Nucleosides containing chemically reactive groups.
5'-Amino-5'-deoxyinosine (1) and 1-(6-amino-2,5,6-trideoxy-beta-D-erythro-hexofuranosyl)thymine (9) were prepared and substituted on the amino group with chemically reactive functions in an effort to find inhibitors of enzymes that metabolize the corresponding nucleotides. The resulting 5'-substituted methynitrosoureas 3, 11a, and 11b, bromoacetamides 4 and 13, phenyl carbamates 5 and 14, and 4-(fluorosulfonyl)benzamides 6 and 15 were tested for cytotoxicity to H.Ep-2 cells in culture and as inhibitors of incorporation of precursors into nucleic acids of L1210 cells. The inosine derivatives were also evaluated as inhibitors of hypoxanthine phosphoribosyltransferase. Compounds 4, 6 and 13 showed moderate inhibition of formation of nucleic acids, and compound 4 demonstrated significant cytotoxicity (ED50 less than 5 microgram/mL).
D001667:Binding, Competitive; D007041:Hypoxanthine Phosphoribosyltransferase / Q000037:antagonists & inhibitors; D007288:Inosine / Q000031:analogs & derivatives*; D009696:Nucleic Acids / Q000096:biosynthesis; D009705:Nucleosides / Q000138:chemical synthesis*; D013936:Thymidine / Q000031:analogs & derivatives*
D009696:Nucleic Acids; D009705:Nucleosides; D007288:Inosine; D007041:Hypoxanthine Phosphoribosyltransferase; D013936:Thymidine