5-(5-Bromothien-2-yl)-2'-deoxyuridine and 5-(5-chlorothien-2-yl)-2'-deoxyuridine are equipotent to (E)-5-(2-bromovinyl)-2'-deoxyuridine in the inhibition of herpes simplex virus type I replication

Abstract

2'-Deoxyuridines with a five-membered heterocyclic substituent in the 5-position were synthesized by palladium-catalyzed coupling reactions of 5-iodo-2'-deoxyuridine with the activated heteroaromatics. Further modification of the compound with the 5-thien-2-yl substituent gave 5-(5-bromothien-2-yl)-2'-deoxyuridine and 5-(5-chlorothienyl-2-yl)-2'-deoxyuridine. Both compounds show potent and selective activity against herpes simplex virus type 1 and varicella-zoster virus.

Synthesis of 5-hetaryluracil derivatives via 1,3-dipolar cycloaddition reaction

“…13 C NMR spectra were recorded at 150 MHz or 75 MHz, respectively. Chemical shifts were measured relative to residual non-deuterated solvent signals.…”

Relationship between structural properties and affinity for herpes simplex virus type 1 thymidine kinase of bromine substituted 5-heteroaromatic 2′-deoxyuridines

“…1. The synthesis of 5- (Wigerinck et al, 1991a) and 5-(3-bromothien-2-yl)-2'-dUrd (V) (Luyten et al, 1995) has been described before. Also their IC 50 for the HSV-1 thymidine kinase is given in Fig.…”

“…In an effort to try to improve the properties of existing 5-substituted pyrimidine nucleoside analogues we have synthesized several 5-heteroaromatic substituted congeners (Wigerinck et al, 1991a;Wigerinck et al, 1991b;Wigerinck et al, 1993). Many among them demonstrate potent anti-HSV-1 activity.…”

Stereoelectronic properties of five anti-HSV-1 2′-deoxynucleosides analogues with heterocyclic substituents in the 5-position: A comparison with BVDU

“…This selectivity is due to the preferential phosphorylation of BVDU in HSV-1 infected cells by the viral thymidine kinase. However, BVDU is not the only selective anti-HSV-1 agent and replacement of the bromovinyl substituent by several 5-membered heterocycles yielded a new series of selective anti-HSV-1 compounds: 5-(5-chlorothien-2-yl)-2'-deoxyuridine (I), 5-(furan-2-yl)-2'-deoxyuridine (II), 5-(5-bromofuran-2-yl)-2'-deoxyuridine (III) (Wigerinck et al, 1991a), 5-(3-bromoisoxazol-5-yl)-2'-deoxyuridine (V) (Wigerinck et al, 1991b) and 5-(isoxazol-5-yl)-2'-deoxyuridine (IV) (Fig. 1) were synthesized as described previously.…”

“…51 0.15 dUrd= deoxyuridine a Data taken from Wigerinck et al (1991aWigerinck et al ( ,b, 1993. b Data taken from Bohman et al (1993).…”