title: 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 (pIC50 = 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.
authors.affiliation: Solvay Pharmaceuticals Research Laboratory, Weesp, The Netherlands. jan.vanmaarseveen@solvay.com
authors.forename: J H
authors.initials: JH
authors.lastname: van Maarseveen
authors.forename: J A
authors.initials: JA
authors.lastname: den Hartog
authors.forename: K
authors.initials: K
authors.lastname: Tipker
authors.forename: J H
authors.initials: JH
authors.lastname: Reinders
authors.forename: J
authors.initials: J
authors.lastname: Brakkee
authors.forename: U
authors.initials: U
authors.lastname: Schön
authors.forename: W
authors.initials: W
authors.lastname: Kehrbach
authors.forename: C G
authors.initials: CG
authors.lastname: Kruse
mesh_terms: D000818:Animals; D006224:Cricetinae; D015195:Drug Design; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010879:Piperazines / Q000737:chemistry*; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control
chemical_list: D005343:Fibrinolytic Agents; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; C031503:phenylpiperazine