Synthesis and in vitro pharmacological activity of oxypropanol analogs of labetalol

At present α- and β-adrenoceptors are classified into α1/α2 and β1/β2 (and also β3) [1] and [2] subtypes on the basis of structural and pharmacological studies. Both α- and β-adrenoceptor antagonists were proved to be effective and useful in the treatment of hypertension. β-Blockers, especially those selectively blocking heart β-adrenoceptors (β1) with little or no activity on bronchial or vascular adrenoceptors (β2), have been widely used and tested on a numbers of patients in all major multicentre intervention trials performed during past years [3], [4] and [5]. α-Adrenoceptor blocking agents have been less widely applied, although selective α1-adrenoceptor antagonists, like prazosin, have been introduced as useful antihypertensive agents. Therapeutically, the combination of α1 and β1-adrenoceptor antagonists is a logical one [6]. These observations led to the synthesis of several compounds combining both α- and β-adrenergic antagonist activities, and labetalol [1] is the first example of combined α- and β-adrenoceptor antagonistic drug [7].