公开(公告)号：US10968210B2

公开(公告)日：2021-04-06

申请号：US16345913

申请日：2017-11-13

申请人： Merck Sharp & Dohme Corp. ,  Thomas J. Greshock ,  James Mulhearn ,  Anthony J. Roecker ,  Tianying Jian ,  Gang Zhou ,  Liangqin Guo ,  Walter Won ,  Ting Zhang ,  Rajan Anand ,  John E. Stelmach ,  Deping Wang ,  Ronald M. Kim ,  Mark E. Layton ,  Christopher S. Burgey ,  Philippe G. Nantermet

发明人： Thomas J. Greshock ,  James Mulhearn ,  Anthony J. Roecker ,  Tianying Jian ,  Gang Zhou ,  Liangqin Guo ,  Walter Won ,  Ting Zhang ,  Rajan Anand ,  John E. Stelmach ,  Deping Wang ,  Ronald M. Kim ,  Mark E. Layton ,  Christopher S. Burgey ,  Philippe G. Nantermet

IPC分类号： C07D417/12 ,  C07D417/14 ,  C07D277/52 ,  C07D471/04 ,  C07D487/10 ,  C07D401/12 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08

摘要： Disclosed are compounds of Formula A, or a salt thereof: Formula (A), wherein: Het, Q and R1A to R4A are defined herein, which compounds have properties for blocking Nav 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating cough, itch, acute pain and neuropathic pain disorders using the same.

公开(公告)号：US10519147B2

公开(公告)日：2019-12-31

申请号：US16061815

申请日：2016-12-15

申请人： Merck Sharp & Dohme Corp. ,  Thomas J. Greshock ,  James Mulhearn ,  Liangqin Guo ,  Ting Zhang ,  Deping Wang ,  Ronald M. Kim ,  Mark E. Layton ,  Michael J. Kelly, III ,  Rajan Anand ,  Philippe Nantermet ,  Tianying Jian ,  Anthony J. Roecker ,  Walter Won ,  Gang Zhou

发明人： Thomas J. Greshock ,  James Mulhearn ,  Liangqin Guo ,  Ting Zhang ,  Deping Wang ,  Ronald M. Kim ,  Mark E. Layton ,  Michael J. Kelly, III ,  Rajan Anand ,  Philippe Nantermet ,  Tianying Jian ,  Anthony J. Roecker ,  Walter Won ,  Gang Zhou

IPC分类号： C07D417/12 ,  A61K45/06 ,  C07D277/52 ,  C07D285/135 ,  A61P25/02 ,  A61P25/04 ,  A61P11/14 ,  A61P17/04

摘要： Disclosed are compounds of Formula A, or a salt thereof, where Q, X, R1 and R2 are as defined herein, which compounds have properties for inhibiting Nav 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating pain (acute, post-operative, neuropathic), or cough or itch disorders using the same.

公开(公告)号：US09708308B2

公开(公告)日：2017-07-18

申请号：US14652237

申请日：2013-12-16

申请人： Merck Sharp & Dohme Corp. ,  Mochida Pharmaceutical Co., Ltd.

发明人： Cameron James Smith ,  John Qiang Tan ,  Ting Zhang ,  James Balkovec ,  William John Greenlee ,  Liangqin Guo ,  Yi-Heng Chen ,  Yili Chen ,  Jiayi Xu ,  Samuel Chackalamannil ,  Tomokazu Hirabayashi ,  Hiroshi Nagasue ,  Kouki Ogawa

IPC分类号： C07D471/04 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D498/04

CPC分类号： C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

摘要： The present invention provides a compound of Formula (I) wherein R1 is H or C1-6 alkyl, R2, is H or C1-6 alkyl or CH2OH, R3 is H or C1-6 alkyl, and R4 is H or C1-6 alkyl, provided that when R1, R2, and R3 are H, R4 is C1-6 alkyl, and when R1, R2, and R4 are H, then R3 is C1-6 alkyl, and when R1, R3, and R4 are H, R2 is C1-6 alkyl or —CH2OH, and when R2, R3, and R4 are H, then R1 is C1-6 alkyl; A is 1) a 9-10 membered bicyclic heterocycle having 1-3 heteroatoms independently selected from N, S and O, which 9-10 membered bicyclic heterocycle is unsubstituted or substituted with R5 and unsubstituted or substituted with R6 and unsubstituted or substituted with NH2, or 2) a 6-9 membered monocyclic or bicyclic carbocyclic ring system unsubstituted or substituted with R5, unsubstituted or substituted with R6, and unsubstituted or substituted with —CH2NH2; and B is 1) a 5- or 6-membered monocyclic heterocycle having 1 or 2 heteroatoms independently selected from N, S or O, which is unsubstituted or substituted on a carbon or nitrogen atom with R7, unsubstituted or substituted on a carbon or nitrogen atom with R8, and unsubstituted or substituted on a carbon or nitrogen atom with R9, or 2) an 8- or 9-membered fused bicyclic heterocycle having 1, 2 or 3 nitrogen atoms which is unsubstituted or substituted on a carbon or nitrogen atom with R7, and unsubstituted or substituted on a carbon or nitrogen atom with R8; and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses.

公开(公告)号：US20220000844A1

公开(公告)日：2022-01-06

申请号：US17296601

申请日：2019-12-02

申请人： Merck Sharp & Dohme Corp.

发明人： Christopher J. Bungard ,  Helen Y. Chen ,  Jason M. Cox ,  Liangqin Guo ,  Michael J. Kelly, III ,  Ronald M. Kim ,  Mark E. Layton ,  Hong Liu ,  Jian Liu ,  Mehul F. Patel ,  James J. Perkins ,  Deping Wang ,  Walter Won ,  Younong Yu ,  Ting Zhang

IPC分类号： A61K31/433 ,  C07D285/08 ,  C07D417/12 ,  C07D239/42 ,  A61K31/4439 ,  A61K31/505 ,  A61K31/5377 ,  A61K31/167

摘要： Disclosed are compounds of Formula (I), Formula (II), or a salt thereof: Formula (I) Formula (II) which compounds have properties for inhibiting Nav 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula (I), Formula (II) or their salts, and methods of treating pain disorders, cough, and itch using the same.

公开(公告)号：US10351558B2

公开(公告)日：2019-07-16

申请号：US15550862

申请日：2016-02-12

申请人： Merck Sharp & Dohme Corp. ,  Dongfang Meng ,  Hong Li ,  Meng Yang ,  Manuel de Lera Ruiz ,  Sunita V. Dewnani ,  Tianying Jian ,  Dann L. Parker, Jr. ,  Ting Zhang ,  Louis-Charles Campeau ,  Harold B. Wood ,  Jiayi Xu ,  Richard Berger ,  Jane Yang Wu ,  Robert K. Orr ,  Shawn P. Walsh ,  Bart Harper

发明人： Dongfang Meng ,  Hong Li ,  Meng Yang ,  Manuel de Lera Ruiz ,  Sunita V. Dewnani ,  Tianying Jian ,  Dann L. Parker, Jr. ,  Ting Zhang ,  Louis-Charles Campeau ,  Harold B. Wood ,  Jiayi Xu ,  Richard Berger ,  Jane Yang Wu ,  Robert K. Orr ,  Shawn P. Walsh ,  Bart Harper

IPC分类号： C07D471/04 ,  C07D403/12 ,  C07D417/14 ,  A61P9/00 ,  C07D413/14 ,  C07D471/14 ,  C07D498/04 ,  C07D513/04

摘要： The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels. The compounds are selective Factor IXa inhibitors.

公开(公告)号：US20190092738A1

公开(公告)日：2019-03-28

申请号：US16086654

申请日：2017-03-17

申请人： Merck Sharp & Dohme Corp.

发明人： Anthony J. Roecker ,  Mark E. Layton ,  Thomas J. Greshock ,  Joseph E. Pero ,  Michael J. Kelly, III ,  Ting Zhang

IPC分类号： C07D277/52 ,  C07D285/08 ,  A61K31/635 ,  A61K45/06

CPC分类号： C07D277/52 ,  A61K31/18 ,  A61K31/426 ,  A61K31/427 ,  A61K31/433 ,  A61K31/635 ,  A61K45/06 ,  C07D285/08 ,  C07F7/0812 ,  A61K2300/00

摘要： Disclosed are compounds of Formula A-1, or a salt thereof: Formula A-1, where J, K, Q and R1 are as defined herein, which compounds have properties for inhibiting sodium ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A-1 or their salts, and methods of treating pain (e.g. chronic pain), or cough or itch disorders using the same.

公开(公告)号：US10189819B2

公开(公告)日：2019-01-29

申请号：US15534029

申请日：2015-12-07

申请人： MERCK SHARP & DOHME CORP. ,  MOCHIDA PHARMACEUTICAL CO., LTD

发明人： Ting Zhang ,  Yi-Heng Chen ,  Liangqin Guo ,  Alan Hruza ,  Tianying Jian ,  Bing Li ,  Dongfang Meng ,  Dann L. Parker ,  Edward C. Sherer ,  Harold B. Wood ,  Isao Sakurada

IPC分类号： C07D403/12 ,  C07D401/14 ,  C07D401/12 ,  C07D471/04 ,  C07D413/14 ,  C07D413/12 ,  C07D417/12

摘要： The present invention provides a compound of Formula I, and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels. The compounds are selective Factor IXa inhibitors.

公开(公告)号：US20180022747A1

公开(公告)日：2018-01-25

申请号：US15550862

申请日：2016-02-12

申请人： Dongfang MENG ,  Hong LI ,  Meng YANG ,  Manuel de Lera RUIZ ,  Sunita V. DEWNANI ,  Tianying JIAN ,  Dann L. PARKER, JR. ,  Ting ZHANG ,  Louis-Charles CAMPEAU ,  Bart HARPER ,  Harold B. WOOD ,  Jiayi XU ,  Richard BERGER ,  Jane Yang WU ,  Robert K. ORR ,  Shawn P. WALSH ,  Merck Sharp & Dohme Corp.

发明人： Dongfang Meng ,  Hong Li ,  Meng Yang ,  Manuel de Lera Ruiz ,  Sunita V. Dewnani ,  Tianying Jian ,  Dann L. Parker, Jr. ,  Ting Zhang ,  Louis-Charles Campeau ,  Harold B. Wood ,  Jiayi Xu ,  Richard Berger ,  Jane Yang Wu ,  Robert K. Orr ,  Shawn P. Walsh ,  Bart Harper

IPC分类号： C07D471/04 ,  C07D403/12 ,  C07D498/04 ,  C07D417/14 ,  C07D513/04 ,  C07D471/14 ,  C07D413/14

CPC分类号： C07D471/04 ,  A61P9/00 ,  C07D403/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/14 ,  C07D498/04 ,  C07D513/04

摘要： The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels. The compounds are selective Factor IXa inhibitors.

公开(公告)号：US09808445B2

公开(公告)日：2017-11-07

申请号：US15303322

申请日：2015-04-10

申请人： Merck Sharp & Dohme Corp. ,  Mochida Pharmaceutical Co., Ltd.

发明人： Isao Sakurada ,  Tomokazu Hirabayashi ,  Yoshitaka Maeda ,  Hiroshi Nagasue ,  Takashi Mizuno ,  Jiayi Xu ,  Ting Zhang ,  Cameron Smith ,  Dann Parker

IPC分类号： A61K31/501 ,  A61K31/439 ,  C07D413/14 ,  C07D261/20 ,  C07D413/04 ,  C07D498/04 ,  C07D209/52 ,  C07D519/00 ,  A61K31/444 ,  A61K31/506 ,  A61K45/06

CPC分类号： A61K31/439 ,  A61K31/444 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D209/52 ,  C07D261/20 ,  C07D413/04 ,  C07D413/14 ,  C07D498/04 ,  C07D519/00

摘要： In its many embodiments, the present invention provides a novel class of benzamide compounds represented by Formula (I) or pharmaceutically acceptable salts or solvates thereof, or pharmaceutical compositions comprising one or more said compounds or pharmaceutically acceptable salts or solvates thereof, and methods for using said compounds or pharmaceutically acceptable salts or solvates thereof for treating or preventing a thromboses, embolisms, hypercoagulability or fibrotic changes.

公开(公告)号：US10221167B2

公开(公告)日：2019-03-05

申请号：US15378465

申请日：2016-12-14

申请人： Merck Sharp & Dohme Corp.

发明人： Thomas J. Greshock ,  James Mulhearn ,  Junying Zheng ,  Ronald M. Kim ,  Ting Zhang ,  Anthony J. Roecker ,  Walter Won ,  Philippe Nantermet ,  Rajan Anand ,  Gang Zhou ,  Deping Wang ,  Liangqin Guo

IPC分类号： C07D417/12 ,  C07D285/08 ,  C07D277/52 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4168 ,  A61K31/426 ,  A61K31/427 ,  A61K31/433 ,  A61K31/551 ,  A61K45/06

摘要： Disclosed are compounds of Formula A, or a salt thereof: wherein R1, R2, and E are defined herein, which compounds have properties for inhibiting Nav 1.7 ion channels found in peripheral and sympathetic neurons. Also described are pharmaceutical formulations comprising the compounds of Formula A or their salts, and methods of treating pain disorders, cough, and itch using the same.