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 I<inf>1</inf>-imidazoline receptor activation / Del Bello, Fabio; Bargelli, Valentina; Cifani, Carlo; Gratteri, Paola; Bazzicalupi, Carla; Diamanti, Eleonora; Giannella, Mario; Mammoli, Valerio; Matucci, Rosanna; Micioni Di Bonaventura, Maria Vittoria; Piergentili, Alessandro; Quaglia, Wilma; Pigini, Maria. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - STAMPA. - 6:(2015), pp. 496-501. [10.1021/acsmedchemlett.5b00115]

Antagonism/agonism modulation to build novel antihypertensives selectively triggering I1-imidazoline receptor activation

BARGELLI, VALENTINA;GRATTERI, PAOLA;BAZZICALUPI, CARLA;MATUCCI, ROSANNA;
2015

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
2015
6
496
501
Del Bello, Fabio; Bargelli, Valentina; Cifani, Carlo; Gratteri, Paola; Bazzicalupi, Carla; Diamanti, Eleonora; Giannella, Mario; Mammoli, Valerio; Matucci, Rosanna; Micioni Di Bonaventura, Maria Vittoria; Piergentili, Alessandro; Quaglia, Wilma; Pigini, Maria
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1005886
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