ROLE OF THE BENZYLIC HYDROXYL GROUP OF ADRENERGIC CATECHOLAMINES IN ELICITING ALPHA-ADRENERGIC ACTIVITY - SYNTHESIS AND ALPHA(1)-ADRENERGICAND ALPHA(2)-ADRENERGIC ACTIVITY OF 3-PHENYL-3-PIPERIDINOLS AND THEIRDEOXY ANALOGS

In order to contribute to the definition of the role played by the ben zylic hydroxyl group of adrenergic catecholamines in eliciting alpha-a drenergic activity, certain 3-phenyl-3-piperidinols (PPOs, 4) and thei r corresponding desoxy 3-phenylpiperidine analogs (PPEs, 6) were synth esized and tested for their alpha(1)- and alpha(2)-adrenergic activity be means of functional tests on isolated preparations. As regards the alpha(1)-adrenergic activity, the values of the activity indices of t he cyclic catecholic compounds (PPO 4a and PPE 6a) indicate that the b enzylic hydroxyl does not play an essential role, provided that the ot her two active groups are in the pharmacophoric conformation. However, the fact that none of the other non-catecholic cyclic analogs are act ive on the alpha(1)-receptor does not allow us to generalize this obse rvation. As regards the alpha(2)-adrenergic activity, the high values of the activity indices of PPEs 6, compared with those of the correspo nding 1-phenyl-2-aminoethanols (PAEs, 3), PPOs (4) and 2-phenylethylam ines (PEAs, 5), confirm that when the aromatic moiety and the amino gr oup 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 alpha(2)-adrenocep tor, but often has a negative effect.