Enantiomers of C(5)-chiral 1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole derivatives: Analytical and semipreparative HPLC separation, chiroptical properties, absolute configuration, and inhibitory activity against monoamine oxidase.
The HPLC enantiomer separation of a novel series of C(5)-chiral 1-acetyl-3-(4-hydroxy- and 2,4-dihydroxyphenyl)-5-phenyl-4,5-dihydro-(1H)-pyrazole derivatives, with inhibitory activity against monoamine oxidases (MAO) type A and B, was accomplished using polysaccharide-based chiral stationary phases (CSPs: Chiralpak AD, Chiralcel OD, and Chiralcel OJ). Pure alcohols, such as ethanol and 2-propanol, and typical normal-phase binary mixtures, such as n-hexane and alcohol modifier, were used as mobile phases. Single enantiomers of several analytes examined were isolated on a semipreparative scale, and their chiroptical properties were measured. The assignment of the absolute configuration was established for one compound by single-crystal X-ray diffraction method and for the other three by CD spectroscopy. The inhibitory activity against MAO of racemic samples and single enantiomers were evaluated in vitro.
Cirilli
Roberto
R
Istituto Superiore di Sanità, Dipartimento del Farmaco, Rome, Italy.
Ferretti
Rosella
R
Gallinella
Bruno
B
Turchetto
Luciana
L
Bolasco
Adriana
A
Secci
Daniela
D
Chimenti
Paola
P
Pierini
Marco
M
Fares
Vincenzo
V
Befani
Olivia
O
La Torre
Francesco
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D019295:Computational Biology; D018360:Crystallography, X-Ray; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular; D008968:Molecular Conformation; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
C499263:1-acetyl-3,5-diphenyl-4,5-dihydro-(1H)-pyrazole; D008996:Monoamine Oxidase Inhibitors; D011720:Pyrazoles