The alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic properties of the 2-(3,4-dihydroxyphenyl)morpholines 3 and 4 (2-DPMs), of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 5 and 6 (3-DPPs), and of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 7 and 8 and the trans-2-amino-6,7-dihydroxytetrahydronaphthalen-1-ols 9 and 10 (2-ADTNs) were evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations and compared with those of norepinephrine (NE, 1) and isoprenaline (ISO, 2). Through a comparison of the stereostructures of the compounds examined with their biopharmacological properties, it was possible to revise previously proposed molecular models for the direct activation of alpha- and beta-adrenergic receptors. The revised models (A-C) provided information about the conformational requirements of adrenergic drugs, which substantially fit in with the results of several published studies involving conformationally-restricted adrenoceptor agonists. The different position of the catecholic hydroxyl groups in model B, which refers to the alpha 2 receptors, and in model C, which refers to the beta receptors, confirms the importance of the rotameric position of the aromatic ring of catecholamines in the interaction with the alpha- and beta-adrenergic receptor.
CONFORMATIONAL EFFECTS ON THE ACTIVITY OF DRUGS .13. A REVISION OF PREVIOUSLY PROPOSED MODELS FOR THE ACTIVATION OF ALPHA-ADRENERGIC AND BETA-ADRENERGIC RECEPTORS
MACCHIA, BRUNO;BRESCHI, MARIA CRISTINA;LAPUCCI, ANNALINA;LUCACCHINI, ANTONIO;MANERA, CLEMENTINA;MARTINELLI, ADRIANO;MARTINI, CLAUDIA;NENCETTI, SUSANNA
1992-01-01
Abstract
The alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic properties of the 2-(3,4-dihydroxyphenyl)morpholines 3 and 4 (2-DPMs), of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 5 and 6 (3-DPPs), and of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 7 and 8 and the trans-2-amino-6,7-dihydroxytetrahydronaphthalen-1-ols 9 and 10 (2-ADTNs) were evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations and compared with those of norepinephrine (NE, 1) and isoprenaline (ISO, 2). Through a comparison of the stereostructures of the compounds examined with their biopharmacological properties, it was possible to revise previously proposed molecular models for the direct activation of alpha- and beta-adrenergic receptors. The revised models (A-C) provided information about the conformational requirements of adrenergic drugs, which substantially fit in with the results of several published studies involving conformationally-restricted adrenoceptor agonists. The different position of the catecholic hydroxyl groups in model B, which refers to the alpha 2 receptors, and in model C, which refers to the beta receptors, confirms the importance of the rotameric position of the aromatic ring of catecholamines in the interaction with the alpha- and beta-adrenergic receptor.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
