Synthesis, stereochemical separation, and biological evaluation of selective inhibitors of human MAO-B: 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazines.
Novel 1-(4-arylthiazol-2-yl)-2-(3-methylcyclohexylidene)hydrazine derivatives have been investigated for their ability to inhibit selectively the activity of the human B isoform of monoamine oxidase. These compounds were obtained as racemates and (R)-enantiomers by a stereoconservative synthetic pattern in high yield and enantiomeric excess. The (S)-enantiomers of the most active derivatives have been separated by enantioselective HPLC. All compounds showed selective activity against hMAO-B with IC(50) ranging between 21.90 and 0.018 microM.
Chimenti
Franco
F
Dipartimento di Chimica e Tecnologie del Farmaco, Universita degli Studi di Roma La Sapienza, P.A. Moro 5, 00185 Roma, Italy.
Secci
Daniela
D
Bolasco
Adriana
A
Chimenti
Paola
P
Granese
Arianna
A
Carradori
Simone
S
Yáñez
Matilde
M
Orallo
Francisco
F
Sanna
M Luisa
ML
Gallinella
Bruno
B
Cirilli
Roberto
R
D002851:Chromatography, High Pressure Liquid; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry; D008995:Monoamine Oxidase / Q000737:chemistry*; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification
D003510:Cyclohexanes; D006834:Hydrazines; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D014230:Triazoles; D008995:Monoamine Oxidase