Orally active PDE4 inhibitor with therapeutic potential.
Eur J Med Chem
; 39(7): 555-71, 2004 Jul.
Article
em En
| MEDLINE
| ID: mdl-15236836
Based on the promising results obtained by the clinical trial of Ariflo, further optimization of the spatial arrangement of the three pharmacophores (the carboxylic acid moiety, nitrile moiety and 3-cyclopentyloxy-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3 ?3 ?0]octane template with more stereochemical diversity than the cyclohexane template of Ariflo 1. Biological evaluation of the decyanated analogs and further optimization of the cyclopentyloxy moiety of 2a-b were also performed. Among the compounds tested, 2a, 7a-b and 12a were found to be orally active and were estimated to have therapeutic potential based on cross-species and same-species comparisons. The structure-activity relationships (SARs) of these compounds were investigated and pharmacokinetic data for 2a and 7b were also obtained by single-dose studies in rats.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores de Fosfodiesterase
/
3',5'-AMP Cíclico Fosfodiesterases
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Ano de publicação:
2004
Tipo de documento:
Article