RESUMEN
Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.
Asunto(s)
11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 1/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Tetrazoles/farmacología , Animales , Humanos , Ratones , Modelos MolecularesRESUMEN
A series of adamantyl amide 11beta-HSD1 inhibitors has been discovered and chemically modified. Selected compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess excellent cellular potency in human and murine 11beta-HSD1 assays. Good pharmacodynamic characteristics are observed in ex vivo assays.