RESUMO
AMPA receptors (AMPARs) are an important therapeutic target in the CNS. A series of substituted benzoxazinone derivatives with good to very good in vitro activity as positive allosteric AMPAR modulators was synthesized and evaluated. The appropriate substituent choice on the benzoxazinone fragment improved the affinity towards the AMPA receptor significantly in comparison to our lead molecule CX614.
Assuntos
Benzoxazinas/química , Receptores de AMPA/efeitos dos fármacos , Regulação Alostérica , Animais , Benzoxazinas/farmacologia , Estrutura Molecular , Prosencéfalo/efeitos dos fármacos , Pirrolidinonas/química , Pirrolidinonas/farmacologia , Ratos , Relação Estrutura-AtividadeRESUMO
AMPA receptors (AMPARs) are an increasingly important therapeutic target in the CNS. Aniracetam, the first identified potentiator of AMPARs, led to the rigid and more potent CX614. This lead molecule was optimized in order to increase affinity towards the AMPA receptor. The substitution of the dioxine with a benzoxazinone ring system increased the activity and allowed further investigation of the sidechain SAR.
