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    Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus
    1.
    发明授权
    Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus 有权

    公开(公告)号：US10703743B2

    公开(公告)日：2020-07-07

    申请号：US16037678

    申请日：2018-07-17

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： C07D405/14 ,  A61K31/496 ,  A61K45/06 ,  A61K9/00

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-HI's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

    CYTOTOXIC-DRUG DELIVERING MOLECULES TARGETING HIV (CDM-HS), CYTOTOXIC ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS AND METHODS OF USE
    2.
    发明申请
    CYTOTOXIC-DRUG DELIVERING MOLECULES TARGETING HIV (CDM-HS), CYTOTOXIC ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS AND METHODS OF USE 有权
    细胞毒素递送分子靶向HIV（CDM-HS），抗人类免疫缺陷病毒的细胞毒活性及其使用方法

    公开(公告)号：US20150087609A1

    公开(公告)日：2015-03-26

    申请号：US14396956

    申请日：2013-03-15

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： C07H15/26 ,  A61K45/06 ,  A61K31/706

    CPC分类号： C07H15/26 ,  A61K31/67 ,  A61K31/7028 ,  A61K31/7034 ,  A61K31/704 ,  A61K31/706 ,  A61K45/06 ,  A61K47/55 ,  A61K47/60 ,  C07D405/14 ,  A61K2300/00

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as CDM-Hs, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by introducing cytotoxic moieties to gp120-expressing cells, thereby causing cell death and preventing cell infection and spread of HIV. It is shown that CDM-Hs bind to gp120 and gp-120 expressing cells competitively with CD4, and these compounds cause cell death of HIV-infected cells, thereby decreasing viral infectivity. Compounds and methods are described herein.

    摘要翻译： 本发明涉及新的双功能化合物和用于治疗HIV感染的方法。 通常称为CDM-Hs的双功能小分子通过正交途径通过抑制gp120-CD4相互作用，并通过将细胞毒素部分引入到表达gp120的细胞中起作用，从而引起细胞死亡并预防细胞感染和HIV扩散。 显示CDM-Hs与CD4的gp120和gp-120表达细胞竞争性地结合，并且这些化合物引起HIV感染细胞的细胞死亡，从而降低病毒感染性。 本文描述了化合物和方法。

    BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
    3.
    发明申请
    BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS 有权

    公开(公告)号：US20220089579A1

    公开(公告)日：2022-03-24

    申请号：US17470393

    申请日：2021-09-09

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： C07D405/14 ,  A61K31/496 ,  A61K45/06 ,  A61K9/00

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-HI's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

    BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
    5.
    发明申请
    BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS 审中-公开

    公开(公告)号：US20190002447A1

    公开(公告)日：2019-01-03

    申请号：US16037678

    申请日：2018-07-17

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： C07D405/14 ,  A61K9/00 ,  A61K45/06 ,  A61K31/496

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-HI's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

    Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus
    6.
    发明授权
    Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the human immunodeficiency virus 有权

    公开(公告)号：US10030008B2

    公开(公告)日：2018-07-24

    申请号：US15379969

    申请日：2016-12-15

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： C07D405/14 ,  A61K31/496 ,  A61K9/00 ,  A61K45/06

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-HI's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

    BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS
    8.
    发明申请
    BIFUNCTIONAL MOLECULES WITH ANTIBODY-RECRUITING AND ENTRY INHIBITORY ACTIVITY AGAINST THE HUMAN IMMUNODEFICIENCY VIRUS 审中-公开
    具有抗人体免疫反应和入侵抑制活性的人类免疫缺陷病毒的双功能分子

    公开(公告)号：US20160082102A1

    公开(公告)日：2016-03-24

    申请号：US14883959

    申请日：2015-10-15

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： A61K39/385 ,  A61K9/00 ,  A61K47/48 ,  A61K45/06

    CPC分类号： A61K39/385 ,  A61K9/0019 ,  A61K9/0053 ,  A61K31/4745 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6897 ,  A61K2039/54 ,  A61K2039/57 ,  A61K2039/58 ,  A61K2039/6012 ,  A61K2039/627 ,  B82Y5/00 ,  C07D403/12 ,  C07D405/04 ,  C07D405/14 ,  C07D471/04 ,  A61K2300/00

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-H's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-H's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.

    摘要翻译： 本发明涉及新的双功能化合物和用于治疗HIV感染的方法。 通常称为ARM-H的双官能小分子通过正交途径通过抑制gp120-CD4相互作用和通过向表达gp120的细胞募集抗DNP抗体，从而防止细胞感染和HIV的扩散而起作用。 已经表明，ARM-H与gp120和gp-120表达细胞结合，与CD4竞争性，从而降低病毒感染性，如MT-2细胞测定所示，通过募集抗DNP抗体导致形成三元复合物的结合 与其结合，存在于三元复合物中的抗体促进表达gp120的细胞的补体依赖性破坏。 本文描述了化合物和方法。

    Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the Human Immunodeficiency Virus
    10.
    发明授权
    Bifunctional molecules with antibody-recruiting and entry inhibitory activity against the Human Immunodeficiency Virus 有权

    公开(公告)号：US11136316B2

    公开(公告)日：2021-10-05

    申请号：US16894362

    申请日：2020-06-05

    申请人： YALE UNIVERSITY

    发明人： David Spiegel ,  Christopher Parker

    IPC分类号： C07D405/14 ,  A61K31/496 ,  A61K45/06 ,  A61K9/00

    摘要： The present invention is directed to new bifunctional compounds and methods for treating HIV infections. The bifunctional small molecules, generally referred to as ARM-HI's, function through orthogonal pathways, by inhibiting the gp120-CD4 interaction, and by recruiting anti-DNP antibodies to gp120-expressing cells, thereby preventing cell infection and spread of HIV. It has been shown that ARM-HI's bind to gp120 and gp-120 expressing cells competitively with CD4, thereby decreasing viral infectivity as shown by an MT-2 cell assay, the binding leading to formation of a ternary complex by recruiting anti-DNP antibodies to bind thereto, the antibodies present in the ternary complex promoting the complement-dependent destruction of the gp120-expressing cells. Compounds and methods are described herein.