Derivatives related to betaxolol with alpha- and beta-adrenergic activities.
The paper describes the synthesis and the pharmacological evaluation of some derivatives of betaxolol, all with a N-aralkylamine instead of the tertiobutylamine. Their general formulas are: (Formula: see text). These compounds have been tested for beta 1-adrenergic receptors antagonism on guinea pig atria, beta 2-adrenergic receptor antagonism on guinea pig trachea and alpha-adrenergic blocking activity on rat aorta. Compound U12 with a marked alpha-blocking activity and compound R8 with a beta 1/alpha ratio = 1 were selected for a haemodynamic study in the dog. The decrease in cardiac work and the diminution of total peripheral resistance exhibited by U12 are consistent with a dual alpha/beta-blocking agent. Finally, structure-activity relationships are discussed.
Leclerc
G
G
Decker
N
N
Schwartz
J
J
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D015784:Betaxolol; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013552:Swine
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D015784:Betaxolol