ElogP(oct): A tool for lipophilicity determination in drug discovery

摘要

We present an RP-HPLC method, for the determination of logP(oct) 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 met-hod are as follows: (i) compound sparing (less than or equal to 1 mt of a 30-50 mu g/mL solution needed), (ii) rapid determinations (20 min on average), (iii) low sensitivity to impurities, (iv) wide lipophilicity range (6 logP(oct) 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 logP(oct) 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 ElogP(oct). [References: 36]