Recent progress in therapeutic applications of fluorinated five-membered heterocycles and their benzo-fused systems

Abstract

Heterocyclic derivatives grafted with fluorine atom(s) have attracted the attention of scientists due to the unique physicochemical properties of the C–F bond. The inclusion of fluorine atom(s) into organic compounds often increases their lipophilicity and metabolic stability, enhancing their bioavailability and affinity for target proteins. Therefore, it is not surprising to find that more than 20% of the medications on the market contain fluorine, and nearly 300 fluorine-containing drugs have been officially approved for use as medicines. In this review article, we are interested in classifying and describing the reports comprising varied therapeutic activities of the directly fluorinated five-membered heterocycles and their fused systems during the last two decades. These therapeutic activities included antiviral, anti-inflammatory, enzymatic inhibitory, antimalarial, anticoagulant, antipsychotic, antioxidant, antiprotozoal, histamine-H₃ receptor, serotonin receptor, chemokine receptor, prostaglandin-D2 receptor, and PBR inhibition activities. In many cases, the activities of fluorinated azoles were almost equal to or exceeded the potency of reference drugs.