Synthesis of Novel G and N-Substituted Bicyclic Sulfones as Potential Inhibitors of Human Herpes Virus 6 (HHY,6)
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Abstract
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.