66597-60-2Relevant academic research and scientific papers
Lipophilicity of aminopyridazinone regioisomers
Anwair, Massud A. S.,Karolyhazy, Laszlo,Szabo, Diana,Balogh, Balazs,Koevesdi, Istvan,Harmat, Veronika,Krenyacz, Judit,Gellert, Akos,Takacs-Novak, Krisztina,Matyus, Peter
, p. 5262 - 5270 (2003)
Ten pairs of pyridazinone regioisomers were prepared, and their lipophilicity was described by the logarithm of the octanol/water partition coefficient (log P) determined experimentally and calculated with prediction methods. The 4- and 5-(substituted amino)-3(2H)-pyridazinone regioisomers were synthesized by nucleophilic substitution of one of the chloro atoms of 4,5-dichloro-2-methyl-3(2H)-pyridazinone or its 6-nitro derivative. Structures of new compounds were proven by spectroscopic methods. The experimental log P values were obtained by a shake flask method in octanol and a Soerensen buffer (pH 7.4) solvent system. A consequent difference was found in the lipophilicity of regioisomers. For each isomer pair, the log P value of the 4-isomer was significantly (average by 0.75 log unit) higher than that of the 5-isomer. Some quantum chemical calculations as well as X-ray analysis of two pairs of regioisomers were also carried out to gain insight into the structural differences of regioisomers. The log P values were calculated by the fragmental approach KOWWIN and a QSPR analysis (3DNET). The a priori KOWWIN gave poor agreement, but with the programs KOWWIN with EVA (experimental value adjusted) and 3DNET, the results were generally in agreement with experiment.
