Synthesis and irreversible beta-adrenergic blockade with a bromoacetamido derivative of betaxolol.
1-[4-(2-Cyclopropylmethoxyethyl)phenoxy]-3-[1-p-(bromoacetamidophe nyl) -2-methyl-2-propylamine]-2-propranol (8), which is a derivative of the beta 1-adrenergic agent betaxolol, was synthesized. Compound 8 showed less potent beta-adrenergic blocking activity than betaxolol in an in vitro test with guinea pig tracheal muscle and left atrium but retained high beta 1-selectivity. Irreversible beta-adrenoceptor antagonism of 8 was assessed by the blockade of the isoproterenol response of the guinea pig atria and by ligand binding studies with rat cerebral cortex.
Amlaiky
N
N
Leclerc
G
G
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol / Q000031:analogs & derivatives*; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C047550:1-(4-(2-cyclopropylmethoxyethyl)phenoxy)-3-(1-(4-bromoacetamidophenyl)-2-methyl-propylamine)-2-propanol; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; D015784:Betaxolol