Quantitative structure-activity relationship study of fibrinogen inhibitors, [[4-(4-amidinophenoxy)butanoyl]aspartyl]valine (FK633) derivatives, using a novel hydrophobic descriptor.

We recently reported a novel hydrophobic descriptor for quantitative structure-activity relationship (QSAR) studies, the logarithm of the partition coefficient micelle/water (log Pmw), which is easily determined by a HPLC system and is thought to be a descriptor for a compound's affinity to a biomembrane. We carried out QSAR studies using log Pmw on the antiplatelet activities of novel fibrinogen inhibitors, [[4-(4-amidinophenoxy)butanoyl]aspartyl]valine (FK633) derivatives, which resulted in a quadratic curve with a good correlation coefficient (n = 12, s = 0.368, F = 14.1**, r = 0.871), indicating that a suitable membrane affinity of the fibrinogen inhibitors is vital for their inhibitory activities. QSAR studies using STERIMOL parameters and/or CLOGP values were unsuccessful.