STRUCTURE-ACTIVITY-RELATIONSHIPS IN 1,4-BENZODIOXAN-RELATED COMPOUNDS.5. EFFECTS OF MODIFICATION OF THE SIDE-CHAIN ON ALPHA-ADRENOCEPTOR BLOCKING ACTIVITY

The observation that the insertion of a phenyl ring at position 3 of W E 4101 (1) afforded a potent and selective alpha(1)-adrenoreceptor ant agonist, phendioxan (2), prompted us to investigate the effect on alph a-adrenoreceptor blocking activity of replacing a hydrogen atom at the 2-position or on the 2-ylmethyl moiety of 1 and 2 by a methyl, ethyl or phenyl group. Thus compounds 3 - 11 were synthesized and their bloc king activity and relative selectivity on alpha(1)- and alpha(2)-adren oreceptors were evaluated in the isolated rat vas deferens in comparis on to 1 and 2. The-results of such investigation showed that this stru ctural modification caused a decrease in affinity for alpha-adrenorece ptors.