Beta-adrenergic blocking agents: substituted phenylalkanolamines. Effect of side-chain length on beta-blocking potency in vitro.
The synthesis of a group of potential beta-blockers bearing a new 5-ethoxysalicylamide substituent on nitrogen is described. These compounds were tested for beta-adrenergic blocking potency in vitro and compared with analogous compounds bearing a tert-butyl group on nitrogen. The new N-substituent increased the beta-blocking potency substantially. In a series of five homologous compounds of the type Ar(CH2)nCHOHCH2NHR (R = 5-ethoxysalicylamide; n = 0-4), two maxima of beta-blocking potency were found for n = 0 and 2. Moreover, the carbon isostere of the corresponding (aryloxy)propanolamine still proved to be a very potent beta-blocker. The ether oxygen in the side chain is therefore not an absolute requirement for activity. Structure-activity relationships are discussed.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D004852:Epoxy Compounds; D011412:Propanolamines; D007545:Isoproterenol