Nucleosides containing chemically reactive groups

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Abstract
5''-Amino-5''-deoxyinosine and 1-(6-amino-2,5,6-trideoxy-.beta.-D-erythro-hexofuranosyl)thymine were prepared and substituted on the amino group with chemically reactive functions to find inhibitors of enzymes that metabolize the corresponding nucleotides. The resulting 5''-substituted methylnitrosoureas, bromoacetamides 4 and 13, phenyl carbamates and 4-(fluorosulfonyl)benzamides (6), were tested for cytotoxicity to H.Ep-2 cells in culture and as inhibitors of incorporation of precursors in nucleic acids of [mouse leukemia] L1210 cells. The inosine derivatives were also evaluated as inhibitors of hypoxanthine phosphoribosyltransferase. Compounds 4 [5''-[(bromoacetyl)amino]-5''-deoxyinosine], 6 [5''-deoxy-5''[[4-fluorosulfonyl)benzoyl]amino]inosine] and 13 [1-[6[(bromoacetyl)amino]-2,5,6-tri-deoxy-.beta.-D-erythro-hexofuranosyl]thymine] showed moderate inhibition of formation of nuclei acids; 4 demonstrated significant cytotoxicity (ED50 < 5 .mu.g/ml).