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 and 5,6-dimethoxy-1-oxo-isoindoline groups 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 and possessed beta1-adrenergic receptor affinity comparable with that of atenolol and both showed a better cardioselectivity than atenolol. Both and are undergoing further pharmacological evaluation.
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh-160014, India.
Dharam P
DP
Jindal
Babita
B
Singh
Mohane S
MS
Coumar
Giancarlo
G
Bruni
Paola
P
Massarelli
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D004082:Dihydroalprenolol / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D007211:Indoles; D011412:Propanolamines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D004082:Dihydroalprenolol; C057812:indoline