Synthesis of 4-(1-oxo-isoindoline) and 4-(5,6-dimethoxy-1-oxo-isoindoline)-substituted phenoxypropanolamines and their beta1-, beta2-adrenergic receptor binding studies

Phenoxypropanolamines with 1-oxo-isoindoline (12–16) and 5,6-dimethoxy-1-oxo-isoindoline groups (17–20) at the para position were synthesized. beta1, beta2-Adrenergic receptor binding affinities for the synthesized compounds were tested and compared with propranolol and atenolol. It was found that the incorporation of para-amidic functionality within the 1-oxo-isoindoline ring and 5,6-dimethoxy-1-oxo-isoindoline ring system led to a high degree of cardioselectivity in the phenoxypropanolamines. Two of the compounds 12 and 20 possessed beta1-adrenergic receptor affinity comparable with that of atenolol and both showed a better cardioselectivity than atenolol. Both 12 and 20 are undergoing further pharmacological evaluation.