公开(公告)号：WO2005113494A2

公开(公告)日：2005-12-01

申请号：PCT/US2005/016346

申请日：2005-05-09

Applicant: AMGEN INC. ,  GEUNS-MEYER, Stephanie, D. ,  HODOUS, Brian, L. ,  CHAFFEE, Stuart, C. ,  TEMPEST, Paul, A. ,  OLIVIERI, Philip, R. ,  JOHNSON, Rebecca, E. ,  ALBRECHT, Brian, K. ,  PATEL, Vinod, F. ,  CEE, Victor, J. ,  KIM, Joseph, L. ,  BELLON, Steven ,  ZHU, Xiaotian ,  CHENG, Yuan ,  XI, Ning ,  ROMERO, Karina ,  NGUYEN, Hanh, Nho ,  DEAK, Holly, L.

Inventor： GEUNS-MEYER, Stephanie, D. ,  HODOUS, Brian, L. ,  CHAFFEE, Stuart, C. ,  TEMPEST, Paul, A. ,  OLIVIERI, Philip, R. ,  JOHNSON, Rebecca, E. ,  ALBRECHT, Brian, K. ,  PATEL, Vinod, F. ,  CEE, Victor, J. ,  KIM, Joseph, L. ,  BELLON, Steven ,  ZHU, Xiaotian ,  CHENG, Yuan ,  XI, Ning ,  ROMERO, Karina ,  NGUYEN, Hanh, Nho ,  DEAK, Holly, L.

IPC: C07D1/04

CPC classification number: C07D213/73 ,  C07D239/42 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D407/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04

Abstract: The present invention relates to chemical compounds having a general formula I wherein A, B, D, E, G, H 1-5 and R 1-4 are defined herein, and synthetic intermediates, which are capable of modulating various protein kinase receptor enzymes and, thereby, influencing various disease states and conditions related to the activities of these kinases. For example, the compounds are capable of modulating kinase enzymes thereby influencing the process of angiogenesis and treating angiogenesis-related diseases and other poliferative disorders, including cancer and inflammation. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of protein kinases.

Abstract translation: 本发明涉及具有通式I的化合物，其中A，B，D，E，G，H 1-5和R 1-4如本文所定义，以及合成中间体，其能够调节各种 蛋白激酶受体酶，从而影响与这些激酶的活性相关的各种疾病状态和状况。 例如，这些化合物能够调节激酶，从而影响血管生成过程并治疗血管生成相关疾病和其它包括癌症和炎症的复发性疾病。 本发明还包括药物组合物，包括该化合物，以及治疗与蛋白激酶活性有关的疾病状态的方法。

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：WO2007061930A1

公开(公告)日：2007-05-31

申请号：PCT/US2006/044833

申请日：2006-11-17

Applicant: AMGEN INC. ,  XUE, Qiufen ,  ALBRECHT, Brian K. ,  ANDERSEN, Denise Lyn ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  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 ,  YANG, Bryant ,  ZHONG, Wenge

Inventor： XUE, Qiufen ,  ALBRECHT, Brian K. ,  ANDERSEN, Denise Lyn ,  BARTBERGER, Michael ,  BROWN, James ,  BROWN, Ryan ,  CHAFFEE, Stuart C. ,  CHENG, Yuan ,  CROGHAN, Michael ,  GRACEFFA, Russell ,  HARRIED, Scott ,  HITCHCOCK, Stephen ,  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 ,  YANG, Bryant ,  ZHONG, Wenge

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

CPC classification number: C07D405/12 ,  C07D413/12

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 R 1 , W, B, 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R 1，W，B，R 3，R 4，R 4， SUP> 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。

公开(公告)号：WO2021119034A1

公开(公告)日：2021-06-17

申请号：PCT/US2020/063844

申请日：2020-12-08

Applicant: AMGEN INC.

Inventor： WU, Bin ,  OLLMANN, Michael ,  HOMANN, Oliver ,  CHENG, Yuan

IPC: C12N15/113 ,  A61K47/54

Abstract: The present invention relates to RNAi constructs for reducing expression of the LPA gene, which encodes apolipoprotein(a), a component of lipoprotein(a) (Lp(a)) particles. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease, peripheral artery disease, stroke, and myocardial infarction, and to reduce serum Lp(a) levels are also described.

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：WO2011090911A1

公开(公告)日：2011-07-28

申请号：PCT/US2011/021423

申请日：2011-01-14

Applicant: AMGEN INC. ,  PARAS, Nick A, ,  BROWN, James ,  CHENG, Yuan ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  MINATTI, Ana Elena ,  NIXEY, Thomas ,  POWERS, Timothy ,  TEGLEY, Christopher M. ,  XUE, Qiufen ,  YANG, Bryant ,  ZHONG, Wenge

Inventor： PARAS, Nick A, ,  BROWN, James ,  CHENG, Yuan ,  HITCHCOCK, Stephen ,  JUDD, Ted ,  LOPEZ, Patricia ,  MINATTI, Ana Elena ,  NIXEY, Thomas ,  POWERS, Timothy ,  TEGLEY, Christopher M. ,  XUE, Qiufen ,  YANG, Bryant ,  ZHONG, Wenge

IPC: C07D215/38 ,  C07D401/10 ,  C07D403/10 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D471/04 ,  C07D471/08 ,  C07D498/08 ,  A61K31/47 ,  A61K31/4709 ,  A61P25/28

CPC classification number: C07D401/10 ,  C07D215/38 ,  C07D403/10 ,  C07D405/04 ,  C07D405/10 ,  C07D405/12 ,  C07D413/10 ,  C07D471/04 ,  C07D471/08 ,  C07D498/08

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 2 , ring Z, m and n 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中的环A，B1，B2，B3，L，R1，R2，环Z，m和n定义在本文中。 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：WO2006060318A3

公开(公告)日：2006-06-08

申请号：PCT/US2005/042935

申请日：2005-11-29

Applicant: AMGEN INC. ,  KIM, Tae-seong ,  BELLON, Steven ,  BOOKER, Shon ,  D'ANGELO, Noel ,  DOMINGUEZ, Celia ,  FELLOWS, Ingrid ,  LEE, Matthew ,  LIU, Longbin ,  RAINBEAU, Elizabeth ,  SIEGMUND, Aaron, C. ,  TASKER, Andrew ,  XI, Ning ,  CHENG, Yuan

Inventor： KIM, Tae-seong ,  BELLON, Steven ,  BOOKER, Shon ,  D'ANGELO, Noel ,  DOMINGUEZ, Celia ,  FELLOWS, Ingrid ,  LEE, Matthew ,  LIU, Longbin ,  RAINBEAU, Elizabeth ,  SIEGMUND, Aaron, C. ,  TASKER, Andrew ,  XI, Ning ,  CHENG, Yuan

IPC: A61K31/4709 ,  C07D401/12 ,  C07D401/14 ,  A61P35/00

Abstract: Selected compounds of Formula (I) are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases such as cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes. R - X - W - A - Y - R Formula (I) wherein R is X is O, S, NR2 or CR3R4 W is an substituted or unsubstituted aryl or substituted or unsubstituted 5- or 6- membered heteroaryl.

公开(公告)号：WO2020123410A1

公开(公告)日：2020-06-18

申请号：PCT/US2019/065294

申请日：2019-12-09

Applicant: AMGEN INC.

Inventor： MURRAY, Justin K. ,  WU, Bin ,  CHENG, Yuan ,  HERBERICH, Bradley J.

IPC: C12N15/11

Abstract: The present invention relates to chemically-modified RNAi constructs for reducing expression of a target gene. In particular, the invention relates to specific patterns of modified nucleotides to be incorporated into RNAi constructs to improve in vivo stability and efficacy. Also described are pharmaceutical compositions comprising the chemically-modified RNAi constructs and methods of inhibiting target gene expression in vivo by administering the chemically-modified RNAi constructs, for example, to treat or ameliorate various disease conditions.

公开(公告)号：WO2014059185A1

公开(公告)日：2014-04-17

申请号：PCT/US2013/064400

申请日：2013-10-10

Applicant: AMGEN INC.

Inventor： LEWIS, Richard T. ,  CHOQUETTE, Deborah ,  EPSTEIN, Oleg ,  GUZMAN-PEREZ, Angel ,  HUA, Zihao ,  HUMAN, Jason Brooks ,  JUDD, Ted ,  LIU, Qingyian ,  LOPEZ, Patricia ,  MINATTI, Ana Elena ,  OLIVIERI, Philip R. ,  ROMERO, Karina ,  SCHENKEL, Laurie ,  STELLWAGEN, John ,  WHITE, Ryan ,  ZHENG, Xiao Mei ,  ALLEN, Jennifer R. ,  CHENG, Yuan ,  HARRINGTON, Paul E. ,  HUNGATE, Randall W. ,  RUMFELT, Shannon ,  RZASA, Robert M. ,  XUE, Qiufen ,  ZHONG, Wenge

IPC: C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D279/12 ,  C07D279/14 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00 ,  A61P25/18 ,  A61P25/28 ,  A61K31/54 ,  A61K31/541 ,  A61K31/547

CPC classification number: C07D279/12 ,  C07D213/79 ,  C07D239/74 ,  C07D241/44 ,  C07D279/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D498/04 ,  C07D513/04 ,  C07D513/10 ,  C07D519/00

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 , R 1 , R 2 , R 3 , R 7 and n 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 Formula II and sub-formula embodiments thereof, intermediates and processes and methods useful for the preparation of compounds of Formulas I-II.

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的变量A4，A5，A6，A8，R1，R2，R3，R7和n独立地在本文中定义。 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化合物及其次级实施方案，可用于制备式I-II化合物的中间体和方法和方法。

公开(公告)号：WO2012019056A1

公开(公告)日：2012-02-09

申请号：PCT/US2011/046667

申请日：2011-08-04

Applicant: AMGEN INC. ,  MINATTI, Ana, Elena ,  CHENG, Yuan ,  ZHONG, Wenge

Inventor： MINATTI, Ana, Elena ,  CHENG, Yuan ,  ZHONG, Wenge

IPC: C07D491/20 ,  C07D491/22 ,  C07D498/20 ,  C07D498/22 ,  A61K31/436 ,  A61K31/437 ,  A61K31/537

CPC classification number: C07D491/20 ,  A61K31/436 ,  A61K31/437 ,  A61K31/537 ,  C07D491/22 ,  C07D498/20 ,  C07D498/22

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: (I). In another embodiment, the compounds have a general Formula II: (II). In another embodiment, the compounds have a general Formula III: (III). Variables A 1 , A 2 , A 3 , A 4 , A 5 , A 6 , R 2 , R 7 , V, W, X, Y and Z of Formulas I, II and III 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 Formulas I, II and III, intermediates and processes useful for the preparation of compounds of Formulas I, II and III.

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：（I）。 在另一个实施方案中，化合物具有通式II：（II）。 在另一个实施方案中，化合物具有通式III：（III）。 式I，II和III的变量A1，A2，A3，A4，A5，A6，R2，R7，V，W，X，Y和Z在本文中定义。 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，II和III的其它实施方案，可用于制备式I，II和III化合物的中间体和方法。