Synthesis of new pyrimidine-fused derivatives as potent and selective antidiabetic α-glucosidase inhibitors.
Carbohydr Res
; 380: 81-91, 2013 Oct 18.
Article
en En
| MEDLINE
| ID: mdl-23978663
The synthesis of a set of pyrimidine-fused derivatives (L1-L8), resulting from the incorporation of different fragments on the pyrimidine-fused heterocycle (PFH) of the earlier reported α-glucosidase (α-Gls) inhibitor (C1-C5), allowed the discovery of new ligands with modest and selective inhibitory activity. The PFH core (substructure 2) was proved to play a significant role in their inhibitory properties. Additionally, the substituent on substructures 1 and 3 of the heterocyclic ring was demonstrated to be important in the enzyme inhibitory action of the pyrimidine-fused derivatives. Moreover, these ligands show selective inhibitory properties for α-Gls over porcine pancreatic α-amylase (α-Amy) which is important in terms of their reduced susceptibility for the possible development of intestinal disturbance side effects. Therefore, low to moderate α-Amy inhibition with effective α-Gls inhibitory action may offer a better therapeutic strategy. Overall, these compounds can potentially offer a new opportunity to develop novel antidiabetic drugs with selective inhibitory action against α-Gls.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Inhibidores de Glicósido Hidrolasas
/
Hipoglucemiantes
Límite:
Animals
Idioma:
En
Revista:
Carbohydr Res
Año:
2013
Tipo del documento:
Article
País de afiliación:
Irán
Pais de publicación:
Países Bajos