公开(公告)号：US10647727B2

公开(公告)日：2020-05-12

申请号：US15579115

申请日：2016-06-20

Applicant: Merck Sharp & Dohme Corp. ,  Gregori J. Morriello ,  Michael P. Dwyer ,  Lehua Chang ,  Yili Chen ,  Ming Wang ,  Ashley Forster ,  Richard Berger ,  Kausik K. Nanda ,  Jamie L. Bunda ,  William D. Shipe

Inventor： Gregori J. Morriello ,  Lehua Chang ,  Ashley Forster ,  Richard Berger ,  Kausik K. Nanda ,  William D. Shipe

IPC: C07D487/04 ,  C07D498/04 ,  C07D473/34 ,  A61P25/06 ,  A61P25/28 ,  A61P25/18 ,  A61P25/16

Abstract: The present invention is directed to pyrimidine carboxamide compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

公开(公告)号：US08178667B2

公开(公告)日：2012-05-15

申请号：US12308929

申请日：2007-06-27

Applicant: Craig Lindsley ,  William D. Shipe ,  Feng Yang ,  Jaime Lynn Bunda

Inventor： Craig Lindsley ,  William D. Shipe ,  Feng Yang ,  Jaime Lynn Bunda

IPC: C07D401/10 ,  C07D401/14 ,  C07D413/14

CPC classification number: C07D401/10 ,  C07D215/56 ,  C07D405/10 ,  C07D417/10

Abstract: The present invention is directed to benzyl-substituted quinolone compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of diseases in which the M1 receptor is involved.

Abstract translation: 本发明涉及通式（I）的苄基取代喹诺酮化合物，它是M1受体阳性变构调节剂，可用于治疗涉及M1受体的疾病，例如阿尔茨海默病，疼痛或睡眠障碍 。 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治疗涉及M1受体的疾病中的用途。

公开(公告)号：US20110077220A1

公开(公告)日：2011-03-31

申请号：US12990014

申请日：2009-04-23

Applicant: Scott D. Kuduk ,  Christina Ng Di Marco ,  William D. Shipe

Inventor： Scott D. Kuduk ,  Christina Ng Di Marco ,  William D. Shipe

IPC: A61K31/695 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14 ,  C07D409/14 ,  C07D401/06 ,  C07D407/14 ,  A61K31/4709 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/4725 ,  A61K31/506 ,  A61K31/501 ,  A61K31/541 ,  A61P25/28 ,  A61P25/18 ,  A61P25/20 ,  A61P25/04

CPC classification number: C07D401/14 ,  C07D401/06 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention is directed to compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

Abstract translation: 本发明涉及作为M1受体阳性变构调节剂的式（I）化合物，其可用于治疗涉及M1受体的疾病，例如阿尔茨海默氏病，精神分裂症，疼痛或睡眠障碍。 本发明还涉及包含该化合物的药物组合物，以及该化合物和组合物在治疗由M1受体介导的疾病中的用途。

公开(公告)号：US20180134712A1

公开(公告)日：2018-05-17

申请号：US15574411

申请日：2016-05-24

Applicant: Dong-Ming SHEN ,  Michael P. DWYER ,  Christopher J. SINZ ,  Deping WANG ,  Shawn J. STACHEL ,  Daniel V. PAONE ,  Ashley FORSTER ,  Richard BERGER ,  William D. SHIPE ,  Yili CHEN ,  Yimin QIAN ,  Shimin XU ,  Chunmei HU ,  Jianmin FU ,  Zhigang GUO ,  Haitang LI ,  Yingjian BO ,  Merck Sharp & Dohme Corp. ,  MSD R & D (China) Co., LTD.

Inventor： Dong-Ming Shen ,  Michael P. Dwyer ,  Christopher J. Sinz ,  Deping Wang ,  Shawn J. Stachel ,  Daniel V. Paone ,  Ashley Forster ,  Richard Berger ,  Yilli Chen ,  Yimin Qian ,  Shimin Xu ,  Chunmel Hu ,  William D. Shipe ,  Jianmin Fu ,  Zhigang Guo ,  HAITANG LI ,  Yingjian Bo

IPC: C07D487/04 ,  A61P25/18 ,  A61P25/00 ,  A61P25/14 ,  A61P25/28 ,  A61P25/16

CPC classification number: C07D487/04 ,  A61K31/519 ,  A61P25/00 ,  A61P25/14 ,  A61P25/16 ,  A61P25/18 ,  A61P25/28

Abstract: The present invention is directed to 6-alkyl dihydropyrazolopyrimidinone compounds of formula (I) which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypo-function or basal ganglia dysfunction.

公开(公告)号：US08389545B2

公开(公告)日：2013-03-05

申请号：US11920717

申请日：2006-12-04

Applicant: William D. Shipe ,  Craig Lindsley ,  David Hallett

Inventor： William D. Shipe ,  Craig Lindsley ,  David Hallett

IPC: A61K31/47 ,  A61P25/00 ,  A61P25/28 ,  C07D215/56

CPC classification number: C07D215/56 ,  C07D215/233 ,  C07D405/06 ,  H04J3/0661 ,  H04L63/123 ,  H04L63/1458

Abstract: The present invention is directed to quinolone compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, pain or sleep disorders, and to novel M1 receptor positive allosteric modulator compounds of formulae (II) to (VIII). The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases in which the M1 receptor is involved.

Abstract translation: 本发明涉及作为M1受体阳性变构调节剂的通式（I）的喹诺酮化合物，其可用于治疗涉及M1受体的疾病，例如阿尔茨海默氏病，疼痛或睡眠障碍，以及 式（II）至（VIII）的新型M1受体正变构调节剂化合物。 本发明还涉及包含该化合物的药物组合物，以及该化合物和组合物在治疗涉及M1受体的疾病中的用途。

公开(公告)号：US20100317692A1

公开(公告)日：2010-12-16

申请号：US11920717

申请日：2006-02-06

Applicant: William D. Shipe ,  Craig Lindsley ,  David Hallett

Inventor： William D. Shipe ,  Craig Lindsley ,  David Hallett

IPC: A61K31/47 ,  C07D215/56 ,  A61P25/28 ,  A61P25/00

CPC classification number: C07D215/56 ,  C07D215/233 ,  C07D405/06 ,  H04J3/0661 ,  H04L63/123 ,  H04L63/1458

Abstract: The present invention is directed to quinolone compounds of general formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, pain or sleep disorders, and to novel M1 receptor positive allosteric modulator compounds of formulae (II) to (VIII). The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases in which the M1 receptor is involved.

Abstract translation: 本发明涉及作为M1受体阳性变构调节剂的通式（I）的喹诺酮化合物，其可用于治疗涉及M1受体的疾病，例如阿尔茨海默氏病，疼痛或睡眠障碍，以及 式（II）至（VIII）的新型M1受体正变构调节剂化合物。 本发明还涉及包含该化合物的药物组合物，以及该化合物和组合物在治疗涉及M1受体的疾病中的用途。

公开(公告)号：US20100222387A1

公开(公告)日：2010-09-02

申请号：US11922390

申请日：2006-06-21

Applicant: James C. Barrow ,  Craig W. Lindsley ,  William D. Shipe ,  Zhi-Qiang Yang

Inventor： James C. Barrow ,  Craig W. Lindsley ,  William D. Shipe ,  Zhi-Qiang Yang

IPC: A61K31/4545 ,  C07D211/14 ,  A61K31/445 ,  C07D401/06 ,  A61P25/02 ,  A61P25/16 ,  A61P25/28 ,  A61P25/20 ,  A61P25/22 ,  A61P25/00 ,  A61K31/4523 ,  C07D413/06

CPC classification number: C07D211/38 ,  C07D405/06 ,  C07D413/06

Abstract: The present invention is directed to 3-fluoro-piperidine compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

Abstract translation: 本发明涉及作为T型钙通道拮抗剂的3-氟哌啶化合物，其可用于治疗或预防其中涉及T型钙通道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T型钙通道的疾病中的用途。

公开(公告)号：US08501773B2

公开(公告)日：2013-08-06

申请号：US11922399

申请日：2006-06-28

Applicant: James C. Barrow ,  Craig W. Lindsley ,  William D. Shipe ,  Zhiqiang Yang ,  David Wisnoski

Inventor： James C. Barrow ,  Craig W. Lindsley ,  William D. Shipe ,  Zhiqiang Yang ,  David Wisnoski

IPC: A01N43/42 ,  A01N43/40 ,  A61K31/47 ,  A61K31/445 ,  C07D211/00 ,  C07D295/00 ,  C07D211/08 ,  C07D401/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00 ,  C07D413/00 ,  C07D417/00 ,  C07D419/00 ,  C07D421/00

CPC classification number: C07D211/38

Abstract: The present invention is directed to 4-fluoro-piperidine compounds which are antagonists of T-type calcium channels, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which T-type calcium channels are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which T-type calcium channels are involved.

Abstract translation: 本发明涉及作为T型钙通道拮抗剂的4-氟哌啶化合物，其可用于治疗或预防涉及T型钙通道的神经和精神疾病及疾病。 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T型钙通道的疾病中的用途。

公开(公告)号：US20200262826A1

公开(公告)日：2020-08-20

申请号：US16646616

申请日：2018-09-14

Applicant: Ian M. BELL ,  Brendan M. CROWLEY ,  Peter J. MANLEY ,  William D. SHIPE ,  Merck Sharp & Dohme Corp.

Inventor： Ian M. Bell ,  Brendan M. Crowley ,  Peter J. Manley ,  William D. Shipe

IPC: C07D413/08 ,  C07D413/14 ,  C07D417/08 ,  C07D417/14 ,  A61P25/28 ,  A61P25/16 ,  A61P25/18

Abstract: The present disclosure relates to compounds of formula I that are useful as modulators of 7 nAChR, compositions comprising such compounds, and the use of such compounds for preventing, treating, or ameliorating disease, particularly disorders of the central nervous system such as cognitive impairments in Alzheimer's disease, Parkinson's disease, and schizophrenia, as well as for L-DOPA induced-dyskinesia and inflammation (I).

公开(公告)号：US08785467B2

公开(公告)日：2014-07-22

申请号：US13820648

申请日：2011-09-26

Applicant: Christopher D. Cox ,  Izzat T. Raheem ,  William D. Shipe ,  Cory R. Theberge

Inventor： Christopher D. Cox ,  Izzat T. Raheem ,  William D. Shipe ,  Cory R. Theberge

IPC: A01N43/54 ,  A61K31/505 ,  A61K31/506 ,  C07D239/30 ,  C07D239/48 ,  C07D239/52 ,  C07D239/56

CPC classification number: A61K31/505 ,  A61K31/506 ,  A61K31/513 ,  C07D239/30 ,  C07D239/48 ,  C07D239/52 ,  C07D239/56 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D513/04

Abstract: The present invention is directed to 2-alkoxy pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

Abstract translation: 本发明涉及可用作治疗与磷酸二酯酶10（PDE10）相关的中枢神经系统疾病的治疗剂的2-烷氧基嘧啶化合物。 本发明还涉及这些化合物用于治疗神经和精神疾病如精神分裂症，精神病或亨廷顿病以及与纹状体功能减退或基底神经节功能障碍相关的疾病的用途。