Abstract
The lipophilicity parameters of azathioprine (P 20 ) and nineteen of its derivatives (P 1 -P 19 ) were determined experimentally (RM0 and log PTLC) by reversed-phase thin-layer chromatography and were compared with theoretical values (log Pcalcd) obtained using 9 computational methods. The parameter RM0 and specific hydrophobic surface area b were significantly intercorrelated showing a congeneric class of the azathioprine derivatives. The parameter RM0 was correlated with molecular descriptors (molar mass, molar volume, and molar refractivity) and was converted into the parameter log PTLC by use of a calibration curve obtained for five standards. The theoretical parameter log Pcalcd differed dramatically depending on the calculating programs. The log Pcalcd values were compared with experimental log PTLC 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.
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.