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.
|Titolo:||Antagonism/Agonism modulation to build novel antihypertensives selectively triggering i1-imidazoline receptor activation|
|Data di pubblicazione:||2015|
|Appare nelle tipologie:||Articolo|
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|ACS 2015.pdf||ARTICOLO FREE FULL TEXT DA PMC (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4434467/)||Versione Editoriale||DRM non definito||Open Access Visualizza/Apri|
|ACS Med. Chem. Lett. 2015 supplementary materials.pdf||Supplementary materials (free access)||Altro materiale allegato||DRM non definito||Open Access Visualizza/Apri|