Synthesis and anti-DNA virus activity of the 5'-monophosphate and the cyclic 3',5'-monophosphate of 9-(.beta.-D-xylofuranosyl)guanine

Abstract

9-(.beta.-D-Xylofuranosyl)guanine (xylo-G) was converted chemically to the 9-(.beta.-D-xylofuranosyl)guanine 5''-monophosphate (xylo-GMP) and 9-(.beta.-D-xylofuranosyl)guanine cyclic 3'',5''-monophosphate (c-xylo-GMP). These compounds were tested against a variety of DNA viruses in tissue culture [KB human oral carcinoma cells] in parallel with 9-(.beta.-D-arabinofuranosyl)adenine (ara-A). This evaluation revealed that xylo-G, xylo-GMP and c-xylo-GMP were all moderately active but less effective than ara-A. When the 4 compounds were administered intracerebrally as a treatment for herpes virus, type 1 induced encephalitis in mice, c-xylo-GMP exhibited superior activity to that shown by the other 3. When administered i.p., c-xylo-GMP had a therapeutic index of about 4, which is less than that for ara-A (.apprx.30) in the same system.