公开(公告)号：WO2019000237A1

公开(公告)日：2019-01-03

申请号：PCT/CN2017/090385

申请日：2017-06-27

申请人： MERCK SHARP & DOHME CORP. ,  MSD R & D (CHINA) CO., LTD. ,  ACTON, John J., III ,  BAO, Jianming ,  DENG, Qiaolin ,  EGBERTSON, Melissa ,  FERGUSON, Ronald ,  GAO, Xiaolei ,  HARRISON, Scott T. ,  HENDERSON, Timothy J. ,  KNOWLES, Sandra L. ,  LO, Michael Man-Chu ,  MAZZOLA, Robert D., Jr ,  SELYUTIN, Oleg ,  ZHANG, Fengqi ,  NA, Meng ,  SUZUKI, Takao

发明人： ACTON, John J., III ,  BAO, Jianming ,  DENG, Qiaolin ,  EGBERTSON, Melissa ,  FERGUSON, Ronald ,  GAO, Xiaolei ,  HARRISON, Scott T. ,  HENDERSON, Timothy J. ,  KNOWLES, Sandra L. ,  LO, Michael Man-Chu ,  MAZZOLA, Robert D., Jr ,  SELYUTIN, Oleg ,  ZHANG, Fengqi ,  NA, Meng ,  SUZUKI, Takao

IPC分类号： C07D231/10 ,  C07D231/02 ,  C07D401/14 ,  A61K31/455 ,  A61P25/00

摘要： Provided are pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. Provided is also use of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. Provided are also compositions comprising these compounds. Provided is also use of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：WO2018226545A1

公开(公告)日：2018-12-13

申请号：PCT/US2018/035772

申请日：2018-06-04

申请人： MERCK SHARP & DOHME CORP. ,  CLAUSEN, Dane James ,  FELLS, James, I. ,  KOZLOWSKI, Joseph, A. ,  LIU, Ping ,  MAZZOLA, Robert, D., Jr.

发明人： CLAUSEN, Dane James ,  FELLS, James, I. ,  KOZLOWSKI, Joseph, A. ,  LIU, Ping ,  MAZZOLA, Robert, D., Jr.

IPC分类号： A61K31/439 ,  A61P11/00 ,  A61P29/00

摘要： The present invention is directed to azabicyclo[4.1.0]heptane compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：WO2012087861A1

公开(公告)日：2012-06-28

申请号：PCT/US2011/065716

申请日：2011-12-19

申请人： MERCK SHARP & DOHME CORP. ,  SCHERING CORPORATION ,  BOYCE, Christopher, W. ,  DEGRADO, Sylvia Joanna ,  CHEN, Xiao ,  QIN, Jun ,  MAZZOLA, Robert, D., Jr. ,  YU, Younong ,  MCCORMICK, Kevin, D. ,  PALANI, Anandan ,  XIAO, Dong ,  ASLANIAN, Robert George ,  WU, Jie ,  RAO, Ashwin Umesh ,  SILIPHAIVANH, Phieng ,  METHOT, Joey Lee ,  ZHANG, Hongjun ,  KELLEY, Elizabeth Helen ,  BROWN, William Colby ,  JIANG, Qin ,  GAUUAN, Jolicia Polivina ,  LEYHANE, Andrew, J. ,  BIJU, Purakkattle Johny ,  DHONDI, Pawan, K. ,  DONG, Li ,  FEVRIER, Salem ,  HUANG, Xianhai ,  VACCARO, Henry, M.

发明人： BOYCE, Christopher, W. ,  DEGRADO, Sylvia Joanna ,  CHEN, Xiao ,  QIN, Jun ,  MAZZOLA, Robert, D., Jr. ,  YU, Younong ,  MCCORMICK, Kevin, D. ,  PALANI, Anandan ,  XIAO, Dong ,  ASLANIAN, Robert George ,  WU, Jie ,  RAO, Ashwin Umesh ,  SILIPHAIVANH, Phieng ,  METHOT, Joey Lee ,  ZHANG, Hongjun ,  KELLEY, Elizabeth Helen ,  BROWN, William Colby ,  JIANG, Qin ,  GAUUAN, Jolicia Polivina ,  LEYHANE, Andrew, J. ,  BIJU, Purakkattle Johny ,  DHONDI, Pawan, K. ,  DONG, Li ,  FEVRIER, Salem ,  HUANG, Xianhai ,  VACCARO, Henry, M.

IPC分类号： C07D241/36 ,  A61K31/498

CPC分类号： C07D241/42 ,  A61K31/498 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/55 ,  A61K45/06 ,  C07D241/38 ,  C07D241/44 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D451/02 ,  C07D471/04 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D491/048 ,  C07D491/107 ,  C07D498/04 ,  C07D498/10

摘要： The invention provides certain quinoxalines and aza-quinoxalines of the Formula (I), and their pharmaceutically acceptable salts, wherein J 1 , J 2 , R 1 , R 2 , R 3 , R 22 , R a , R b , R c , R d , X, Y, b, n, and q are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions associated with with uncontrolled or inappropriate stimulation of CRTH 2 function.

摘要翻译： 本发明提供了式（I）的某些喹喔啉和氮杂 - 喹喔啉及其药学上可接受的盐，其中J1，J2，R1，R2，R3，R22，Ra，Rb，Rc，Rd，X，Y，b，n ，和q如本文所定义。 本发明还提供包含这些化合物的药物组合物，以及使用该化合物治疗与不受控制或不适当刺激CRTH2功能有关的疾病或病症的方法。

公开(公告)号：WO2009005729A1

公开(公告)日：2009-01-08

申请号：PCT/US2008/008042

申请日：2008-06-27

申请人： SCHERING CORPORATION ,  ZHU, Zhaoning ,  GREENLEE, William, J. ,  MAZZOLA, Robert, D. ,  QIN, Jun ,  HUANG, Xianhai ,  PALANI, Anandan

发明人： ZHU, Zhaoning ,  GREENLEE, William, J. ,  MAZZOLA, Robert, D. ,  QIN, Jun ,  HUANG, Xianhai ,  PALANI, Anandan

IPC分类号： C07D401/10 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  A61K31/519 ,  A61P25/28

CPC分类号： C07D487/04 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  C07D471/04

摘要： In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

公开(公告)号：WO2018118734A1

公开(公告)日：2018-06-28

申请号：PCT/US2017/066917

申请日：2017-12-18

申请人： MERCK SHARP & DOHME CORP. ,  MSD R&D (CHINA) CO., LTD. ,  BAO, Jianming ,  FERGUSON, Ronald ,  GAO, Xiaolei ,  HARRISON, Scott ,  KNOWLES, Sandra, L. ,  LO, Michael Man-Chu ,  MAZZOLA, Robert, D., Jr. ,  SCHUBERT, Jeffrey, W.

发明人： BAO, Jianming ,  FERGUSON, Ronald ,  GAO, Xiaolei ,  HARRISON, Scott ,  KNOWLES, Sandra, L. ,  LO, Michael Man-Chu ,  MAZZOLA, Robert, D., Jr. ,  SCHUBERT, Jeffrey, W.

IPC分类号： A61K31/445 ,  A61K31/495 ,  A61K31/496 ,  C07D401/00 ,  C07D401/02 ,  C07D401/04

摘要： The present invention is directed to heteroarylpiperidine ether compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：WO2007146225A3

公开(公告)日：2008-03-06

申请号：PCT/US2007013684

申请日：2007-06-07

申请人： SCHERING CORP ,  WU YUSHENG ,  ISERLOH ULRICH ,  CUMMING JARED ,  LIU XIAOXIANG ,  MAZZOLA ROBERT D ,  SUN ZHONG-YUE ,  HUANG YING ,  STAMFORD ANDREW ,  MCKITTRICK BRIAN ,  ZHU ZHAONING

发明人： WU YUSHENG ,  ISERLOH ULRICH ,  CUMMING JARED ,  LIU XIAOXIANG ,  MAZZOLA ROBERT D ,  SUN ZHONG-YUE ,  HUANG YING ,  STAMFORD ANDREW ,  MCKITTRICK BRIAN ,  ZHU ZHAONING

IPC分类号： C07D239/20 ,  A61K31/513 ,  A61P25/28 ,  C07D401/04 ,  C07D401/10 ,  C07D403/04 ,  C07D405/04 ,  C07D409/14 ,  C07D411/04 ,  C07D417/04 ,  C07D417/10 ,  C07D495/20

CPC分类号： C07D239/20 ,  C07D401/04 ,  C07D401/10 ,  C07D403/04 ,  C07D405/04 ,  C07D409/14 ,  C07D411/04 ,  C07D417/04 ,  C07D417/14 ,  C07D495/20

摘要： Disclosed are compounds of formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, U, W, X, R 1 , R 2 , R 6 , R 7 , R 30 and R 31 are as described above in the specification. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases. 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 m1 agonist or m2 antagonist.

摘要翻译： 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合物，U，W，X，R 1，R 2， SUP> 6，R 7，R 30和R 31如上文在说明书中所述。 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，认知和神经变性疾病的方法。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱m1激动剂或m2拮抗剂组合治疗认知或神经变性疾病的方法。

公开(公告)号：WO2006065277A3

公开(公告)日：2007-01-25

申请号：PCT/US2005020446

申请日：2005-06-09

申请人： SCHERING CORP ,  PHARMACOPEIA DRUG DISCOVERY ,  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

发明人： 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分类号： 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

CPC分类号： 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

摘要： Disclosed are compounds of the formula (I) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, 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.

摘要翻译： 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合物，以及包含式（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，认知和神经变性疾病的方法，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 H 2拮抗剂组合来治疗认知或神经退行性疾病的方法。

公开(公告)号：WO2019005587A1

公开(公告)日：2019-01-03

申请号：PCT/US2018/038888

申请日：2018-06-22

申请人： MERCK SHARP & DOHME CORP. ,  MSD R&D (CHINA) CO., LTD. ,  ACTON, John, J., III ,  BAO, Jianming ,  DENG, Qiaolin ,  EGBERTSON, Melissa ,  FERGUSON, Ronald, III ,  GAO, Xiaolei ,  HARRISON, Scott Timothy ,  KNOWLES, Sandra, L. ,  LI, Chunsing ,  LO, Michael Man-Chu ,  MAZZOLA, Robert, D., Jr. ,  MENG, Zhaoyang ,  NA, Meng ,  RUDD, Michael, T. ,  SELYUTIN, Oleg, B. ,  TELLERS, David, M. ,  TONG, Ling ,  ZHANG, Fengqi

发明人： ACTON, John, J., III ,  BAO, Jianming ,  DENG, Qiaolin ,  EGBERTSON, Melissa ,  FERGUSON, Ronald, III ,  GAO, Xiaolei ,  HARRISON, Scott Timothy ,  KNOWLES, Sandra, L. ,  LI, Chunsing ,  LO, Michael Man-Chu ,  MAZZOLA, Robert, D., Jr. ,  MENG, Zhaoyang ,  NA, Meng ,  RUDD, Michael, T. ,  SELYUTIN, Oleg, B. ,  TELLERS, David, M. ,  TONG, Ling ,  ZHANG, Fengqi

IPC分类号： A61K31/4155 ,  C07D231/10

摘要： The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：WO2019000236A1

公开(公告)日：2019-01-03

申请号：PCT/CN2017/090384

申请日：2017-06-27

申请人： MERCK SHARP & DOHME CORP. ,  MSD R & D (CHINA) CO., LTD. ,  ACTON, John J. ,  BAO, Jianming ,  DENG, Qiaolin ,  EGBERTSON, Melissa ,  FERGUSON, Ronald ,  GAO, Xiaolei ,  HARRISON, Scott Timothy ,  KNOWLES, Sandra L. ,  LI, Chunsing ,  LO, Michael Man-Chu ,  MAZZOLA, Robert D., Jr. ,  NA, Meng ,  MENG, Zhaoyang ,  RUDD, Michael T. ,  SELYUTIN, Oleg ,  TELLERS, David M. ,  TONG, Ling ,  ZHANG, Fengqi

发明人： ACTON, John J. ,  BAO, Jianming ,  DENG, Qiaolin ,  EGBERTSON, Melissa ,  FERGUSON, Ronald ,  GAO, Xiaolei ,  HARRISON, Scott Timothy ,  KNOWLES, Sandra L. ,  LI, Chunsing ,  LO, Michael Man-Chu ,  MAZZOLA, Robert D., Jr. ,  NA, Meng ,  MENG, Zhaoyang ,  RUDD, Michael T. ,  SELYUTIN, Oleg ,  TELLERS, David M. ,  TONG, Ling ,  ZHANG, Fengqi

IPC分类号： C07D231/10 ,  C07D213/04 ,  A61K31/455 ,  A61P25/00

摘要： Disclosed are pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor, uses of the compounds described herein in the potential treatment of prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved, compositions comprising these compounds, uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：WO2018118736A1

公开(公告)日：2018-06-28

申请号：PCT/US2017/066921

申请日：2017-12-18

申请人： MERCK SHARP & DOHME CORP. ,  GAO, Xiaolei ,  KNOWLES, Sandra, L. ,  LI, Chunsing ,  LO, Michael Man-Chu ,  MAZZOLA, Robert, D., Jr. ,  ONDEYKA, Debra, L.

发明人： GAO, Xiaolei ,  KNOWLES, Sandra, L. ,  LI, Chunsing ,  LO, Michael Man-Chu ,  MAZZOLA, Robert, D., Jr. ,  ONDEYKA, Debra, L.

IPC分类号： A61K31/4196 ,  A61K31/435 ,  A61K31/445 ,  C07D249/08 ,  C07D401/02 ,  C07D401/04

摘要： The present invention is directed to 6,5-fused heteroarylpiperidine ether compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.