Fluorinated conformationally restricted gamma-aminobutyric acid aminotransferase inhibitors.
J Med Chem
; 49(25): 7404-12, 2006 Dec 14.
Article
en En
| MEDLINE
| ID: mdl-17149870
ABSTRACT
On the basis of the structures of several potent inhibitor molecules for gamma-aminobutryric acid aminotransferase (GABA-AT) that were previously reported, six modified fluorine-containing conformationally restricted analogues were designed, synthesized, and tested as GABA-AT inhibitors. The syntheses of all six molecules followed from a readily synthesized ketone intermediate. Three of the molecules were found to be irreversible inhibitors of GABA-AT with comparable or larger k(inact)/K(I) values than that of vigabatrin, a clinically used antiepilepsy drug, and the other three were reversible inhibitors. A possible mechanism for inactivation by one of the inactivators is proposed.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Compuestos Aza
/
Compuestos Bicíclicos Heterocíclicos con Puentes
/
Ciclopentanos
/
Flúor
/
4-Aminobutirato Transaminasa
/
Heptanos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos