Quinolines as a novel structural class of potent and selective PDE4 inhibitors: Optimisation for oral administration

A series of quinoline-3-carboxamides has been identified as potent inhibitors of PDE4. The SAR has been explored and these studies have highlighted compounds 43 and 48 which show good potency, selectivity and rat PK suitable for oral dosing. The crystal structure of an example quinoline bound into the active site of PDE4 is also described.