Heterocyclic chemistry for therapeutic and PET imaging inovation
Innovation in heterocyclic chemistry and engineering for translational medicine
Team of Professeur Sylvain ROUTIER, Pr. emeritus Jean-Yves MÉROUR, Dr. Frédéric BURON and Dr. Karen PLÉ
Research in the Routier group is oriented toward molecular innovation in medicinal chemistry with the ultimate goal being the discovery of drug candidates or diagnostic tools in different pathologies. His group is a member of two LabEx “Laboratoire d’Excellence” IRON and SYNORG. Pr. Routier is the coordinator of the Marine Natural Products Strand in the Cancéropôle grand ouest (Western Canceropole consortium made up of more than 20 groups in chemistry, biology, and clinical studies). He also organizes and coordinates several translational research programs starting from the conception of active molecules, their optimization to pre-clinical and/or clinical trials in therapy and imagery. His research interests stem from the operation of biological systems and the structure of biological mediators as well as from marine natural products and plants.
Figure 1 : Research Interests
From the beginning, the Routier group has dealt with various biological targets in pathologies such as Alzheimer and Parkinson’s disease, multiple sclerosis, diabetes, and above all, cancer.
Different biological targets are addressed through translational projects with academic and industrial partners, from medicinal chemistry to the conception and synthesis of probes for PET imaging. These targets include integrins, orphan receptors, ion channels, and epigenetic transporters or targets. In particular, our group has a recognized expertise in the synthesis and optimization of protein kinase inhibitors involved in cancer or CNS disorders.
Figure 2 : (Top) Principle biological targets where our group has a known expertise in the design of new molecules which bind (ligand) or inhibit (antagonist) or reinforce (agonist) their potential in the nano and subnano molar range. (Bottom) Two examples of products that were validated in small animal preclinical trials as anti-cancer agents (kinase inhibitors) or PET imaging molecular probes (α7 nicotinic receptors).
Specialized in heterocyclic and medicinal chemistry, our group combines work in fundamental and applied research. With a focus on rare heterocycles, different synthetic methods have been developed to access and functionalize these structures in order to generate new entities and further explore the available chemical space. This approach guarantees originality and Intellectual Property (IP) through patents or publications.
The group uses modern synthetic technology such as metal catalyzed coupling reactions (Pd, Au, Ag) as well as more traditional methods: anion chemistry, (pseudo)peptide synthesis, protection and deprotection reactions.
Figure 3 : Methodology with different heterocycles: construction and/or functionalization
The Routier group has also developed a technological research axis oriented toward reaction activation, originally starting with microwave synthesis. The group has recently invested in a Flow chemistry apparatus. Using this current technology, reaction pathways (aromatic or heteroaromatic chemistry, asymmetric synthesis) can be conceived, innovated or revisited. This methodology offers our partners (both industrial and academic) an innovative and rapid access to synthetic intermediates in an efficient and selective manner while developing eco-friendly, “green” chemistry. This research which involves organic chemistry, chemical engineering, and industrial partners is carried out in collaboration with Dr. S. Bostyn (ICARE, CNRS) a specialist in chemical engineering.
Figure 4 : Flow chemistry apparatus and examples of different reaction developed by the group.