公开(公告)号：WO2014078314A1

公开(公告)日：2014-05-22

申请号：PCT/US2013/069697

申请日：2013-11-12

Applicant: AMGEN INC.

Inventor： WHITE, Ryan ,  EPSTEIN, Oleg ,  HUMAN, Jason, Brooks ,  ZHENG, Xiao Mei ,  SHAM, Kelvin ,  LIU, Qingyian ,  CHEN, Ning ,  CHENG, Yuan

IPC: C07D498/10 ,  C07D498/20 ,  A61K31/537 ,  A61P25/28

CPC classification number: C07D519/00 ,  C07D311/80 ,  C07D491/052 ,  C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

Abstract: The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A 1, A 2 , A 3 , A 4 , A 5 , A 6 , L, R 2 , R 7 , X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Abstract translation: 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，L，R2，R7，X，Y和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的疾病和病症的用途。 这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：WO2011143366A1

公开(公告)日：2011-11-17

申请号：PCT/US2011/036149

申请日：2011-05-11

Applicant: AMGEN INC. ,  ALLEN, Jennifer ,  FROHN, Michael ,  HARRINGTON, Paul ,  PICKRELL, Alexander ,  RZASA, Robert ,  SHAM, Kelvin ,  HU, Essa

Inventor： ALLEN, Jennifer ,  FROHN, Michael ,  HARRINGTON, Paul ,  PICKRELL, Alexander ,  RZASA, Robert ,  SHAM, Kelvin ,  HU, Essa

IPC: C07D401/14 ,  C07D403/14 ,  C07D407/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  A61K31/4523 ,  A61K31/497 ,  A61K31/506 ,  A61P3/00 ,  A61P25/18

CPC classification number: C07D417/14 ,  C07D401/14 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Heteroaryloxycarbocyclyl compounds of formula (I), and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive -compulsive disorder, and the like. Formula (I)

Abstract translation: 式（I）的杂芳氧基碳环化合物和含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖性糖尿病，精神分裂症，亨廷顿氏病，双相性精神障碍，强迫症 - 障碍性疾病等。 式（I）

公开(公告)号：WO2014165277A2

公开(公告)日：2014-10-09

申请号：PCT/US2014/025062

申请日：2014-03-12

Applicant: AMGEN INC.

Inventor： MURRAY, Justin K. ,  HOLDER, Jerry Ryan ,  WANSKA, Malgorzata ,  TEGLEY, Christopher M. ,  FALSEY, James R. ,  DOHERTY, Elizabeth M. ,  MIRANDA, Leslie P. ,  BISWAS, Kaustav ,  WU, Bin ,  SHAM, Kelvin ,  LONG, Jason C.

IPC: C07K14/435

CPC classification number: C07K14/43518 ,  A61K38/00 ,  A61K38/1767 ,  A61K47/48284 ,  A61K47/48438 ,  A61K47/643 ,  A61K47/6817

Abstract: Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted Nav1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of Nav1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

Abstract translation: 公开了包含分离的多肽的物质组合物，其是外周限制的Nav1.7抑制剂。 在一些公开的实施方案中，分离的多肽是Nav1.7的抑制剂。 其它实施方案是本发明组合物和包含本发明组合物的药物组合物的共轭实施方案。 公开了编码本发明多肽和表达载体的一些实施方案的分离的核酸，以及含有它们的重组宿主细胞。 还公开了治疗或预防疼痛的方法。

公开(公告)号：WO2014138484A1

公开(公告)日：2014-09-12

申请号：PCT/US2014/021412

申请日：2014-03-06

Applicant: AMGEN INC.

Inventor： MINATTI, Ana Elena ,  LOW, Jonathan, D. ,  ALLEN, Jennifer, R. ,  AMEGADZIE, Albert ,  BROWN, James ,  FROHN, Michael, J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul, E. ,  LOPEZ, Patricia ,  MA, Vu Van ,  NISHIMURA, Nobuko ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert, M. ,  SHAM, Kelvin ,  SMITH, Adrian, L. ,  WHITE, Ryan ,  XUE, Qiufen

IPC: C07D413/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D265/12 ,  C07D491/048 ,  A61P25/00 ,  A61K31/536

CPC classification number: C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

Abstract: PERFLUORINATED CYCLOPROPYL FUSED 1,3-OXAZIN-2-AMINE COMPOUNDS AS BETA-SECRETASE INHIBITORS AND METHODS OF USE ABSTRACT OF THE DISCLOSURE The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: {INSERT STRUCTURE HERE} I wherein variables A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

Abstract translation: 作为β-分泌酶抑制剂的全氟化环丙氯联-1,3-氧化物-2-胺化合物及其使用方法本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 该化合物具有通式I：其中式I中的各个R a，R b，R 1，R 2，R 3和R 7各自独立地定义的变量A4，A5，A6，A8的定义如下。 本发明还提供包含该化合物的药物组合物，以及该化合物和组合物用于治疗由BACE的生物学活性产生的与A-β斑块形成和沉积有关的病症和/或病症的用途。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。 本发明还提供式II和III的化合物及其分子式实施方案，用于制备本发明化合物的中间体和方法。

公开(公告)号：WO2018136440A1

公开(公告)日：2018-07-26

申请号：PCT/US2018/013918

申请日：2018-01-16

Applicant: AMGEN INC.

Inventor： CHENG, Yuan ,  NETIROJJANAKUL, Chawita ,  HOLDER, Jerry Ryan ,  WU, Bin ,  FALSEY, James R. ,  HERBERICH, Bradley J. ,  SHAM, Kelvin ,  MIRANDA, Leslie P. ,  LU, Shu-Chen ,  VENIANT-ELLISON, Murielle M. ,  STANISLAUS, Shanaka ,  YIE, Junming ,  XU, Jing

IPC: A61K39/395 ,  C07K16/28 ,  A61P3/10

Abstract: Methods of treating metabolic diseases and disorders using a composition comprising an antigen binding protein specific for the GIPR polypeptide conjugated to a GLP-1 receptor agonist are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the composition comprises an antibody or functional fragment thereof comprising a cysteine at one or more conjugation site(s) wherein the GLP-1 receptor agonist is conjugated to the antibody or functional fragment thereof through the side-chain of the cysteine residue.

公开(公告)号：WO2010077992A1

公开(公告)日：2010-07-08

申请号：PCT/US2009/068330

申请日：2009-12-16

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  CHEN, Ning ,  FALSEY, James R. ,  FROHN, Michael ,  HARRINGTON, Paul ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MERCEDE, Stephanie J. ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  SHAM, Kelvin ,  SIEGMUND, Aaron C. ,  TEGLEY, Christopher M. ,  YAO, Guomin

Inventor： ALLEN, Jennifer R. ,  CHEN, Ning ,  FALSEY, James R. ,  FROHN, Michael ,  HARRINGTON, Paul ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MERCEDE, Stephanie J. ,  NGUYEN, Thomas T. ,  PICKRELL, Alexander J. ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  SHAM, Kelvin ,  SIEGMUND, Aaron C. ,  TEGLEY, Christopher M. ,  YAO, Guomin

IPC: C07D213/74 ,  C07D213/84 ,  C07D401/12 ,  C07D401/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  A61K31/444 ,  A61P25/18

CPC classification number: C07D401/04 ,  C07D213/74 ,  C07D213/84 ,  C07D401/12 ,  C07D401/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14

Abstract: Pyridine and pyrimidine compounds: (I); or a pharmaceutically acceptable salt thereof, wherein m, n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , and Y are as defined in the specification; (II); or a pharmaceutically acceptable salt thereof, wherein ring A, m, n, y, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , X 1 , X 2 , and ring A are as defined in the specification; and (III); or a pharmaceutically acceptable salt thereof, wherein m, n, y, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , X 1 , X 2 , and ring A are as defined in the specification; compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 吡啶和嘧啶化合物：（I）; 或其药学上可接受的盐，其中m，n，R1，R2，R3，R4，R5，R6，R7，X1，X2，X3，X4，X5，X6，X7，X8和Y如本说明书 ; （II）; 或其药学上可接受的盐，其中环A，m，n，y，R 2，R 3，R 4，R 5，R 6，R 7，R 8，R 9，X 1，X 2和环A如说明书中所定义; 和（III）; 或其药学上可接受的盐，其中m，n，y，R2，R3，R4，R5，R6，R7，R9，X1，X2和环A如说明书中所定义; 含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖型糖尿病，精神分裂症，双相性精神障碍，强迫症等。

公开(公告)号：WO2014025651A1

公开(公告)日：2014-02-13

申请号：PCT/US2013/053514

申请日：2013-08-02

Applicant: AMGEN INC.

Inventor： BISWAS, Kaustav ,  BROWN, James ,  CHEN, Jian, J. ,  GORE, Vijay, Keshav ,  HARRIED, Scott ,  HORNE, Daniel, B. ,  KALLER, Matthew, R. ,  MA, Vu, Van ,  NGUYEN, Thomas, T. ,  SHAM, Kelvin ,  ZHONG, Wenge

IPC: C07D311/68 ,  C07D491/04 ,  A61K31/436 ,  A61K31/352 ,  A61P25/04

CPC classification number: C07D311/68 ,  C07D491/04

Abstract: Chroman compounds and derivatives of Formula (I) are useful inhibitors of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula (I) have the following structure: (I) where the definitions of the variables are provided herein.

Abstract translation: 色甘酸化合物和式（I）的衍生物是TRPM8的有用的抑制剂。 这些化合物可用于治疗多种TRPM8介导的病症和病症，并且可用于制备用于治疗这种病症和病症的药物和药物组合物。 这些疾病的实例包括但不限于偏头痛和神经性疼痛。 式（I）的化合物具有以下结构：（I）其中本文提供变量的定义。

公开(公告)号：WO2013044092A1

公开(公告)日：2013-03-28

申请号：PCT/US2012/056658

申请日：2012-09-21

Applicant: AMGEN INC. ,  WHITE, Ryan ,  CHENG, Yuan ,  MINATTI, Ana Elena ,  YANG, Bryant ,  ZHENG, Xiao Mei ,  LOPEZ, Patricia ,  HUMAN, Jason B. ,  EPSTEIN, Oleg ,  JUDD, Ted ,  SHAM, Kelvin ,  XUE, Qiufen

Inventor： WHITE, Ryan ,  CHENG, Yuan ,  MINATTI, Ana Elena ,  YANG, Bryant ,  ZHENG, Xiao Mei ,  LOPEZ, Patricia ,  HUMAN, Jason B. ,  EPSTEIN, Oleg ,  JUDD, Ted ,  SHAM, Kelvin ,  XUE, Qiufen

IPC: C07D498/10 ,  A61K31/537 ,  A61P25/28

CPC classification number: C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

Abstract: The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , L, R 2 , R 7 , X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

Abstract translation: 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，L，R2，R7，X，Y和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的疾病和病症的用途。 这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：WO2010057126A1

公开(公告)日：2010-05-20

申请号：PCT/US2009/064643

申请日：2009-11-16

Applicant: AMGEN INC. ,  ALLEN, Jennifer R. ,  BISWAS, Kaustav ,  CHAVEZ, Frank, Jr. ,  CHEN, Ning ,  DEMORIN, Frenel Fils ,  FALSEY, James R. ,  FROHN, Mike ,  HARRINGTON, Paul ,  HORNE, Dan ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MONENSCHEIN, Holger ,  NGUYEN, Tom ,  PICKRELL, Alex ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Rob ,  SHAM, Kelvin ,  YAO, Guomin

Inventor： ALLEN, Jennifer R. ,  BISWAS, Kaustav ,  CHAVEZ, Frank, Jr. ,  CHEN, Ning ,  DEMORIN, Frenel Fils ,  FALSEY, James R. ,  FROHN, Mike ,  HARRINGTON, Paul ,  HORNE, Dan ,  HU, Essa ,  KALLER, Matthew R. ,  KUNZ, Roxanne ,  MONENSCHEIN, Holger ,  NGUYEN, Tom ,  PICKRELL, Alex ,  REICHELT, Andreas ,  RUMFELT, Shannon ,  RZASA, Rob ,  SHAM, Kelvin ,  YAO, Guomin

IPC: C07D401/12 ,  C07D401/14 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  A61K31/4184 ,  A61P25/18 ,  A61P3/00

CPC classification number: C07D413/14 ,  C07D401/12 ,  C07D401/14 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00

Abstract: Pyridine and pyrimidine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

Abstract translation: 吡啶和嘧啶化合物，以及含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖型糖尿病，精神分裂症，双相情感障碍，强迫症等。

公开(公告)号：WO2006039718A3

公开(公告)日：2006-04-13

申请号：PCT/US2005/035873

申请日：2005-10-03

Applicant: AMGEN INC

Inventor： PATEL, Vinod F. ,  KIM, Joseph L. ,  GEUNS-MEYER, Stephanie D. ,  CHAFFEE, Stuart C. ,  CEE, Victor J. ,  HODOUS, Brian L. ,  BELLON, Steven ,  HARMANGE, Jean-christophe ,  OLIVIERI, Philip R. ,  THAMAN, Maya C. ,  DIMAURO, Erin F. ,  BUCHANAN, John L. ,  MCGOWAN, David C. ,  ALBRECHT, Brian K. ,  DEAK, Holly L. ,  BEMIS, Jean E. ,  WHITE, Ryan ,  MARTIN, Matthew W. ,  HABGOOD, Gregory J. ,  TEMPEST, Paul A. ,  MASSE, Craig E. ,  BUCKNER, William H. ,  HERBERICH, Bradley J. ,  GRACEFFA, Russell ,  ZHANG, Dawei ,  XU, Shimin ,  SHAM, Kelvin ,  RZASA, Robert M. ,  FALSEY, James Richard ,  CHAKRABARTI, Partha P. ,  CAO, Guo-qiang ,  TOMLINSON, Susan Ann ,  PETTUS, Liping H. ,  SMITH, Adrian Leonard ,  PARAS, Nick A. ,  LIU, Gang ,  DEMORIN, Frenel F. ,  TASKER, Andrew ,  REED, Anthony

IPC: C07D239/84 ,  C07D239/95 ,  C07D401/12 ,  C07D409/04 ,  C07D405/12 ,  C07D409/14 ,  C07D405/04 ,  C07D403/10 ,  C07D401/04 ,  C07D471/04 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  C07D409/12 ,  C07D215/12

Abstract: The present invention comprises a new class of compounds useful for the prophylaxis and treatment of protein kinase mediated diseases, including inflammation, cancer and related conditions. The compounds have a general Formula I, wherein A1, A2, A3, B, R1, R2, R3 and R4 are defined herein. Accordingly, the invention also comprises pharmaceutical compositions comprising the compounds of the invention, methods for the prophylaxis and treatment of kinase mediated diseases using the compounds and compositions of the invention, and intermediates and processes useful for the preparation of compounds of the invention.