@article{fdi:010096002,
  title = {{D}iscovery of antileishmanial hits in the 3-nitroimidazo[1,2-a]pyridine series via newly optimized tetrakis(dimethylamino)ethylene ({TDAE}) methodology at position 2},
  author = {{J}acquet, {I}. and {P}aoli-{L}ombardo, {R}. and {C}astera-{D}ucros, {C}. and {P}omares, {H}. and {B}ourgeade-{D}elmas, {S}andra and {V}anelle, {P}. and {P}rimas, {N}.},
  editor = {},
  language = {{ENG}},
  abstract = {{T}o explore the antileishmanial structure-activity relationships at position 2 of the 3-nitroimida-zo[1,2-a]pyridine scaffold, we developed a new synthetic method using {T}etrakis(dimethylamino)ethylene ({TDAE}) and {N}-tosylbenzylimines. {T}his original synthetic route was optimized to provide simple and reproducible access to diverse analogues functionalized at position 2. {A} library of 25 new derivatives was generated via efficient diversification at position 8 using nucleophilic aromatic substitution ({SNA}r) and {S}uzuki-{M}iyaura cross-coupling reactions. {T}he 8-brominated analogues emerged as the most promising series, with six compounds exhibiting submicromolar activity against {L}eishmania infantum axenic amastigotes. {F}urther substitution at position 8 with 4-pyridinyl or para-chlorothiophenol groups significantly decreased potency. {T}he most active compound was also active on intramacrophagic amastigotes (half maximal inhibitory concentration ({IC}50) = 0.35 mu {M}) without displaying any cytotoxicity on {THP}1 cell line (50 % cytotoxic concentration ({CC}50) > 100 mu {M}). {T}he reduction of its nitro group afforded an amino analogue, which retained antileishmanial activity ({IC}50 = 2.77 mu {M}), indicating potential alternative mechanisms of action beyond nitro bioactivation. {D}espite its low solubility (<1 mu {M}), this scaffold represents a novel and versatile entry point for antileishmanial drug discovery.},
  keywords = {{TDAE} ; {N}-{T}osylbenzylimine ; {L}eishmania ; {N}itroaromatic compounds ; {N}ucleophilic aromatic substitution ; {P}alladium-catalyzed cross-coupling ; 3-{N}itroimidazo[1,2-a]pyridine},
  booktitle = {},
  journal = {{E}uropean {J}ournal of {M}edicinal {C}hemistry},
  volume = {304},
  numero = {},
  pages = {118506 [14 ]},
  ISSN = {0223-5234},
  year = {2026},
  DOI = {10.1016/j.ejmech.2025.118506},
  URL = {https://www.documentation.ird.fr/hor/fdi:010096002},
}