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

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

  • Bioorg Med Chem. 2012 Jan 1;20(1):498-509. doi: 10.1016/j.bmc.2011.10.022.
David J Rawson 1,  Stephen Ballard,  Christopher Barber,  Laura Barker,  Kevin Beaumont,  Mark Bunnage,  Susan Cole,  Martin Corless,  Stephen Denton,  David Ellis,  Marion Floc'h,  Laura Foster,  James Gosset,  Frances Holmwood,  Charlotte Lane,  David Leahy,  John Mathias,  Graham Maw,  William Million,  Cedric Poinsard,  Jenny Price,  Rachel Russel,  Stephen Street,  Lesa Watson
Affiliations

Affiliation

  • 1 Worldwide Medicinal Chemistry, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. [email protected]
PMID: 22100260 DOI: 10.1016/j.bmc.2011.10.022
Abstract

This paper describes our recent efforts to design and synthesise potent and selective PDE5 inhibitors and the use of in vitro predictors of clearance, absorption and permeability to maximise the potential for dose-proportional pharmacokinetics and good oral bioavailability in man. Optimisation of the preclinical profile resulted in the identification of UK-369003 (19a) and its nomination as a clinical candidate. The clinical pharmacokinetic and safety profile has enabled us to progress the compound to test its efficacy in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and a paper describing its efficacy has recently been published.

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