title: Lipophilicity screening of novel drug-like compounds and comparison to clog P.
abstract: We determined the distribution coefficients of solutes between a polymer film phase (polyvinyl chloride (PVC) with 67% (w/w) dioctyl sebacate (DOS)) and an aqueous phase in a 96-well format. The parallel measurement approach is efficient and uses very little material. Polymer-water distribution coefficients (D(pw)) at different pH values yield the pKa and polymer-water partition coefficient values (P(pw)) of the solutes. log P(pw) of a prominent drug-like compound, 2H-1,2,6-thiadiazine, 3-methyl-5-phenyl-,1,1-dioxide, is in good agreement with clog P, while the pK(a) value is substantially different from calculated values. This method has been also successfully applied to a library of novel drug-like compounds. log D(pw) values (at pH 4.0, 7.0, 10.0) of 24 novel drug-like compounds have been determined with good reproducibility with the 96-well plate approach. Differences between experimental values and a variety of available calculated values are significant. This emphasizes the need for laboratory separations-based measurements of log D.
authors.affiliation: Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Dujuan
authors.initials: D
authors.lastname: Lu
authors.forename: Peter
authors.initials: P
authors.lastname: Chambers
authors.forename: Peter
authors.initials: P
authors.lastname: Wipf
authors.forename: Xiang-Qun
authors.initials: XQ
authors.lastname: Xie
authors.forename: Danielle
authors.initials: D
authors.lastname: Englert
authors.forename: Stephen
authors.initials: S
authors.lastname: Weber
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008956:Models, Chemical; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011143:Polyvinyl Chloride; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations; D011143:Polyvinyl Chloride