title: ElogPoct: a tool for lipophilicity determination in drug discovery.
abstract: We present an RP-HPLC method, for the determination of logPoct values for neutral drugs, which combines ease of operation with high accuracy and which has been shown to work for a set of 36 molecules comprised largely of drugs. The general features of the method are as follows: (i) compound sparing (< or = 1 mL of a 30-50 microg/mL solution needed), (ii) rapid determinations (20 min on average), (iii) low sensitivity to impurities, (iv) wide lipophilicity range (6 logPoct units), (v) good accuracy, (vi) excellent reproducibility. A linear free energy relationship (LFER) analysis, based on solvation parameters, shows that the method encodes the same information obtained from a shake-flask logPoct determination. To the best of our knowledge a similar performance, on a set of noncongeneric drugs, has not been previously reported. We refer to the value generated via this method as ElogPoct.
authors.affiliation: Central Research Division, Pfizer Inc, Groton, Connecticut 06340, USA. franco_lombardo@groton.pfizer.com
authors.forename: F
authors.initials: F
authors.lastname: Lombardo
authors.forename: M Y
authors.initials: MY
authors.lastname: Shalaeva
authors.forename: K A
authors.initials: KA
authors.lastname: Tupper
authors.forename: F
authors.initials: F
authors.lastname: Gao
authors.forename: M H
authors.initials: MH
authors.lastname: Abraham
mesh_terms: D020003:1-Octanol; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012997:Solvents
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D020003:1-Octanol