公开(公告)号：US08461162B2

公开(公告)日：2013-06-11

申请号：US12669843

申请日：2008-07-16

申请人： Matthew G. Stanton ,  Njamkou Noucti ,  David L. Sloman ,  Jongwon Lim ,  Benito Munoz

发明人： Matthew G. Stanton ,  Njamkou Noucti ,  David L. Sloman ,  Jongwon Lim ,  Benito Munoz

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/00

CPC分类号： C07D519/00 ,  C07D487/04

摘要： Compounds of the following formula (I) are inhibitors of microtubule affinity regulating kinase, and hence find use in the treatment of neurodegenerative diseases associated with hyperphosphorylation of tau.

摘要翻译： 下式（I）的化合物是微管亲和调节激酶的抑制剂，因此可用于治疗与tau的过度磷酸化有关的神经变性疾病。

公开(公告)号：US20130137690A1

公开(公告)日：2013-05-30

申请号：US13751789

申请日：2013-01-28

申请人： Paul Harrington ,  Richard W. Heidebrecht, JR. ,  Solomon Kattar ,  Thomas A. Miller ,  Karin M. Otte ,  Phieng Siliphaivanh ,  Matthew G. Stanton ,  Paul Tempest ,  Kevin J. Wilson ,  David J. Witter

发明人： Paul Harrington ,  Richard W. Heidebrecht, JR. ,  Solomon Kattar ,  Thomas A. Miller ,  Karin M. Otte ,  Phieng Siliphaivanh ,  Matthew G. Stanton ,  Paul Tempest ,  Kevin J. Wilson ,  David J. Witter

IPC分类号： C07D295/155 ,  A61K31/5377 ,  C07D213/55 ,  C07D403/02 ,  C07D413/14 ,  A61K31/496 ,  C07D409/14

CPC分类号： C07D295/155 ,  C07C237/40 ,  C07C237/42 ,  C07C271/22 ,  C07C271/38 ,  C07C271/54 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07D207/08 ,  C07D207/14 ,  C07D207/16 ,  C07D209/44 ,  C07D209/48 ,  C07D211/14 ,  C07D213/30 ,  C07D213/38 ,  C07D213/40 ,  C07D213/55 ,  C07D213/56 ,  C07D213/74 ,  C07D217/04 ,  C07D231/12 ,  C07D233/64 ,  C07D241/12 ,  C07D263/20 ,  C07D277/28 ,  C07D295/125 ,  C07D307/22 ,  C07D333/10 ,  C07D333/20 ,  C07D401/04 ,  C07D409/12 ,  C07D413/12

摘要： The present invention relates to a novel class of 4-carboxybenzylamino derivatives. The 4-carboxybenzylamino compounds can be used to treat cancer. The 4-carboxybenzylamino 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 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 4-carboxybenzylamino derivatives and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the 4-carboxybenzylamino derivatives in vivo.

摘要翻译： 本发明涉及一类新的4-羧基苄基氨基衍生物。 4-羧基苄基氨基化合物可用于治疗癌症。 4-羧基苄基氨基化合物也可以抑制组蛋白脱乙酰酶，适用于选择性诱导末端分化，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 神经退行性疾病 本发明进一步提供包含4-羧基苄基氨基衍生物和这些药物组合物的安全投药方案的药物组合物，其易于遵循，并且其在体内导致治疗有效量的4-羧基苄基氨基衍生物。

公开(公告)号：US20110195933A1

公开(公告)日：2011-08-11

申请号：US13057510

申请日：2009-07-27

申请人： Jason D. Katz ,  Sandra L. Knowles ,  James P. Jewell ,  David L. Sloman ,  Matthew G. Stanton ,  Njamkou Noucti

发明人： Jason D. Katz ,  Sandra L. Knowles ,  James P. Jewell ,  David L. Sloman ,  Matthew G. Stanton ,  Njamkou Noucti

IPC分类号： A61K31/675 ,  C07D471/04 ,  A61K31/437 ,  A61K31/496 ,  C07D413/14 ,  A61K31/5377 ,  C07D471/10 ,  A61K31/438 ,  A61K31/397 ,  C07F9/576 ,  A61K31/5513 ,  A61P25/28

CPC分类号： A61K31/425 ,  C07D417/04 ,  C07D417/14

摘要： The invention encompasses pyrazolo[1,5-a]pyridine derivatives which selectively inhibit microtubule affinity regulating kinase (MARK) and are therefore useful for the treatment or prevention of Alzheimer's disease. Pharmaceutical compositions and methods of use are also included.

摘要翻译： 本发明包括选择性抑制微管亲和调节激酶（MARK）的吡唑并[1,5-a]吡啶衍生物，因此可用于治疗或预防阿尔茨海默氏病。 还包括药物组合物和使用方法。

公开(公告)号：US07968571B2

公开(公告)日：2011-06-28

申请号：US11547994

申请日：2005-04-20

申请人： James C. Barrow ,  Georgia B. McGaughey ,  Philippe G. Nantermet ,  Hemaka A. Rajapakse ,  Harold G. Selnick ,  Shaun R. Stauffer ,  Joseph P. Vacca ,  Shawn J. Stachel ,  Craig A. Coburn ,  Matthew G. Stanton

发明人： James C. Barrow ,  Georgia B. McGaughey ,  Philippe G. Nantermet ,  Hemaka A. Rajapakse ,  Harold G. Selnick ,  Shaun R. Stauffer ,  Joseph P. Vacca ,  Shawn J. Stachel ,  Craig A. Coburn ,  Matthew G. Stanton

IPC分类号： A61K31/443 ,  C07D413/04

CPC分类号： C07D413/04 ,  C07D401/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14

摘要： The present invention is directed to 2,4,6-substituted pyridyl derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

摘要翻译： 本发明涉及作为β-分泌酶的抑制剂并可用于治疗其中涉及β-分泌酶的疾病如阿尔茨海默氏病的2,4,6-取代的吡啶衍生物化合物。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在治疗涉及β-分泌酶的疾病中的用途。

公开(公告)号：US20100324092A1

公开(公告)日：2010-12-23

申请号：US12666415

申请日：2008-06-24

申请人： Richard W. Heidebrecht, JR. ,  Thomas A. Miller ,  Matthew G. Stanton ,  David J. Witter

发明人： Richard W. Heidebrecht, JR. ,  Thomas A. Miller ,  Matthew G. Stanton ,  David J. Witter

IPC分类号： A61K31/4418 ,  C07D213/74 ,  C07D401/12 ,  A61K31/444 ,  A61P35/00

CPC分类号： C07D213/75 ,  C07D409/04 ,  C07D409/14

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

摘要翻译： 本发明涉及一类新的吡啶基和嘧啶基衍生物。 吡啶基和嘧啶基化合物可用于治疗癌症。 吡啶基和嘧啶基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疾病（CNS），例如 神经退行性疾病 本发明还提供包含吡啶基和嘧啶基衍生物的药物组合物和这些药物组合物的安全给药方案，其易于遵循，并且其导致治疗有效量的体内吡啶基和嘧啶基衍生物。

公开(公告)号：US07834034B2

公开(公告)日：2010-11-16

申请号：US11918913

申请日：2006-04-14

申请人： Dawn M. Mampreian ,  Thomas A. Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin J. Wilson ,  David J. Witter

发明人： Dawn M. Mampreian ,  Thomas A. Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin J. Wilson ,  David J. Witter

IPC分类号： A61K31/445 ,  C07D409/12

CPC分类号： C07D333/70 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/14

摘要： The present invention relates to a novel class of benzothiophene amide derivatives. The hydroxamic acid compounds can be used to treat cancer. The benzothiophene amide 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 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 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的苯并噻吩酰胺衍生物。 异羟肟酸化合物可用于治疗癌症。 苯并噻吩酰胺化合物也可以抑制组蛋白脱乙酰酶，适用于选择性诱导末端分化，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 神经退行性疾病 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：US20090012075A1

公开(公告)日：2009-01-08

申请号：US12087624

申请日：2007-01-08

申请人： Thomas A. Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin J. Wilson ,  David J. Witter

发明人： Thomas A. Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin J. Wilson ,  David J. Witter

IPC分类号： A61K31/381 ,  C07D409/12 ,  C07D333/50 ,  C07D409/14 ,  C07D413/10 ,  C07D413/14 ,  A61K31/4436 ,  A61K31/5377 ,  A61K31/4025 ,  A61K31/4245 ,  A61P35/00 ,  A61K31/415 ,  A61K31/496

CPC分类号： C07D231/40 ,  C07D333/20 ,  C07D333/70 ,  C07D409/12 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D413/14

摘要： The present invention relates to a novel class of fluorinated arylamide derivatives. The instant compounds can be used to treat cancer. The fluorinated arylamide derivatives 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 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 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氟化芳基酰胺衍生物。 本化合物可用于治疗癌症。 氟化芳基酰胺衍生物还可以抑制组蛋白脱乙酰酶，并且适用于选择性诱导终末分化，并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：US06610692B1

公开(公告)日：2003-08-26

申请号：US09429741

申请日：1999-10-28

申请人： Philip E. Sanderson ,  Bruce D. Dorsey ,  Terry A. Lyle ,  Matthew G. Stanton ,  Donnette Staas ,  Adel M. Naylor-Olsen ,  Craig Coburn ,  Matthew M. Morrissette

发明人： Philip E. Sanderson ,  Bruce D. Dorsey ,  Terry A. Lyle ,  Matthew G. Stanton ,  Donnette Staas ,  Adel M. Naylor-Olsen ,  Craig Coburn ,  Matthew M. Morrissette

IPC分类号： A61K31497

CPC分类号： C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04

摘要： Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions having the following structure: or a pharmaceutically acceptable salt thereof, wherein b is NY or O; c is CY2 or N; d is CY3 or N; e is CY4 or N; f is CY5 or N; g is CY6 or N; Y4, Y5, and Y6 are independently hydrogen, C1-4 alkyl, or halogen; Y1 and Y2 are independently hydrogen, C1-4 alkyl, C3-7 cycloalkyl, halogen, NH2, OH or C1-4 alkoxy, and Y3 is hydrogen, C1-4 alkyl, C3-7 cycloalkyl, halogen, —CN, NH2, OH or C1-4 alkoxy; A is and W, W1, R1, R3, R4, R5, X and Z are defined in the specification.

摘要翻译： 本发明的化合物可用于抑制具有以下结构的凝血酶和相关的血栓形成闭塞：或其药学上可接受的盐，其中b为NY或O; c为CY2或N; d为CY3或N; e为CY4或N; f是CY5或N; g为CY6或N; Y4，Y5和Y6独立地是氢，C1-4烷基或卤素; Y1和Y2独立地是氢，C1-4烷基，C3-7环烷基，卤素，NH2，OH或C1-4烷氧基，Y3是氢，C1-4烷基，C3-7环烷基，卤素，-CN，NH2， OH或C 1-4烷氧基; A和W，W 1，R 1，R 3，R 4，R 5，X和Z在说明书中定义。

公开(公告)号：US20130225836A1

公开(公告)日：2013-08-29

申请号：US13883487

申请日：2011-10-31

申请人： Matthew G. Stanton ,  Gregory L. Beutner

发明人： Matthew G. Stanton ,  Gregory L. Beutner

IPC分类号： C07D207/12

CPC分类号： C12N15/1137 ,  A61K9/5123 ,  C07D207/12 ,  C07D211/40 ,  C07D223/08 ,  C12N15/113 ,  C12N2310/14 ,  C12N2320/32

摘要： The instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids comprising at least one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

公开(公告)号：US20130217756A1

公开(公告)日：2013-08-22

申请号：US13881415

申请日：2011-10-25

申请人： Mark Cancilla ,  James John Cunningham ,  Michael W. Flanagan ,  Henry J. Haringsma ,  Denise M. Kenski ,  Matthew G. Stanton ,  Steven M. Stirdivant ,  Aarron T. Willingham

发明人： Mark Cancilla ,  James John Cunningham ,  Michael W. Flanagan ,  Henry J. Haringsma ,  Denise M. Kenski ,  Matthew G. Stanton ,  Steven M. Stirdivant ,  Aarron T. Willingham

IPC分类号： C07H21/02

CPC分类号： C12N15/113 ,  C07H21/02 ,  C12N15/111 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/3231 ,  C12N2310/331 ,  C12N2310/344 ,  C12N2310/346 ,  C12N2310/351 ,  C12N2320/32 ,  C12N2320/51 ,  C12N2310/3527 ,  C12N2310/3521 ,  C12N2310/322 ,  C12N2310/3533

摘要： The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of gene expression and/or activity, and/or modulate a gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against target gene expression.

摘要翻译： 本发明涉及用于研究，诊断和治疗响应于基因表达和/或活性的调节和/或调节基因表达途径的性状，疾病和病症的化合物，组合物和方法。 具体地说，本发明涉及包括小核酸分子的双链核酸分子，例如能够介导或介导针对靶基因表达的RNA干扰（RNAi）的短干扰核酸（siNA）分子。