PDE5 inhibitors: An original access to novel potent arylated analogues of tadalafil

A method to access totally new analogues of tadalafil was explored. The Buchwald reaction was adapted and used to replace the methyl group of tadalafil by various aryl groups. Inhibition potencies on PDE5 of these analogues were determined and proved to be comparable to the one of tadalafil. Using the same route, compounds with the same level of activity but improved water solubility were produced by introducing a pyridine or a pyrimidine ring. This original route also opens access to new unpatented compounds.

The synthesis of potent PDE5 inhibitors is reported. Some heteroarylated compounds (e.g., 14a) display an improved aqueous solubility, when compared to tadalafil.Figure optionsDownload as PowerPoint slide