公开(公告)号：US10072003B2

公开(公告)日：2018-09-11

申请号：US15506269

申请日：2015-08-24

Applicant: Merck Sharp & Dohme Corp. ,  Merck Canada Inc.

Inventor： Ashok Arasappan ,  Christopher James Bungard ,  Jessica L. Frie ,  Yongxin Han ,  Scott B. Hoyt ,  Peter J. Manley ,  Robert S. Meissner ,  James J. Perkins ,  Iyassu K. Sebhat ,  Robert R. Wilkening ,  Kenneth J. Leavitt

IPC: C07D471/04

CPC classification number: C07D471/04 ,  A61K31/4375

Abstract: The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, L, X1, X2, and X3, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.

公开(公告)号：US09994587B2

公开(公告)日：2018-06-12

申请号：US15123111

申请日：2015-03-02

Applicant: MERCK CANADA INC.

Inventor： John A. McCauley ,  David Jonathan Bennett ,  Christopher J. Bungard ,  Thomas J. Greshock ,  M. Katharine Holloway ,  Peter D. Williams ,  Christian Beaulieu ,  Sheldon Crane ,  Stephanie Lessard ,  Daniel Mckay ,  Carmela Molinaro ,  Oscar Miguel Moradei ,  Vijayasaradhi Sivalenka ,  Vouy Linh Truong ,  Satyanarayana Tummanapalli

IPC: C07D498/10 ,  C07D265/30 ,  A61K31/5375 ,  C07D413/12 ,  A61K31/5377 ,  C07D417/14 ,  C07D413/14 ,  C07D487/04 ,  C07D471/04 ,  C07D413/06 ,  C07D265/36 ,  A61K31/5386 ,  A61K45/06

CPC classification number: C07D498/10 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/5386 ,  A61K45/06 ,  C07D265/30 ,  C07D265/36 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention is directed to 2,6-morpholine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein Z1, Z2, V1, V2, V3, R6, R6A, and X are defined herein. The invention also relates to methods of using the 2,6-morpholine derivatives of the invention for the inhibition of HV protease, the inhibition of HV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

公开(公告)号：US20170217986A1

公开(公告)日：2017-08-03

申请号：US15123111

申请日：2015-03-02

Applicant: John A. MCCAULEY ,  David Johathan BENNETT ,  Christopher J. BUNGARD ,  Thomas J. GRESHOCK ,  M. Katharine HOLLOWAY ,  Peter D. WILLIAMS ,  Christian BEAULIEU ,  Sheldon CRANE ,  Stephanie LESSARD ,  Daniel MCKAY ,  Carmela MOLINARO ,  Oscar Miguel MORADEI ,  Vijayasaradhi SIVALENKA ,  Vouy Linh TRUONG ,  Satyanarayana TUMMANAPALLI ,  Merck Canada Inc.

Inventor： John A. McCauley ,  David Jonathan Bennett ,  Christopher J. Bungard ,  Thomas J. Greshock ,  M. Katharine Holloway ,  Peter D. Williams ,  Christian Beaulieu ,  Sheldon Crane ,  Stephanie Lessard ,  Daniel Mckay ,  Carmela Molinaro ,  Oscar Miguel Moradei ,  Vijayasaradhi Sivalenka ,  Vouy Linh Truong ,  Satyanarayana Tummanapalli

IPC: C07D498/10 ,  A61K31/5375 ,  C07D413/12 ,  A61K31/5377 ,  C07D417/14 ,  A61K45/06 ,  C07D487/04 ,  C07D471/04 ,  C07D413/06 ,  C07D265/36 ,  A61K31/5386 ,  C07D265/30 ,  C07D413/14

CPC classification number: C07D498/10 ,  A61K31/5375 ,  A61K31/5377 ,  A61K31/5386 ,  A61K45/06 ,  C07D265/30 ,  C07D265/36 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention is directed to 2,6-morpholine derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein Z1, Z2, V1, V2, V3, R6, R6A, and X are defined herein. The invention also relates to methods of using the 2,6-morpholine derivatives of the invention for the inhibition of HV protease, the inhibition of HV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

公开(公告)号：US20160296527A1

公开(公告)日：2016-10-13

申请号：US15104782

申请日：2014-12-17

Applicant: MERCK SHARP & DOHME CORP. ,  MERCK CANADA INC.

Inventor： John A. McCauley ,  Christian Beaulieu ,  David Jonathan Bennett ,  Christopher J. Bungard ,  Sheldon Crane ,  Thomas J. Greshock ,  Katharine M. Holloway ,  Helen Juteau ,  Daniel McKay ,  Carmela Molinaro ,  Oscar Miguel Moradei ,  Christian Nadeau ,  Daniel Simard ,  Satyanarayana Tummanapalli ,  Vouy Linh Truong ,  Karine M. Villeneuve ,  Peter D. Williams

IPC: A61K31/5377 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04 ,  A61K45/06 ,  C07D413/04

CPC classification number: A61K31/5377 ,  A61K45/06 ,  C07D265/30 ,  C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention is directed to 5-heteroarylmorpholine derivatives and their use in the inhibition of HIV protease, the inhibition of HIV replication, the prophylaxis of infection by HIV, the treatment of infection by HIV, and the prophylaxis, treatment, and delay in the onset or progression of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

Abstract translation: 本发明涉及5-杂芳基吗啉衍生物及其用于抑制HIV蛋白酶，HIV复制的抑制，HIV预防感染，HIV感染治疗以及预防，治疗和延迟的用途 艾滋病的发病或进展。 化合物及其盐可以用作药物组合物中的成分，任选与其它抗病毒剂，免疫调节剂，抗生素或疫苗组合使用。

公开(公告)号：US09353066B2

公开(公告)日：2016-05-31

申请号：US14422419

申请日：2013-08-15

Applicant: Merck Sharp & Dohme Corp. ,  Merck Canada Inc.

Inventor： Andrew M. Haidle ,  Jason Burch ,  Daniel Guay ,  Jacques Yves Gauthier ,  Joel Robichaud ,  Jean Francois Fournier ,  John Michael Ellis ,  Matthew Christopher ,  Solomon D. Kattar ,  Graham F. Smith ,  Alan B. Northrup

IPC: C07D239/42 ,  C07D403/12 ,  A61K31/506 ,  A61K31/505 ,  C07D401/12 ,  C07D239/47

CPC classification number: C07D239/42 ,  A61K31/505 ,  A61K31/506 ,  A61K45/06 ,  C07D239/47 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D471/10

Abstract: The invention provides certain substituted phenyl compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, Rcy, and t are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk).

Abstract translation: 本发明提供某些取代的式（I）的苯基化合物或其药学上可接受的盐，其中R 1，R 2，R 3，R 4，Rcy和t如本文所定义。 本发明还提供包含这些化合物的药物组合物，以及使用该化合物治疗由脾脏酪氨酸激酶（Syk）介导的疾病或病症的方法。

公开(公告)号：US20160060255A1

公开(公告)日：2016-03-03

申请号：US14786464

申请日：2014-04-22

Applicant: Neville J. ANTHONY ,  Brain M. ANDERSEN ,  Alan B. NORTHRUP ,  Kaleen K. CHILDERS ,  Anthony FRIO ,  Thomas A. MILLER ,  Yuan LIU ,  Michelle R. MACHACEK ,  Hyun Chong WOO ,  Kerrie B. SPENCER ,  John Michael ELLIS ,  Micheal D. ALTMAN ,  Eric T. ROMEO ,  Daniel GUAY ,  Jonathan GRIMM ,  Marie-Eve LEBRUN ,  Joel S. ROBICHAUD ,  Liping WANG ,  Byron DUBOIS ,  Qiaolin DENG ,  MERICK SHARP & DOHNE CORP. ,  MERCK CANADA INC.

Inventor： Neville J. Anthony ,  Brian M. Andresen ,  Alan B. Northrup ,  Kaleen K. Childers ,  Anthony Donofrio ,  Thomas A. Miller ,  Yuan Liu ,  Michelle R. Machacek ,  Hyun Chong Woo ,  Kerrie B. Spencer ,  John Michael Ellis ,  Michael D. Altman ,  Eric T. Romeo ,  Daniel Guay ,  Jonathan Grimm ,  Marie-Eve Lebrun ,  Joel S. Robichaud ,  Liping Wang ,  Byron DuBois ,  Qiaolin Deng

IPC: C07D417/14 ,  A61K31/53 ,  A61K31/4439 ,  A61K31/501 ,  A61K31/506 ,  A61K31/497

CPC classification number: C07D417/14 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/53 ,  C07D417/12

Abstract: The invention provides certain thiazole-substituted aminoheteroaryl compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein X1, X2, X3, X4, Y1, Y2, Y3, Y4, and R4 are as defined herein. The invention also provides pharmaceutical compositions comprising such compounds, and methods of using the compounds for treating diseases or conditions mediated by Spleen Tyrosine Kinase (Syk).

Abstract translation: 本发明提供式（I）的某些噻唑取代的氨基杂芳基化合物或其药学上可接受的盐，其中X 1，X 2，X 3，X 4，Y 1，Y 2，Y 3，Y 4和R 4如本文所定义。 本发明还提供包含这些化合物的药物组合物，以及使用该化合物治疗由脾脏酪氨酸激酶（Syk）介导的疾病或病症的方法。

公开(公告)号：US20140296136A1

公开(公告)日：2014-10-02

申请号：US14358050

申请日：2012-11-09

Applicant: MERCK SHARP & DOHME CORP. ,  MERCK CANADA INC. ,  ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.R.L.

Inventor： Michael T. Rudd ,  John McCauley ,  Nigel Liverton ,  Christiane Grisé-Bard ,  Marie-Christine Brochu ,  Sylvie Charron ,  Virender Aulakh ,  Benoit Bachand ,  Patrick Beaulieu ,  Helmi Zaghdane ,  Yongxin Han ,  Marco Ferrara ,  Steven Harper ,  Vincenzo Summa ,  Samuel Chackalamannil ,  Srikanth Venkatraman ,  Unmesh Shah ,  Francisco Velazquez

IPC: C07K5/08 ,  A61K31/4745 ,  A61K31/7056 ,  A61K31/5377 ,  A61K38/06 ,  A61K38/00 ,  A61K31/675

CPC classification number: C07K5/08 ,  A61K31/4745 ,  A61K31/5377 ,  A61K31/675 ,  A61K31/7056 ,  A61K38/005 ,  A61K38/06 ,  A61K38/12 ,  A61K38/21 ,  C07K5/0804 ,  C07K5/0808 ,  C07K5/0812 ,  C07K5/0821 ,  A61K2300/00

Abstract: The present invention relates to macrocyclic compounds of formula (I) that are useful as inhibitors of the hepatitis C virus (HCV) NS3 protease, their synthesis, and their use for treating or preventing HCV infections.

Abstract translation: 本发明涉及可用作丙型肝炎病毒（HCV）NS3蛋白酶抑制剂及其合成及其用于治疗或预防HCV感染的用途的式（I）的大环化合物。

公开(公告)号：US20170305902A1

公开(公告)日：2017-10-26

申请号：US15506269

申请日：2015-08-24

Applicant: Merck Sharp & Dohme Corp. ,  Merck Canada Inc.

Inventor： Ashok Arasappan ,  Christopher James Bungard ,  Jessica L. Frie ,  Yongxin Han ,  Scott B. Hoyt ,  Peter J. Manley ,  Robert S. Meissner ,  James J. Perkins ,  Iyassu K. Sebhat ,  Robert R. Wilkening ,  Kenneth J. Leavitt

IPC: C07D471/04

CPC classification number: C07D471/04 ,  A61K31/4375

Abstract: The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, L, X1, X2, and X3, are as defined herein. The compounds of the invention, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions comprising them, are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and may be useful in methods of treating a person in need thereof for diseases or disorders in which the mGluR2-NAM receptor plays a causative role, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders.

公开(公告)号：US09487504B2

公开(公告)日：2016-11-08

申请号：US14409147

申请日：2013-06-18

Applicant: Merck Sharp & Dohme Corp. ,  Merck Canada Inc.

Inventor： Jongwon Lim ,  Michael H. Reutershan ,  John Michael Ellis ,  Kaleen Konrad Childers ,  Anthony Donofrio ,  Michael D. Altman ,  Andrew M. Haidle ,  Anna Zabierek ,  Matthew Christopher ,  Jonathan Grimm ,  Jason Burch ,  Maria Emilia Di Francesco ,  Alessia Petrocchi ,  Christian Beaulieu ,  Vouy Linh Truong ,  Alan B. Northrup ,  Marc Blouin

IPC: C07D403/12 ,  C07D403/14 ,  C07D401/14

CPC classification number: C07D403/12 ,  C07D401/14 ,  C07D403/14

Abstract: The present invention provides novel imidazole analogs of Formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

Abstract translation: 本发明提供了式I的新型咪唑类似物，其是脾脏酪氨酸激酶的有效抑制剂，并且可用于治疗和预防由所述酶介导的疾病，例如哮喘，COPD，类风湿性关节炎和癌症。

公开(公告)号：US20150175575A1

公开(公告)日：2015-06-25

申请号：US14409147

申请日：2013-06-18

Applicant: Merck Sharp & Dohme Corp. ,  Merck Canada Inc.

Inventor： Jongwon Lim ,  Michael H. Reutershan ,  John Michael Ellis ,  Kaleen Konrad Childers ,  Anthony Donofrio ,  Michael D. Altman ,  Andrew M. Haidle ,  Anna Zabierek ,  Matthew Christopher ,  Jonathan Grimm ,  Jason Burch ,  Maria Emilia Di Francesco ,  Alessia Petrocchi ,  Christian Beaulieu ,  Vouy Linh Truong ,  Alan B. Northrup ,  Marc Blouin

IPC: C07D403/12 ,  C07D401/14

CPC classification number: C07D403/12 ,  C07D401/14 ,  C07D403/14

Abstract: The present invention provides novel imidazole analogs of Formula I which are potent inhibitors of spleen tyrosine kinase, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

Abstract translation: 本发明提供了式I的新型咪唑类似物，其是脾脏酪氨酸激酶的有效抑制剂，并且可用于治疗和预防由所述酶介导的疾病，例如哮喘，COPD，类风湿性关节炎和癌症。