公开(公告)号：US20110076230A1

公开(公告)日：2011-03-31

申请号：US12995353

申请日：2009-05-28

Applicant: James C. Barrow ,  Scott Harrison ,  James Mulhearn ,  Scott Wolkenberg

Inventor： James C. Barrow ,  Scott Harrison ,  James Mulhearn ,  Scott Wolkenberg

IPC: A61K51/00 ,  A61K49/00 ,  A61K49/06 ,  A61K31/4439 ,  A61K31/437 ,  C07D471/04 ,  C07D401/04 ,  C07D401/14 ,  A61K31/497 ,  A61P25/28 ,  A61P25/18

CPC classification number: C07D471/04 ,  C07D401/04 ,  C07D401/14

Abstract: The present invention relates to novel amyloid binding compounds and methods for measuring effects of the compounds, by measuring changes of amyloid plaque level in living patients. More specifically, the present invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study amyloid deposits in brain in vivo to allow diagnosis of Alzheimer's disease. Thus, the present invention relates to use of the novel amyloid binding compounds as a diagnostic. The invention further relates to a method of measuring clinical efficacy of Alzheimer's disease therapeutic agents. Specifically, the present invention relates to novel aryl or heteroaryl substituted indole derivatives, compositions, and therapeutic uses and processes for making such compounds.

Abstract translation: 本发明涉及通过测量活体患者淀粉样斑块水平的变化来测量化合物的效果的新型淀粉样蛋白结合化合物和方法。 更具体地说，本发明涉及在正电子发射断层摄影（PET）成像中使用本发明化合物作为示踪剂的方法，以在体内研究脑中的淀粉样蛋白沉积物以允许诊断阿尔茨海默氏病。 因此，本发明涉及新型淀粉样蛋白结合化合物作为诊断用途。 本发明还涉及测量阿尔茨海默病治疗剂的临床疗效的方法。 具体地，本发明涉及新的芳基或杂芳基取代的吲哚衍生物，组合物，以及用于制备这些化合物的治疗用途和方法。

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.

公开(公告)号：US20110081297A1

公开(公告)日：2011-04-07

申请号：US12995412

申请日：2009-05-28

Applicant: James C. Barrow ,  Scott Harrison ,  James Mulhearn ,  Cyrille Sur ,  David L. Williams ,  Scott Wolkenberg

Inventor： James C. Barrow ,  Scott Harrison ,  James Mulhearn ,  Cyrille Sur ,  David L. Williams ,  Scott Wolkenberg

IPC: A61K49/10 ,  C07D413/04 ,  A61K31/4439 ,  A61P25/28 ,  A61K49/00 ,  A61K49/04 ,  C07D413/10 ,  A61K31/4245 ,  C07D231/12 ,  A61K31/415 ,  C07D471/02 ,  A61K31/437

CPC classification number: C07D231/12 ,  C07D271/06 ,  C07D271/10 ,  C07D403/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  F22B35/001 ,  F22B35/002 ,  F22B37/00 ,  F23C9/00 ,  F23J15/006 ,  F23J15/06 ,  F23L7/007 ,  Y02E20/344 ,  Y02E20/363

Abstract: The present invention relates to novel amyloid binding compounds and methods for measuring effects of the compounds, by measuring changes of amyloid plaque level in living patients. More specifically, the present invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET) imaging to study amyloid deposits in brain in vivo to allow diagnosis of Alzheimer's disease. Thus, the present invention relates to use of the novel amyloid binding compounds as a diagnostic. The invention further relates to a method of measuring clinical efficacy of Alzheimer's disease therapeutic agents. Specifically, the present invention relates to novel aryl or heteroaryl substituted pyrazole derivatives, compositions, and therapeutic uses and processes for making such compounds.

Abstract translation: 本发明涉及通过测量活体患者淀粉样斑块水平的变化来测量化合物的效果的新型淀粉样蛋白结合化合物和方法。 更具体地说，本发明涉及在正电子发射断层摄影（PET）成像中使用本发明化合物作为示踪剂的方法，以在体内研究脑中的淀粉样蛋白沉积物以允许诊断阿尔茨海默氏病。 因此，本发明涉及新型淀粉样蛋白结合化合物作为诊断用途。 本发明还涉及测量阿尔茨海默病治疗剂的临床疗效的方法。 具体地，本发明涉及新的芳基或杂芳基取代的吡唑衍生物，组合物，以及用于制备这些化合物的治疗用途和方法。

公开(公告)号：US09024032B2

公开(公告)日：2015-05-05

申请号：US13582601

申请日：2011-02-28

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

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

IPC: A61K31/44 ,  C07D211/90 ,  C07D213/69 ,  A61K31/4412 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/69 ,  A61K45/06 ,  C07D213/73 ,  C07D213/74 ,  C07D401/10 ,  C07D401/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/10 ,  C07D471/04 ,  C07F5/02 ,  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.

Abstract translation: 本发明涉及作为儿茶酚O-甲基转移酶（COMT）的抑制剂的4-吡啶酮化合物，可用于治疗和预防涉及COMT酶的神经和精神疾病和疾病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及COMT的疾病中的用途。

公开(公告)号：US20130084346A1

公开(公告)日：2013-04-04

申请号：US13582601

申请日：2011-02-28

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

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

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

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：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：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：US09273040B2

公开(公告)日：2016-03-01

申请号：US14353488

申请日：2012-10-26

Applicant: 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

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

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。

公开(公告)号：US08530483B2

公开(公告)日：2013-09-10

申请号：US12995314

申请日：2009-05-28

Applicant: James C. Barrow ,  Scott Harrison ,  James Mulhearn ,  Cyrille Sur ,  David L. Williams ,  Scott Wolkenberg ,  Eric Hostetler

Inventor： James C. Barrow ,  Scott Harrison ,  James Mulhearn ,  Cyrille Sur ,  David L. Williams ,  Scott Wolkenberg ,  Eric Hostetler

IPC: A01N43/90 ,  A01N43/42 ,  A61K31/519 ,  A61K31/44 ,  C07D239/00 ,  C07D471/00 ,  C07D491/00 ,  C07D513/02 ,  C07D515/02 ,  C07D471/02 ,  C07D491/02 ,  C07D498/02

CPC classification number: C07D498/04 ,  C07D519/00

Abstract: The present invention relates to novel amyloid binding compounds of formula (I) and methods for measuring effects of the compounds, by measuring changes of amyloid plaque level in living patients. More specifically, the present invention relates to a method of using the compounds of this invention as tracers in positron emission tomography (PET/) imaging to study amyloid deposits in brain in vivo to allow diagnosis of Alzheimer's disease. Thus, the present invention relates to use of the novel amyloid binding compounds as a diagnostic. The invention further relates to a method of measuring clinical efficacy of Alzheimer's disease therapeutic agents. Specifically, the present invention relates to novel aryl or heteroaryl substituted azabenzoxazole derivatives, compositions, and therapeutic uses and processes for making such compounds, or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, wherein: X is O or S; A and Y independently are N, or CH.

Abstract translation: 本发明涉及式（I）的新型淀粉样蛋白结合化合物和通过测定活体患者淀粉样斑块水平的变化来测定化合物的效果的方法。 更具体地说，本发明涉及使用本发明化合物作为正电子发射断层摄影（PET /）成像中的示踪剂来研究脑中淀粉样蛋白沉积物以允许诊断阿尔茨海默病的方法。 因此，本发明涉及新型淀粉样蛋白结合化合物作为诊断用途。 本发明还涉及测量阿尔茨海默病治疗剂的临床疗效的方法。 具体地，本发明涉及新的芳基或杂芳基取代的氮杂苯并恶唑衍生物，组合物，以及用于制备这些化合物或其药学上可接受的盐，溶剂合物或体内可水解的酯的治疗用途和方法，其中：X是O或S; A和Y独立地为N或CH。