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

  • Bioorg Med Chem Lett. 2019 Mar 1;29(5):755-760. doi: 10.1016/j.bmcl.2018.12.050.
Stéphane Sengmany  1 ,  Mathilde Sitter  1 ,  Eric Léonel  2 ,  Erwan Le Gall  1 ,  Gervaise Loirand  3 ,  Thierry Martens  1 ,  Didier Dubreuil  4 ,  Florian Dilasser  3 ,  Morgane Rousselle  3 ,  Vincent Sauzeau  3 ,  Jacques Lebreton  4 ,  Muriel Pipelier  4 ,  Rémy Le Guével  5
Affiliations
  • 1. Electrochimie et Synthèse Organique, Université Paris Est, ICMPE (UMR 7182), CNRS, UPEC, 2 rue Henri Dunant, F-94320 Thiais, France.
  • 2. Electrochimie et Synthèse Organique, Université Paris Est, ICMPE (UMR 7182), CNRS, UPEC, 2 rue Henri Dunant, F-94320 Thiais, France. Electronic address: [email protected].
  • 3. INSERM, UMR1087, CNRS, UNIV Nantes, l'institut du thorax, 8 quai Moncousu - BP 70721, F-44007 Nantes Cedex 1, France.
  • 4. Laboratoire de Synthèse Organique, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation, UMR 6513, CNRS-Université de Nantes, 2 rue de la Houssinière, BP 92208, F-44322 Nantes Cedex 3, France.
  • 5. Plate-Forme ImPACcell, Structure Fédérative de Recherche BIOSIT, Université de Rennes 1, Campus de Villejean, 2 Avenue du Pr. Leon Bernard CS34317, F-35043 Rennes Cedex, France.
PMID: 30655216 DOI: 10.1016/j.bmcl.2018.12.050
Abstract

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.

Keywords
Arylpyridazines; Biological evaluation; Cytotoxic activity; Electrosynthesis; Nickel catalysis.