Synthesis of 4-(1-oxo-isoindoline)-,4-(5,6-dimehtoxy-1-oxo-isoindoline) and 4-acetamido-substituted phenoxy-3-amino-propane dervatives and their beta_1-,beta_2-adrenergic receptor binding studies

摘要

In continuation toour previous study of 4-(1-oxo-isoindoline)- and 4-(5,6-dimethoxy-1-oxo-isoindoline)-substituted phenoxypropanolamines as potential cardioselective beta-adrenergic 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 bindign affinity and selectivity in turkey erythrocyte membrane (beta_1) and lung homogenate of rates(beta_2) isreported.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-[3,4-Dimethoxyphenylethylamino)propoxy]-phenyl}-1-oxo-isoindoline 7 hydrochloride shows beta_1-adrenergic receptor binding affinity lower than propranolol,but comparrable to that of atenolol with better cardioselectivity.Compound 7 has been selected for further pharmacological investigations.