Chiral resolution, determination of absolute configuration, and biological evaluation of (1,2-benzothiazin-4-yl)acetic acid enantiomers as aldose reductase inhibitors.
J Enzyme Inhib Med Chem
; 30(5): 846-51, 2015.
Article
en En
| MEDLINE
| ID: mdl-25431147
ABSTRACT
A novel series of (1,2-benzothiazin-4-yl)acetic acid enantiomers was prepared by chiral resolution, and their absolute configurations were determined using the PGME method. The biological evaluation of the racemate and single enantiomers has shown a remarkable difference for the aldose reductase inhibitory activity and selectivity. The (R)-(-)-enantiomer exhibited the strongest aldose reductase activity with an IC(50) value of 0.120 µM, which was 35 times more active than the S-(+)-enantiomer. Thus, the stereocenter at the C4 position of this scaffold was shown to have a major impact on the activity and selectivity.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Tiazinas
/
Aldehído Reductasa
/
Inhibidores Enzimáticos
/
Acetatos
Límite:
Animals
/
Humans
Idioma:
En
Año:
2015
Tipo del documento:
Article