The discovery of UK-369003, a novel PDE5 inhibitor with the potential for oral bioavailability and dose-proportional pharmacokinetics.
Bioorg Med Chem
; 20(1): 498-509, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22100260
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinonas
/
Sulfonamidas
/
Nucleotídeo Cíclico Fosfodiesterase do Tipo 5
/
Inibidores da Fosfodiesterase 5
Tipo de estudo:
Etiology_studies
Limite:
Humans
/
Male
Idioma:
En
Revista:
Bioorg Med Chem
Ano de publicação:
2012
Tipo de documento:
Article