This doctoral thesis focuses on the study of purinergic signaling in cancer, specifically targeting adenosine receptors. The main objective is the development of potent and selective nonxanthine- based antagonists for adenosine A2B receptors, with potential applications in cancer-targeted therapies. Molecular design strategies, synthesis, biological evaluation, structureactivity relationships, enantiospecific recognition and molecular modeling are explored. To the end, a rational method for dual A2A/A2B antagonists were obtained. The optimization and preclinical validation of new ligands for cancer (immuno)therapy are investigated, revealing promising data in terms of pharmacokinetics and pharmacodynamics.
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