Determination of lipophilicity of γ-butyrolactone derivatives with anticonvulsant and analgesic activity using micellar electrokinetic chromatography

摘要

The lipophilicity of a library of 30 derivatives of dihydrofuran-2(3H)-one (γ-butyrolactone) was determined by MEKC. Calibration curve prepared for ten reference drugs enabled to calculate partition coefficient (log P) for novel compounds. The results of MEKC analysis were compared with lipophilicity coefficients determined by RP-TLC (RM0) and computational (Mlog P, Clog P) methods. Good correlation was observed between the results obtained by both experimental methods: the MEKC parameters log k and relative lipophilicity RMO. The relationship between determined log P values and results of the computational prediction was weaker. Analysis of the relationship between lipophilicity and anticonvulsant activity showed statistically significant differences between mean values of log P coefficients for group of active (2.18) and inactive (1.51) compounds in the maximal electroshock test.