2′-Deoxyuridines with a 5-Heteroaromatic Substituent: Synthesis and Biological Evaluation

A series of novel 2'-deoxyuridines with a thienyl substituent in the 5-position were synthesized as potential anti-HSV-1 agents. The brominated derivatives (1d, 1e and 3b) were obtained via halogenation reactions of the protected 5-(thien-2-yl)-2'-deoxyuridine and 5-(thien-3-yl)-2'-deoxyuridine, respectively. The palladium-catalysed cross-coupling reaction with stannylated thiophene was used for the synthesis of (E)-5-(2-thienylvinyl)-2'-deoxyuridine and 5-(5,2'-dithien-2-yl)-2'-deoxyuridine. These compounds show moderate to good activity against herpes simplex virus type 1 (HSV-1) in the order of decreasing activity 1d>4>1e>3b similar to 5. Finally, two substituted 5-isoxazol derivatives of 2'-deoxyuridine (6a and 6b) were obtained via a 1,3-dipolar cycloaddition of the protected 5-ethynyl-2'-deoxyuridine. These new compounds demonstrated poor affinity for the virus-specific enzyme thymidine kinase. ispartof: Antiviral Chemistry & Chemotherapy vol:6 issue:4 pages:262-270 status: published