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.
Tanaka
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Basic Research Laboratories, Fujisawa Pharmaceutical Company Ltd., Yodogawa-ku, Osaka, Japan.
Fujiwara
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D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology*; D005340:Fibrinogen / Q000037:antagonists & inhibitors*; D006801:Humans; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004151:Dipeptides; D010975:Platelet Aggregation Inhibitors; C103087:((4-(4-amidinophenoxy)butanoyl)aspartyl)valine; D005340:Fibrinogen