title: Cardiovascular hybrid drugs: new benzazepinone derivatives as bradycardic agents endowed with selective beta1-non-competitive antagonism.
abstract: The synthesis and pharmacological profile of some hybrid compounds bearing both the benzazepinone moiety present in Zatebradine and typical beta-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 beta(1)-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 beta(1)-adrenoceptors, while (-)-(S)-enantiomer shows specificity for vessel smooth muscle.
authors.affiliation: Department of Pharmaceutical Sciences, University of Bologna, via Belmeloro 6, 40126, Bologna, Italy. albisi@alma.unibo.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisi
authors.forename: Angela
authors.initials: A
authors.lastname: Rampa
authors.forename: Roberta
authors.initials: R
authors.lastname: Budriesi
authors.forename: Silvia
authors.initials: S
authors.lastname: Gobbi
authors.forename: Federica
authors.initials: F
authors.lastname: Belluti
authors.forename: Pierfranco
authors.initials: P
authors.lastname: Ioan
authors.forename: Ermanno
authors.initials: E
authors.lastname: Valoti
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarini
authors.forename: Piero
authors.initials: P
authors.lastname: Valenti
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects; D001552:Benzazepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D002317:Cardiovascular Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007545:Isoproterenol / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D013237:Stereoisomerism; D014132:Trachea / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D002317:Cardiovascular Agents; D007202:Indicators and Reagents; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol