247583-79-5Relevant academic research and scientific papers
The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics
Rawson, David J.,Ballard, Stephen,Barber, Christopher,Barker, Laura,Beaumont, Kevin,Bunnage, Mark,Cole, Susan,Corless, Martin,Denton, Stephen,Ellis, David,Floc'H, Marion,Foster, Laura,Gosset, James,Holmwood, Frances,Lane, Charlotte,Leahy, David,Mathias, John,Maw, Graham,Million, William,Poinsard, Cedric,Price, Jenny,Russel, Rachel,Street, Stephen,Watson, Lesa
, p. 498 - 509 (2012)
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.2,3.
Pyrazolopyrimidinone cGMP PDE5 inhibitors for the treatment of sexual dysfunction
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, (2008/06/13)
Compounds of the formulae (IA) and (IB): wherein R1is C1to C3alkyl optionally substituted with phenyl, Het or a N-linked heterocyclic group selected from piperidinyl and morpholinyl; wherein said phenyl group is optionally substituted by one or more substitutents selected from C1to C4alkoxy; halo; CN; CF3; OCF3or C1to C4alkyl wherein said C1to C4alkyl group is optionally substituted by C1to C4haloalkyl or haloalkoxy either of which is substituted by one or more halo atoms; R2is C1to C6alkyl and R13is OR3or NR5R6, or pharmaceutically or veterinarily acceptable salts thereof, or pharmaceutically or veterinarily acceptable solvates of either entity are potent and selective inhibitors of type 5 cyclic guanosine 3′,5′-monophosphate phosphodiesterase (cGMP PDE5) and have utility in the treatment of, inter alia, male erectile dysfunction (MED) and female sexual dysfunction (FSD).
