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 |
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| Authors: | Zhi-Xian Wang Weili Duan Leonard I. Wiebe Erik De Clercq Jan Balzarini Edward E. Knaus |
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| Affiliation: | 1. Faculty of Pharmacy and Pharmaceutical Sciences , University of Alberta , Edmonton, Alberta, Canada , T6G 2N8;2. Rega Institute for Medical Research , Minderbroedersstraat 10, Leuven, B-3000, Belgium |
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| Abstract: | Abstract A group of 1-[(2-hydroxyethoxy)methyl]- (12) and 1-[(1,3-dihydroxy-2-propoxy)methyl]- (13) derivatives of 2,4-difluorobenzene possessing a variety of C-5 substituents (R = Me, H, I, NO2) were designed with the expectation that they may serve as acyclic 5-substituted-2′-deoxyuridine (thymidine) mimics. Compounds 12 and 13 (R = Me, H, I) were inactive as anticancer agents (C50 = 10?3 to 10?4 M range), whereas the 5-nitro compounds (12d, 13d) exhibited weak-to-moderate cytotoxicity (CC50 = 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 that also included the human immunodeficiency virus (HIV-1 and HIV-2) and herpes simplex virus (HSV-1 and HSV-2). |
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