Synthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents

Stephane Sengmany (1) , Mathilde Sitter (1) , Eric Léonel (1) , Erwan Le Gall (1) , Gervaise Loirand (2) , Thierry Martens (1) , Didier Dubreuil (3) , Florian Dilasser (2) , Morgane Rousselle (2) , Vincent Sauzeau (2) , Jacques Lebreton (3) , Muriel Pipelier (3) , Rémy Le Guével (4)

1 ICMPE - Institut de Chimie et des Matériaux Paris-Est
2 ITX - ITX - unité de recherche de l'institut du thorax
3 LSOHOOM - Laboratoire de Synthèse Organique (Hétérochimie organique, organoéléments et matériaux)
4 ImPACcell - Plate-forme ImPACcell

Various 3-amino-, 3-aryloxy- and alkoxy-6-arylpyridazines have been synthesized by an electrochemical reductive cross-coupling between 3-amino-, 3-aryloxy- or 3-alkoxy-6-chloropyridazines and aryl or heteroaryl halides. In vitro antiproliferative activity of these products was evaluated against a representative panel of cancer cell lines (HuH7, CaCo-2, MDA-MB-231, HCT116, PC3, NCI-H727, HaCaT) and oncogenicity prevention of the more efficient derivatives was highlighted on human breast cancer cell line MDA-MB 468-Luc prior establishing their interaction with p44/42 and Akt-dependent signaling pathways.

Mots clés: Biological evaluation; Cytotoxic activity; Arylpyridazines; Electrosynthesis; Nickel catalysis

Domaines: Chimie thérapeutique

Stephane Sengmany, Mathilde Sitter, Eric Léonel, Erwan Le Gall, Gervaise Loirand, et al.. Synthesis and biological evaluation of 3-amino-, 3-alkoxy- and 3-aryloxy-6-(hetero)arylpyridazines as potent antitumor agents. Bioorganic and Medicinal Chemistry Letters, 2019, 29 (5), pp.755-760. ⟨10.1016/j.bmcl.2018.12.050⟩. ⟨hal-02053836⟩