The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics

A potent series of PDE5 inhibitors has been synthesised which show PDE5 potency, selectivity over PDE6, metabolic stability and flux in the Caco-2 model of membrane permeability. The lead compound, UK-369003 (19a), has been progressed to man and shows efficacy in patients with lower urinary tract symptoms associated with benign prostate hyperplasia.