Síntese de novos análogos triazólicos do fentanil

Abstract

Fentanyl is a synthetic opioid widely used for pain control. Due to its high and fast analgesic action, fentanyl is one of the most commonly used anesthetics in intraoperative procedures in the world. However, fentanyl has serious side effects such as respiratory depression, emesis, constipation and, mainly, physical dependence. Currently, there is a great concern about the use of fentanyl for the treatment of severe pain, due to the increase in cases of abuse of this opioid. Since its discovery, several fentanyl analogs have been synthesized, to modulate its pharmacological properties, but there is still a demand for an ideal opioid, which maintains its high analgesic property but mitigates its side effects. Thus, this work presents the synthesis of new fentanyl derivatives containing a triazole ring in its structure, to evaluate the changes generated by the insertion of a triazole nucleus to the fentanyl molecule. The synthesis strategy used to obtain the derivatives of interest was based on the total synthesis of fentanyl already described in the literature. The synthesis of the 1,2,3-triazole rings used in this work was carried out through the click reaction between an organic azide and an alkyne. The organic azide used as a starting material for this reaction required the application of new methodologies. Altogether, four new fentanyl derivatives and eleven new substances containing a triazole nucleus were synthesized. Biological tests using the substances obtained in this work will be performed later, to evaluate which types of activity will be presented by these molecules.