Conférence 19 novembre 2025

Dr Claudia Lalli (Institut des Sciences Chimiques de Rennes)

Hétérocycles azotés : De la méthodologie à l’application à la découverte de médicaments grâce à l’approche par fragments.

Fragment-Based Drug Discovery (FBDD) has emerged in the recent years as powerful tool in the drug discovery process and has led to six marketed drugs as well as numerous candidates under clinical trials. In spite of this success, the available fragment libraries are mainly based on sp²-rich (hetero)aromatic planar compounds. Consequently, efforts are made to optimize fragment collections with the elaboration of original 3D-fragments, able to better explore the chemical space. We have addressed this issue by synthesizing different libraries of Csp3 rich, three dimensional piperidines. Methodological developments were needed, bringing on one hand to some advances in i) tandem triflation-allylation and RCM and ii) aza-Prins cyclization with ketones. On the other hand, a library of fluorinated piperidines has been evaluated by chemoinformatic tools in order to establish modification of the pKa, and three-dimensional character. Finally, a random screening revealed that one scaffold is recognized by the catalytic pocket of 3CLPro (main protease of SARS-CoV-2 coronavirus).