Recent Advances in the Synthesis of Fluorinated Heterocycles and A Close Look on the Recent FDA-Approved Fluorinated Drugs

Abstract

Since the date of inception of artificial drugs and agrochemicals to human society, the presence of a heterocyclic framework in the drug dominates and this could be due to the inspiration of many heterocyclic compounds from nature that show significant and diverse biological activity, which are useful to alleviate different diseases. Furthermore, in recent decades, fluorinated compounds have emerged as a prominent and rapidly growing class, securing a vital role in the research and development of new drugs. This could be attributed to the significant inherent properties of fluorine atom, which, in many cases, solve the problems related to the metabolic stability of drugs, enhance the lipophilicity, and change the pKa in favor of drugs. Now the belief in fluorinated compounds has become so strong that the judicious incorporation of fluorine into organic compounds has become one of the important tools for improving the chances of getting better therapeutically effective compounds. The fusion of the above two individually dominating fields—heterocyclic framework and fluorine atom in the potential drug compounds offers an even greater likelihood of discovering therapeutically useful agents. And this is one of the main reasons why a significant number of fluorinated heterocyclic drugs approved by FDA each year. Although fluorinated compounds have many benefits but the introduction of fluorine substituent remains challenging, particularly, it increases the complexity of the introduction of fluorine atoms into the heterocyclic framework. Over the last few decades, several methods have been developed to introduce fluorine into organic compounds; however, fluorination of heterocyclic compounds remains an elusive task, though gradually growing. Here, in this report, we present the most recent development in the fluorination of heterocyclic compounds and discuss the chemistry of fluorinated heterocyclic compounds approved in the last and current year.