SYNTHESE, ETUDE PHYSICO-CHIMIQUE ET ACTIVITE BIOLOGIQUE DE NOUVEAUX SYSTEMES HETEROCYCLIQUES COMPORTANT LE MOTIF INDAZOLE.

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Indazole and its derivatives have gained considerable importance in medicinal chemistry due to their promising pharmacological properties. This led us to develop the synthesis, electrochemical, spectroscopic and biological study of new heterocyclic systems comprising the indazole motif. In the first chapter, the study of the spectroscopic and electrochemical properties of the N-alkylated derivatives of 5- and 6-nitroindazoles provided a clear representation of the electron distribution in the molecules studied, useful for understanding the NMR experimental data and the Process of reduction of nitro groups. In addition, a good fit was found between the experimental results and the DFT calculations. In the second chapter, we synthesized new heterocyclic systems via the aromatic nucleophilic substitution (SNAr) of nitroheteroaryls by arylacetonitriles in basic methanol solution. Subsequently, the study of the reactivity of indazolic oximes, with respect to arylsulfonyl chlorides, made it possible to synthesize a new class of sulfonamide based on indazole. In the study of the metallo-catalyzed reduction of the N-alkyl-7-nitroindazole derivatives carried out in the third chapter, we have shown that the choice of metallic catalyst (SnCl2 or Indium) plays a fundamental role in obtaining 7- Aminoindazoles functionalized with alkylsulfanyl or alkoxy groups. Finally, the antiproliferative, apoptotic and cell cycle analysis tests carried out in the last chapter showed significant cytotoxic activities against the human cell lines A2780 (ovarian carcinoma), A549 (small pulmonary adenocarcinoma Cells), T47D (breast cancer), MDA-MB-231 (breast adenocarcinoma), and Gilin (neuroblastoma), with IC50s between 0.64 and 21μM, for a large majority (60%) of the synthesized molecules.

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