title: Recent advances in the development of selective human MAO-B inhibitors: (hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines.
abstract: A large series of (4-substituted-thiazol-2-yl)hydrazine derivatives was synthesized in good yield and assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity. Most of them showed inhibitory activity in the nanomolar range and hMAO-B selective inhibition higher than reference drugs, demonstrating our interest in this privileged scaffold. The structure-activity relationship of the different rings on the N1-hydrazine position indicated that a pyridine ring was preferred with the presence of electron-withdrawing substituents on the aryl group at C4 of the thiazole nucleus. The substituent on the α-carbon to the N1-hydrazine moiety (methyl or hydrogen) had a great influence on the activity and hMAO-B selectivity. Moreover, the reversibility of the enzyme inhibition for the best active compound was reported.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma La Sapienza, P.le A. Moro 5, 00185 Rome, Italy. daniela.secci@uniroma1.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Secci
authors.forename: Adriana
authors.initials: A
authors.lastname: Bolasco
authors.forename: Simone
authors.initials: S
authors.lastname: Carradori
authors.forename: Melissa
authors.initials: M
authors.lastname: D'Ascenzio
authors.forename: Riccardo
authors.initials: R
authors.lastname: Nescatelli
authors.forename: Matilde
authors.initials: M
authors.lastname: Yáñez
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase