Conformational effects on the activity of drugs. 10. Synthesis, conformation, and pharmacological properties of 1-(2,5-dimethoxyphenyl)-2-aminoethanols and their morpholine analogues

1-(2,5-Dimethoxyphenyl)-2-aminoethanols I (R = H, Me, or CHMe2) and their morpholine analogs II (R = H, Me, or CHMe2) were synthesized and tested for agonistic and antagonistic adrenergic activity. The preferred conformation of the amino alcs. and their cyclic analogs was studied by NMR and IR. I (R = H) oxalate salt [83436-86-6] and I (R = Me)-HCl [63991-17-3] had both α-stimulating and -blocking activity in the rat vas deferens, whereas I (R = CHMe2)-HCl [83436-85-5] and II oxalates had only α-blocking activity. The only β-adrenergic activity obsd. was shown by I (R = CHMe)-HCl salt, which had a moderate blocking effect in the isolated guinea pig atria. Apparently, the changes in the pharmacol. activity involved in the transformation of the adrenergic drugs into their morpholine analogs are influenced more by characteristics of the arom. moiety than by the ethanolamine or propanolamine structure of the drugs