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-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 (CC50 = 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).
Wang
Z X
ZX
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Duan
W
W
Wiebe
L I
LI
De Clercq
E
E
Balzarini
J
J
Knaus
E E
EE
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D018716:Molecular Mimicry; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry*; D013936:Thymidine / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014780:Viruses / Q000187:drug effects
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D001555:Benzene Derivatives; D009705:Nucleosides; D013936:Thymidine