RESUMO
The dissociated glucocorticoid receptor (GR) agonist ZK 216348 is rendered GR-selective over other nuclear hormone receptors through replacing the methylbenzoxazine with a quinoline moiety. Compounds were shown to be efficacious in cell assays with respect to inflammation endpoints, along with reduced activity in a transactivation assay, hinting at an improved therapeutic window over corticosteroids.
Assuntos
Anti-Inflamatórios/química , Quinolinas/química , Receptores de Glucocorticoides/agonistas , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Genes Reporter/genética , Humanos , Quinolinas/síntese química , Quinolinas/farmacologia , Receptores de Glucocorticoides/metabolismo , Ativação TranscricionalRESUMO
The synthesis of new ansa(1)-N(4)5-ethylene cytidines such as 3-ss-D-ribofuranosyl-3,5,6,7-tetrahydro-2H-pyrrolo[2,3-d]pyrimidin-2-one is described and the problems connected with the ring closure to the desired tetrahydro-2H-pyrrolo[2,3-d]pyrimidine base discussed. The lack of biological activities of the new ansa(1-) cytidines is furthermore commented on.
