SYNTHESIS AND ADRENERGIC BETA-BLOCKING ACTIVITY OF ORTHO-OXYPROPANOLAMINO-SUBSTITUTED, META-OXYPROPANOLAMINO-SUBSTITUTED AND PARA-OXYPROPANOLAMINO-SUBSTITUTED [(BENZYLIDENEAMINO)OXY]PROPANOLAMINES

The N-isopropyl- and N-t-butyl-substituted oxypropoxy)benzylideneamino xy]-3-amino-2-propanols (7a,b) and their meta (8a,b) and para (9a,b) i somers, in which a single aromatic ring is substituted both by the oxy propanolaminic chain of (aryloxy)propanolaminic P-adrenergic antagonis ts (AQPAs) and the [(methyleneamino)oxy]propanolaminic chain of [(meth yleneamino)oxy]propanolaminic beta-blocking drugs (MAOPAs), were synth esized and assayed for their P-adrenergic activity by functional tests on isolated preparations. Compounds 7-9 represent a new type of molec ular duplication of P-adrenergic drugs, formally deriving from the sha ring of the aromatic portions of two different pharmacophoric subunits , namely the (aryloxy)propanolaminic portion of AOPAs and the [(benzyl ideneamino)oxy]propanolaminic portion of aryl-substituted MAOPAs. The pharmacological results showed that the beta-blocking activity of comp ounds 7-9 is closely related to the way in which the two subunits are linked by the aromatic nucleus: the activity decreases on passing from the ortho-compounds (7a,b) to the meta (8a,b) and then to the para (9 a,b) isomers. A comparison of this activity trend with those found for series of both beta-blocking AOPAs and aryl-substituted MAOPAs seems to indicate that compounds 7-9 can be considered more as AOPAs substit uted on the phenyl ring by [(methyleneamino)oxy]propanolaminic chain r ather than as aromatic MAOPAs substituted on the same phenyl moiety by an oxypropanolaminic portion.