公开(公告)号：WO2020112706A1

公开(公告)日：2020-06-04

申请号：PCT/US2019/063146

申请日：2019-11-26

Applicant: MERCK SHARP & DOHME CORP. ,  ZHANG, Yonglian ,  ALI, Amjad ,  CUMMING, Jared ,  DEMONG, Duane ,  DENG, Qiaolin ,  GRAHAM, Thomas, H. ,  HENNESSY, Elisabeth ,  LARSEN, Matthew, A. ,  LIU, Kun ,  LIU, Ping ,  MANSOOR, Umar Faruk ,  PAN, Jianping ,  PLUMMER, Christopher, W. ,  SATHER, Aaron ,  SWAMINATHAN, Uma ,  WANG, Huijun

Inventor： ZHANG, Yonglian ,  ALI, Amjad ,  CUMMING, Jared ,  DEMONG, Duane ,  DENG, Qiaolin ,  GRAHAM, Thomas, H. ,  HENNESSY, Elisabeth ,  LARSEN, Matthew, A. ,  LIU, Kun ,  LIU, Ping ,  MANSOOR, Umar Faruk ,  PAN, Jianping ,  PLUMMER, Christopher, W. ,  SATHER, Aaron ,  SWAMINATHAN, Uma ,  WANG, Huijun

IPC: C07D487/04 ,  C07D487/08 ,  C07D487/18

Abstract: In its many embodiments, the present invention provides certain 7-, 8-, and 10-substituted amino triazolo quinazoline derivatives of Formula (I): or a pharmaceutically acceptable salt thereof, wherein ring A, R1, R2, and R4 are as defined herein, pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other therapeutic agents), and methods for their preparation and use, alone and in combination with other therapeutic agents, as antagonists of A2a and/or A2b receptors, and their use in the treatment of a variety of diseases, conditions, or disorders that are mediated, at least in part, by the adenosine A2a receptor and/or the adenosine A2b receptor.

公开(公告)号：WO2018118665A1

公开(公告)日：2018-06-28

申请号：PCT/US2017/066557

申请日：2017-12-15

Applicant: MERCK SHARP & DOHME CORP. ,  CEMERSKI, Saso ,  CUMMING, Jared, N. ,  FLATELAND, Lauren, M. ,  KOPINJA, Johnny, E. ,  MA, Yanhong ,  PERERA, Samanthi, A. ,  TROTTER, Benjamin Wesley ,  TSE, Archie Ngai-Chiu

Inventor： CEMERSKI, Saso ,  CUMMING, Jared, N. ,  FLATELAND, Lauren, M. ,  KOPINJA, Johnny, E. ,  MA, Yanhong ,  PERERA, Samanthi, A. ,  TROTTER, Benjamin Wesley ,  TSE, Archie Ngai-Chiu

IPC: A61K31/7084 ,  A61P35/00 ,  C07H21/00

Abstract: Therapies comprising administering at least one cyclic dinucleotide compound that activates the Stimulator of Interferon Genes (STING) pathway, and the use of such therapies in the treatment of cell-proliferation disorders such as cancer, are disclosed herein.

公开(公告)号：WO2017142825A3

公开(公告)日：2017-08-24

申请号：PCT/US2017/017603

申请日：2017-02-13

Applicant: MERCK SHARP & DOHME CORP. ,  THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH ,  KHAN, Tanweer, A. ,  CUMMING, Jared, N. ,  OLSEN, David, B. ,  BODDEY, Justin, A. ,  COWMAN, Alan, F. ,  SLEEBS, Brad, E.

Inventor： KHAN, Tanweer, A. ,  CUMMING, Jared, N. ,  OLSEN, David, B. ,  BODDEY, Justin, A. ,  COWMAN, Alan, F. ,  SLEEBS, Brad, E.

IPC: A61K31/519 ,  A61K31/506

Abstract: The present invention provides methods of treating malaria comprising administration of an N3-substituted iminopyrimidinone of Formula (I) or a pharmaceutically acceptable salt thereof, to a subject in need thereof, wherein the variables R 1 , R 2 , R 3 , R 4 , R 5 , A, B, L, m, and n are as defined herein. The invention also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin V activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.

公开(公告)号：WO2017142821A1

公开(公告)日：2017-08-24

申请号：PCT/US2017/017590

申请日：2017-02-13

Applicant: MERCK SHARP & DOHME CORP. ,  THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH ,  KHAN, Tanweer, A. ,  CUMMING, Jared, N. ,  OLSEN, David, B. ,  BODDEY, Justin, A. ,  COWMAN, Alan, F. ,  SLEEBS, Brad, E.

Inventor： KHAN, Tanweer, A. ,  CUMMING, Jared, N. ,  OLSEN, David, B. ,  BODDEY, Justin, A. ,  COWMAN, Alan, F. ,  SLEEBS, Brad, E.

IPC: A61K31/497 ,  A61K31/41 ,  A61K31/4439 ,  A61K31/5395 ,  C07D401/10

CPC classification number: A61K31/5395 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/495 ,  A61K31/496 ,  A61K31/4985 ,  Y02A50/411

Abstract: The present invention provides methods of treating malaria by administration of a compound of Formula (I): or a pharmaceutically acceptable salt of said compound, to a subject in need thereof, wherein the variables X, R1, R3, R4, R5, A, B, L, m and n are as defined herein. The invention also provides uses of the compounds of Formula (I), as defined herein, for inhibiting plasmepsin V activity, for treating a Plasmodium infection, and for treating malaria. Also provided are methods of treatment further comprising administration of one or more additional anti-malarial compounds.

Abstract translation: 本发明提供了通过将式（I）化合物或所述化合物的药学上可接受的盐给予有需要的受试者来治疗疟疾的方法，其中变量X，R 1， R3，R4，R5，A，B，L，m和n如本文所定义。 本发明还提供了如本文所定义的式（I）化合物用于抑制plasmepsin V活性，治疗疟原虫感染和治疗疟疾的用途。 还提供了进一步包括施用一种或多种另外的抗疟疾化合物的治疗方法。

公开(公告)号：WO2017139210A1

公开(公告)日：2017-08-17

申请号：PCT/US2017/016636

申请日：2017-02-06

Applicant: MERCK SHARP & DOHME CORP. ,  WALSH, Shawn, P. ,  CUMMING, Jared, N. ,  DAI, Xing

Inventor： WALSH, Shawn, P. ,  CUMMING, Jared, N. ,  DAI, Xing

IPC: A61K31/549 ,  C07D513/04 ,  A61P25/28

CPC classification number: C07D513/04

Abstract: In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminothiadiazine dioxide compounds bearing an ether linker, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R N , R 1 , R 2 , R A , ring A, ring C, and m are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了带有醚接头的某些C5-C6-氧杂环稠合的亚氨基噻二嗪二氧化物化合物，包括式（I）的化合物或其互变异构体，以及所述 化合物和所述互变异构体，其中R 1，R 2，R 1，R 2，R A，环A，环 C和m如本文所定义。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其有关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其他活性剂组合）的药物组合物，以及它们的制备和使用方法，包括用于可能治疗阿尔茨海默氏病的方法。

公开(公告)号：WO2016118404A1

公开(公告)日：2016-07-28

申请号：PCT/US2016/013509

申请日：2016-01-15

Applicant: MERCK SHARP & DOHME CORP. ,  WU, Wen-Lian ,  HE, Shuwen ,  WALSH, Shawn, P. ,  CUMMING, Jared, N.

Inventor： WU, Wen-Lian ,  HE, Shuwen ,  WALSH, Shawn, P. ,  CUMMING, Jared, N.

IPC: A01N43/42

CPC classification number: C07D417/14 ,  A61P3/10 ,  A61P9/04 ,  A61P25/16 ,  A61P25/28 ,  A61P27/06 ,  C07D417/12

Abstract: In its many embodiments, the present invention provides certain iminothiazine dioxide compounds, including compounds Formula (I): or a tautomers thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R 1 , R 2 , ring A, R A , m, ring B, R B , and n are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基噻嗪二氧化物化合物，包括式（I）化合物或其互变异构体以及所述化合物和所述互变异构体的药学上可接受的盐，其中R1，R2，环A，RA，m，环B ，RB和n如本文所定义。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括用于治疗阿尔茨海默氏病的药物组合物。

公开(公告)号：WO2012138734A1

公开(公告)日：2012-10-11

申请号：PCT/US2012/032135

申请日：2012-04-04

Applicant: MERCK SHARP & DOHME CORP. ,  CUMMING, Jared, N. ,  GILBERT, Eric, J. ,  STAMFORD, Andrew, W.

Inventor： CUMMING, Jared, N. ,  GILBERT, Eric, J. ,  STAMFORD, Andrew, W.

IPC: C07D285/00 ,  A61K31/54

CPC classification number: C07D513/04 ,  A61K31/54 ,  A61K31/549 ,  A61K45/06 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula : (I) and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of ring A, ring B, ring C, R 2 , R 3 , R 4 , m, n, p, and -L 1 - is as defined herein. The novel compounds of the invention may be useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基二嗪二氧化物化合物，包括式（I）化合物及其互变异构体和立体异构体，以及所述化合物，所述互变异构体和所述立体异构体的药学上可接受的盐，其中环A，环B， 环C，R 2，R 3，R 4，m，n，p和-L 1如本文所定义。 本发明的新化合物可用作BACE抑制剂和/或用于治疗和预防与其相关的各种病症。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括阿尔茨海默氏病。

公开(公告)号：WO2006065277A2

公开(公告)日：2006-06-22

申请号：PCT/US2005/020446

申请日：2005-06-09

Applicant: SCHERING CORPORATION ,  PHARMACOPEIA DRUG DISCOVERY, INC. ,  ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan, C. ,  VOIGT, Johannes, H. ,  STRICKLAND, Corey ,  SMITH, Elizabeth, M. ,  STAMFORD, Andrew ,  GREENLEE, William, J. ,  MAZZOLA, Robert ,  CALDWELL, John ,  CUMMING, Jared ,  WANG, Lingyan ,  WU, Yusheng ,  ISERLOH, Ulrich ,  GUO, Tao ,  LE, Thuy, X., H. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D. ,  HUNTER, Rachael, C. ,  MORRIS, Michelle, L. ,  GU, Huizhong ,  QIAN, Gang ,  TADESSE, Dawit

Inventor： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan, C. ,  VOIGT, Johannes, H. ,  STRICKLAND, Corey ,  SMITH, Elizabeth, M. ,  STAMFORD, Andrew ,  GREENLEE, William, J. ,  MAZZOLA, Robert ,  CALDWELL, John ,  CUMMING, Jared ,  WANG, Lingyan ,  WU, Yusheng ,  ISERLOH, Ulrich ,  GUO, Tao ,  LE, Thuy, X., H. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D. ,  HUNTER, Rachael, C. ,  MORRIS, Michelle, L. ,  GU, Huizhong ,  QIAN, Gang ,  TADESSE, Dawit

IPC: A61K31/4168 ,  A61K31/4178 ,  C07D233/46 ,  C07D233/88 ,  C07D239/22 ,  C07D271/06 ,  C07D273/00 ,  C07D401/10 ,  C07D403/06 ,  C07D403/12 ,  C07D407/10 ,  C07D409/04 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  A61P9/00 ,  A61P25/00

CPC classification number: C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/655 ,  A61K45/06 ,  C07D233/46 ,  C07D233/70 ,  C07D235/02 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D295/15 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  Y02A50/411

Abstract: Disclosed are compounds of the formula (I) a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, -C(=S)-, -S(O)-, -S(O) 2 -, -C(=O)-, -O-, -C(R 6 )(R 7 )-, -N(R 5 )- or -C(=N(R 5 ))-; X is -O-, -N(R 5 )- or -C(R 6 )(R 7 )-; provided that when X is -O-, U is not -O-, -S(O)-, -S(O)2-, -C(=O)- or -C(=NR5)-; U is a bond, -S(O)-, -S(O) 2 -, -C(O)-, -O-, -P(O)(OR 15 )-, -C(=NR 5 )-, -(C(R 6 )(R 7 )) b - or -N(R 5 )-; wherein b is 1 or 2; provided that when W is -S(O)-, -S(O)2-, -O-, or -N(R5)-, U is not -S(O)-, -S(O) 2 -, -O-, or -N(R 5 )-; provided that when X is -N(R 5 )- and W is -S(O)-, -S(O) 2 -, -O-, or -N(R 5 )-, then U is not a bond; and R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula (I). Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m 1 agonist or m 2 antagonist.

Abstract translation: 公开了式（I）的立体异构体，互变异构体或其药学上可接受的盐或溶剂化物的化合物，其中W是键，-C（= S） - ， - S（O） - ， - S（O） -C（= O） - ， - O - ， - C（R 6） - ， - N（R - 或-C（= N（R 5）） - ; X是-O-，-N（R 5） - 或-C（R 6）（R 7）。 条件是当X是-O-时，U不是-O-，-S（O） - ， - S（O）2 - ， - C（= O） - 或-C（= NR5） - ; U是一个键，-S（O） - ， - S（O）2 - ， - C（O） - ， - O - ，-P（O） （C（R 6）） - ， - （C（R 6）） - ， - C（= NR 5） > - 或-N（R 5） - ; 其中b为1或2; 条件是当W是-S（O） - ， - S（O）2 - ， - O-或-N（R 5） - 时，U不是-S（O） - ， - S（O） 2 - ， - O-或-N（R 5） - ; 条件是当X是-N（R 5） - 且W是-S（O） - ，-S（O）2 - ， - O-或 - N（R 5） - ，则U不是键; 和R 1，R 2，R 3，R 4，R 5， R 6，R 6和R 7如说明书中所定义; 和包含式（I）化合物的药物组合物。 还公开了抑制天冬氨酰蛋白酶的方法，特别是治疗心血管疾病，认知和神经退行性疾病的方法，以及抑制人类免疫缺陷病毒，plasmepins，组织蛋白酶D和原生动物酶的方法。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱m 1激动剂或m 2 N拮抗剂组合治疗认知或神经变性疾病的方法。

公开(公告)号：WO2005058311A1

公开(公告)日：2005-06-30

申请号：PCT/US2004/041700

申请日：2004-12-13

Applicant: SCHERING CORPORATION ,  PHARMACOPEIA DRUG DISCOVERY, INC. ,  ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan, C. ,  VOIGT, Johannes, H. ,  STRICKLAND, Corey ,  SMITH, Elizabeth, M. ,  STAMFORD, Andrew ,  GREENLEE, William, J. ,  WU, Yusheng ,  ISERLOH, Ulrich ,  MAZZOLA, Robert ,  CALDWELL, John ,  CUMMING, Jared ,  WANG, Lingyan ,  GUO, Tao ,  LE, Thuy, X. H. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D. ,  HUNTER, Rachael, C.

Inventor： ZHU, Zhaoning ,  MCKITTRICK, Brian ,  SUN, Zhong-Yue ,  YE, Yuanzan, C. ,  VOIGT, Johannes, H. ,  STRICKLAND, Corey ,  SMITH, Elizabeth, M. ,  STAMFORD, Andrew ,  GREENLEE, William, J. ,  WU, Yusheng ,  ISERLOH, Ulrich ,  MAZZOLA, Robert ,  CALDWELL, John ,  CUMMING, Jared ,  WANG, Lingyan ,  GUO, Tao ,  LE, Thuy, X. H. ,  SAIONZ, Kurt, W. ,  BABU, Suresh, D. ,  HUNTER, Rachael, C.

IPC: A61K31/4168

CPC classification number: C07D233/88 ,  C07D235/02 ,  C07D239/22 ,  C07D271/07 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/10 ,  C07D405/12 ,  C07D405/14 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12

Abstract: Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula (I) in combination with a cholinesterase inhibitor or a muscarinic antagonist.

Abstract translation: 公开了式（I）的化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂化物。 还公开了抑制天冬氨酰蛋白酶的方法，特别是治疗心血管疾病，认知和神经退行性疾病的方法，以及抑制人类免疫缺陷病毒，plasmepins，组织蛋白酶D和原生动物酶的方法。 还公开了使用式（I）化合物与胆碱酯酶抑制剂或毒蕈碱拮抗剂组合治疗认知或神经退行性疾病的方法。

公开(公告)号：WO2019245890A1

公开(公告)日：2019-12-26

申请号：PCT/US2019/037140

申请日：2019-06-14

Applicant: MERCK SHARP & DOHME CORP. ,  ACHAB, Abdelghani Abe ,  CUMMING, Jared, N. ,  FISCHER, Christian ,  GATHIAKA, Symon ,  LESBURG, Charles, A. ,  LI, Derun ,  LU, Min ,  MITCHELTREE, Matthew, J. ,  PALANI, Anandan ,  PALTE, Rachel, L. ,  SLOMAN, David, L. ,  ZHANG, Hongjun

Inventor： ACHAB, Abdelghani Abe ,  CUMMING, Jared, N. ,  FISCHER, Christian ,  GATHIAKA, Symon ,  LESBURG, Charles, A. ,  LI, Derun ,  LU, Min ,  MITCHELTREE, Matthew, J. ,  PALANI, Anandan ,  PALTE, Rachel, L. ,  SLOMAN, David, L. ,  ZHANG, Hongjun

IPC: C07F5/02

Abstract: Described herein are compounds of Formula (I) or a pharmaceutically acceptable salt thereof. The compounds of Formula (I) act as arginase inhibitors and can be useful in preventing, treating or acting as a remedial agent for arginase-related diseases.