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

      Rouillard, Kaitlyn R.; Department of Chemistry and Physics (Augusta University, 2015-05)
      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.
    • Synthesis of Novel G and N-Substituted Bicyclic Sulfones as Potential Inhibitors of Human Herpes Virus 6 (HHY,6)

      Murray, Emily J.; Department of Chemistry and Physics (Augusta University, 2013-05)
      Human herpes virus 6 (HHV-6) is a member of the betaherpesvirus family and one of eight known human herpes viruses. HHV-6 commonly manifests itself by age three in more than ninety percent of the world's population as roseola infantum, an illness characterized by upper respiratory congestion, fever, febrile seizure, and rash. HHV-6 is also thought to play a role in the progression of pathogenic diseases such as epilepsy, multiple sclerosis, chronic fatigue syndrome, and some cancers. Currently, only two drugs, Cytovene and Foscavir, are commonly used for treatment of HHV-6. Unfortunately, both have high toxicity levels and viral resistance is building against them. Previous research in our lab and that of our collaborator has shown that certain bi cyclic sulfones are potent inhibitors of HHV-6. Our goal in this research has been to develop C- and N-substituted analogs of the original lead compound. Currently, one novel compound that contains both a cyclopropyl group on the nitrogen and a benzyl group on one of the carbons has been successfully synthesized by a multi-step process beginning with lcyanomethylsuifonyl-2-fluorobenzene. Reactions employed in the synthesis include Nucleophilic Aromatic Substitution (NAS), Aldo! Condensation, and SN2 Substitution. This new sulfone derivative has been sent to the Rega Institute for Medical Research in Leuven, Belgium for testing, and we are currently awaiting antiviral results. Meanwhile, work is ongoing to create additional analogs for testing. This work was funded in part by the HHV-6 Foundation.