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    Methods for introducing a sulfhydryl amino or hydroxyl groups to a compound
    6.
    发明授权
    Methods for introducing a sulfhydryl amino or hydroxyl groups to a compound 失效
    将巯基氨基或羟基引入化合物的方法

    公开(公告)号：US5017693A

    公开(公告)日：1991-05-21

    申请号：US454295

    申请日：1989-12-19

    申请人： Mark D. Hylarides ,  Ananthachari Srinivasan ,  Jeffrey N. Fitzner ,  Vivekananda M. Vrudhula

    发明人： Mark D. Hylarides ,  Ananthachari Srinivasan ,  Jeffrey N. Fitzner ,  Vivekananda M. Vrudhula

    IPC分类号： A61K47/48

    CPC分类号： A61K47/48715 ,  A61K2121/00 ,  A61K2123/00

    摘要： The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of target cell an agent free of its targeting molecular carrier. A diagnostically therapeutically effective dose of a cleavable conjugate is administered to a warm-blooded animal such as man.Another aspect of the invention provides methods for isolating a compound. The compound binds covalently to a solid phase which has been derivatized with the linkers described above and is released in native form by a variety of mild conditions.An additional aspect of the invention provides methods for introducing into a compound a free sulfhydryl, amino, or hydroxyl group by use of reagents structurally related to the linkers described above. Preferred uses of the method are to add a free amino or a free sulfhydryl group to a protein, such as an antibody, or a drug.

    摘要翻译： 本发明提供了可切割的缀合物，其接头含有在多种温和条件下可裂解的不稳定键，包括弱酸性。 由于试剂可以直接与接头键合，所以裂解可导致天然试剂的释放。 本发明还提供了用于产生可切割缀合物的方法。 优选的试剂包括药物，毒素，生物反应调节剂，放射性诊断化合物，放射治疗化合物及其衍生物。 本发明中使用的靶向分子可以是完整分子，其片段或其功能等同物。 在特别优选的实施方案中，靶向分子是针对人类中与肿瘤相关抗原的单克隆抗体。 本发明还提供了向靶细胞的细胞质递送不含靶向分子载体的试剂的方法。 将可切割缀合物的诊断治疗有效剂量施用于温血动物如人。 本发明的另一方面提供了分离化合物的方法。 该化合物共价结合到已经用上述接头衍生化的固相，并且通过各种温和条件以天然形式释放。 本发明的另一方面提供了通过使用与上述接头结构相关的试剂将化合物引入游离巯基，氨基或羟基的方法。 该方法的优选用途是将游离氨基或游离巯基添加到蛋白质例如抗体或药物中。

    Synthesis of 1-haloestradiols
    7.
    发明授权
    Synthesis of 1-haloestradiols 失效
    1-卤代雌二醇的合成

    公开(公告)号：US4676932A

    公开(公告)日：1987-06-30

    申请号：US687035

    申请日：1984-12-28

    申请人： Mark D. Hylarides ,  Fred A. Mettler, Jr.

    发明人： Mark D. Hylarides ,  Fred A. Mettler, Jr.

    IPC分类号： C07J1/00 ,  C07J41/00

    CPC分类号： C07J1/007 ,  C07J41/0011

    摘要： Estrogens characterized by an aromatic ring of the formula ##STR1## are halogenated by electrophilic substitution of a halo atom at the 1-position of the aromatic ring after protection of the sensitive 3-hydroxyl substituent and amination at the 4-position. Preferred starting materials include estrones or derivatives thereof. The estrones are preferably reduced after masking and amination to form the corresponding estradiols, which are then halogenated, deaminated and deprotected to provide the novel 1-haloestradiols.

    摘要翻译： 以保护敏感的3-羟基取代基并在4-位氨基化之后，通过芳香环的1-位上的卤素原子的亲电取代而被芳族化合物“IMAGE”表征的雌酮被卤化。 优选的原料包括爱因子或其衍生物。 优选地，在掩蔽和胺化之后，减少心耳，以形成相应的雌二醇，然后将其卤化，脱氨基和去保护，以提供新的1-卤代雌二醇。