Síntesis de nuevos compuestos con actividad farmacológica diseñados a través de simulaciones computacionales

Abstract

The complex process of drug research requires the joint efforts between different scientific disciplines. Although the discovery and development of new drugs has been carried out for many years using only experimental methods, in recent decades the process has achieved a higher level of efficiency thanks to the use of computational methods such as docking simulations, molecular dynamics, pharmacophore models and virtual screenings. These computational methods save time and resources in the expensive creation process, as well as allow a more efficient design of the target compounds and their synthetic routes. In this doctoral thesis, a reflection of current trends on the creation of new biologically active compounds can be observed, based on short and efficient synthetic routes to generate compounds with a relatively simple structure, on which previous work has been carried out through computational tools. In this work, compounds related to different topics have been designed, synthesized and pharmacologically evaluated, with promising results, such as: (i) new antagonists of allatostatin A receptors (ASTA-R) to deepen the study of the response mechanism of bees against stress; (ii) new inhibitors of Calcineurin-NFATc (CN-NFATc) signalling for immunosuppressive therapies and to reduce tumour angiogenesis; (iii) new transthyretin (TTR) stabilizers against transthyretin peptide amyloidosis (ATTR); and (iv) new allosteric modulators of cannabinoid receptors (CBR) from cannabidiol (CBD) analogues.