Selective inhibitors of cyclic AMP-specific phosphodiesterase: heterocycle-condensed purines.
J Med Chem
; 40(20): 3248-53, 1997 Sep 26.
Article
en En
| MEDLINE
| ID: mdl-9379444
ABSTRACT
To reverse the adverse reactions of alkylxanthines and to develop novel inhibitors of cyclic AMP-specific phosphodiesterase (PDE IV), a series of heterocycle-condensed purines were designed and synthesized. Some of these new compounds had similar or more potent and selective inhibitory activity against PDE IV than known PDE IV inhibitors. The tracheal-relaxant activity of these compounds was closely correlated with their PDE IV-inhibitory activity. Moreover, these purine analogues did not have any positive-chronotropic action or adenosine-antagonistic action on isolated heart preparations, which are the particular adverse reactions of alkylxanthines. Among them, 3,4-dipropyl-4,5,7,8-tetrahydro-3H-imidazo[1,2-i]-purin-5-one (1c), which was the most selective and potent PDE IV inhibitor, did not cause emesis in Suncus murinus at a dosage range of 10-100 mg/kg (po), while an imidazole analogue of 1c (4c) and known PDE IV inhibitors such as rolipram and denbufylline caused emesis even at 10 or 30 mg/kg.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inhibidores de Fosfodiesterasa
/
Purinas
/
3',5'-AMP Cíclico Fosfodiesterasas
/
Isoenzimas
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1997
Tipo del documento:
Article
País de afiliación:
Japón