Advances in different technological and scientific fields have led to the development of tools that allow the design of drugs in a rational way, using defined therapeutic targets, through simulations that offer a molecular view of the ligand-receptor interactions, giving precise information for the design and synthesis of new compounds. Ion channels are of great relevance as therapeutic targets since they play roles in different pathologies. Several ion channels are expressed in the atria and constitute a therapeutic target for the treatment of atrial fibrillation (AF), the most common type of arrhythmia and an important risk factor for an increase in cerebrovascular accidents. The action potential (AP) of a cardiomyocyte is initiated by depolarization of the membrane through the inflow of sodium (Na⁺). The repolarization currents are carried out by different potassium (K⁺) channels. Background shows that TASK-1 channels can contribute to PA. TASK-1 channel blockers could become innovative strategies against FA, the compounds used in this study will be based on local anesthetic (LA) -type compounds that have been shown to be TASK-1 channel blockers such as lidocaine, ropivacaine and bupivacaine, and have antiarrhythmic capacity, becoming potentially effective drugs for the treatment of AF.

The main objective of this study is, based on the common characteristics of LAs, to propose the synthesis of analogues of LAs and evaluate them in-silico as TASK-1 channel blockers.