Description du projet
Une nouvelle technologie chimique ouvre un nouveau chapitre dans le domaine de la découverte de médicaments
Le cyclopropane est une entité chimique constituée de trois groupes méthylène dont l’assemblage forme une boucle triangulaire. Il est souvent introduit dans les médicaments impliquant des petites molécules aux premiers stades de la synthèse afin d’améliorer leur stabilité métabolique, leur conformation et leur pharmacocinétique. Le projet LateCPC, financé par l’UE, entend développer une méthode innovante qui génère des cyclopropanes à partir de liaisons carbone-hydrogène et qui peut donc être exploitée pour la synthèse de médicaments complexes. Outre l’extension du champ d’application du cyclopropane dans le domaine de la chimie médicinale, cette méthode devrait aider à répondre à des besoins médicaux actuellement non satisfaits, grâce à la découverte de nouveaux médicaments.
Objectif
The cyclopropane ring is the 10th most commonly observed core in small-molecule drugs. This is due to the fact that cyclopropanes can positively influence metabolic stability, conformation, pKa, entropy, membrane permeability or pharmacokinetics in drug leads. The cyclopropane ring is often introduced in drug candidates at the early stages of the synthesis, however, the late-stage construction of multi-substituted cyclopropanes using C–H bonds as a functional group has not been developed yet. This concept promise to reach a “cyclopropanated” chemical space not possible by current strategies and that may impact how medicinal chemists will discover cyclopropane-based drugs that address unmet medical needs. LateCPC aims to develop an innovative technology to rapidly construct cyclopropanes from C–H bonds in feedstock and fine aromatic molecules as well as in complex drug molecules. Our approach will rely on the diazo activation of bespoke carbyne sources developed in the host group with metal catalysts, allowing the catalytic generation of metal-carbynoids. A key strength of this conceptually new and multidisciplinary proposal is the introduction of a secondment phase in Novartis (Basel) to explore real-life applications. The ambitious action merges perfectly the expertise of the host in novel C−H functionalization strategies based on the catalytic generation of innovative carbyne equivalents with the strong background of the applicant in metal-catalyzed Tsuji-Trost reactions, thus enhancing two-way transfer of knowledge between the ER and the host group. Successful development of this project will enable the ER to become a leader for the next generation in the field of chemical synthesis and late-stage functionalization techniques. The ER will be exposed to a wide range of cutting-edge chemistry and biomedical sciences in an interdisciplinary and international environment (ICIQ) that will aid the fellow’s competencies and cultivate him as independent researcher.
Champ scientifique
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
43007 Tarragona
Espagne