Lipophilicity of regioisomers: a case study on 3(2H)-pyridazinones

Two pairs of 4- and 5-aminopyridazinone regioisomers were prepared and the logarithm of their octanol/water partition coefficients (log P) was determined experimentally. The experimental log P values of the 4-isomers were found to be significantly higher than those of the respective 5-isomers. The log P values were also calculated by 3DNET, Q log P, Ghose–Crippen, Villar, ScilogPUltra and KOWWIN (with EVA) methods. Of them, only the last two methods were able to reproduce the observed tendency. [Copyright &y& Elsevier]