Lipophilicity of aminopyridazinone regioisomers

Massud A.S. Anwair, László Károlyházy, Diána Szabó, Balázs Balogh, István Kövesdi, Veronika Harmat, Judit Krenyácz, Ákos Gellért, Krisztina Takács-Novák, Péter Mátyus

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Abstract

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 Sörensen 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.

Original languageEnglish
Pages (from-to)5262-5270
Number of pages9
JournalJournal of Agricultural and Food Chemistry
Volume51
Issue number18
DOIs
Publication statusPublished - Aug 27 2003

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Keywords

  • Aminopyridazinone regioisomers
  • Log P
  • Log P calculators
  • Nucleophilic substitution
  • Octanol/water partitioning
  • X-ray

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

Cite this

Anwair, M. A. S., Károlyházy, L., Szabó, D., Balogh, B., Kövesdi, I., Harmat, V., Krenyácz, J., Gellért, Á., Takács-Novák, K., & Mátyus, P. (2003). Lipophilicity of aminopyridazinone regioisomers. Journal of Agricultural and Food Chemistry, 51(18), 5262-5270. https://doi.org/10.1021/jf0343938