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

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.

journal_name

Bioorg Med Chem

authors

Rawson DJ,Ballard S,Barber C,Barker L,Beaumont K,Bunnage M,Cole S,Corless M,Denton S,Ellis D,Floc'h M,Foster L,Gosset J,Holmwood F,Lane C,Leahy D,Mathias J,Maw G,Million W,Poinsard C,Price J,Russel R,Street S

doi

10.1016/j.bmc.2011.10.022

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

498-509

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(11)00830-3

journal_volume

20

pub_type

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