Preparation of new fluorinated analogs of GABA and development of new inhibitors of antiapoptotic proteins with anticancer activity

The thesis is divided into two parts : Fluorine Chemistry and Medicinal Chemistry. The first part devoted to the synthesis of nitrogen heterocycles bearing a fluorinated side chain contains three chapters: in the first one we recall the importance of nitrogen heterocycles as well as fluorine chemistry in medicinal chemistry. In the second chapter, we describe the synthesis of new γ-lactams bearing gemdifluorinated side chains as well as the tests carried out to obtain GABA analogs. The third chapter is devoted to the synthesis from a fluorinated propargyl intermediate of three series of new nitrones bearing a fluorinated chain. In the second part dedicated to the search for novel molecules with anti-tumor activity, our objective was to reinduce apoptosis in cancer cells based on the revised structure of MIM1, a known inhibitor of the anti-apoptotic protein Mcl-1. Based on a molecular modeling study, we designed and prepared 38 original analogues that were tested on IGROV1 cells. Some of these compounds induce promising apoptotic activity in cancer cells. A study of structureactivity relationships and molecular modeling work were performed and allowed us to rationalize the results obtained.