Design and synthesis of an orally active GPIIb/IIIa antagonist based on a phenylpiperazine scaffold.

Abstract The design and synthesis of an orally active LMW non-peptide GPIIb/IIIa antagonist, based on a N , N ′-bisphenylpiperazine scaffold, is described. The optimal compound showed a high in vitro binding potency (pIC 50 =8.7) in combination with potent oral antithrombotic activity (30–40% inhibition of thrombus growth at 0.3–3 mg/kg) with a duration of action of >90 min. in a hamster cheek pouch model.