Tanaka A, Nakamura K, Nakanishi I, Fujiwara H
New Drug Research Laboratories, Fujisawa Pharmaceutical Company Ltd., Osaka, Japan.
J Med Chem. 1994 Dec 23;37(26):4563-6. doi: 10.1021/jm00052a016.
Herein we describe the introduction and application of a novel and useful descriptor, logarithm of micelle-water partition coefficients (log Pmw), for hydrophobicity of compounds. A QSAR study using log Pmw on antiplatelet activities ex vivo of 2-substituted phenyl and benzimidazolyl-5-methyl-4-(3-pyridyl)imidazoles showed its usefulness. Antiplatelet activities could be rationalized by means of only log Pmw with an excellent correlation (r = 0.772, s = 0.257, F = 11.07 **, n = 18), while use of other descriptors such as CLOGP values and retention factors (k') failed. Pmw values can easily be obtained using a normal HPLC system using a micelle aqueous solution as the mobile phase. HPLC techniques offer the advantage of tolerating lower sample purity, smaller sample size, and being dynamic range, compared with the flask-shaking method for measurement of logarithm of 1-octanol/water partition coefficients (log P), which is widely used in QSAR study. These indicated that log Pmw could be a useful descriptor for hydrophobicity of compounds.
在此，我们描述了一种用于化合物疏水性的新型实用描述符——胶束-水分配系数的对数（log Pmw）的引入和应用。一项使用log Pmw对2-取代苯基和苯并咪唑基-5-甲基-4-(3-吡啶基)咪唑的体外抗血小板活性进行的定量构效关系（QSAR）研究表明了其有用性。仅通过log Pmw就能合理地解释抗血小板活性，且具有出色的相关性（r = 0.772，s = 0.257，F = 11.07 **，n = 18），而使用其他描述符如CLOGP值和保留因子（k'）则无法做到。使用以胶束水溶液为流动相的常规高效液相色谱（HPLC）系统可以轻松获得Pmw值。与广泛用于QSAR研究的通过摇瓶法测量1-辛醇/水分配系数的对数（log P）相比，HPLC技术具有容忍较低样品纯度、较小样品量和较宽动态范围的优势。这些表明log Pmw可能是用于化合物疏水性的一个有用描述符。
