公开(公告)号：US09399651B2

公开(公告)日：2016-07-26

申请号：US14671452

申请日：2015-03-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Scott Wolkenberg ,  James C. Barrow ,  Michael S. Poslusney ,  Scott T. Harrison ,  Wesley B. Trotter ,  James Mulhearn ,  Kausik K. Nanda ,  Peter J. Manley ,  Zhijian Zhao ,  Jeffrey W. Schubert ,  Nathan R. Kett ,  Amy Zartman

IPC: C07D213/84 ,  A61K31/44 ,  C07F5/02 ,  A61K31/4412 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/69 ,  A61K45/06 ,  C07D213/69 ,  C07D213/73 ,  C07D213/74 ,  C07D401/10 ,  C07D401/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  C07D401/04 ,  C07D401/06

CPC classification number: C07F5/025 ,  A61K31/4412 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/69 ,  A61K45/06 ,  C07D213/69 ,  C07D213/73 ,  C07D213/74 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04

Abstract: The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved.

公开(公告)号：US10221167B2

公开(公告)日：2019-03-05

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 ,  C07D285/08 ,  C07D277/52 ,  A61K31/4178 ,  A61K31/4196 ,  A61K31/4168 ,  A61K31/426 ,  A61K31/427 ,  A61K31/433 ,  A61K31/551 ,  A61K45/06

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：US09624208B2

公开(公告)日：2017-04-18

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: C07D413/12 ,  C07D413/14 ,  C07D263/58 ,  A61K31/44

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.

公开(公告)号：US20190233406A1

公开(公告)日：2019-08-01

申请号：US16246068

申请日：2019-01-11

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 ,  A61K31/426 ,  A61K31/433 ,  A61K31/427 ,  A61K31/551 ,  C07D277/52 ,  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：US10022461B2

公开(公告)日：2018-07-17

申请号：US15724402

申请日：2017-10-04

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Abbas M. 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

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：US20180071412A1

公开(公告)日：2018-03-15

申请号：US15724402

申请日：2017-10-04

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Abbas M. 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：US20150299227A1

公开(公告)日：2015-10-22

申请号：US14671452

申请日：2015-03-27

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Scott Wolkenberg ,  James C. Barrow ,  Michael S. Poslusney ,  Scott T. Harrison ,  Wesley B. Trotter ,  James Mulhearn ,  Kausik K. Nanda ,  Peter J. Manley ,  Zhijian Zhao ,  Jeffrey W. Schubert ,  Nathan R. Kett ,  Amy Zartman

IPC: C07F5/02 ,  A61K31/4418 ,  C07D401/04 ,  A61K31/4439 ,  C07D213/73 ,  C07D213/74 ,  A61K31/69 ,  A61K31/444 ,  C07D401/14 ,  C07D471/04 ,  C07D401/06 ,  A61K31/4725 ,  A61K31/4709 ,  A61K45/06 ,  C07D213/69

CPC classification number: C07F5/025 ,  A61K31/4412 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/69 ,  A61K45/06 ,  C07D213/69 ,  C07D213/73 ,  C07D213/74 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04

Abstract: The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved.

公开(公告)号：US20210395224A1

公开(公告)日：2021-12-23

申请号：US17286591

申请日：2019-10-24

Applicant: Merck Sharp & Dohme Corp. ,  MSD R&D (China) Co. LTD.

Inventor： John J. Acton, III ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Timothy J. Henderson ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  James Mulhearn ,  Vanessa L. Rada ,  Jeffrey W. Schubert ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang ,  Jianming Bao ,  Chunsing Li

IPC: C07D401/14 ,  C07D405/14

Abstract: The present invention is directed to cinnolinyl and quinolinyl 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：US10968210B2

公开(公告)日：2021-04-06

申请号：US16345913

申请日：2017-11-13

Applicant: 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

Inventor： 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: C07D417/12 ,  C07D417/14 ,  C07D277/52 ,  C07D471/04 ,  C07D487/10 ,  C07D401/12 ,  C07D471/08 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08

Abstract: 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

Applicant: 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

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 ,  A61K45/06 ,  C07D277/52 ,  C07D285/135 ,  A61P25/02 ,  A61P25/04 ,  A61P11/14 ,  A61P17/04

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 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.