Syntheses of 1-[(2-hydroxyethoxy)methyl]- and 1-[(1,3-dihydroxy-2-propoxy)methyl]-derivatives of 5-substituted-2,4-difluorobenzene: Unnatural acyclo thymidine mimics for evaluation as anticancer and antiviral agents

A group of 1 -[(2-hydroxyethoxy)methyl] - (12) and 1-[(1,3-dihydroxy-2-prop oxy)methyl]- (13) derivatives of 2,4-difluorobenzene possessing a variety o f C-5 substituents (R = Me, H, I, NO2) were designed with the expectation t hat they may serve as acyclic 5-substituted-2'-deoxyuridine (thymidine) mim ics. Compounds 12 and 13 (R= Me, H, I) were inactive as anticancer agents ( CC50 = 10(-3) to 10(-4) M range), whereas the 5-nitro compounds (12d, 13d) exhibided weak-to-moderate cytotoxicity (ICC50 = 10(-5) to 10(-6) M range) against a variety of cancer cell lines. All compounds prepared (12a-d, 13a- d) were inactive as antiviral agents in a broad-spectrum antiviral screen t hat also included the human immunodeficiency virus (HIV-1 and HIV-2) and he rpes simplex virus(HSV-1 and HSV-2).