公开(公告)号：US20200247754A1

公开(公告)日：2020-08-06

申请号：US16341595

申请日：2017-10-09

Applicant: Michael T. RUDD ,  Zhaoyang MENG ,  Jenny WAI ,  David Jonathan BENNETT ,  Edward J. BRNARDIC ,  Nigel J. LIVERTON ,  Shawn J. STACHEL ,  Yongxin HAN ,  Paul TEMPEST ,  Jiuxiang ZHU ,  Xuewang XU ,  Bin ZHU ,  Merck Sharp & Dohme Corp.

Inventor： Michael T. Rudd ,  Zhaoyang Meng ,  Jenny Wai ,  David Jonathan Bennett ,  Edward J. Brnardic ,  Nigel J. Liverton ,  Shawn J. Stachel ,  Yongxin Han ,  Paul Tempest ,  Jiuxiang Zhu ,  Xuewang Xu ,  Bin Zhu

IPC: C07D221/20 ,  C07D401/12 ,  C07D417/12 ,  C07D405/12 ,  C07D211/22 ,  C07D401/14 ,  C07D417/14

Abstract: In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, L, R4, L1, Q, and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US20200039951A1

公开(公告)日：2020-02-06

申请号：US16341602

申请日：2017-10-09

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael T. Rudd ,  Zhaoyang Meng ,  Jenny Wai ,  David Jonathan Bennett ,  Edward J. Brnardic ,  Nigel J. Liverton ,  Shawn J. Stachel ,  Yongxin Han ,  Paul Tempest ,  Jiuxiang Zhu ,  Xuewang Xu

IPC: C07D401/04 ,  C07D405/14 ,  C07D211/26

Abstract: In its many embodiments, the present invention provides certain substituted N-aryl and N-heteroaryl piperidine compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, L, R4, L1, Q, R5 and R6 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, may be useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US20180327374A1

公开(公告)日：2018-11-15

申请号：US15774157

申请日：2016-11-07

Applicant: Michael T. RUDD ,  Edward J. BRNARDIC ,  Yuntae KIM ,  Robert S. MEISSNER ,  Vanessa RADA ,  Shawn J. STACHEL ,  Celina V. ZERBINATTI ,  Merck Sharp & Dohme Corp.

Inventor： Michael T. Rudd ,  Edward J. Brnardic ,  Yuntae Kim ,  Robert S. Meissner ,  Vanessa L. Rada ,  Shawn J. Stachel ,  Celina V. Zerbinatti

IPC: C07D295/16 ,  C07D243/08 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/08 ,  C07D487/08 ,  C07D513/04 ,  A61P25/28 ,  A61P25/18 ,  A61P25/16 ,  A61P3/10

CPC classification number: C07D295/16 ,  A61K31/496 ,  A61P3/10 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  C07D213/74 ,  C07D213/85 ,  C07D243/08 ,  C07D295/192 ,  C07D295/205 ,  C07D401/04 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/08 ,  C07D487/08 ,  C07D487/18 ,  C07D513/04 ,  C07D515/04

Abstract: In its many embodiments, the present invention provides substituted cyanopyridine containing compounds of the Formula (I): and acceptable salts thereof, wherein R1, R2, R3, R4, R5, X, Y, Q, and the moiety are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US09663506B2

公开(公告)日：2017-05-30

申请号：US15047213

申请日：2016-02-18

Applicant: Merck Sharp & Dohme Corp

Inventor： Christopher James Bungard ,  Antonella Converso ,  Pablo De Leon ,  Barbara Hanney ,  Timothy John Hartingh ,  Jesse Josef Manikowski ,  Peter J. Manley ,  Robert Meissner ,  Zhaoyang Meng ,  James J. Perkins ,  Michael T. Rudd ,  Youheng Shu

IPC: C07D413/14 ,  C07D417/14 ,  C07D401/14 ,  C07D215/48 ,  C07D401/04 ,  C07D401/06 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D471/04 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  C07D491/10

CPC classification number: C07D413/14 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  C07D215/48 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/10

Abstract: The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, including potentially Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

公开(公告)号：US20160158217A1

公开(公告)日：2016-06-09

申请号：US15047224

申请日：2016-02-18

Applicant: Merck Sharp & Dohme Corp

Inventor： Christopher James Bungard ,  Antonella Converso ,  Pablo De Leon ,  Barbara Hanney ,  Timothy John Hartingh ,  Jesse Josef Manikowski ,  Peter J. Manley ,  Robert Meissner ,  Zhaoyang Meng ,  James J. Perkins ,  Michael T. Rudd ,  Youheng Shu

IPC: A61K31/47 ,  A61K31/541 ,  A61K31/506 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/4709 ,  A61K31/5377

CPC classification number: C07D413/14 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  C07D215/48 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/10

Abstract: The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, including potentially Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

Abstract translation: 本发明提供式（I）的喹啉羧酰胺和喹啉腈化合物，其中环A，RQ，-L-，R1，n，R2和R3如本文所定义。 本发明的化合物可用作非竞争性mGluR2拮抗剂或mGluR2负变构调节剂（NAM），以及用于治疗患有（优选人）的mGluR2-NAM受体涉及的疾病或病症的方法，包括 通过向患者施用治疗有效量的本发明化合物或其药学上可接受的盐，可能导致阿尔茨海默氏病，认知障碍，精神分裂症和其他情绪障碍，疼痛障碍和睡眠障碍。 本发明还涉及包含本发明化合物或其药学上可接受的盐（任选与一种或多种另外的活性成分组合）和药学上可接受的载体的药物组合物，以及该化合物和药物组合物的用途 的本发明治疗这些疾病。

公开(公告)号：US20190000824A1

公开(公告)日：2019-01-03

申请号：US16062500

申请日：2016-12-19

Applicant: Merck Sharp & Dohme Corp.

Inventor： John J. Acton, III ,  Jianming Bao ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Michael T. Rudd ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Jenny Miu-Chun Wai

IPC: A61K31/4439 ,  A61K31/437 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28

CPC classification number: A61K31/4439 ,  A61K31/437 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28 ,  C07D401/14 ,  C07D405/14 ,  C07D471/04

Abstract: The present invention is directed to 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 5 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：US09636337B2

公开(公告)日：2017-05-02

申请号：US15047224

申请日：2016-02-18

Applicant: Merck Sharp & Dohme Corp

Inventor： Christopher James Bungard ,  Antonella Converso ,  Pablo De Leon ,  Barbara Hanney ,  Timothy John Hartingh ,  Jesse Josef Manikowski ,  Peter J. Manley ,  Robert Meissner ,  Zhaoyang Meng ,  James J. Perkins ,  Michael T. Rudd ,  Youheng Shu

IPC: A61K31/47 ,  A61K31/506 ,  A61K31/4985 ,  A61K31/496 ,  A61K31/4709 ,  A61K31/541 ,  A61K31/5377 ,  C07D401/14 ,  C07D413/14 ,  C07D215/48 ,  C07D401/04 ,  C07D401/06 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/10

CPC classification number: C07D413/14 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  C07D215/48 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14 ,  C07D409/04 ,  C07D413/06 ,  C07D417/06 ,  C07D417/14 ,  C07D471/04 ,  C07D491/10

Abstract: The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, including potentially Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

公开(公告)号：US11655216B2

公开(公告)日：2023-05-23

申请号：US16341595

申请日：2017-10-09

Applicant: Merck Sharp & Dohme Corp. ,  Michael T. Rudd ,  Zhaoyang Meng ,  Jenny Wai ,  David Jonathan Bennett ,  Edward J. Brnardic ,  Nigel J. Liverton ,  Shawn J. Stachel ,  Yongxin Han ,  Paul Tempest ,  Jiuxiang Zhu ,  Xuewang Xu ,  Bin Zhu

Inventor： Michael T. Rudd ,  Zhaoyang Meng ,  Jenny Wai ,  David Jonathan Bennett ,  Edward J. Brnardic ,  Nigel J. Liverton ,  Shawn J. Stachel ,  Yongxin Han ,  Paul Tempest ,  Jiuxiang Zhu ,  Xuewang Xu ,  Bin Zhu

IPC: C07D221/20 ,  C07D401/12 ,  C07D417/12 ,  C07D405/12 ,  C07D211/22 ,  C07D401/14 ,  C07D417/14

CPC classification number: C07D221/20 ,  C07D211/22 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D417/12 ,  C07D417/14

Abstract: In its many embodiments, the present invention provides certain substituted aryl and heteroaryl ether compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, L, R4, L1, Q, and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US10894775B2

公开(公告)日：2021-01-19

申请号：US16341591

申请日：2017-10-09

Applicant: Merck Sharp & Dohme Corp. ,  Michael T. Rudd ,  Zhaoyang Meng ,  Jenny Wai ,  David Jonathan Bennett ,  Edward J. Brnardic ,  Nigel J. Liverton ,  Shawn J. Stachel ,  Yongxin Han ,  Paul Tempest ,  Jiuxiang Zhu ,  Xuewang Xu ,  Bin Zhu ,  Chuanman Huang

Inventor： Michael T. Rudd ,  Zhaoyang Meng ,  Jenny Wai ,  David Jonathan Bennett ,  Edward J. Brnardic ,  Nigel J. Liverton ,  Shawn J. Stachel ,  Yongxin Han ,  Paul Tempest ,  Jiuxiang Zhu ,  Xuewang Xu ,  Bin Zhu ,  Chuanman Huang

IPC: C07D221/20 ,  C07D211/16 ,  C07D211/96

Abstract: In its many embodiments, the present invention provides certain piperidine compounds of the Formula (I): and pharmaceutically acceptable salts thereof, wherein X, Y, R1, R2, R3, L, R4, L1, Q, and R5 are as defined herein. The novel compounds of the invention, and pharmaceutically acceptable compositions comprising a compound thereof, are useful as Liver X-β receptor (LXRβ) agonists, and may be useful for treating or preventing pathologies related thereto. Such pathologies include, but are not limited to, inflammatory diseases and diseases characterized by defects in cholesterol and lipid metabolism, such as Alzheimer's disease.

公开(公告)号：US20200069671A1

公开(公告)日：2020-03-05

申请号：US16674546

申请日：2019-11-05

Applicant: Merck Sharp & Dohme Corp.

Inventor： John J. Acton, III ,  Jianming Bao ,  Melissa Egbertson ,  Xiaolei Gao ,  Scott T. Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, JR. ,  Zhaoyang Meng ,  Michael T. Rudd ,  Oleg B. Selyutin ,  David M. Tellers ,  Ling Tong ,  Jenny Miu-Chun Wai

IPC: A61K31/4439 ,  A61P25/28 ,  A61P25/18 ,  A61P25/16 ,  A61K31/437 ,  C07D401/14 ,  C07D405/14 ,  C07D471/04

Abstract: The present invention is directed to 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.