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    • 43. 发明专利
    • Inhibitors of inflammation and reperfusion injury and methods of use thereof
    • AU4991801A
    • 2001-10-23
    • AU4991801
    • 2001-04-06
    • INOTEK CORP
    • JAPTAP PRAKASHSOUTHAN GARRYSALZMAN ANDREWSZABO CSABARAM SIYA
    • A61P19/02C07D209/46C07D401/12C07D403/12C07D473/34C07D473/40C07H19/04C07D209/00
    • 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 Z 1 and Z 2 respectively, to a linker, L; and A is: wherein: X 1 and X 2 are N; X 3 is -N-CH; R 1 and R 2 are independently H, alkyl, NH 2 , OH, SH, Cl, NHR 9 , or N-NR 9 , where R 9 is alkyl, aryl, or arylalkyl; R 5 and R 6 are independently alkyl, or R 5 and R 6 taken together form a -C(CH 3 ) 2 - group; Z 1 is -CH 2 O-, -CH 2 NR 10 -, -CH 2 NR 10 C(O)-, -CONR 10 -, -CO 2 -, -CH 2 NHCONH-, -CH 2 -, -CH 2 NHCSNH-, -CO-, -CH 2 CO 2 -, -NHCO 2 -, -S-, -SO 2 -, -CH 2 S-, or -SO-; Z 2 is -NR 10 CO-, -C(O)NR 10 -, -NHCONH-, -OC(O)-, -C(O)O-, NHCS, -CSNH-, -NHCSNH-, -O-, -CO-, -OCO-, -OCONH-, -NH-, -CH 2 -, -CH-alkyl-, -NHCO 2 -, -S-, -SO 2 -, 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 Z 1 is O, and when L=H, Z 2 and G are absent; and G is H, OH, SH, NH 2 , CO 2 H, 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.