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：US07550481B2

公开(公告)日：2009-06-23

申请号：US10582856

申请日：2004-12-15

申请人： James C. Barrow ,  Craig A. Coburn ,  Philippe G. Nantermet ,  Harold G. Selnick ,  Shawn J. Stachel ,  Matthew G. Stanton ,  Shaun R. Stauffer ,  Linghang Zhuang ,  Jennifer R. Davis

发明人： James C. Barrow ,  Craig A. Coburn ,  Philippe G. Nantermet ,  Harold G. Selnick ,  Shawn J. Stachel ,  Matthew G. Stanton ,  Shaun R. Stauffer ,  Linghang Zhuang ,  Jennifer R. Davis

IPC分类号： C07D401/02 ,  A61K31/44

CPC分类号： C07D213/81 ,  C07D213/75 ,  C07D257/04 ,  C07D401/04 ,  C07D409/12 ,  C07D413/12

摘要： The present invention is directed to phenylamide and pyridylamide derivative compounds of 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： 本发明涉及苯酰胺和吡啶酰胺衍生物化合物，其是β-分泌酶的抑制剂，可用于治疗其中涉及β-分泌酶的疾病，例如阿尔茨海默氏病。 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：US09669097B2

公开(公告)日：2017-06-06

申请号：US13823830

申请日：2011-09-20

申请人： Matthew G. Stanton ,  Brian W. Budzik ,  Gregory L. Beutner ,  Hongbiao Liao

发明人： Matthew G. Stanton ,  Brian W. Budzik ,  Gregory L. Beutner ,  Hongbiao Liao

IPC分类号： C07C211/04 ,  C07C211/08 ,  C07C211/21 ,  A61K48/00 ,  A61K47/18 ,  C12N15/88 ,  C07D207/06 ,  C07C211/17 ,  A61K45/00

CPC分类号： A61K47/18 ,  A61K45/00 ,  A61K48/00 ,  C07C211/04 ,  C07C211/08 ,  C07C211/17 ,  C07C211/21 ,  C07D207/06 ,  C12N15/88

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 with one short lipid chain to enhance the efficiency and tolerability of in vivo delivery of siRNA.

公开(公告)号：US09181295B2

公开(公告)日：2015-11-10

申请号：US13390702

申请日：2010-08-18

申请人： Mark Cameron ,  Jennifer R. Davis ,  Andrea R. Geiser ,  Matthew G. Stanton ,  Vladislav V. Telyatnikov ,  Lu Tian ,  Weimin Wang

发明人： Mark Cameron ,  Jennifer R. Davis ,  Andrea R. Geiser ,  Matthew G. Stanton ,  Vladislav V. Telyatnikov ,  Lu Tian ,  Weimin Wang

IPC分类号： C07J41/00 ,  A61K9/127 ,  C07J43/00

CPC分类号： A61K9/1272 ,  A61K31/7088 ,  C07J41/0055 ,  C07J43/003

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 siRNA, to facilitate the cellular uptake and endosomal escape, and to knockdown target mRNA both in vitro and in vivo.

摘要翻译： 本发明提供了可以与其它脂质组分如胆固醇和PEG-脂质组合使用以与siRNA形成脂质纳米颗粒以促进细胞摄取和内体逃逸以及在体外和 体内。

公开(公告)号：US09029590B2

公开(公告)日：2015-05-12

申请号：US13880254

申请日：2011-10-17

申请人： Steven L. Colletti ,  Matthew G. Stanton

发明人： Steven L. Colletti ,  Matthew G. Stanton

IPC分类号： C07C229/00 ,  C07C205/00 ,  C07C261/00 ,  C07C269/00 ,  C07C271/00 ,  C07C229/12 ,  C12N15/88 ,  A61K48/00

CPC分类号： C07C229/12 ,  A61K9/5123 ,  A61K31/221 ,  A61K48/00 ,  C12N15/88

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.

摘要翻译： 本发明提供了可以与其它脂质组分如胆固醇和PEG-脂质组合使用以与寡核苷酸形成脂质纳米颗粒的新型阳离子脂质。 本发明的目的是提供一种阳离子脂质支架，由于肝中脂质水平降低，其表现出增强的功效以及较低的肝毒性。 本发明使用包含至少一个短脂链的低分子量阳离子脂质，以提高siRNA的体内递送的效率和耐受性。

公开(公告)号：US08802863B2

公开(公告)日：2014-08-12

申请号：US13699451

申请日：2011-05-18

申请人： Brian W. Budzik ,  Steven L. Colletti ,  Darla Danile Seifried ,  Matthew G. Stanton ,  Lu Tian

发明人： Brian W. Budzik ,  Steven L. Colletti ,  Darla Danile Seifried ,  Matthew G. Stanton ,  Lu Tian

IPC分类号： C07D263/14 ,  C07C215/24

CPC分类号： A61K47/18 ,  A61K31/713 ,  C07C217/28 ,  C07C217/40 ,  C07D263/14 ,  C12N15/87

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 is more efficacious than traditional cationic lipids. The present invention employs amino alcohols to enhance the efficiency of in vivo delivery of siRNA.

摘要翻译： 本发明提供了可以与其它脂质组分如胆固醇和PEG-脂质组合使用以与寡核苷酸形成脂质纳米颗粒的新型阳离子脂质。 本发明的目的是提供比传统阳离子脂质更有效的阳离子脂质支架。 本发明使用氨基醇来提高siRNA的体内递送效率。

公开(公告)号：US20130210838A1

公开(公告)日：2013-08-15

申请号：US13521382

申请日：2011-01-11

申请人： Jongwon Lim ,  Brandon M. Taoka ,  Sandra Lee ,  Alan Northrup ,  Michael D. Altman ,  David L. Sloman ,  Matthew G. Stanton ,  Njamkou Noucti

发明人： Jongwon Lim ,  Brandon M. Taoka ,  Sandra Lee ,  Alan Northrup ,  Michael D. Altman ,  David L. Sloman ,  Matthew G. Stanton ,  Njamkou Noucti

IPC分类号： C07D487/04

CPC分类号： C07D487/04

摘要： The invention encompasses pyrazolo[1,5-a]pyrimidine 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]嘧啶衍生物，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：US20090291965A1

公开(公告)日：2009-11-26

申请号：US12084268

申请日：2006-10-30

申请人： Joshua Close ,  Richard W. Heidebrecht ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G. Stanton ,  Paul Tempest ,  David J. Witter

发明人： Joshua Close ,  Richard W. Heidebrecht ,  Solomon Kattar ,  Thomas A. Miller ,  David Sloman ,  Matthew G. Stanton ,  Paul Tempest ,  David J. Witter

IPC分类号： A61K31/496 ,  C07D401/02 ,  A61K31/4439 ,  C07D231/10 ,  A61K31/415 ,  C07D271/10 ,  A61K31/4245 ,  C07D403/14 ,  A61P35/00

CPC分类号： C07D401/12 ,  C07D231/40 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： The present invention relates to a novel class of histone deacetylase inhibitors with aryl-pyrazolyl motifs. The compounds of this invention can be used to treat cancer. The compounds of this invention 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 present invention further provides pharmaceutical compositions comprising the compounds of this invention and safe dosing regimens of these pharmaceutical compositions, which are easy to follow, and which result in a therapeutically effective amount of the compounds of this invention in vivo.

摘要翻译： 本发明涉及新一类具有芳基 - 吡唑基基序的组蛋白脱乙酰酶抑制剂。 本发明的化合物可用于治疗癌症。 本发明的化合物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。 本发明进一步提供包含本发明化合物和这些药物组合物的安全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本发明化合物。

公开(公告)号：US07544695B2

公开(公告)日：2009-06-09

申请号：US11600426

申请日：2006-11-16

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 ,  C07D498/10

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。

公开(公告)号：US20170189441A1

公开(公告)日：2017-07-06

申请号：US15033715

申请日：2014-11-03

申请人： Steven L. COLLETTI ,  Thomas J. TUCKER ,  David M. TELLERS ,  Boyoung KIM ,  Rob BURKE ,  Kathleen B. CALATI ,  Matthew G. STANTON ,  Rubina G. PARMAR ,  Jeffrey G. AARONSON ,  Weimin WANG ,  MERCK SHARP & DOHME CORP.

发明人： Steven L. Colletti ,  Thomas J. Tucker ,  David M. Tellers ,  Boyoung Kim ,  Rob Burke ,  Kathleen B. Calati ,  Matthew G. Stanton ,  Rubina G. Parmar ,  Jeffery G. Aaronson ,  Weimin Wang

IPC分类号： A61K31/7125 ,  A61K38/10 ,  A61K38/16 ,  A61K31/713

CPC分类号： A61K31/7125 ,  A61K31/713 ,  A61K38/10 ,  A61K38/16 ,  C07K2319/10 ,  C12N15/111 ,  C12N15/113 ,  C12N15/87 ,  C12N2310/14 ,  C12N2310/351 ,  C12N2320/31

摘要： Disclosed herein is a method for inhibiting expression of a gene of a subject comprising administering (1) a composition comprising R-(L)a-(G)b; wherein R is an oligonucleotide selected from the group consisting of DNA, RNA, siRNA, and microRNA; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; each of a and b is independently 0, 1, 2, 3 or 4; and (2) a composition comprising (P)c-(L)d-(G)e; wherein P is a peptide and each occurrence of P is independently selected from Table 2; L is a linker and each occurrence of L is independently selected from Table 3; G is a targeting ligand and each occurrence of G is independently selected from Table 4; d is 0, 1, 2, 3, 4, 5 or 6; and each of c and e is independently 1, 2, 3, 4, 5 or 6. Compositions in (1) and (2) can be co-administered or sequentially administered.