公开(公告)号：US09808542B2

公开(公告)日：2017-11-07

申请号：US15317333

申请日：2015-06-09

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Abbas W. Walji ,  Eric Hostetler ,  Thomas J. Greshock ,  Jing Li ,  Keith P. Moore ,  Idriss Bennacef ,  James Mulhearn ,  Harold Selnick ,  Yaode Wang ,  Kun Yang ,  Jianmin Fu

IPC: A61K51/04 ,  C07D519/00 ,  C07D471/04

CPC classification number: A61K51/0455 ,  A61K51/0459 ,  C07B2200/05 ,  C07D471/04 ,  C07D519/00

Abstract: The present invention is directed to pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.

公开(公告)号：US20180362518A1

公开(公告)日：2018-12-20

申请号：US16061815

申请日：2016-12-15

Applicant: 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.

Inventor： 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: C07D417/12 ,  C07D285/135 ,  C07D277/52 ,  A61P11/14 ,  A61P17/04 ,  A61P25/04 ,  A61P25/02

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

Abstract: 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：US20170174674A1

公开(公告)日：2017-06-22

申请号：US15378465

申请日：2016-12-14

Applicant: Merck Sharp & Dohme Corp.

Inventor： 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: C07D417/12 ,  C07D277/52 ,  A61K31/551 ,  A61K31/427 ,  A61K31/433 ,  A61K31/426 ,  C07D285/08 ,  A61K45/06

CPC classification number: C07D417/12 ,  A61K31/426 ,  A61K31/427 ,  A61K31/433 ,  A61K31/551 ,  A61K45/06 ,  C07D277/52 ,  C07D285/08 ,  A61K2300/00

Abstract: 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.

公开(公告)号：US20170119912A1

公开(公告)日：2017-05-04

申请号：US15317333

申请日：2015-06-09

Applicant: Abbas W. Walji ,  Eric Hostetler ,  Thomas J. Greshock ,  Jing Li ,  Keith P. Moore ,  Idriss Bennacef ,  James Mulhearn ,  Harold Selnick ,  Yaode Wang ,  Kun Yang ,  Jianmin Fu ,  MERCK SHARP & DOHME CORP.

Inventor： Abbas W. Walji ,  Eric Hostetler ,  Thomas J. Greshock ,  Jing Li ,  Keith P. Moore ,  Idriss Bennacef ,  James Mulhearn ,  Harold Selnick ,  Yaode Wang ,  Kun Yang ,  Jianmin Fu

IPC: A61K51/04 ,  C07D519/00 ,  C07D471/04

CPC classification number: A61K51/0455 ,  A61K51/0459 ,  C07B2200/05 ,  C07D471/04 ,  C07D519/00

Abstract: The present invention is directed to pyrrolopyridine compounds of formula (I) or their pharmaceutically acceptable salts, which may be suitable for imaging tau aggregates, b-sheet aggregates, beta-amyloid aggregates or alpha-synuclein aggregates, and hence are useful in binding and imaging tau aggregates in Alzheimer's patients. More specifically, this invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study tau deposits in brain in vivo to allow diagnosis of Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology. The invention further relates to a method of measuring clinical efficacy of therapeutic agents for Alzheimer's disease and other neurodegenerative diseases characterized by tau pathology.

公开(公告)号：US20150252034A1

公开(公告)日：2015-09-10

申请号：US14437315

申请日：2013-10-23

Applicant: Merck Sharp & Dohme Corp.

Inventor： Joseph E. Pero ,  Hannah D.G.F. Lehman ,  Michael J. Kelly, III ,  Lianyun Zhao ,  Michael A. Rossi ,  Dansu Li ,  Kevin F. Gilbert ,  Scott Wolkenberg ,  James Mulhearn ,  Mark E. Layton ,  Pablo de Leon

IPC: C07D413/14 ,  C07D413/12

CPC classification number: C07D413/14 ,  A61K31/44 ,  C07D263/58 ,  C07D413/12

Abstract: Disclosed are compounds of Formula A: 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.

Abstract translation: 公开了式A的化合物：式A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或其盐的化合物的药物制剂，以及使用其制备治疗神经性疼痛障碍的方法。

公开(公告)号：US20140303143A1

公开(公告)日：2014-10-09

申请号：US14353488

申请日：2012-10-26

Applicant: MERCK SHARP & DOHME CORP.

Inventor： 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: C07D417/12 ,  C07D491/107 ,  C07D471/04 ,  C07D493/10 ,  C07D417/14 ,  C07D451/02

CPC classification number: C07D417/12 ,  C07D417/14 ,  C07D451/02 ,  C07D471/04 ,  C07D491/107 ,  C07D493/10

Abstract: 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.

Abstract translation: 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。