RP TLC ASSAY OF THE LIPOPHILICITY OF NEW AZATHIOPRINE ANALOGS

Abstract

The lipophilicity parameters of azathioprine (P ₂₀ ) and nineteen of its derivatives (P ₁ -P ₁₉ ) were determined experimentally (R_M0 and log P_TLC) by reversed-phase thin-layer chromatography and were compared with theoretical values (log P_calcd) obtained using 9 computational methods. The parameter R_M0 and specific hydrophobic surface area b were significantly intercorrelated showing a congeneric class of the azathioprine derivatives. The parameter R_M0 was correlated with molecular descriptors (molar mass, molar volume, and molar refractivity) and was converted into the parameter log P_TLC by use of a calibration curve obtained for five standards. The theoretical parameter log P_calcd differed dramatically depending on the calculating programs. The log P_calcd values were compared with experimental log P_TLC values showing low prediction power of calculated programs for compounds P ₁ -P ₂₀ . All compounds P ₁ -P ₁₉ were more lipophilic than azathioprine. The determined parameters were discussed in the terms of the structure-lipophilicity relationships.

Keywords:

• azathioprine derivatives
• congeneric class
• lipophilicity
• RP TLC
• structure-lipophilicity relationship

ACKNOWLEDGMENT

The work is supported by the Medical University of Silesia (grant KNW-1-008/10).

Notes

n = 9.

p = 0.0005.

n = 9.

p < 0.001.

Note: b(slope), a (intercept), r (correlation coefficient), and s (standard errors) from the correlation: R _M0 = b × log P _calcd + a.

n = 19.