Abstract
Ten pairs of pyridazinone regioisomers were prepared, and their lipophilicity was described using the logarithm of the octanol/water partition coefficient (log P), which was determined experimentally and calculated using prediction methods. The 4- and 5-(substituted amino)-3(2H)-pyridazinone regioisomers were synthesized via nucleophilic substitution of one of the chloro atoms in 4,5-dichloro-2-methyl-3(2H)-pyridazinone or its 6-nitro derivative. The structures of the new compounds were confirmed by spectroscopic methods. Experimental log P values were obtained using a shake flask method in octanol and a Sörensen buffer (pH 7.4) solvent system. A notable difference in lipophilicity between the regioisomers was observed. For each pair of isomers, the log P value of the 4-isomer was significantly higher (on average by 0.75 log units) compared to that of the 5-isomer. Additionally, quantum chemical calculations and X-ray analysis of two pairs of regioisomers were performed.