d-Phenylglycinol-derived non-covalent factor Xa inhibitors: Effect of non-peptidic S4 linkage elements on affinity and anticoagulant activity

Autor: Scott Martin Sheehan, Nikolay Y. Chirgadze, Gerald F. Smith, Jolie Anne Bastian, Michael Robert Wiley, Trelia J. Craft, Daniel Jon Sall, Jeffrey K. Smallwood, Jothirajah Marimuthu, John Walter Nr Macclesfield Liebeschuetz, Marcia K. Chastain, Philip Sipes, Jeffry Bernard Franciskovich, Brian Morgan Watson, Ronald S. Foster, Valentine J. Klimkowski
Rok vydání: 2007
Předmět:
Zdroj: Bioorganic & Medicinal Chemistry Letters. 17:5801-5805
ISSN: 0960-894X
Popis: Analogs to a series of D-phenylglycinamide-derived factor Xa inhibitors were discovered. It was found that the S4 amide linkage can be replaced with an ether linkage to reduce the peptide character of the molecules and that this substitution leads to an increase in binding affinity that is not predicted based on modeling. Inhibitors which incorporate ether, amino, or alkyl S4 linkage motifs exhibit similar levels of binding affinity and also demonstrate potent in vitro functional activity, however, binding affinity in this series is strongly dependent on the nature of the S1 binding element.
Databáze: OpenAIRE