An approach to the knowledge of the steric requirements for alpha-adrenoreceptor direct activation. alpha-Adrenergic properties of new 3-piperidinols

The pharmacol. study of 1-aryl-2-aminoethanols I (R = H, Me, CHMe2) and of their corresponding morpholine cyclic analogs II (R = H, Me, CHMe2) showed that 2-arylmorpholines II maintain the intrinsic α-sympathomimetic activity of their open-chain parent compds. I. The piperidine derivs. III (R = H, Me, CHMe2) represent a further kind of cyclic analog of I: in this case the alc. OH remains free while in the II both the alc. O and the amine N are a part of the ring. III were synthesized to compare their pharmacol. properties with those of I and II. Whether I or their cyclic analogs II and III interact with the receptor site in their preferred conformation could not be detd., however, both the open chain and cyclic analogs must interact with the receptor in an equiv. conformation. The α-adrenergic activity of III was evaluated and compared with those of I and II, using the isolated rat vas deferens prepn. III had an α-intrinsic activity comparable with those of I and II. On the basis of these results and of conformational and steric considerations it is possible to propose a steric model for the stimulation of the α-adrenergic receptor.