title: Measurement and prediction of hydrophobicity parameters for highly lipophilic compounds: application of the HPLC column-switching technique to measurement of log P of diarylpyrazines.
abstract: In the preparatory stage of structure-activity relationship (QSAR) studies of anti-platelet aggregant pyrazine derivatives, log P values (P: 1-octanol/water partition coefficient) of diarylpyrazines were measured by a newly developed HPLC column-switching technique. The system consists of two processes: (1) adsorption of the sample at the top end of a short precolumn, and then (2) quantifying the enriched analyte by a conventional analytical column. By using the log P values thus obtained, the correction factor for the steric hindrance caused by the vicinal diphenyl groups was estimated. The log k values (k; retention factor) were also measured with methanol-buffer (pH 7.4) eluents and related to log P. The eluent of 50% methanol content (M50) gave a good linear relationship over a wide range of log P (-0.3< log P < 5.2), indicating that log k(M50) parameter is useful for predicting the log P value.
authors.affiliation: Kobe Pharmaceutical University, Motoyamakita-machi, Higashinada, Kobe, 658-8558, Japan. yamagami@kobepharma-u.ac.jp
authors.forename: C
authors.initials: C
authors.lastname: Yamagami
authors.forename: K
authors.initials: K
authors.lastname: Araki
authors.forename: K
authors.initials: K
authors.lastname: Ohnishi
authors.forename: K
authors.initials: K
authors.lastname: Hanasato
authors.forename: H
authors.initials: H
authors.lastname: Inaba
authors.forename: M
authors.initials: M
authors.lastname: Aono
authors.forename: A
authors.initials: A
authors.lastname: Ohta
mesh_terms: D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D008055:Lipids / Q000737:chemistry*; D010087:Oxides / Q000737:chemistry; D011719:Pyrazines / Q000737:chemistry*; D012995:Solubility; D014867:Water
chemical_list: D008055:Lipids; D010087:Oxides; D011719:Pyrazines; D014867:Water