Lipophilicity characterization of new N ‐phenylamino‐azaspiranes as potential anticonvulsant agents

The lipophilicity of a library of N ‐phenylamino‐2‐azaspiro[4.4]nonane‐ and [4.5]decane‐1,3‐dione derivatives has been determined by reversed‐phase thin‐layer chromatography with n ‐propanol–Tris buffer (pH 7.4) mixtures as mobile phases. Examination of chromatographic behaviour revealed a linear correlation between R M values and the concentration of n ‐propanol in the mobile phase. The partition coefficients (log P ) were also calculated by use of the Prolog P module of the Pallas computer program. Comparison of R M0 values and calculated (log P PALLAS ) data revealed the correlation expressed by the equation: log P PALLAS = 0.9995 R M0 + 1.3451 ( n = 28; r = 0.8971; F = 107.13; p < 0.05). The role of the lipophilicity in the anticonvulsant activity of a set of compounds examined is discussed: the active anticonvulsants were less lipophilic than inactive ones. Copyright © 2006 John Wiley & Sons, Ltd.