title: Simple, potent, and selective pyrrole inhibitors of monoamine oxidase types A and B.
abstract: 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.
authors.affiliation: Dipartimento di Studi Farmaceutici, Università degli Studi di Roma La Sapienza, P.le Aldo Moro, 5, I-00185 Roma, Italy. romano.silvestri@uniroma1.it
authors.forename: Romano
authors.initials: R
authors.lastname: Silvestri
authors.forename: Giuseppe
authors.initials: G
authors.lastname: La Regina
authors.forename: Gabriella
authors.initials: G
authors.lastname: De Martino
authors.forename: Marino
authors.initials: M
authors.lastname: Artico
authors.forename: Olivia
authors.initials: O
authors.lastname: Befani
authors.forename: Marianna
authors.initials: M
authors.lastname: Palumbo
authors.forename: Enzo
authors.initials: E
authors.lastname: Agostinelli
authors.forename: Paola
authors.initials: P
authors.lastname: Turini
mesh_terms: 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
chemical_list: D000480:Alkynes; D000577:Amides; D000588:Amines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D011758:Pyrroles; D008995:Monoamine Oxidase