Targeting Type 2 Diabetes with Allene-containing Molecules Using a C-N Bond Cleavage Tool

Type 2 Diabetes is a chronic disease affecting more than 450 million people world-wide and is still an unmet medical need. PPAR´s(Peroxisome Proliferator-Activated Receptors) and G-protein-coupled receptors (GPCR) FFARs (Free Fatty Acid Receptors) are wellclinical validated targets for type-2 diabetes. Although selective GPR40 agonists have reached clinical phase III, the trials wererecently terminated due to signs of liver toxicity in patients. ALLENEDRUG is designed to provide a new chemical series of GPR40ligands aiming to bring a safer type-2 diabetes therapy. To achieve this goal, we will use a synthetic tool developed in our laboratoryto prepare enantiomerically enriched allenes through a selective C-N bond cleavage. This ERC-PoC will allow us to test the newchemical series as potential GPR40 agonists and to get insight into a SAR (Structure Activity Relationship) correlation with liver toxicityin order to compare the new molecules prepared in this proposal with those currently in clinical phase III trials.