Antitumor and Antiviral Nucleoside Analogues

Wayne State University, Detroit MI

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Abstract

DESCRIPTION (provided by applicant): New nucleoside and nucleotide analogues will be prepared and studied as antiviral and antitumor agents. These compounds will include (i) enantiomeric triphosphates and non-hydrolyzable triphosphates of methylenecyclopropanes, (ii) ethynyl methylenecyclopropanes, (iii) fluorinated analogues of gem-bis (hydroxymethyl)methylenecyclopropanes, (iv) tris-(hydroxymethy)methylenecyclopropanes and (v) cyclopropavir phosphonates, acyclic and cyclic. Antiviral activity will be investigated in the following viral assays: Human immunodeficiency virus (HIV), human and murine cytomegalovirus (HCMV and MCMV), herpes simplex virus type 1 and 2 (HSV-1 and HSV-2), human herpes virus 6 and 8 (HHV-6 and HHV-8) and hepatitis B virus (HBV). In vivo activity and mechanism of action of active analogues will also be studied. Selected compounds will also be tested for antitumor activity