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    O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE INACTIVATORS AND BETA-GLUCURONIDASE CLEAVABLE PRODRUGS
    2.
    发明申请
    O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE INACTIVATORS AND BETA-GLUCURONIDASE CLEAVABLE PRODRUGS 失效
    O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE灭活剂和BETA-GLUCURONIDASE CLEAVABLE PRODRUGS

    公开(公告)号：US20070213279A1

    公开(公告)日：2007-09-13

    申请号：US11683310

    申请日：2007-03-07

    申请人： Robert MOSCHEL ,  Natalia LOKTIONOVA ,  Guangping WEI ,  Anthony PEGG ,  Gary PAULY ,  Matthew MOSCHEL

    发明人： Robert MOSCHEL ,  Natalia LOKTIONOVA ,  Guangping WEI ,  Anthony PEGG ,  Gary PAULY ,  Matthew MOSCHEL

    IPC分类号： A61K31/7076 ,  A61K31/70 ,  C07H17/02 ,  C07H19/16

    CPC分类号： C07D473/18

    摘要： Disclosed are prodrugs of inactivators of O6-alkylguanine-DNA alkyltransferase (AGT). The prodrugs are cleavable by the β-glucuronidase enzyme, which is either administered to the patient or produced by necrotic tumor cells. The prodrugs are represented by the formula A-B-C, wherein A is a glucuronosyl residue linked through its 1-oxygen to the phenyl ring of B; B is a benzyloxycarbonyl group, optionally ring-substituted with one or more electron withdrawing groups; and C is an inactivator of AGT, e.g., a substituted or unsubstituted O6-benzylguanine or O6-benzyl-2′-deoxyguanosine, Also disclosed are additional inactivators of AGT, pharmaceutical compositions comprising an inactivator or prodrug and a pharmaceutically acceptable carrier, and a method of use of the inactivator or prodrug in enhancing the chemotherapeutic treatment of tumor cells in a mammal, e.g., a human, with an antineoplastic alkylating agent that causes cytotoxic lesions at the O6-position of guanine.

    摘要翻译： 公开了O6-6-烷基鸟嘌呤-DNA烷基转移酶（AGT）的灭活剂的前药。 前药可以被β-葡糖醛酸糖苷酶切割，β-葡糖醛酸糖苷酶被施用于患者或由坏死的肿瘤细胞产生。 前药由式A-B-C表示，其中A是通过其1-氧连接到B的苯环的葡萄糖醛酸残基; B是一个苄氧基羰基，任选被一个或多个吸电子基团取代; 和C是AGT的灭活剂，例如取代或未取代的O6-苄基鸟嘌呤或O6 - 苄基-2'-脱氧鸟苷。还公开了另外的AGT灭活剂 ，包含灭活剂或前药和药学上可接受的载体的药物组合物，以及使用灭活剂或前药在增强哺乳动物（例如人）中的肿瘤细胞的化学治疗与引起细胞毒性损伤的抗肿瘤烷化剂的方法 在鸟嘌呤的O 6位上。

    2-Amino-o4-substituted pteridines and their use as inactivators of o6-alkylguanine-dna alkyltransferase
    3.
    发明申请
    2-Amino-o4-substituted pteridines and their use as inactivators of o6-alkylguanine-dna alkyltransferase 审中-公开
    2-氨基-4-取代的蝶啶及其作为O-烷基鸟嘌呤 - dna烷基转移酶的灭活剂的用途

    公开(公告)号：US20070155752A1

    公开(公告)日：2007-07-05

    申请号：US10585566

    申请日：2004-12-10

    申请人： Rorbert Moschel ,  Michael Nelson ,  Anthony Pegg ,  Natalia Loktionova

    发明人： Rorbert Moschel ,  Michael Nelson ,  Anthony Pegg ,  Natalia Loktionova

    IPC分类号： A61K31/525 ,  C07D475/02

    CPC分类号： C07D475/04

    摘要： Disclosed are pteridine derivatives of formula (I): (I), wherein, for example, R1 and R2 are hydrogen, C1-C6 alkyl, carboxyl, formyl, C1-C6 hydroxyalkyl, C1-C6 carboxyalkyl, C1-C6 formyl alkyl, C1-C6 alkoxy, acyloxy, acyloxyalkyl wherein the alkyl is C1-C6, halogen, or hydroxy, or a group of formula II: (II); and R3 is (a) phenyl or (b) a cyclic group having at least one 5 or 6-membered heterocyclic ring, optionally with a carbocyclic or heterocyclic ring fused thereto, wherein each heterocyclic ring has at least one hetero atom chosen from O, N, or S; or (c) a phenyl group or a cyclic group, the cyclic group optionally with a carbocyclic or heterocyclic ring fused thereto, which is substituted with 1 to 5 substituents. Disclosed also are pharmaceutical compositions, a method of enhancing the chemotherapeutic effectiveness of cancer treatment agents, a method of deactivating the O6-alkylguanine-DNA alkyltransferase enzyme, and a method of inhibiting the reaction of O6-alkylguanine-DNA alkyltransferase enzyme with an alkylated DNA.

    摘要翻译： 公开了式（I）的蝶啶衍生物：（I），其中例如R 1和R 2是氢，C 1〜 -C 6烷基，羧基，甲酰基，C 1 -C 6羟烷基，C 1 -C 3 C 6 -C 6烷基，C 1 -C 6烷基，C 1 -C 6烷氧基 ，酰氧基，酰氧基烷基，其中烷基是C 1 -C 6 - ，卤素或羟基，或式II的基团：（II）; 和R 3是（a）苯基或（b）具有至少一个5或6元杂环的环状基团，任选地与其中稠合的碳环或杂环，其中每个杂环具有 至少一个选自O，N或S的杂原子; 或（c）苯基或环状基团，所述环状基团任选具有稠合到其上的碳环或杂环，其被1至5个取代基取代。 还公开了药物组合物，增强癌症治疗剂的化学治疗效力的方法，使O-烷基鸟嘌呤-DNA烷基转移酶失活的方法，以及抑制O