QSAR study of the peptidic fibrinogen inhibitors FK633, FR158999 and related derivatives, using a novel and useful hydrophobic descriptor (logPmw)

Bioorg Med Chem Lett. 1998 Sep 22;8(18):2483-8. doi: 10.1016/s0960-894x(98)00405-3.

Abstract

A QSAR study using the novel hydrophobic descriptor (logPmw), which is a descriptor for membrane affinity, of our fibrinogen inhibitors FK633 (1), FR158999 (21), and related derivatives was performed, and resulted in good correlation (n = 19, s = 0.268, F = 6.38**, r = 0.667). Based on these results, we constructed a hypothesis by which these potent inhibitors bind to the receptor via the biomembrane and the C-terminal moiety functions as an anchor moiety.

MeSH terms

  • Blood Platelets / metabolism
  • Cell Membrane / metabolism*
  • Chromatography, High Pressure Liquid
  • Dipeptides / chemistry*
  • Dipeptides / metabolism
  • Fibrinolytic Agents / chemical synthesis*
  • Fibrinolytic Agents / chemistry*
  • Fibrinolytic Agents / metabolism
  • Membranes, Artificial
  • Micelles
  • Models, Biological
  • Models, Chemical
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / metabolism
  • Structure-Activity Relationship

Substances

  • Dipeptides
  • FR 158999
  • Fibrinolytic Agents
  • Membranes, Artificial
  • Micelles
  • Platelet Aggregation Inhibitors
  • ((4-(4-amidinophenoxy)butanoyl)aspartyl)valine