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.