Conformational Effects on the Activity of Drugs. 10. Synthesis, Conformation, and Pharmacological Properties of 1-(2,5-Dimethoxyphenyl)-2-aminoethanols and Their Morpholine Analogues

Article abstract of DOI:10.1021/jm00356a026

In order to obtain a better understanding of the effects that structural parameters have on the changes of adrenergic activity when 1-aryl-2-aminoethanol derivatives are converted into their corresponding 2-arylmorpholine cyclic analogues, we synthesized 1-(2,5-dimethoxyphenyl)-2-aminoethanol derivatives 5-7 and their morpholine analogues 8-10.The preferred conformations of amino alcohols and their cyclic analogues have been determined through an 1H NMR and IR study.Compounds 5 and 6 showed both α-stimulating and α-blocking activity on rat vas deferens, the effect depending on the concentration employed; on the same isolated tissue, N-isopropyl derivative 7 and the morpholine analogues 8-10 exhibited only α-blocking activity.As for the β-adrenergic activity, only the open-chain compound 7 possessed a moderate blocking effect on isolated guinea pig atria.The results of this work seem to indicate that the changes of pharmacological activity involved in the transformation of the adrenergic drugs into their morpholine analogues are influenced more by characteristic features of the aromatic moiety than by the ethanolamine or propanolamine structure of the drug.