Deuterium enriched analogues of tadalafil as PDE5 inhibitors

摘要

The present invention relates to derivatives of tadalafil represented by the formula:; or a salt thereof, wherein:X¹ and X² are simultaneously fluoro; or X¹ is deuterium and X² is selected from hydrogen or deuterium;each Y is independently selected from deuterium or hydrogen;the hydrogen attached to the indole nitrogen is optionally replaced by deuterium; andeach carbon is independently optionally replaced by ¹³C. These compounds are selective PDE5 inhibitors and possess advantageous biopharmaceutical and pharmacokinetic properties. The invention further provides compositions comprising these compounds and methods of treating diseases and conditions that are responsive to PDE5 inhibition, alone and in combination with additional agents.