Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B.
N-Benzyl- and N-propargyl-1H-pyrrole-2-carboxyamides and some related methylenamines were synthesized and tested for their monoamine oxidase types A and B inhibitory activity. 2-(N-Methyl-N-propargylaminomethyl)-1H-pyrrole (24) was the most potent MAO-A inhibitor of the series [K(i)(MAO-A) = 0.0054 microM], but it was not selective. Inhibitors N-4-fluorobenzyl-1H-pyrrole-2-carboxamide (12) and N-cyclohexylmethyl-1H-pyrrole-2-carboxamide (25) showed the highest MAO-A selectivity indexes (SI) corresponding to 2025 and >2500, respectively, while 2-(N-methyl-N-benzylaminomethyl)-1H-pyrrole (21) was the most selective MAO-B inhibitor, having an SI of 0.0057.
Silvestri
Romano
R
Dipartimento di Studi Farmaceutici, Università degli Studi di Roma La Sapienza, P.le Aldo Moro, 5, I-00185 Roma, Italy. romano.silvestri@uniroma1.it
La Regina
Giuseppe
G
De Martino
Gabriella
G
Artico
Marino
M
Befani
Olivia
O
Palumbo
Marianna
M
Agostinelli
Enzo
E
Turini
Paola
P
D000480:Alkynes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000648:ultrastructure; D002417:Cattle; D007527:Isoenzymes / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000480:Alkynes; D000577:Amides; D000588:Amines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011758:Pyrroles; D008995:Monoamine Oxidase