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。

公开(公告)号：US08461189B2

公开(公告)日：2013-06-11

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： A01N43/40 ,  A01N47/10 ,  A61K31/44 ,  C07D213/55

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 in 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（CNS）的疾病，例如 神经退行性疾病 本发明进一步提供包含吡啶基和嘧啶基衍生物的药物组合物以及易于遵循的这些药物组合物的安全给药方案，并且其在体内导致治疗有效量的吡啶基和嘧啶基衍生物。

公开(公告)号：US20130137752A1

公开(公告)日：2013-05-30

申请号：US13813465

申请日：2011-08-02

申请人： Duncan Brown ,  James J. Cunningham ,  Marian Gindy ,  Victoria Pickering ,  Matthew G. Stanton ,  Steven M. Stirdivant ,  Walter R. Strapps

发明人： Duncan Brown ,  James J. Cunningham ,  Marian Gindy ,  Victoria Pickering ,  Matthew G. Stanton ,  Steven M. Stirdivant ,  Walter R. Strapps

IPC分类号： C12N15/113

CPC分类号： C12N15/1138 ,  C12N15/113 ,  C12N2310/14 ,  C12N2310/315 ,  C12N2310/321 ,  C12N2310/332 ,  C12N2310/346 ,  C12N2310/3521 ,  C12N2320/32

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 CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin 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), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.

公开(公告)号：US08389553B2

公开(公告)日：2013-03-05

申请号：US12666384

申请日：2008-06-24

申请人： Paul Harrington ,  Solomon Kattar ,  Thomas A. Miller ,  Matthew G. Stanton ,  Paul Tempest ,  David J. Witter

发明人： Paul Harrington ,  Solomon Kattar ,  Thomas A. Miller ,  Matthew G. Stanton ,  Paul Tempest ,  David J. Witter

IPC分类号： A01N43/40 ,  A01N47/10 ,  A61K31/44 ,  A61K31/27 ,  C07D213/55 ,  C07D213/00 ,  C07D211/30 ,  C07D211/32 ,  C07D217/00

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.

公开(公告)号：US20120010209A1

公开(公告)日：2012-01-12

申请号：US13144123

申请日：2010-01-12

申请人： Michael D. Altman ,  Mark T. Bilodeau ,  Jongwon Lim ,  Alan Nortrup ,  Matthew G. Stanton ,  Brandon M. Taoka

发明人： Michael D. Altman ,  Mark T. Bilodeau ,  Jongwon Lim ,  Alan Nortrup ,  Matthew G. Stanton ,  Brandon M. Taoka

IPC分类号： A61K31/5025 ,  A61P25/28 ,  A61K31/437 ,  C07D487/04 ,  C07D471/04

CPC分类号： A61K31/5025 ,  C07D471/04 ,  C07D487/04

摘要： The invention encompasses imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine 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）的咪唑并[1,2-a]吡啶和咪唑并[1,2-b]哒嗪衍生物，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：US07834026B2

公开(公告)日：2010-11-16

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： A01N43/42 ,  A01N43/12 ,  A01N43/26 ,  A61K31/44 ,  A61K31/34 ,  A61K31/335 ,  C07D237/00 ,  C07D239/00 ,  C07D241/00 ,  C07D491/10 ,  C07D491/20 ,  C07D495/10 ,  C07D495/20 ,  C07D497/10 ,  C07D497/20 ,  C07D311/96 ,  C07D313/06 ,  C07D313/20 ,  C07D315/00

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（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，并且其在体内产生治疗有效量的这些化合物。

公开(公告)号：US20090105264A1

公开(公告)日：2009-04-23

申请号：US12084272

申请日：2006-10-30

申请人： Christopher Hamblett ,  Dawn M. Mampreian ,  Joey L. Methot ,  Thomas Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin Wilson

发明人： Christopher Hamblett ,  Dawn M. Mampreian ,  Joey L. Methot ,  Thomas Miller ,  David L. Sloman ,  Matthew G. Stanton ,  Kevin Wilson

IPC分类号： A61K31/496 ,  C07D401/04 ,  C07D241/36 ,  A61P35/00 ,  C07D409/14 ,  A61K31/497

CPC分类号： C07D213/56 ,  C07D239/28 ,  C07D401/12 ,  C07D487/08

摘要： The present invention relates to a novel class of substituted nicotinamides. 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： 本发明涉及一类新型的取代烟酰胺。 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：US20090069250A1

公开(公告)日：2009-03-12

申请号：US12224466

申请日：2007-02-23

申请人： Jonathan B. Grimm ,  Jed L. Hubbs ,  Thomas Miller ,  Karin M. Otte ,  Phieng Siliphaivanh ,  Matthew G. Stanton ,  Kevin Wilson ,  David Witter ,  Hua Zhou

发明人： Jonathan B. Grimm ,  Jed L. Hubbs ,  Thomas Miller ,  Karin M. Otte ,  Phieng Siliphaivanh ,  Matthew G. Stanton ,  Kevin Wilson ,  David Witter ,  Hua Zhou

IPC分类号： A61K38/05 ,  C07D213/56 ,  A61K31/4406 ,  A61K31/381 ,  C07D333/24 ,  C07D409/12 ,  A61K31/397

CPC分类号： C07C237/42 ,  C07D333/20

摘要： The present invention relates to a novel class of 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 sale 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疾病（CNS），例如 神经退行性疾病 本发明还提供包含本发明化合物和这些药物组合物的销售给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这些化合物。