1-Hydroxypyrazole as a bioisostere of the acetic acid moiety in a series of aldose reductase inhibitors.
Bioorg Med Chem
; 21(17): 4951-7, 2013 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-23891165
ABSTRACT
Therapeutic intervention with aldose reductase inhibitors appears to be promising for major pathological conditions (i.e., long-term diabetic complications and inflammatory pathologies). So far, however, clinical candidates have failed due to adverse side-effects (spiroimides) or poor bioavailability (carboxylic acids). In this work, we succeeded in the bioisosteric replacement of an acetic acid moiety with that of 1-hydroxypyrazole. This new scaffold appears to have a superior physicochemical profile, while attaining inhibitory activity in the submicromolar range.
Palavras-chave
1,4-dihydroxynonene; 4-hydroxynonenal; AGEs; ALR1; ALR2; ARI; Aldose reductase inhibitors; BEI; Bioisosterism; DHN; GSH; HNE; Inflammatory pathologies; LE; LELP; LLE; Long-term diabetic complications; Molecular obesity; ROS; SDH; advanced glycation end-products; aldehyde reductase; aldose reductase; aldose reductase inhibitor; binding efficiency index; glutathione; ligand efficiency; ligand efficiency-dependent lipophilicity; lipophilic ligand efficiency; reactive oxygen species; sorbitol dehydrogenase
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Aldeído Redutase
/
Ácido Acético
/
Inibidores Enzimáticos
Limite:
Animals
Idioma:
En
Revista:
Bioorg Med Chem
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Grécia