Discovery of potent, selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-ylmethylcarbamate (CKD 533).
Bioorg Med Chem Lett
; 20(1): 383-6, 2010 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-19906530
ABSTRACT
In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking of this metabolic hot spot led to discovery of 10 (CKD533) which is highly potent, selective and orally efficacious in conscious rabbit model for erectile dysfunction and now is undergoing preclinical toxicology study.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Quinazolinas
/
Carbamatos
/
Inibidores Enzimáticos
/
Inibidores da Fosfodiesterase 5
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article