Synthesis and antileishmanial activity of new 1-(pyridin-2- yl)imidazolidin-2-ones derived from 2-amino-4,6-dimethylpyridine

Hiam Abdala, Jean Michel Robert, Patrice Le Pape*, Gaétane Wielgosz, Sylvie Robert-Piessard, Guillaume Le Baut

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Derivatives of 2-amino-4,6-dimethylpyridine resulting from the integration of the amino function into a 2-imidazolidinone were synthesized via the corresponding 2-chloroethylurea. N3-benzylation, acylation or sulfonylation afforded the target compounds 6-14 which were evaluated for their in vitro and in vivo antileishmanial activity. Two compounds, the N3- benzyl derivative 7 and the N3-tolylsulfonyl derivative 14, exhibited potent inhibition against cultured extracellular promastigotes of Leishmania mexicana with IC50 comparable to that of the previously studied N-(4,6- dimethylpyridin-2-yl) furan-2-carboxamide 2: 32.4, 46 and 69 μmol/l, respectively. Experimentation of their activity against mice macrophage amastigotes pointed out that IC50 of imidazolidones 7 and 14 were 7 and 13- fold lower than that of amide 2: 13.7 and 89 μmol/l. In vivo evaluation in Balb/c mice, intradermally infested with Leishmania mexicana, confirmed that, in the lesion site, compound 14 was able to significantly reduce the parasite burden at a daily i.p. dose of 10 mg/kg. It was demonstrated that these N- pyridinylimidazolidinones could act by interference with the parasite PLA2 activity.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalArzneimittel-Forschung/Drug Research
Volume50
Issue number5
DOIs
StatePublished - Jan 1 2000

Keywords

  • 1-(4,6-dimethylpyridin-2- yl)imidazolidin-2-ones
  • 2-Amino-4,6-dimethylpiridine derivatives
  • Anti-leishmania activity
  • PLA inhibition

ASJC Scopus subject areas

  • Drug Discovery

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