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    • 85. 发明授权
    • Substituted O6-benzyl-8-aza-guanines and 6(4)-benzyloxypyrimidines
    • 取代的O6-苄基-8-氮杂 - 鸟嘌呤和6(4) - 苄氧基嘧啶
    • US06172070B2
    • 2001-01-09
    • US09318238
    • 1999-05-25
    • Robert C. MoschelAnthony E. PeggM. Eileen DolanMi-Young Chae
    • Robert C. MoschelAnthony E. PeggM. Eileen DolanMi-Young Chae
    • A01N4354
    • C07D239/47C07D239/48C07D239/50C07D251/52C07D473/06C07D473/18C07D473/40C07D487/04Y10S514/922
    • The present invention provides 8-substituted O6-benzylguanine, 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidine, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidine derivatives which have been found to be effective AGT inactivators, as well as pharmaceutical compositions comprising such derivatives along with a pharmaceutically acceptable carrier. The present invention further provides a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O6-position of guanine, by administering to a mammal an effective amount of one of the aforesaid derivatives, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O6-benzylguanine, and administering to the mammal an effective amount of an antineoplastic alkylating agent which causes cytotoxic lesions at the O6-position of guanine.
    • 本发明提供8-取代的O6-苄基鸟嘌呤,4(6) - 取代的2-氨基-5-硝基-6(4) - 苄氧基嘧啶和4(6) - 取代的2-氨基-5-亚硝基-6(4 已经被发现是有效的AGT灭活剂的苄氧基嘧啶衍生物,以及包含这些衍生物以及药学上可接受的载体的药物组合物。 本发明还提供了一种通过向哺乳动物施用有效量的上述衍生物之一来增强哺乳动物中肿瘤细胞的化学治疗方法,所述抗肿瘤烷化剂通过在鸟嘌呤的O6位引起细胞毒性损伤, 2,4-二氨基-6-苄氧基-s-三嗪,5-取代的2,4-二氨基-6-苄氧基嘧啶或8-氮杂-O6-苄基鸟嘌呤,并向哺乳动物施用有效量的抗肿瘤烷化剂, 在鸟嘌呤的O6位引起细胞毒性病变。