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：US20180362518A1

公开(公告)日：2018-12-20

申请号：US16061815

申请日：2016-12-15

申请人： Thomas J. GRESHOCK ,  James MULHEARN ,  Liangqin GUO ,  Ting ZHANG ,  Deping WANG ,  Ronald M. KIM ,  Mark E. LAYTON ,  Michael J. KELLY, III ,  Rajan ANAND ,  Tianying JIAN ,  Philippe NANTERMET ,  Anthony J. ROECKER ,  Walter WON ,  Gang ZHOU ,  Merck Sharp & Dohme Corp.

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 ,  C07D285/135 ,  C07D277/52 ,  A61P11/14 ,  A61P17/04 ,  A61P25/04 ,  A61P25/02

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

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 Na 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：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：US20220305035A1

公开(公告)日：2022-09-29

申请号：US17615769

申请日：2020-06-08

申请人： Anthony J. ROECKER ,  Mark E. LAYTON ,  Deping WANG ,  Xiu WANG ,  Xuanjia PENG ,  Merck Sharp & Dohme Corp.

发明人： Anthony J. Roecker ,  Mark E. Layton ,  Deping Wang ,  Xiu Wang ,  Xuanjia Peng

IPC分类号： A61K31/635 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed are compounds of Formula A, or a salt thereof: Wherein “A1”, R1, R2, R3, R6, and R7 are as 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 and neuropathic pain disorders using the same.

公开(公告)号：US09273040B2

公开(公告)日：2016-03-01

申请号：US14353488

申请日：2012-10-26

申请人： Mark E. Layton ,  Joseph E. Pero ,  Hannah Fiji ,  Michael J. Kelly, III ,  Pablo de Leon ,  Michael A. Rossi ,  Kevin F. Gilbert ,  Anthony J. Roecker ,  Zhijian Zhao ,  Swati I P. Mercer ,  Scott Wolkenberg ,  James Mulhearn ,  Lianyun Zhao ,  Dansu Li

发明人： Mark E. Layton ,  Joseph E. Pero ,  Hannah Fiji ,  Michael J. Kelly, III ,  Pablo de Leon ,  Michael A. Rossi ,  Kevin F. Gilbert ,  Anthony J. Roecker ,  Zhijian Zhao ,  Swati I P. Mercer ,  Scott Wolkenberg ,  James Mulhearn ,  Lianyun Zhao ,  Dansu Li

IPC分类号： A61K31/00 ,  C07D417/12 ,  C07D417/14 ,  C07D451/02 ,  C07D471/04 ,  C07D491/107 ,  C07D493/10

CPC分类号： C07D417/12 ,  C07D417/14 ,  C07D451/02 ,  C07D471/04 ,  C07D491/107 ,  C07D493/10

摘要： Disclosed are compounds of Formula (A) or a salt thereof, wherein “Het”, Ra, and Rb are defined herein, which 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 neuropathic pain disorders using the same.

摘要翻译： 公开了式（A）的化合物或其盐，其中“Het”，Ra和Rb在本文中定义，其具有用于阻断在外周和交感神经元中发现的Nav 1.7离子通道的性质。 还描述了包含式（A）化合物或其盐的药物制剂，以及使用其制备神经性疼痛障碍的方法。

公开(公告)号：US09586968B2

公开(公告)日：2017-03-07

申请号：US15038805

申请日：2014-11-24

申请人： Merck Sharp & Dohme Corp. ,  Dansu Li ,  Mark E. Layton ,  Anthony J. Roecker ,  Melissa Egbertson ,  Kristen L. G. Jones ,  Xiu Wang ,  Xuanjia Peng

发明人： Mark E. Layton ,  Anthony J. Roecker ,  Melissa Egbertson ,  Kristen L. G. Jones ,  Dansu Li ,  Xiu Wang ,  Xuanjia Peng

IPC分类号： C07D487/04 ,  A61K31/407 ,  C07D471/04 ,  A61K31/4353 ,  C07D491/20 ,  C07D487/10 ,  C07D277/52 ,  C07D213/76 ,  C07D239/42 ,  C07D237/20 ,  C07D285/135

CPC分类号： C07D487/04 ,  C07D213/76 ,  C07D237/20 ,  C07D239/42 ,  C07D277/52 ,  C07D285/135 ,  C07D471/04 ,  C07D487/10 ,  C07D491/20

摘要： Disclosed are compounds of Formula A-a, or a salt thereof: Where “B1” and “R1” through “R5” are as 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-a or their salts, and methods of treating neuropathic pain disorders using the same.

摘要翻译： 公开了式A-a或其盐的化合物：其中“B1”和“R1”至“R5”如本文所定义，这些化合物具有阻断外周和交感神经元中的Nav 1.7离子通道的性质。 还描述了包含式A-a化合物或其盐的药物制剂，以及使用其制备神经性疼痛病症的方法。

公开(公告)号：US20170002008A1

公开(公告)日：2017-01-05

申请号：US15038805

申请日：2014-11-24

申请人： Dansu LI ,  Mark E. LAYTON ,  Anthony J. ROECKER ,  Melissa EGBERTSON ,  Kristen L. G. JONES ,  Xiu WANG ,  Xuanjia PENG ,  MERCK SHARP & DOHME CORP.

发明人： Mark E. Layton ,  Anthony J. Roecker ,  Melissa Egbertson ,  Kristen L. G. Jones ,  Dansu Li ,  Xiu Wang ,  Xuanjia Peng

IPC分类号： C07D487/04 ,  C07D487/10 ,  C07D471/04 ,  C07D285/135 ,  C07D213/76 ,  C07D239/42 ,  C07D237/20 ,  C07D491/20 ,  C07D277/52

CPC分类号： C07D487/04 ,  C07D213/76 ,  C07D237/20 ,  C07D239/42 ,  C07D277/52 ,  C07D285/135 ,  C07D471/04 ,  C07D487/10 ,  C07D491/20

摘要： Disclosed are compounds of Formula A-a, or a salt thereof: Where “B1” and “R1” through “R5” are as 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-a or their salts, and methods of treating neuropathic pain disorders using the same.

摘要翻译： 公开了式A-a或其盐的化合物：其中“B1”和“R1”至“R5”如本文所定义，这些化合物具有阻断外周和交感神经元中的Nav 1.7离子通道的性质。 还描述了包含式A-a化合物或其盐的药物制剂，以及使用其制备神经性疼痛病症的方法。

公开(公告)号：US20230227405A1

公开(公告)日：2023-07-20

申请号：US18009310

申请日：2021-06-14

申请人： Ashok ARASAPPAN ,  Ian M. BELL ,  Jason M. COX ,  Michael J. KELLY, III ,  Mark E. LAYTON ,  Hong LIU ,  Jian LIU ,  Akshay A. SHAH ,  Michael D. VANHEYST ,  MERCK SHARP & DOHME CORP.

发明人： Ashok Arasappan ,  Ian M. Bell ,  Jason Michael Cox ,  Michael J. Kelly, III ,  Mark E. Layton ,  Hong Liu ,  Jian Liu ,  Akshay A. Shah ,  Michael David VanHeyst

IPC分类号： C07D207/277 ,  C07D401/12 ,  C07D417/12

CPC分类号： C07D207/277 ,  C07D401/12 ,  C07D417/12

摘要： Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are inhibitors of Nav1.8 channel activity and may be useful in the treatment, prevention, management, amelioration, control and suppression of diseases mediated by Nav1.8 channel activity. The compounds of the present invention may be useful in the treatment, prevention or management of pain disorders, cough disorders, acute itch disorders, and chronic itch disorders.

公开(公告)号：US20230227441A1

公开(公告)日：2023-07-20

申请号：US18009306

申请日：2021-06-14

申请人： Ashok ARASAPPAN ,  Ian M. BELL ,  Christopher James BUNGARD ,  Christopher S. BURGEY ,  Jason M. COX ,  Deodial Guy GUIADEEN ,  Michael J. KELLY ,  Mark E. LAYTON ,  Hong LIU ,  Jian LIU ,  James T. OLSEN ,  James J. PERKINS ,  Jeffrey W. SCHUBERT ,  Akshay A. SHAH ,  Michael D. VANHEYST ,  Zhe WU ,  Shawn J. STACHEL ,  MERCK SHARP & DOHME CORP.

发明人： Ashok Arasappan ,  Ian M. Bell ,  Christopher James Bungard ,  Christopher S. Burgey ,  Jason Michael Cox ,  Deodial Guy Guiadeen, III ,  Michael J. Kelly, III ,  Mark E. Layton ,  Hong Liu ,  Jian Liu ,  James T. Olsen ,  James J. Perkins ,  Jeffrey W. Schubert ,  Akshay A. Shah ,  Shawn J. Stachel ,  Michael David VanHeyst ,  Zhe Wu

IPC分类号： C07D413/12 ,  C07D263/24 ,  C07D417/12

CPC分类号： C07D413/12 ,  C07D263/24 ,  C07D417/12

摘要： Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are inhibitors of Nav1.8 channel activity and may be useful in the treatment, prevention, management, amelioration, control and suppression of diseases mediated by Nav1.8 channel activity. The compounds of the present invention may be useful in the treatment, prevention or management of pain disorders, cough disorders, acute itch disorders, and chronic itch disorders.

公开(公告)号：US20110288090A1

公开(公告)日：2011-11-24

申请号：US13147392

申请日：2010-01-25

申请人： Donna J. Armstrong ,  Yasuhiro Goto ,  Takashi Hashihayata ,  Tetsuya Kato ,  Michael J. Kelly, III ,  Mark E. Layton ,  Craig W. Lindsley ,  Yoshio Ogino ,  Yu Onozaki ,  Kenvin J. Rodzinak ,  Michael A. Rossi ,  Philip E. Sanderson ,  Jiabing Wang ,  Melissa M. Yaroschak

发明人： Donna J. Armstrong ,  Yasuhiro Goto ,  Takashi Hashihayata ,  Tetsuya Kato ,  Michael J. Kelly, III ,  Mark E. Layton ,  Craig W. Lindsley ,  Yoshio Ogino ,  Yu Onozaki ,  Kenvin J. Rodzinak ,  Michael A. Rossi ,  Philip E. Sanderson ,  Jiabing Wang ,  Melissa M. Yaroschak

IPC分类号： A61K31/5377 ,  A61K31/4985 ,  A61K31/496 ,  A61K31/506 ,  A61K31/498 ,  A61K31/438 ,  A61K31/4375 ,  C07D475/04 ,  C07D471/04 ,  C07D401/12 ,  A61P35/00 ,  A61K31/519

CPC分类号： C07D471/04 ,  C07D217/24 ,  C07D241/42 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D475/02 ,  C07D475/04 ,  C07D487/04 ,  C07D519/00

摘要： The instant invention provides for compounds that inhibit Akt activity. In particular, the compounds disclosed selectively inhibit one or two of the Akt isoforms. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting Akt activity by administering the compound to a patient in need of treatment of cancer.

摘要翻译： 本发明提供抑制Akt活性的化合物。 特别地，所公开的化合物选择性地抑制一种或两种Akt同种型。 本发明还提供了包含这种抑制化合物的组合物和通过将该化合物给予需要治疗癌症的患者来抑制Akt活性的方法。