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Bioorg Med Chem. 2012 Jan 1;20(1):498-509. doi: 10.1016/j.bmc.2011.10.022. Epub 2011 Oct 24.

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

Author information

1
Worldwide Medicinal Chemistry, Ramsgate Road, Sandwich, Kent CT13 9NJ, UK. davidrawson1@gmail.com

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.

PMID:
22100260
DOI:
10.1016/j.bmc.2011.10.022
[Indexed for MEDLINE]

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