The invention provides a novel class of substituted nucleoside derivatives having
the formula:
wherein:
- A and G are connected via Z1 and Z2 respectively,
to a linker, L; and A is:
##STR1##
wherein:
- X1 and X2 are N;
- X3 is NCH;
- R1 and R2 are independently H, alkyl, NH2,
OH, SH, Cl, NHR9, or NNR9, where R9 is
alkyl, aryl, or arylalkyl;
- R5 and R6 are independently alkyl, or R5
and R6 taken together form a C(CH3)2 group;
- Z1 is CH2O, CH2NR10,
CH2NR10C(O), CONR10,
CO2, CH2NHCONH, CH2,
CH2NHCSNH, CO, CH2CO2,
NHCO2, S, SO2,
CH2S, or SO;
- Z2 is NR10CO, C(O)NR10,
NHCONH, OC(O), C(O)O, NHCS, CSNH,
NHCSNH, O, CO, OCO,
OCONH, NH, CH2, CHalkyl,
NHCO2, S, SO2,
CS, or SO;
- L is H, O, S, C1-15 alkylene chain optionally substituted in one or
more positions, a 5, 6 or 7 membered carbocycle, piperidine, piperazine, pyrole,
imidazole, benzimidazole, tetrazoles, indole, isoquinoline, quinoline, or pyrrolidine,
any of the 5, 6 or 7 membered carbocycle, piperidine, piperazine, pyrole, imidazole,
benzimidazole, tetrazoles, indole, isoquinoline, quinoline, or pyrrolidine groups
being unsubstituted or substituted with one or more lower alkyl, hydroxyl, keto,
amino, aminoalkyl, halo, or alkoxy groups, provided that L is not H when Z1
is O, and when L=H, Z2 and G are absent; and
- G is H, OH, SH, NH2, CO2H, unsubstituted or substituted
alkyl, aryl, alkylaryl, carbocyclic, biphenyl, piperidine, piperazine, pyrole,
imidazole, benzimidazole, tetrazole, indole, isoquinoline, quinoline, isoindolinyl,
tetrahydroindolinonyl, phthalimidyl, or pyrrolidine.
Pharmaceutical compositions, and methods of making and using the compounds,
or pharmaceutically acceptable salts, hydrates, or mixtures thereof are also described.
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