Synthesis of Fluorine Substituted Derivatives of a Bicyclic Aryl Sulfone as Potential Inhibitors of HHV-6 and HCMV

Abstract

Human herpesvirus 6 (HHV‐6) and human cytomegalovirus (HCMV) are two strains of betaherpesviruses. HHV‐6 causes roseola in children and retinitis in AIDS patients, and HCMV is the leading viral cause of birth defects, including deafness. There are no drugs specifically designed for HHV‐6, though the antivirals used to treat HCMV, foscarnet and ganciclovir, are used to treat HHV‐6 off‐label. However, both drugs exhibit toxicity that limits clinical usefulness. Our group, in collaboration with Dr. Lieve Naesens from Katholieke Universiteit in Leuven, Belgium, has developed a series of compounds that are effective at inhibiting HHV‐6 in a cell culture. A previously developed bicyclic sulfone compound has shown strong antiviral activity, and several derivatives of this compound have been synthesized in an effort to develop a more effective drug. Recent data has shown that bromine substituents on this compound increase antiviral activity, and in an attempt to further improve activity, a fluorine atom will be added as well. The specific purpose of this research is to investigate the antiviral activity of compounds with a fluorine substituent on the phenyl ring located at the 3‐position of the bicyclic sulfone ring system.