Synthesis and in vitro and in vivo characteristics of an iodinated analogue of the beta-adrenoceptor antagonist carazolol.
J Med Chem
; 39(17): 3256-62, 1996 Aug 16.
Article
em En
| MEDLINE
| ID: mdl-8765508
ABSTRACT
A new (radio)iodinated, beta-adrenoceptor ligand, (S)-(-)-4-[3-[(1,1-dimethyl-3-iodo-(2E)-propenyl)-amino]-2- hydroxypropoxy]carbazole (CYBL8E, 1), was prepared. 1 is an iodinated analogue of the high-affinity beta-adrenoceptor antagonist carazolol (2). The asymmetric synthesis was achieved in four steps starting from 4-hydroxycarbazole. The iodine-123-labeled form was obtained by an iododestannylation reaction with [123I]NaI in the presence of H2O2. Using classical in vitro displacement experiments with membrane fractions of cardiac left ventricular muscle, 1 proved to have a high affinity for the receptor (Ki = 0.31 +/- 0.03). Biodistribution studies performed in New Zealand white rabbits demonstrated the specificity of the binding in vivo to the receptor. Uptake of [123I]1 was reduced significantly in both atrial muscle, left ventricular muscle, frontal cortex, cerebellum, and striatum, by the pretreatment of the animals with different beta-adrenoceptor antagonists. In conclusion, 1 is a potent nonselective beta-adrenoceptor antagonist, which binds specifically to the beta-adrenoceptor in vivo, and is therefore a promising radioligand for the imaging of beta-adrenoceptors using single photon emission computerized tomography.
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Base de dados:
MEDLINE
Assunto principal:
Propanolaminas
/
Encéfalo
/
Carbazóis
/
Receptores Adrenérgicos beta
/
Antagonistas Adrenérgicos beta
Limite:
Animals
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
1996
Tipo de documento:
Article
País de afiliação:
Holanda