SYNTHESES AND PLATELET-AGGREGATION INHIBITORY AND ANTITHROMBOTIC PROPERTIES OF [2-[(OMEGA-AMINOALKOXY)PHENYL]ETHYL]BENZENES

A series of [2-[(⍵-aminoalkoxy)phenyl] ethyl] benzene derivatives were synthesized and evaluated for their ability to inhibit collagen-induced platelet aggregation in vitro and to protect experimental thrombosis in mice. The results showed that the compounds were in vitro inhibitors of collagen-induced platelet aggregation. Most of them were also effective in the mouse antithrombotic assay. The compounds were found to be potent antagonists to S2 serotonergic receptor, and good correlation (r = 0.85) between their S2 serotonergic receptor antagonism and their potency as platelet antiaggregatory drugs was observed. Among the compounds studied, mono[2-(dimethylamino)-l-[[2-[2-(3-methoxyphenyl) ethyl] phenoxy] methyl] ethyl] succinate hydrochloride (12b, MCI-9042) was selected for further pharmacological and toxicological evaluation. © 1990, American Chemical Society. All rights reserved.