New Ligands and Pharmacological Tools for the Study of G Protein-Coupled Receptors Using Multicomponent Reactions

Abstract

This PhD thesis describes the synthesis and optimization of novel families of potent and selective A2B antagonists and D2 biased partial agonists, thus contributing to the discovery of therapeutic agents for the treatment of pathologies such as cancer, schizophrenia, or Parkinson's disease. The chemical entities obtained were conceived using different design criteria and assembled using convergent, highly exploratory, and experimentally simple multicomponent reactions. The pharmacological characterization of the obtained libraries enabled the identification of A2BAR antagonists eliciting excellent potency, selectivity, and metabolic stability; as well as the identification of previously unexplored DRD2 biased partial agonists.