The most selective hMAO-B inhibitor was the 3-methyl analogue 3f with an SI higher than 909.
Dipartimento di Chimica e Tecnologie del Farmaco, Università La Sapienza, Rome, Italy. rossella.fioravanti@uniroma1.it
Rossella
R
Fioravanti
Nicoletta
N
Desideri
Mariangela
M
Biava
Luca
L
Proietti Monaco
Laura
L
Grammatica
Matilde
M
Yáñez
D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C587367:1-methyl-3,5-diphenyl-4,5-dihydro-1H-pyrazole; D004791:Enzyme Inhibitors; D011720:Pyrazoles; D008995:Monoamine Oxidase
Monoamine oxidases; Pyrazole derivatives; hMAO inhibitors