A highly selective, non-hydantoin, non-carboxylic acid inhibitor of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran- 2-sulfonyl)-2-H-pyridazin-3-one.
J Med Chem
; 46(12): 2283-6, 2003 Jun 05.
Article
en En
| MEDLINE
| ID: mdl-12773033
ABSTRACT
We report here on the discovery path that led to a structurally unprecedented non-hydantoin, non-carboxylic acid aldose reductase inhibitor, 24, which shows remarkably potent oral activity in normalizing elevated sorbitol levels and, more significantly, fructose levels in the sciatic nerve of chronically diabetic rats, with ED(90) values of 0.8 and 3 mpk, respectively. It is well absorbed in rats (oral bioavailability, 98%) and has a long plasma t(1/2) (26 +/- 3 h).
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Piridazinas
/
Sulfonas
/
Aldehído Reductasa
/
Diabetes Mellitus Experimental
/
Inhibidores Enzimáticos
/
Hipoglucemiantes
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos