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    METHODS TO MOBILIZE PROGENITOR/STEM CELLS
    1.
    发明申请
    METHODS TO MOBILIZE PROGENITOR/STEM CELLS 审中-公开
    移动原核细胞/干细胞的方法

    公开(公告)号：US20110129448A1

    公开(公告)日：2011-06-02

    申请号：US13023381

    申请日：2011-02-08

    Applicant: Gary J. BRIDGER ,  Michael J. Abrams ,  Geoffrey W. Henson ,  Ronald Trevor MacFarland ,  Gary B. Calandra ,  Hal E. Broxmeyer ,  David C. Dale

    Inventor： Gary J. BRIDGER ,  Michael J. Abrams ,  Geoffrey W. Henson ,  Ronald Trevor MacFarland ,  Gary B. Calandra ,  Hal E. Broxmeyer ,  David C. Dale

    IPC: A61K35/12 ,  A61P37/00

    CPC classification number: A61K31/395 ,  A61K31/33 ,  A61K31/4427 ,  A61K31/496 ,  A61K31/55 ,  A61K31/551 ,  A61K31/555 ,  A61K35/28 ,  A61K38/193 ,  A61K38/195 ,  A61K2035/124 ,  C12N5/0647 ,  A61K2300/00

    Abstract: Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′  (1) or pharmaceutically acceptable salt thereof wherein Z is a cyclic polyamine containing 9-32 ring members of which 3-8 are nitrogen atoms, said nitrogen atoms separated from each other by at least 2 carbon atoms, and wherein said heterocycle may optionally contain additional heteroatoms besides nitrogen and/or may be fused to an additional ring system; or Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ may be embodied in a form as defined by Z above, or alternatively may be of the formula —N(R)—(CR2)n—X wherein each R is independently H or straight, branched or cyclic alkyl (1-6C), n is 1 or 2, and X is an aromatic ring, including heteroaromatic rings, or is a mercaptan; “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.

    Abstract translation: 公开了使用结合趋化因子受体CXCR4的化合物来提高动物受试者祖细胞和干细胞计数的方法。 这种化合物的优选实施方案是式Z-接头-Z'（1）或其药学上可接受的盐，其中Z是含有9-32个环成员的环状多胺，其中3-8个是氮原子，所述氮原子从每个 另外通过至少2个碳原子，并且其中所述杂环可以任选地含有除氮之外的另外的杂原子和/或可以与另外的环系稠合; 或Z具有下式：其中A包含含有至少一个N的单环或双环稠合环体系，B是H或1-20个原子的有机部分，Z'可以以上述Z所定义的形式实施，或 或者可以是式-N（R） - （CR 2）n -X，其中每个R独立地为H或直链，支链或环状烷基（1-6C），n为1或2，X为芳环， 包括杂芳环，或是硫醇; “接头”表示键，亚烷基（1-6C）或可包含亚烷基链中所含的芳基，稠合芳基，氧原子，或可含有酮基或氮或硫原子。

    Synthesis of enantiomerically pure amino-substituted fused bicyclic rings
    3.
    发明授权
    Synthesis of enantiomerically pure amino-substituted fused bicyclic rings 有权
    对映体纯氨基取代稠合双环的合成

    公开(公告)号：US07135570B2

    公开(公告)日：2006-11-14

    申请号：US10959823

    申请日：2004-10-06

    Applicant: Ernest J. McEachern ,  Gary J. Bridger ,  Krystyna A. Skupinska ,  Renato T. Skerlj ,  Wen Yang

    Inventor： Ernest J. McEachern ,  Gary J. Bridger ,  Krystyna A. Skupinska ,  Renato T. Skerlj ,  Wen Yang

    IPC: C07D215/00

    CPC classification number: C07D217/22 ,  C07D215/06 ,  C07D215/20 ,  C07D215/38 ,  C07D215/40 ,  C07D215/42 ,  C07D215/48 ,  C07D221/04 ,  C07D241/42 ,  C07D307/79 ,  C07D491/04

    Abstract: This invention describes various processes for synthesis and resolution of racemic amino-substituted fused bicyclic ring systems. One process utilizes selective hydrogenation of an amino-substituted fused bicyclic aromatic ring system. An alternative process prepares the racemic amino-substituted fused bicyclic ring system via nitrosation. In addition, the present invention describes the enzymatic resolution of a racemic mixture to produce the (R)— and (S)— forms of amino-substituted fused bicyclic rings as well as a racemization process to recycle the unpreferred enantioner. Further provided by this invention is an asymmetric synthesis of the (R)— or (S)— enantiomer of primary amino-substituted fused bicyclic ring systems.

    Abstract translation: 本发明描述了合成和拆分外消旋氨基取代的稠合双环体系的各种方法。 一个方法利用氨基取代的稠合双环芳族环系统的选择性氢化。 另一种方法是通过亚硝化制备外消旋氨基取代的稠合双环体系。 此外，本发明描述了外消旋混合物的酶拆分以产生（R） - 和（S） - 形式的氨基取代的稠合双环，以及外消旋化方法以回收未预期的对映异构体。 本发明进一步提供的是伯氨基取代的稠合双环体系的（R） - 或（S） - 对映异构体的不对称合成。

    Combination Therapy
    5.
    发明申请
    Combination Therapy 审中-公开
    联合治疗

    公开(公告)号：US20100178271A1

    公开(公告)日：2010-07-15

    申请号：US12376591

    申请日：2007-08-07

    Applicant: Gary J. Bridger ,  Louis M. Pelus

    Inventor： Gary J. Bridger ,  Louis M. Pelus

    IPC: A61K38/19 ,  A61P35/00 ,  A61P35/02

    CPC classification number: A61K38/195 ,  A61K31/395 ,  A61K38/193 ,  A61K2300/00

    Abstract: Methods to mobilize progenitor and/or stem cells from the bone marrow to the bloodstream by administering a combination of at least one CXCR4 inhibitor, at least one CXCR2 agonist, and G-CSF are described. The combinations may also be used to increase the effectiveness of chemotherapy and radiation therapies for hematopoietic malignancies.

    Abstract translation: 描述了通过施用至少一种CXCR4抑制剂，至少一种CXCR2激动剂和G-CSF的组合将祖细胞和/或干细胞从骨髓移动到血流的方法。 这些组合也可用于增加造血恶性肿瘤的化疗和放射治疗的有效性。

    Synthesis of enantiomerically pure amino-substituted fused bicyclic rings
    7.
    发明授权
    Synthesis of enantiomerically pure amino-substituted fused bicyclic rings 有权
    对映体纯氨基取代稠合双环的合成

    公开(公告)号：US07452994B2

    公开(公告)日：2008-11-18

    申请号：US11598955

    申请日：2006-11-14

    Applicant: Ernest J. McEachern ,  Gary J. Bridger ,  Krystyna A. Skupinska ,  Renato T. Skerlj ,  Wen Yang

    Inventor： Ernest J. McEachern ,  Gary J. Bridger ,  Krystyna A. Skupinska ,  Renato T. Skerlj ,  Wen Yang

    IPC: C07D215/00 ,  C07D217/00

    CPC classification number: C07D217/22 ,  C07D215/06 ,  C07D215/20 ,  C07D215/38 ,  C07D215/40 ,  C07D215/42 ,  C07D215/48 ,  C07D221/04 ,  C07D241/42 ,  C07D307/79 ,  C07D491/04

    Abstract: This invention describes various processes for synthesis and resolution of racemic amino-substituted fused bicyclic ring systems. One process utilizes selective hydrogenation of an amino-substituted fused bicyclic aromatic ring system. An alternative process prepares the racemic amino-substituted fused bicyclic ring system via nitrosation. In addition, the present invention describes the enzymatic resolution of a racemic mixture to produce the (R)- and (S)-forms of amino-substituted fused bicyclic rings as well as a racemization process to recycle the unpreferred enantioner. Further provided by this invention is an asymmetric synthesis of the (R)- or (S)-enantiomer of primary amino-substituted fused bicyclic ring systems.

    Abstract translation: 本发明描述了合成和拆分外消旋氨基取代的稠合双环体系的各种方法。 一个方法利用氨基取代的稠合双环芳族环系统的选择性氢化。 另一种方法是通过亚硝化制备外消旋氨基取代的稠合双环体系。 此外，本发明描述了外消旋混合物的酶拆分以产生氨基取代的稠合双环的（R） - 和（S）形式，以及外消旋化方法以回收未预期的对映异构体。 本发明进一步提供的是主要氨基取代的稠合双环体系的（R） - 或（S） - 对映体的不对称合成。

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