The synthesis and pharmacological profile of some hybrid compounds bearing both the benzazepinone moiety present in Zatebradine and typical β-blocker aryloxypropanolamine groups are described. The new compounds proved to be endowed with negative chronotropic and inotropic activity and are weak vasorelaxant agents. The cardiodepressant action is probably due to selective β1-noncompetitive reversible antagonism. Both enantiomers of the most active compound 5c were synthesized and they showed a different cardiovascular profile, that is (+)-(R)-enantiomer displays affinity for cardiac β1-adrenoceptors, while (-)-(S)-enantiomer shows specificity for vessel smooth muscle. © 2003 Elsevier Science Ltd. All rights reserved.
Bisi A., Rampa A., Budriesi R., Gobbi S., Belluti F., Ioan P., et al. (2003). Cardiovascular hybrid drugs: New benzazepinone derivatives as bradycardic agents endowed with selective β1-Non-competitive antagonism. BIOORGANIC & MEDICINAL CHEMISTRY, 11(7), 1353-1361 [10.1016/S0968-0896(02)00621-1].
Cardiovascular hybrid drugs: New benzazepinone derivatives as bradycardic agents endowed with selective β1-Non-competitive antagonism
Bisi A.;Rampa A.;Budriesi R.;Gobbi S.;Belluti F.;Ioan P.;Chiarini A.;Valenti P.
2003
Abstract
The synthesis and pharmacological profile of some hybrid compounds bearing both the benzazepinone moiety present in Zatebradine and typical β-blocker aryloxypropanolamine groups are described. The new compounds proved to be endowed with negative chronotropic and inotropic activity and are weak vasorelaxant agents. The cardiodepressant action is probably due to selective β1-noncompetitive reversible antagonism. Both enantiomers of the most active compound 5c were synthesized and they showed a different cardiovascular profile, that is (+)-(R)-enantiomer displays affinity for cardiac β1-adrenoceptors, while (-)-(S)-enantiomer shows specificity for vessel smooth muscle. © 2003 Elsevier Science Ltd. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
