使用一种新型疏水性描述符对纤维蛋白原抑制剂[[4-(4-脒基苯氧基)丁酰基]天冬氨酰]缬氨酸(FK633)衍生物进行定量构效关系研究。

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

作者信息

Tanaka A, Fujiwara H

机构信息

Basic Research Laboratories, Fujisawa Pharmaceutical Company Ltd., Yodogawa-ku, Osaka, Japan.

出版信息

J Med Chem. 1996 Dec 6;39(25):5017-20. doi: 10.1021/jm960557i.

DOI:10.1021/jm960557i

PMID:8960563

Abstract

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.

摘要

我们最近报道了一种用于定量构效关系（QSAR）研究的新型疏水描述符，即胶束/水分配系数的对数（log Pmw），它可以通过高效液相色谱系统轻松测定，并且被认为是化合物对生物膜亲和力的描述符。我们使用log Pmw对新型纤维蛋白原抑制剂[[4-(4-脒基苯氧基)丁酰基]天冬氨酰]缬氨酸（FK633）衍生物的抗血小板活性进行了QSAR研究，结果得到了一条具有良好相关系数的二次曲线（n = 12，s = 0.368，F = 14.1**，r = 0.871），表明纤维蛋白原抑制剂具有合适的膜亲和力对其抑制活性至关重要。使用STERIMOL参数和/或CLOGP值进行的QSAR研究未成功。