Synthesis and antiviral activity of 5-heteroaryl-substituted 2'-deoxyuridines.
The synthesis of 5-heteroaryl-substituted 2'-deoxyuridines is described. The heteroaromatics were obtained from three different 5-substituted 2'-deoxyuridines. Cycloaddition reaction of nitrile oxides on the 5-ethynyl derivative 1 gave the isoxazoles 4a-e. The thiazole derivatives 14a-c were obtained from the 5-thiocarboxamide 11, while 5-pyrrol-1-yl-2'-deoxyuridine (17) could be synthesized directly from 5-amino-2'-deoxyuridine. The compounds were evaluated for antiviral activity. Selective activity against herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) was noted for 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (4c). The compound was inactive against herpes simplex virus type 2, cytomegalovirus, and thymidine kinase (TK)-deficient mutants of HSV-1 and VZV, which indicates that, most likely, its antiviral activity depends on phosphorylation by the virus-specified TK.
Wigerinck
P
P
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Snoeck
R
R
Claes
P
P
De Clercq
E
E
Herdewijn
P
P
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis; D002470:Cell Survival / Q000187:drug effects; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet
D000998:Antiviral Agents; D006571:Heterocyclic Compounds; D003857:Deoxyuridine