公开(公告)号：WO2018039647A1

公开(公告)日：2018-03-01

申请号：PCT/US2017/048757

申请日：2017-08-25

Applicant: AMGEN INC.

Inventor： OLLMANN, Michael ,  LI, Yang ,  ZHANG, Jun ,  BISWAS, Kaustav ,  HOMANN, Oliver ,  MIRANDA, Leslie P. ,  MURRAY, Justin K. ,  WU, Bin ,  YOON, Oh Kyu ,  ALLEN, John Gordon ,  NETIROJJANAKUL, Chawita ,  CHENG, Yuan

IPC: C12N15/113

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

Abstract translation: 本发明涉及用于减少ASGR1基因表达的RNAi构建体。 还描述了使用这种RNAi构建体来治疗或预防心血管疾病（例如冠状动脉疾病和心肌梗塞）并降低血清非HDL胆固醇水平的方法。

公开(公告)号：WO2016022724A1

公开(公告)日：2016-02-11

申请号：PCT/US2015/043868

申请日：2015-08-05

Applicant: AMGEN INC.

Inventor： ALLEN, Jennifer R. ,  AMEGADZIE, Albert ,  BOURBEAU, Matthew P. ,  BROWN, James A. ,  CHEN, Jian J. ,  CHENG, Yuan ,  FROHN, Michael J. ,  GUZMAN-PEREZ, Angel ,  HARRINGTON, Paul E. ,  LIU, Longbin ,  LIU, Qingyian ,  LOW, Jonathan D. ,  MA, Vu Van ,  MANNING, James ,  MINATTI, Ana Elena ,  NGUYEN, Thomas T. ,  NISHMURA, Nobuko ,  NORMAN, Mark H. ,  PETTUS, Liping H. ,  PICKRELL, Alexander J. ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  SIEGMUND, Aaron C. ,  STEC, Markian M. ,  WHITE, Ryan ,  XUE, Qiufen

IPC: C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  A61K31/5415 ,  A61P25/28 ,  C07D279/08

CPC classification number: C07D417/12 ,  C07D279/08 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D513/10

Abstract: 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): wherein variables A 4 , A 5 , A 6 , A 8 , and each of R a , R b , R 1 , R 2 , R 3 and R 7 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 15 deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimers 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: 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式（I）：其中式（I）的各个变量A4，A5，A6，A8和R a，R b，R 1，R 2，R 3和R 7各自独立地在本文中定义。 本发明还提供了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生物活性导致的A-β斑块形成和15沉积相关的病症和/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：WO2014134341A1

公开(公告)日：2014-09-04

申请号：PCT/US2014/019100

申请日：2014-02-27

Applicant: AMGEN INC.

Inventor： MINATTI, Ana Elena ,  LOW, Jonathan D. ,  ALLEN, Jenifer R. ,  CHEN, Jian ,  CHEN, Ning ,  CHENG, Yuan ,  JUDD, Ted ,  LIU, Qingyian ,  LOPEZ, Patricia ,  QIAN, Wenyuan ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  TAMAYO, Nuria A. ,  XUE, Qiufen ,  YANG, Bryant ,  ZHONG, Wenge

IPC: C07D413/14 ,  A61K31/535 ,  A61K31/5355 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D471/04 ,  C07D265/08 ,  C07D498/04 ,  C07D513/04 ,  A61P25/00

CPC classification number: C07D413/14 ,  C07D265/08 ,  C07D413/04 ,  C07D413/10 ,  C07D413/12 ,  C07D471/04 ,  C07D498/04 ,  C07D513/04 ,  C07F7/0812

Abstract: 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): wherein variables A 4 , A 5 , A 6 , A 8 , each of R 1 and R 2 , R 3 and R 7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and corresponding 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 processes and methods useful for the preparation of compounds of Formulas I-III.

Abstract translation: 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式（I）：其中式I中的各个R 1和R 2，R 3和R 7各自独立地定义的变量A4，A5，A6，A8在本文中定义。 本发明还提供包含该化合物的药物组合物，以及用于治疗由BACE的生物学活性产生的A-β斑块形成和沉积相关的病症和/或病症的化合物和组合物的相应用途。 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的化合物及其分式实施方案，可用于制备式I-III化合物的中间体和方法和方法。

公开(公告)号：WO2011063272A1

公开(公告)日：2011-05-26

申请号：PCT/US2010/057488

申请日：2010-11-19

Applicant: AMGEN INC. ,  PARAS, Nick A, ,  CHENG, Yuan ,  POWERS, Timothy ,  BROWN, James ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  XUE, Qiufen ,  YANG, Bryant

Inventor： PARAS, Nick A, ,  CHENG, Yuan ,  POWERS, Timothy ,  BROWN, James ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  XUE, Qiufen ,  YANG, Bryant

IPC: C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  A61K31/4709 ,  A61P25/28

CPC classification number: C07D401/06 ,  C07D401/12 ,  C07D401/14

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 ring A, B 1 , B 2 , B 3 , L, R 1 , R 4 , ring Z, m and p 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 (AD), 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，其中本文定义式I的环A，B1，B2，B3，L，R 1，R 4，环Z，m和p。 本发明还包括这些化合物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病症和病症的用途。 这些疾病包括例如阿尔茨海默氏病（AD），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：WO2005073224A2

公开(公告)日：2005-08-11

申请号：PCT/US2005/002304

申请日：2005-01-24

Applicant: AMGEN INC

Inventor： HARMANGE, Jean-Christophe ,  BOOKER, Shon ,  BAUER, David ,  KIM, Tae-Seong ,  CHENG, Yuan ,  XU, Shimin ,  XI, Ning ,  KIM, Joseph, L. ,  TASKER, Andrew

IPC: C07D417/00

CPC classification number: C07D495/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选化合物对于预防和治疗诸如HGF介导的疾病等疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：WO2005070891A2

公开(公告)日：2005-08-04

申请号：PCT/US2005/002326

申请日：2005-01-24

Applicant: AMGEN INC

Inventor： POTASHMAN, Michele ,  KIM, Tae-seong ,  BELLON, Steven ,  BOOKER, Shon ,  CHENG, Yuan ,  KIM, Joseph, L. ,  TASKER, Andrew ,  XI, Ning ,  XU, Shimin ,  HARMANGE, Jean-Christophe ,  BORG, George ,  WEISS, Matthew ,  HODOUS, Brian, L. ,  GRACEFFA, Russell ,  BUCKNER, Willian, H. ,  MASSE, Craig, E. ,  CHOQUETTE, Deborah ,  MARTIN, Matthew, W. ,  GERMAIN, Julie ,  DIPIETRO, Lucian, V. ,  CHAFFEE, Stuart, C. ,  NUNES, Joseph, J. ,  BUCHANAN, John, L. ,  HABGOOD, Gregory, J. ,  MCGOWAN, David, C. ,  WHITTINGTON, Douglas, A.

IPC: C07D215/00

CPC classification number: C07D213/64 ,  C07D213/81 ,  C07D215/233 ,  C07D215/38 ,  C07D215/48 ,  C07D215/54 ,  C07D237/34 ,  C07D239/34 ,  C07D239/47 ,  C07D239/84 ,  C07D239/94 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutically compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选化合物对于预防和治疗诸如HGF介导的疾病等疾病是有效的。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗涉及癌症等的疾病和其它疾病或病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

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：WO2011063233A1

公开(公告)日：2011-05-26

申请号：PCT/US2010/057428

申请日：2010-11-19

Applicant: AMGEN INC. ,  CHENG, Yuan ,  POWERS, Timothy ,  ASHTON, Kate ,  BROWN, James ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  NIXEY, Thomas ,  PARAS, Nick A, ,  POON, Steve F. ,  ST. JEAN JR., David J. ,  XUE, Qiufen ,  ZHONG, Wenge

Inventor： CHENG, Yuan ,  POWERS, Timothy ,  ASHTON, Kate ,  BROWN, James ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  NIXEY, Thomas ,  PARAS, Nick A, ,  POON, Steve F. ,  ST. JEAN JR., David J. ,  XUE, Qiufen ,  ZHONG, Wenge

IPC: C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04 ,  A61K31/4709 ,  A61P25/28

CPC classification number: C07D215/38 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D405/12 ,  C07D417/04

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 ring A, B 1 , B 2 , B 3 , L, R 1 , R 4 , R 5 and m 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 (AD), 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的环A，B 1，B 2，B 3，L，R 1，R 4，R 5和m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。 这些疾病包括例如阿尔茨海默氏病（AD），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：WO2008079292A1

公开(公告)日：2008-07-03

申请号：PCT/US2007/026064

申请日：2007-12-19

Applicant: AMGEN INC. ,  CHENG, Yuan ,  CHOQUETTE, Deborah ,  HARMANGE, Jean-Christophe ,  TASKER, Andrew

Inventor： CHENG, Yuan ,  CHOQUETTE, Deborah ,  HARMANGE, Jean-Christophe ,  TASKER, Andrew

IPC: C07D401/06 ,  C07D401/14 ,  C07D417/14 ,  A61K31/4427 ,  A61K31/4725 ,  A61P35/00 ,  A61P29/00

CPC classification number: C07D401/06 ,  C07D401/14 ,  C07D417/14

Abstract: Selected compounds of formula (I) are effective for prophylaxis and treatment of diseases, such as VEGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

Abstract translation: 所选择的式（I）化合物可有效预防和治疗诸如VEGF介导的疾病之类的疾病。 本发明包括新颖的化合物，类似物，前药和药学上可接受的盐，用于预防和治疗疾病和其它疾病或涉及癌症等的病症的药物组合物和方法。 本发明还涉及制备这些化合物的方法以及在这些方法中有用的中间体。

公开(公告)号：WO2007061670A1

公开(公告)日：2007-05-31

申请号：PCT/US2006/044058

申请日：2006-11-13

Applicant: AMGEN INC. ,  ZHONG, Wenge ,  HITCHCOCK, Stephen ,  ALBRECHT, Brian K ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HICKMAN, Dean ,  HORNE, Daniel ,  HUNGATE, Randall ,  JUDD, Ted ,  KALLER, Matthew ,  KREIMAN, Charles ,  LA, Daniel ,  LOPEZ, Patricia ,  MASSE, Craig E. ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  NIXEY, Thomas ,  PATEL, Vinod F. ,  PENNINGTON, Lewis ,  WEISS, Matthew ,  XUE, Qiufen ,  YANG, Bryant

Inventor： ZHONG, Wenge ,  HITCHCOCK, Stephen ,  ALBRECHT, Brian K ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HICKMAN, Dean ,  HORNE, Daniel ,  HUNGATE, Randall ,  JUDD, Ted ,  KALLER, Matthew ,  KREIMAN, Charles ,  LA, Daniel ,  LOPEZ, Patricia ,  MASSE, Craig E. ,  MONENSCHEIN, Holger ,  NGUYEN, Thomas ,  NIXEY, Thomas ,  PATEL, Vinod F. ,  PENNINGTON, Lewis ,  WEISS, Matthew ,  XUE, Qiufen ,  YANG, Bryant

IPC: C07D405/12 ,  C07D413/12 ,  A61K31/44 ,  A61P25/28

CPC classification number: C07D405/12 ,  C07D311/68 ,  C07D413/12 ,  C07D491/052

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, B, W, R 3 , R 4 , R 5 , i and j are defined herein. The invention also comprises pharmaceutical compositions including one or more compounds of Formula (I), methods of use for these compounds, including treatment of AD and related diseases, by administering the compound(s) of Formula (I), or compositions including them, to a subject. The invention also comprises further embodiments of Formulas (II) and (III), intermediates and processes useful for the preparation of compounds of the invention.

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A，B，W，R 3，R 4，R 5，i和j在本文中定义。 本发明还包括药物组合物，其包括一种或多种式（I）化合物，这些化合物的使用方法，包括治疗AD和相关疾病，通过施用式（I）化合物或其组合物，包括它们， 到一个主题。 本发明还包括式（II）和（III）的其它实施方案，可用于制备本发明化合物的中间体和方法。