CYTOTOXIC AGENTS COMPRISING NEW ANSAMITOCIN DERIVATIVES
    7.
    发明申请
    CYTOTOXIC AGENTS COMPRISING NEW ANSAMITOCIN DERIVATIVES 审中-公开
    包含新的氨基苯甲酸衍生物的细胞毒性试剂

    公开(公告)号:WO2012061590A1

    公开(公告)日:2012-05-10

    申请号:PCT/US2011/059131

    申请日:2011-11-03

    IPC分类号: A61K39/00

    摘要: New ansamitocin derivatives bearing a linking group are disclosed. Also disclosed are methods for the synthesis of these new ansamitocin derivatives and methods for their linkage to cell-binding agents. The ansamitocin derivative- cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

    摘要翻译: 公开了具有连接基团的新型安息霉素衍生物。 还公开了合成这些新的安沙霉素衍生物的方法及其与细胞结合剂的连接方法。 安曲霉素衍生物 - 细胞结合剂缀合物可用作治疗剂,其特异性递送至靶细胞并且是细胞毒性的。 与先前描述的试剂相比,这些缀合物在动物肿瘤模型中显示出显着改善的治疗功效。

    TRICARBONYL TECHNETIUM-99M OR RHENIUM-188 LABEL RING RGD DERIVATIVE, A PREPARATION METHOD THEREOF, AND A PHARMACEUTICAL COMPOSITION CONTAINING THE DERIVATIVE AS AN ACTIVE INGREDIENT FOR USE IN THE DIAGNOSIS OR TREATMENT OF ANGIOGENESIS-RELATED DISEAS
    8.
    发明申请
    TRICARBONYL TECHNETIUM-99M OR RHENIUM-188 LABEL RING RGD DERIVATIVE, A PREPARATION METHOD THEREOF, AND A PHARMACEUTICAL COMPOSITION CONTAINING THE DERIVATIVE AS AN ACTIVE INGREDIENT FOR USE IN THE DIAGNOSIS OR TREATMENT OF ANGIOGENESIS-RELATED DISEAS 审中-公开
    TRICARBONYL TECHNETIUM-99M或RHENIUM-188 LABEL RING RGD衍生物及其制备方法以及含有衍生物作为活性成分的药物组合物用于诊断或治疗血管发生相关疾病

    公开(公告)号:WO2011149250A3

    公开(公告)日:2012-03-22

    申请号:PCT/KR2011003801

    申请日:2011-05-24

    摘要: The present invention relates to a tricarbonyl technetium-99m or rhenium-188 label ring RGD derivative, a preparation method thereof, and a pharmaceutical composition containing the derivative as an active ingredient for use in the diagnosis or treatment of angiogenesis-related diseases. The tricarbonyl technetium-99m or rhenium-188 label ring RGD derivative of the present invention has a high subnanomolar affinity to avß3 integrin (also called as a vitronectin receptor that is activated in an angiogenic action induced by a tumor, reflects a high tumor image after an animal in which cancer cells are transplanted received an initial intake of the tricarbonyl technetium-99m label ring RGD derivative, and acts exclusively upon cancer cells having selectively activated avß3 integrin because of a substantially low intake into the liver and intestines, compared to existing known radioactive isotope label ring RGD derivatives. These results show that the rhenium-188 label derivative, a therapeutic nuclide using the same precursor as used in the technetium-99m label, effectively inhibits the growth of a tumor and demonstrates therapeutic efficacy when administered via tail vein injection to an animal model of a tumor, compared to a case where only saline has been injected, thereby making it useful as a medicine for the diagnosis or treatment of angiogenesis-related diseases.

    摘要翻译: 本发明涉及三羰基锝-99m或铼-188标记环RGD衍生物,其制备方法和含有该衍生物作为用于诊断或治疗血管生成相关疾病的活性成分的药物组合物。 本发明的三羰基锝-99m或铼-188标记环RGD衍生物对avß3整联蛋白(也称为在肿瘤诱导的血管生成作用中被激活的玻连蛋白受体)具有高亚纳摩尔亲和力,反映了肿瘤后高的肿瘤形象 其中移植了癌细胞的动物接受三羰基锝-99m标记环RGD衍生物的初始摄入,并且仅与具有选择性活化的avß3整联蛋白的癌细胞起作用,因为与现有已知的 这些结果表明,使用与锝-99m标记中使用相同前体的治疗性核素铼-188标签衍生物有效地抑制了肿瘤的生长并且通过尾静脉施用时表现出治疗功效 注射到肿瘤的动物模型,与仅注射盐水的情况相比,t 因此可用作诊断或治疗血管生成相关疾病的药物。

    PYRIDOINDOLOBENZOX-AND THIAZEPINE DERIVATIVIES AND USES THEREOF
    9.
    发明申请
    PYRIDOINDOLOBENZOX-AND THIAZEPINE DERIVATIVIES AND USES THEREOF 审中-公开
    吡咯烷酮和噻唑衍生物及其用途

    公开(公告)号:WO2012002928A1

    公开(公告)日:2012-01-05

    申请号:PCT/US2010/003263

    申请日:2010-12-31

    IPC分类号: A01N43/42

    CPC分类号: C07D513/16 C07D498/16

    摘要: The present invention discloses pyridoindolobenzox- and thiazepine compositions of Formula 1, wherein Formula I A is -CH(R 9 )-X- -XCH(R 9 )-; -CO-X- or -X-CO-; X is -O-, -S-, -SO-, or -SO 2 -. Y is a single bond or a double bond. D and E are independently -(CH2)n-; and 'n' varies from O to 2. R 1 to R 9 are various electron donating, electron withdrawing, hydrophilic, or lipophilic groups selected to optimize the physicochemical and biological properties of compounds of Formula I.

    摘要翻译: 本发明公开了式1的吡啶并二苯并氧氮杂和硫氮杂组合物,其中式ⅠA是-CH(R9)-X--XCH(R9) - ; -CO-X或-X-CO-; X是-O - , - S - , - SO-或-SO 2 - 。 Y是单键或双键。 D和E独立地为 - (CH 2)n - ; 并且'n'从O变化到2. R1至R9是选择用于优化式I化合物的物理化学和生物学性质的各种给电子,吸电子,亲水或亲脂基团。