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    METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS
    14.
    发明申请
    METHODS OF SYNTHESIZING SUBSTITUTED PURINE COMPOUNDS 有权
    合成取代的嘌呤化合物的方法

    公开(公告)号：US20160024134A1

    公开(公告)日：2016-01-28

    申请号：US14777317

    申请日：2014-03-14

    Applicant: EPIZYME, INC.

    Inventor： Edward James Olhava

    IPC: C07H19/16 ,  C07D235/12

    CPC classification number: C07H19/16 ,  A61K31/4184 ,  A61K31/7076 ,  C07B2200/13 ,  C07D235/12 ,  C07H1/06 ,  C07H19/06 ,  C07H19/067 ,  C07H19/167 ,  Y02A50/401 ,  Y02A50/409 ,  Y02A50/411

    Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning calorimetry profile, as well as a unique crystalline structure.

    Abstract translation: 本发明提供了合成（2R，3R，4S，5R）-2-（6-氨基-9H-嘌呤-9-基）-5 - （（（（1r，3S）-3- （2-（5-（叔丁基）-1H-苯并[d]咪唑-2-基）乙基）环丁基）（异丙基）氨基）甲基）四氢呋喃-3,4-二醇及其水合物和治疗疾病的方法 通过将这些化合物和药物组合物施用于有需要的受试者，其中DOT1介导的蛋白质甲基化部分起作用，例如癌症和神经障碍。 本发明还提供了（2R，3R，4S，5R）-2-（6-氨基-9H-嘌呤-9-基）-5 - （（（（1r，3S）-3- （5-（叔丁基）-1H-苯并[d]咪唑-2-基）乙基）环丁基）（异丙基）氨基）甲基）四氢呋喃-3,4-二醇及其水合物（A型，B型， 和形式C），其特征在于独特的X射线衍射图和差示扫描量热分析图，以及独特的晶体结构。

    Methods of synthesizing substituted purine compounds
    15.
    发明授权
    Methods of synthesizing substituted purine compounds 有权
    合成取代嘌呤化合物的方法

    公开(公告)号：US09175032B2

    公开(公告)日：2015-11-03

    申请号：US14210888

    申请日：2014-03-14

    Applicant: Epizyme, Inc.

    Inventor： Edward James Olhava

    IPC: A01N43/04 ,  A61K31/70 ,  C07H19/16 ,  A61K31/7076 ,  A61K31/4184 ,  C07D235/12

    CPC classification number: C07H19/16 ,  A61K31/4184 ,  A61K31/7076 ,  C07B2200/13 ,  C07D235/12 ,  C07H1/06 ,  C07H19/06 ,  C07H19/067 ,  C07H19/167 ,  Y02A50/401 ,  Y02A50/409 ,  Y02A50/411

    Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

    Abstract translation: 本发明提供了合成（2R，3R，4S，5R）-2-（6-氨基-9H-嘌呤-9-基）-5 - （（（（1r，3S）-3- （2-（5-（叔丁基）-1H-苯并[d]咪唑-2-基）乙基）环丁基）（异丙基）氨基）甲基）四氢呋喃-3,4-二醇及其水合物和治疗疾病的方法 通过将这些化合物和药物组合物施用于有需要的受试者，其中DOT1介导的蛋白质甲基化部分起作用，例如癌症和神经障碍。 本发明还提供了（2R，3R，4S，5R）-2-（6-氨基-9H-嘌呤-9-基）-5 - （（（（1r，3S）-3- （5-（叔丁基）-1H-苯并[d]咪唑-2-基）乙基）环丁基）（异丙基）氨基）甲基）四氢呋喃-3,4-二醇及其水合物（A型，B型， 和C型），其特征在于独特的X射线衍射图和差示扫描量热法，以及独特的晶体结构。

    Methods of synthesizing substituted purine compounds
    18.
    发明授权
    Methods of synthesizing substituted purine compounds 有权

    公开(公告)号：US10968247B2

    公开(公告)日：2021-04-06

    申请号：US16356384

    申请日：2019-03-18

    Applicant: Epizyme, Inc.

    Inventor： Edward James Olhava

    IPC: A01N43/04 ,  A61K31/70 ,  C07H19/16 ,  A61K31/7076 ,  A61K31/4184 ,  C07D235/12 ,  C07H19/06 ,  C07H19/067 ,  C07H1/06 ,  C07H19/167

    Abstract: The present invention provides an efficient process for the synthesis of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof and methods for treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer and neurological disorders, by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also provides novel crystalline forms of (2R,3R,4S,5R)-2-(6-amino-9H-purin-9-yl)-5-((((1r,3S)-3-(2-(5-(tert-butyl)-1H-benzo[d]imidazol-2-yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran-3,4-diol and hydrates thereof (Form A, Form B, and Form C), characterized by a unique X-ray diffraction pattern and Differential Scanning Calorimetry profile, as well as a unique crystalline structure.

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