Pharmacological studies have suggested that I1-imidazoline receptors are involved in the regulation of cardiovascular function and that selective I1-agonists, devoid of the side effects associated with the common hypotensive α2-adrenoreceptor agonists, might be considered as a second generation of centrally acting antihypertensives. Therefore, in the present study, inspired by the antihypertensive behavior of our selective I1-agonist 4, we designed, prepared, and studied the novel analogues 5-9. A selective I1-profile, associated with significant hemodinamic effects, was displayed by 5, 8, and 9. Interestingly, the highest potency and longest lasting activity displayed by 8 (carbomethyline) suggested that van der Waals interactions, promoted by the ortho methyl decoration of its aromatic moiety, are particularly advantageous. In addition, in analogy to what was noted for (S)-(+)-4, the observation that only (S)-(+)-8 displayed significant hemodynamic effects unequivocally confirmed the stereospecific nature of the I1 proteins.
Antagonism/Agonism modulation to build novel antihypertensives selectively triggering i1-imidazoline receptor activation
DEL BELLO, FABIO;CIFANI, Carlo;DIAMANTI, ELEONORA;GIANNELLA, Mario;MAMMOLI, VALERIO;MICIONI DI BONAVENTURA, Maria Vittoria;PIERGENTILI, Alessandro;QUAGLIA, Wilma;PIGINI, Maria
2015-01-01
Abstract
Pharmacological studies have suggested that I1-imidazoline receptors are involved in the regulation of cardiovascular function and that selective I1-agonists, devoid of the side effects associated with the common hypotensive α2-adrenoreceptor agonists, might be considered as a second generation of centrally acting antihypertensives. Therefore, in the present study, inspired by the antihypertensive behavior of our selective I1-agonist 4, we designed, prepared, and studied the novel analogues 5-9. A selective I1-profile, associated with significant hemodinamic effects, was displayed by 5, 8, and 9. Interestingly, the highest potency and longest lasting activity displayed by 8 (carbomethyline) suggested that van der Waals interactions, promoted by the ortho methyl decoration of its aromatic moiety, are particularly advantageous. In addition, in analogy to what was noted for (S)-(+)-4, the observation that only (S)-(+)-8 displayed significant hemodynamic effects unequivocally confirmed the stereospecific nature of the I1 proteins.File | Dimensione | Formato | |
---|---|---|---|
ACS 2015.pdf
accesso aperto
Descrizione: ARTICOLO FREE FULL TEXT DA PMC (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434467/)
Tipologia:
Versione Editoriale
Licenza:
DRM non definito
Dimensione
1.3 MB
Formato
Adobe PDF
|
1.3 MB | Adobe PDF | Visualizza/Apri |
ACS Med. Chem. Lett. 2015 supplementary materials.pdf
accesso aperto
Descrizione: Supplementary materials (free access)
Tipologia:
Altro materiale allegato
Licenza:
DRM non definito
Dimensione
300.87 kB
Formato
Adobe PDF
|
300.87 kB | Adobe PDF | Visualizza/Apri |
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.