公开(公告)号：US07872024B2

公开(公告)日：2011-01-18

申请号：US11918911

申请日：2006-04-14

申请人： Joey Methot ,  Thomas A. Miller ,  David J. Witter

发明人： Joey Methot ,  Thomas A. Miller ,  David J. Witter

IPC分类号： A61K31/40 ,  A61K31/445 ,  C07D405/00 ,  C07D333/52

CPC分类号： C07D333/70

摘要： The present invention relates to a novel class of hydroxamic acid derivatives carbamate, urea, amide and sulfonamide substitutions. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also 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 are also 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 hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

摘要翻译： 本发明涉及一类新型异羟肟酸衍生物氨基甲酸酯，脲，酰胺和磺酰胺取代物。 异羟肟酸化合物可用于治疗癌症。 异羟肟酸化合物也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（CNS）的疾病，例如神经变性 疾病 本发明进一步提供包含异羟肟酸衍生物和这些药物组合物的安全投药方案的药物组合物，它们易于遵循，并且其在体内导致治疗有效量的异羟肟酸衍生物。

公开(公告)号：US20090318541A1

公开(公告)日：2009-12-24

申请号：US11918911

申请日：2006-04-14

申请人： Joey Methot ,  Thomas A. Miller ,  David J. Witter

发明人： Joey Methot ,  Thomas A. Miller ,  David J. Witter

IPC分类号： A61K31/381 ,  C07D333/64 ,  A61P35/00 ,  A61P25/00

CPC分类号： C07D333/70

摘要： The present invention relates to a novel class of hydroxamic acid derivatives carbamate, urea, amide and sulfonamide substitutions. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also 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 are also 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 hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

摘要翻译： 本发明涉及一类新型异羟肟酸衍生物氨基甲酸酯，脲，酰胺和磺酰胺取代物。 异羟肟酸化合物可用于治疗癌症。 异羟肟酸化合物也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（CNS）的疾病，例如神经变性 疾病 本发明进一步提供包含异羟肟酸衍生物和这些药物组合物的安全投药方案的药物组合物，它们易于遵循，并且其在体内导致治疗有效量的异羟肟酸衍生物。

公开(公告)号：US07772238B2

公开(公告)日：2010-08-10

申请号：US11918912

申请日：2006-04-14

申请人： Jed Lee Hubbs ,  Sam Kattar ,  Joey Methot ,  Thomas Miller ,  Phieng Siliphaivanh ,  Matthew Stanton ,  Kevin Wilson ,  David J. Witter

发明人： Jed Lee Hubbs ,  Sam Kattar ,  Joey Methot ,  Thomas Miller ,  Phieng Siliphaivanh ,  Matthew Stanton ,  Kevin Wilson ,  David J. Witter

IPC分类号： A61K31/496 ,  A61K31/381 ,  C07D405/04 ,  C07D333/56

CPC分类号： C07D333/70 ,  A61K31/38 ,  A61K31/381 ,  A61K31/41

摘要： The present invention relates to a novel class of hydroxamic acid derivatives. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also 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 are also 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 hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

摘要翻译： 本发明涉及一类新型异羟肟酸衍生物。 异羟肟酸化合物可用于治疗癌症。 异羟肟酸化合物也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（CNS）的疾病，例如神经变性 疾病 本发明进一步提供包含异羟肟酸衍生物和这些药物组合物的安全投药方案的药物组合物，它们易于遵循，并且其在体内导致治疗有效量的异羟肟酸衍生物。

公开(公告)号：US20090069391A1

公开(公告)日：2009-03-12

申请号：US11918912

申请日：2006-04-14

申请人： Jed Lee Hubbs ,  Sam Kattar ,  Joey Methot ,  Thomas Miller ,  Phieng Siliphaivanh ,  Matthew Stanton ,  Kevin Wilson ,  David J. Witter

发明人： Jed Lee Hubbs ,  Sam Kattar ,  Joey Methot ,  Thomas Miller ,  Phieng Siliphaivanh ,  Matthew Stanton ,  Kevin Wilson ,  David J. Witter

IPC分类号： A61K31/381 ,  C07D333/52 ,  A61K31/4245 ,  A61P25/00 ,  A61P35/00 ,  C07D271/10

CPC分类号： C07D333/70 ,  A61K31/38 ,  A61K31/381 ,  A61K31/41

摘要： The present invention relates to a novel class of hydroxamic acid derivatives. The hydroxamic acid compounds can be used to treat cancer. The hydroxamic acid compounds can also 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 are also 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 hydroxamic acid derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the hydroxamic acid derivatives in vivo.

摘要翻译： 本发明涉及一类新型异羟肟酸衍生物。 异羟肟酸化合物可用于治疗癌症。 异羟肟酸化合物也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（CNS）的疾病，例如神经变性 疾病 本发明进一步提供包含异羟肟酸衍生物和这些药物组合物的安全投药方案的药物组合物，它们易于遵循，并且其在体内导致治疗有效量的异羟肟酸衍生物。

公开(公告)号：US20120022044A1

公开(公告)日：2012-01-26

申请号：US13139830

申请日：2009-12-07

申请人： Christian Fischer ,  Joey Methot ,  Hua Zhou ,  Adam J. Schell ,  Benito Munoz ,  Alexey A. Rivkin ,  Sean P. Ahearn ,  Stephanie Chichetti ,  Rachel N. MacCoss ,  Sam Kattar ,  Matthew Christopher ,  Chaomin Li ,  Andrew Rosenau ,  William Colby Brown

发明人： Christian Fischer ,  Joey Methot ,  Hua Zhou ,  Adam J. Schell ,  Benito Munoz ,  Alexey A. Rivkin ,  Sean P. Ahearn ,  Stephanie Chichetti ,  Rachel N. MacCoss ,  Sam Kattar ,  Matthew Christopher ,  Chaomin Li ,  Andrew Rosenau ,  William Colby Brown

IPC分类号： A61K31/55 ,  C07D403/04 ,  C07D409/14 ,  A61P25/28 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04 ,  C07D401/14 ,  C07D417/14

CPC分类号： A61K31/41 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： According to the invention there is provided a compound of formula I or a pharmaceutically acceptable salt or hydrate thereof; wherein the variables are as defined herein. The compounds selectively attenuate the production of Aβ42 and hence are useful in treatment of Alzheimer's disease and related conditions.

摘要翻译： 根据本发明，提供式I化合物或其药学上可接受的盐或水合物; 其中变量如本文所定义。 这些化合物选择性地减弱A＆bgr的产生42，因此可用于治疗阿尔茨海默病和相关病症。

公开(公告)号：US20100234415A1

公开(公告)日：2010-09-16

申请号：US12708924

申请日：2010-02-19

申请人： Carl Berthelette ,  Michael Boyd ,  John Colucci ,  Karine Villeneuve ,  Joey Methot

发明人： Carl Berthelette ,  Michael Boyd ,  John Colucci ,  Karine Villeneuve ,  Joey Methot

IPC分类号： A61K31/437 ,  C07D471/02 ,  A61P43/00

CPC分类号： C07D471/04 ,  C07D403/04 ,  C07D403/08

摘要： Compound of formula I are antagonists of the PGD2 receptor, CRTH2, and as such are useful in the treatment and/or prevention of CRTH2-mediated diseases such as asthma.

摘要翻译： 式I化合物是PGD2受体CRTH2的拮抗剂，因此可用于治疗和/或预防CRTH2介导的疾病如哮喘。

公开(公告)号：US08575150B2

公开(公告)日：2013-11-05

申请号：US13139830

申请日：2009-12-07

申请人： Christian Fischer ,  Joey Methot ,  Hua Zhou ,  Adam J. Schell ,  Benito Munoz ,  Alexey A. Rivkin ,  Sean P. Ahearn ,  Stephanie Chichetti ,  Rachel N. MacCoss ,  Sam Kattar ,  Matthew Christopher ,  Chaomin Li ,  Andrew Rosenau ,  William Colby Brown

发明人： Christian Fischer ,  Joey Methot ,  Hua Zhou ,  Adam J. Schell ,  Benito Munoz ,  Alexey A. Rivkin ,  Sean P. Ahearn ,  Stephanie Chichetti ,  Rachel N. MacCoss ,  Sam Kattar ,  Matthew Christopher ,  Chaomin Li ,  Andrew Rosenau ,  William Colby Brown

IPC分类号： C07D249/14 ,  A61K31/4196

CPC分类号： A61K31/41 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04

摘要： According to the invention there is provided a compound of formula I or a pharmaceutically acceptable salt or hydrate thereof; wherein the variables are as defined herein. The compounds selectively attenuate the production of Aβ42 and hence are useful in treatment of Alzheimer's disease and related conditions.

摘要翻译： 根据本发明，提供式I化合物或其药学上可接受的盐或水合物; 其中变量如本文所定义。 这些化合物选择性地减弱Abeta42的产生，因此可用于治疗阿尔茨海默病和相关病症。

公开(公告)号：US08242150B2

公开(公告)日：2012-08-14

申请号：US12663432

申请日：2008-06-09

申请人： Christian Fischer ,  Ben Munoz ,  Susan Zultanski ,  Joey Methot ,  Hua Zhou ,  W. Colby Brown

发明人： Christian Fischer ,  Ben Munoz ,  Susan Zultanski ,  Joey Methot ,  Hua Zhou ,  W. Colby Brown

IPC分类号： A61K31/41 ,  C07D249/00 ,  C07D249/08

CPC分类号： C07D403/10 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D455/04 ,  C07D471/04 ,  C07D487/04 ,  C07D487/06 ,  C07D491/048 ,  C07D495/04 ,  C07D513/04

摘要： Compounds of formula I: Selectively attenuate production of Aβ(1-42) and hence find use in treatment or prevention of diseases associated with deposition of Aβ in the brain, in particular Alzheimer's disease.

摘要翻译： 式I化合物：选择性减弱A＆Bgr的产生（1-42），因此可用于治疗或预防与A＆Bgr沉积相关的疾病; 在大脑中，特别是阿尔茨海默病。

公开(公告)号：US08119685B2

公开(公告)日：2012-02-21

申请号：US12226628

申请日：2007-04-20

申请人： Richard Heidebrecht ,  Joey Methot ,  Dawn Mampreian ,  Thomas Miller ,  Phieng Siliphaivanh

发明人： Richard Heidebrecht ,  Joey Methot ,  Dawn Mampreian ,  Thomas Miller ,  Phieng Siliphaivanh

IPC分类号： A61K31/381 ,  A61K31/166 ,  C07C233/02 ,  C07C311/08 ,  C07D333/24

CPC分类号： C07D333/20 ,  C07C229/60 ,  C07C237/04 ,  C07C237/40

摘要： The present invention relates to a novel class of disubstituted aniline 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二取代苯胺化合物。 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。

公开(公告)号：US20090239849A1

公开(公告)日：2009-09-24

申请号：US12227417

申请日：2007-05-14

申请人： Christopher Hamblett ,  Solomon Kattar ,  Dawn Mampreian ,  Joey Methot ,  Thomas Miller ,  Paul Tempest

发明人： Christopher Hamblett ,  Solomon Kattar ,  Dawn Mampreian ,  Joey Methot ,  Thomas Miller ,  Paul Tempest

IPC分类号： A61K31/551 ,  C07D471/10 ,  A61K31/438 ,  A61P35/00

CPC分类号： C07D471/10 ,  C07D401/04 ,  C07D491/107

摘要： The present invention relates to a novel class of aryl-fused 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： 本发明涉及一类新颖的芳基稠合的螺环化合物。 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。