DESIGN AND SYNTHESIS OF AN ORALLY-ACTIVE GPIIB IIIA ANTAGONIST BASED ON A PHENYLPIPERAZINE SCAFFOLD/

Authors
VANMAARSEVEEN JH DENHARTOG JAJ TIPKER K REINDERS JH BRAKKEE J SCHON U KEHRBACH W KRUSE CG
Citation
Jh. Vanmaarseveen et al., DESIGN AND SYNTHESIS OF AN ORALLY-ACTIVE GPIIB IIIA ANTAGONIST BASED ON A PHENYLPIPERAZINE SCAFFOLD/, Bioorganic & medicinal chemistry letters, 8(12), 1998, pp. 1531-1536
Citations number
11
Categorie Soggetti
Chemistry Inorganic & Nuclear","Chemistry Medicinal
Journal title
Bioorganic & medicinal chemistry letters → ACNP
ISSN journal
0960894X
Volume
8
Issue
12
Year of publication
1998
Pages
1531 - 1536
Database
ISI
SICI code
0960-894X(1998)8:12<1531:DASOAO>2.0.ZU;2-2
Abstract
The design and synthesis of an orally active LMW non-peptide GPIIb/III a antagonist, based on a N,N'-bisphenylpiperazine scaffold, is describ ed. The optimal compound showed a high in vitro binding potency (pIC(5 0)=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 act ion of >90 min. in a hamster cheek pouch model. (C) 1998 Elsevier Scie nce Ltd. All rights reserved.