Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes
    22.
    发明授权
    Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes 失效
    用于产生凝血酶抑制剂和内源性载体的新型缀合物的方法和组合物,导致具有延长的使用寿命的抗血栓素

    公开(公告)号:US06277863B1

    公开(公告)日:2001-08-21

    申请号:US09599379

    申请日:2000-06-22

    IPC分类号: A01N4342

    摘要: Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

    摘要翻译: 提供了包含化学反应中间体的新型化合物,其可与血液成分上的可用反应性官能团反应以形成共价键,其中发现所得的共价结合的缀合物具有凝血酶抑制活性。 具体地,本发明的凝血酶抑制剂化合物是已知的凝血酶抑制剂阿加曲班的衍生物,其可以与各种血液成分上的化学反应性官能团共价连接。 与未缀合的母体药物相比,缀合的凝血酶抑制剂在血液中的寿命延长,因此与未缀合的母体药物相比,能够延长凝血酶抑制活性。 本文还提供用于抑制体内凝血酶活性的方法,包括向哺乳动物宿主的血流施用本发明的新化合物。

    Affinity labeling libraries and applications thereof
    23.
    发明授权
    Affinity labeling libraries and applications thereof 失效
    亲和标记库及其应用

    公开(公告)号:US06277583B1

    公开(公告)日:2001-08-21

    申请号:US08598054

    申请日:1996-02-07

    IPC分类号: G01N3353

    摘要: Novel methods and compositions are provided for preferentially bonding an oligomeric molecule to a macromolecular target where the target is a member of a complex mixture and/or there is preferential bonding at one of a plurality of available bonding sites of the macromolecular target. The methods represent a complete system for both producing and identifying affinity label molecules from a combinatorial library which preferentially bind to a marcomolecular target or target site and preferentially binding those affinity labels to a macromolecule of interest either ex vivo or in vivo. Macromolecular targets include a variety of cellular- and non-cellular-associated proteins.

    摘要翻译: 提供了新颖的方法和组合物,用于将寡聚分子优先键合到靶是复合物混合物成分的大分子靶和/或在大分子靶的多个可用结合位点之一处具有优先键合。 该方法代表一个完整的系统,用于产生和鉴定来自组合文库的亲和标记分子,其优先结合于分子靶标或靶位点,并优先将这些亲和标记物结合到感兴趣的大分子体外或体内。 大分子靶标包括多种细胞和非细胞相关蛋白。

    Methods and compositions for producing novel conjugates of thrombin
inhibitors and endogenous carriers resulting in anti-thrombins with
extended lifetimes
    24.
    发明授权
    Methods and compositions for producing novel conjugates of thrombin inhibitors and endogenous carriers resulting in anti-thrombins with extended lifetimes 失效
    用于产生凝血酶抑制剂和内源性载体的新型缀合物的方法和组合物,导致具有延长的使用寿命的抗血栓素

    公开(公告)号:US5840733A

    公开(公告)日:1998-11-24

    申请号:US674315

    申请日:1996-07-01

    摘要: Novel compounds comprising chemically reactive intermediates which can react with available reactive functionalities on blood components to form covalent linkages, where the resulting covalently-bound conjugates are found to have thrombin inhibition activity are provided. Specifically, the thrombin inhibitor compounds of the present invention are derivatives of the known thrombin inhibitor argatroban, which can be covalently linked to chemically reactive functionalities on various blood components. The conjugated thrombin inhibitors thereby have extended lifetimes in the bloodstream, as compared to the unconjugated parent drug, and are, therefore, capable of maintaining thrombin inhibitory activity for extended periods of time as compared to the unconjugated parent drug. Also provided herein are methods for inhibiting thrombin activity in vivo comprising administering to the bloodstream of a mammalian host the novel compounds of the present invention.

    摘要翻译: 提供了包含化学反应中间体的新型化合物,其可与血液成分上的可用反应性官能团反应以形成共价键,其中发现所得的共价结合的缀合物具有凝血酶抑制活性。 具体地,本发明的凝血酶抑制剂化合物是已知的凝血酶抑制剂阿加曲班的衍生物,其可以与各种血液成分上的化学反应性官能团共价连接。 与未缀合的母体药物相比,缀合的凝血酶抑制剂在血液中的寿命延长,因此与未缀合的母体药物相比,能够延长凝血酶抑制活性。 本文还提供用于抑制体内凝血酶活性的方法,包括向哺乳动物宿主的血流施用本发明的新化合物。

    Ynenolactone protease inhibitors
    26.
    发明授权
    Ynenolactone protease inhibitors 失效
    内酯内酯蛋白酶抑制剂

    公开(公告)号:US4602006A

    公开(公告)日:1986-07-22

    申请号:US608340

    申请日:1984-05-09

    CPC分类号: C07D309/32 C07D307/58

    摘要: Compounds of the formula ##STR1## wherein n is 1-3; R.sup.1, R.sup.2 and R.sup.3 are the same or different and are hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl or aryl lower alkyl wherein when aryl is phenyl it is unsubstituted or independently substituted with one or more halo, lower alkyl or lower alkoxy groups; and R.sup.4 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, trialkylsilyl, aryl or aryl lower alkyl wherein when aryl is phenyl it is unsubstituted or independently substituted by one or more halo, lower alkyl or lower alkoxy groups; excluding those compounds wherein R.sup.1 and R.sup.2 are hydrogen and R.sup.4 is ethyl, propyl or butyl. These compounds are useful as protease inhibitors.

    摘要翻译: 其中n为1-3的式(Ⅰ)化合物; R 1,R 2和R 3相同或不同,为氢,低级烷基,低级烯基,低级炔基,芳基或芳基低级烷基,其中当芳基为苯基时,其未取代或独立地被一个或多个卤素,低级烷基或低级烷氧基 团体 R4是氢,低级烷基,低级烯基,低级炔基,三烷基甲硅烷基,芳基或芳基低级烷基,其中当芳基是苯基时,它是未被取代的或独立地被一个或多个卤素,低级烷基或低级烷氧基取代的; 不包括其中R 1和R 2为氢且R 4为乙基,丙基或丁基的那些化合物。 这些化合物可用作蛋白酶抑制剂。