Design, synthesis, and biological activities of pyrrolylethanoneamine derivatives, a novel class of monoamine oxidases inhibitors.
Pyrrolylethanoneamines 1-12, 18-23 and related amino alcohols 13-15, 24-27 were synthesized and tested against monoamine oxidases A and B (MAO-A and MAO-B) enzymes. In general, aminoketones 1-12, 18-23 were found to be potent and selective MAO-A inhibitors. In particular, 18 was more potent and selective against the MAO-A isoenzyme than reference drugs. Interestingly, amino alcohol 25 selectively inhibited MAO-B enzyme and could be a lead compound for designing more potent and selective MAO-B inhibitors.
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici (Dip. 63), Università di Roma La Sapienza, Piazzale A. Moro 5, I-00185 Roma, Italy. roberto.disanto@uniroma1.it
Roberto
R
Di Santo
Roberta
R
Costi
Alessandra
A
Roux
Marino
M
Artico
Olivia
O
Befani
Tiziana
T
Meninno
Enzo
E
Agostinelli
Paola
P
Palmegiani
Paola
P
Turini
Roberto
R
Cirilli
Rosella
R
Ferretti
Bruno
B
Gallinella
Francesco
F
La Torre
D015195:Drug Design; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D023303:Oxazolidinones / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D008996:Monoamine Oxidase Inhibitors; D023303:Oxazolidinones; D010879:Piperazines; D010880:Piperidines; D011759:Pyrrolidines; C010798:toloxatone; C038213:brofaromine