Novel phosphodiesterase type 5 modulators: a patent survey (2008 - 2010).

INTRODUCTION: The inhibition of cyclic nucleotide PDE5 has been clinically validated as an effective treatment for erectile dysfunction and pulmonary arterial hypertension. There are three PDE5 inhibitors (sildenafil, vardenafil and tadalafil) approved worldwide and a further two agents (udenafil and mirodenafil) approved only in Korea. These first generation agents are perceived to have flaws in selectivity over other PDEs: slow onset, duration of action or CNS penetration, which has driven further research to identify optimal PDE5 inhibitors for the current pathologies. Several clinical trials have been reported to investigate the potential for PDE5 inhibitors to treat additional indications, which might require agents with different biological and/or pharmacokinetic profiles.

AREAS COVERED: This review provides a summary of developments in the patent and open literature over the period 2008 - 2010.

EXPERT OPINION: Avanafil, the first of a new generation of PDE5 inhibitors, has shown encouraging efficacy in clinical trials, and is likely to result in a new drug application filing during 2011, followed by a possible launch in 2012. Judging by the wealth of different structural series being claimed in patents, it seems that the selectivity and pharmacokinetic issues facing the first generation can be addressed through novel chemical matter.