Design, synthesis, and evaluation of orally active fibrinogen inhibitors

Low molecular weight and orally active fibrinogen inhibitors are described. The compounds studied in this work were rationally designed based on a metabolic study of a peptidic fibrinogen inhibitor, 4-(4-amidinophenoxy)butanoylaspartylvaline (1, FK633), which led to the synthesis of a potent and orally active antiplatelet agent, 4-(4-amidinophenoxy)butanoylaspartylvalylthiomorpholine 1,1-dioxide (3f, FR158999).