Synthesis, β-adrenergic receptor binding and antihypertensive potential of vanillin-derived phenoxypropanolamines

Synthesis of vanillin-derived phenoxypropanolamines is carried out by condensing 4-hydroxy-3-methoxybenzaldehyde (vanillin) 1 with epichlorohydrin, followed by treatment with iso-propylamine or tert-butylamine to open the epoxy ring. Percentage inhibition of [³H]dihydroalprenolol binding to both β₁- and β₂-adrenergic receptors by the newly synthesized compounds is assessed in vitro using turkey erythrocyte membrane (β₁) and lung homogenate of rats (β₂). Formyl derivatives 8 and 9 showed maximum inhibitory effect in binding assay and are non-selective similar to propranolol. On the other-hand, aldoxime compounds 10 and 11 have preference for β₁adrenergic receptors similar to atenolol. Also four of the compounds 8-11 are evaluated for their anti-hypertensive potential, in left renal artery ligation and fructose induced hypertension models. 4-(3-tert-Butylamino-2-hydroxy-propoxy)-3-methoxy- benzaldehyde oxime 11 shows antihypertensive effect better than propranolol.