beta-Adrenergic blocking agents with acute antihypertensive activity

Modification of the pharmacological profile of the vasodilating/beta-adrenergic blocking agent 2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-4-(trifluoromethyl)imidazole (1) has been investigated. Introduction of selected substitutents onto the imidazole ring, in place of the trifluoromethyl group, has yielded highly cardioselective beta-adrenergic blocking agents such as 7, 17, and 18. The placement of alkyl or chloro groups onto the aryl ring of 1, as illustrated by 33, has produced a class of compounds characterized as antihypertensive beta-adrenergic blocking agents. In these examples, the acute antihypertensive activity does not appear to be due to either vasodilating or beta 2-agonist properties.