ABSTRACT
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.
Subject(s)
Anti-Inflammatory Agents/chemistry , Quinolines/chemistry , Receptors, Glucocorticoid/agonists , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/pharmacology , Cell Line , Drug Evaluation, Preclinical , Genes, Reporter/genetics , Humans , Quinolines/chemical synthesis , Quinolines/pharmacology , Receptors, Glucocorticoid/metabolism , Transcriptional ActivationABSTRACT
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.
