In order to contribute to the definition of the role played by the benzylic hydroxyl group of adrenergic catecholamines in eliciting α-adrenergic activity, certain 3-phenyl-3-piperidinols (PPOs, 4) and their corresponding desoxy 3-phenylpiperidine analogs (PPEs, 6) were synthesized and tested for their (α1- and α2-adrenergic activity by means of functional tests on isolated preparations. As regards the α1-adrenergic activity, the values of the activity indices of the cyclic catecholic compounds (PPO 4a and PPE 6a) indicate that the benzylic hydroxyl does not play an essential role, provided that the other two active groups are in the pharmacophoric conformation. However, the fact that none of the other non-catecholic cyclic analogs are active on the α1-receptor does not allow us to generalize this observation. As regards the α2-adrenergic activity, the high values of the activity indices of PPEs 6, compared with those of the corresponding 1-phenyl-2-aminoethanols (PAEs, 3), PPOs (4) and 2-phenylethylamines (PEAs, 5), confirm that when the aromatic moiety and the amino group are constrained into the pharmacophoric relationship, the presence of the alcoholic hydroxyl is not only unnecessary for the purposes of the expression of the activity at the level of the α2-adrenoceptor, but often has a negative effect.

Role of the benzylic hydroxyl group of adrenergic catecholamines in eliciting a-adrenergic activity. Synthesis and a1- and a2-adrenergic activity of 3-phenyl-3-piperidinols and of their desoxy analogs

MACCHIA, MARCO;MANERA, CLEMENTINA;NENCETTI, SUSANNA;ORLANDINI, ELISABETTA;ROSSELLO, ARMANDO
1995

Abstract

In order to contribute to the definition of the role played by the benzylic hydroxyl group of adrenergic catecholamines in eliciting α-adrenergic activity, certain 3-phenyl-3-piperidinols (PPOs, 4) and their corresponding desoxy 3-phenylpiperidine analogs (PPEs, 6) were synthesized and tested for their (α1- and α2-adrenergic activity by means of functional tests on isolated preparations. As regards the α1-adrenergic activity, the values of the activity indices of the cyclic catecholic compounds (PPO 4a and PPE 6a) indicate that the benzylic hydroxyl does not play an essential role, provided that the other two active groups are in the pharmacophoric conformation. However, the fact that none of the other non-catecholic cyclic analogs are active on the α1-receptor does not allow us to generalize this observation. As regards the α2-adrenergic activity, the high values of the activity indices of PPEs 6, compared with those of the corresponding 1-phenyl-2-aminoethanols (PAEs, 3), PPOs (4) and 2-phenylethylamines (PEAs, 5), confirm that when the aromatic moiety and the amino group are constrained into the pharmacophoric relationship, the presence of the alcoholic hydroxyl is not only unnecessary for the purposes of the expression of the activity at the level of the α2-adrenoceptor, but often has a negative effect.
B., Macchia; Macchia, Marco; Manera, Clementina; E., Martinotti; Nencetti, Susanna; Orlandini, Elisabetta; R., Scatizzi; Rossello, Armando
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/205704
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