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    • 27. 发明授权
      US06903079B2 Nucleoside compounds and compositions thereof 失效
    • Nucleoside compounds and compositions thereof
    • US06903079B2
    • 2005-06-07
    • US10320780
    • 2002-12-16
    • Prakash Jagtap , Garry Southan , Andrew Salzman , Csaba Szabo , Siya Ram
    • Prakash Jagtap , Garry Southan , Andrew Salzman , Csaba Szabo , Siya Ram
    • A61P19/02 , C07D209/46 , C07D401/12 , C07D403/12 , C07D473/34 , C07D473/40 , C07H19/04 , C07H19/167 , A61K31/7076
    • C07D401/12 , C07D209/46 , C07D403/12 , C07D473/34 , C07D473/40 , C07H19/04
    • The invention provides a novel class of substituted nucleoside derivatives having the formula: A-Z1-L-Z2-G wherein: A and G are connected via Z1 and Z2 respectively, to a linker, L; and A is: wherein: X1 and X2 are N; X3 is —N═CH; R1 and R2 are independently H, alkyl, NH2, OH, SH, Cl, NHR9, or N═NR9, 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—, —CH—alkyl—, —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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