title: A novel and useful descriptor for hydrophobicity, partition coefficient micellar-water, and its application to a QSAR study of antiplatelet agents.
abstract: 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.
authors.affiliation: New Drug Research Laboratories, Fujisawa Pharmaceutical Company Ltd., Osaka, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tanaka
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: I
authors.initials: I
authors.lastname: Nakanishi
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000494:pharmacology; D008823:Micelles; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D008823:Micelles; D010975:Platelet Aggregation Inhibitors