Synthesis of 4-(1-oxo-isoindoline)-, 4-(5,6-dimethoxy-1-oxo-isoindoline) and 4-acetamido- substituted phenoxy-3-amino-propane derivatives and their beta1-, beta2-adrenergic receptor binding studies

In continuation to our previous study of 4-(1-oxo-isoindoline)- and 4-(5,6-dimethoxy-1-oxo-isoindoline)-substituted phenoxypropanolamines as potential cardioselective beta-adrencrgic blocking agents, the synthesis of 4-(1-oxo-isoindoline) and 4-(5,6-dimethoxy-1-oxo-isoindoline)-substituted phenoxy-3-amino-propane derivatives and their beta adrenoceptor binding affinity and selectivity in turkey erythrocyte membrane (beta(1)) and lung homogenate of rats (beta(2)) is reported. Also 4-acetamido substituted derivatives are synthesized and tested. All the tested compounds exhibit better cardioselectivity, with the 4-acetamido substituted derivatives being the most cardioselective. N-[4-[3-(3,4-Dimethoxyphenylethylamino)propoxylphenyl}-1-oxo-isoindoline 7 hydrochloride shows beta(1)-adrenergic receptor binding affinity lower than propranolol, but comparable to that of atenolol with better cardioselectivity. Compound 7 has been selected for further pharmacological investigations.