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    Spirocyclic Compounds
    7.
    发明申请
    Spirocyclic Compounds 有权
    螺环化合物

    公开(公告)号：US20090209566A1

    公开(公告)日：2009-08-20

    申请号：US12085396

    申请日：2006-11-17

    申请人： Scott C. Berk ,  Joshua Close ,  Christopher Hamblett ,  Richard W. Heidebrecht ,  Solomon D. Kattar ,  Laura T. Kliman ,  Dawn M. Mampreian ,  Joey L. Methot ,  Thomas Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Paul Tempest ,  Anna A. Zabierek

    发明人： Scott C. Berk ,  Joshua Close ,  Christopher Hamblett ,  Richard W. Heidebrecht ,  Solomon D. Kattar ,  Laura T. Kliman ,  Dawn M. Mampreian ,  Joey L. Methot ,  Thomas Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Paul Tempest ,  Anna A. Zabierek

    IPC分类号： A61K31/438 ,  C07D471/10 ,  C07D491/107 ,  C07D498/10 ,  C07D487/10 ,  A61K31/4439 ,  A61K31/506 ,  A61P35/00

    CPC分类号： C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D491/107 ,  C07D498/10

    摘要： The present invention relates to a novel class of substituted spirocyclic compounds, represented by the following structural Formula: I Wherein A, B and D are independently selected from CR12, NR1a, C(O) and O; E is selected from a bond, CR12, NR1a, C(O) and O; wherein at least one of A, B, D or E is CR12; and provided that when A is O, then E is not O; G is CR12; R is selected from NH2 and OH; These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing termin differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

    摘要翻译： 本发明涉及由下列结构式表示的新一类取代的螺环化合物：其中A，B和D独立地选自CR12，NR1a，C（O）和O; E选自键，CR12，NR1a，C（O）和O; 其中A，B，D或E中的至少一个为CR 12; 并且条件是当A为O时，则E不为O; G是CR12; R选自NH 2和OH; 这些化合物可以抑制组蛋白脱乙酰酶，适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统疾病（CNS），例如 神经退行性疾病 本发明进一步提供包含本发明化合物和易于遵循的这些药物组合物的安全给药方案的药物组合物，并且其在体内导致治疗有效量的这些化合物。

    Spirocyclic compounds
    10.
    发明申请
    Spirocyclic compounds 有权
    螺环化合物

    公开(公告)号：US20070117824A1

    公开(公告)日：2007-05-24

    申请号：US11600426

    申请日：2006-11-16

    申请人： Scott Berk ,  Joshua Close ,  Christopher Hamblett ,  Richard Heidebrecht ,  Solomon Kattar ,  Laura Kliman ,  Dawn Mampreian ,  Joey Methot ,  Thomas Miller ,  David Sloman ,  Matthew Stanton ,  Paul Tempest ,  Anna Zabierek

    发明人： Scott Berk ,  Joshua Close ,  Christopher Hamblett ,  Richard Heidebrecht ,  Solomon Kattar ,  Laura Kliman ,  Dawn Mampreian ,  Joey Methot ,  Thomas Miller ,  David Sloman ,  Matthew Stanton ,  Paul Tempest ,  Anna Zabierek

    IPC分类号： A61K31/4747 ,  C07D471/10

    CPC分类号： C07D471/10 ,  C07D487/10 ,  C07D491/10 ,  C07D491/107 ,  C07D498/10

    摘要： The present invention relates to a novel class of substituted spirocyclic compounds. These compounds can inhibit histone deacetylase and are suitable for use in selectively inducing terminal differentiation, and arresting cell growth and/or apoptosis of neoplastic cells, thereby inhibiting proliferation of such cells. Thus, the compounds of the present invention are useful in treating a patient having a tumor characterized by proliferation of neoplastic cells. The compounds of the invention may also be useful in the prevention and treatment of TRX-mediated diseases, such as autoimmune, allergic and inflammatory diseases, and in the prevention and/or treatment of diseases of the central nervous system (CNS), such as neurodegenerative diseases. The present invention further provides pharmaceutical compositions comprising the compounds of the instant invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of these compounds in vivo.

    摘要翻译： 本发明涉及一类新的取代的螺环化合物。 这些化合物可以抑制组蛋白脱乙酰酶，适用于选择性诱导终末分化，阻止肿瘤细胞的细胞生长和/或细胞凋亡，从而抑制这些细胞的增殖。 因此，本发明的化合物可用于治疗具有以肿瘤细胞增殖为特征的肿瘤的患者。 本发明的化合物还可用于预防和治疗TRX介导的疾病，例如自身免疫性，过敏性和炎性疾病，以及预防和/或治疗中枢神经系统（CNS）的疾病，例如 神经退行性疾病 本发明进一步提供包含本发明化合物和易于遵循的这些药物组合物的安全给药方案的药物组合物，并且其在体内导致治疗有效量的这些化合物。