A series of 2-[(substituted phenylpiperazin-1-yl)methyl]- and 2-[(substituted phenylpiperidin-1-yl)methyl]-2,3-dihydroimidazo[1,2- c]quinazolin-5(6H)-ones or -5(6H)-thiones, and 3-[(substituted phenylpiperazin-1-yl)methyl]-2,3-dihydroimidazo[1,2-c]quinaz oline derivatives were synthesized, as conformationally restricted analogues of SGB-1534 and ketanserin, for evaluation as alpha-antagonists and antihypertensive agents. Most compounds containing a (substituted phenylipiperazinyl)methyl side chain displayed high binding affinity for alpha 1-adrenoceptor with no significant activity at alpha 2-sites. Compounds having a (substituted phenylpiperazinyl)methyl at the 3-position of 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one ring system had a better activity than those with the same substituent at the 2-position. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented and indicate that compounds with substitution at the ortho position on the benzene ring of the phenylpiperazine side chain moiety are more potent than those without substitution and/or substitutions at the 3- and 4-positions. Computer-assisted superimposition of SGB-1534 and 20b showed little structural correspondence between the quinazolinone and 2,3-dihydroimidazo[1,2-c]quinazoline nucleus, and specific interactions of these molecular fragments with the receptor protein appear unlikely. Antihypertensive activity was evaluated via intravenous administration of each compound to spontaneously hypertensive rats, and compounds (16a, 16b, 20b, and 28b) illustrated similar efficacy to SGB-1534 when assessed after 6 h. The pA2 value for 16a against phenylephedrine in rat aorta was much higher than that of prazosin. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compounds 20b and 28b warrant further evaluation.