Investigation of the terminal P4 domain in a series of D-phenylglycinamide-based factor Xa inhibitors

Bioorg Med Chem Lett. 2007 Dec 15;17(24):6910-3. doi: 10.1016/j.bmcl.2007.09.105. Epub 2007 Oct 24.

Abstract

Several P4 domain derivatives of the general d-phenylglycinamide-based scaffold (2) were synthesized and evaluated for their ability to bind to the serine protease factor Xa. Some of the more potent compounds were evaluated for their anticoagulant effects in vitro. A select subset containing various P1 indole constructs was further evaluated for their pharmacokinetic properties after oral administration to rats.

MeSH terms

  • Anticoagulants / chemical synthesis
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology
  • Antithrombin III / chemical synthesis*
  • Antithrombin III / chemistry
  • Antithrombin III / pharmacology*
  • Crystallography, X-Ray
  • Factor Xa / chemistry
  • Factor Xa / metabolism
  • Glycine / analogs & derivatives*
  • Glycine / chemical synthesis
  • Glycine / chemistry
  • Glycine / pharmacology
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Anticoagulants
  • phenylglycinamide
  • Antithrombin III
  • Factor Xa
  • Glycine