Approaches to vasodilating/beta-adrenergic blocking agents: examples of the dihydrolutidine type.

The aminohydroxypropoxy moiety has been incorporated into the dihydrolutidine class of vasodilators. In the spontaneously hypertensive rat, one of these, (S)-4-[2-methyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-3,5-dicarboethoxy-1,4-dihydrolutidine (4c), exhibited antihypertensive activity on the order of the standard 4-[2-(trifluoromethyl)phenyl]-3,5-dicarboethoxy-1,4-dihydrolutidine (2a). This antihypertensive activity could not be explained in terms of a vasodilating effect, as determined in the dog. In this latter model, 2a decreased both mean arterial and hindlimb perfusion pressures.