公开(公告)号：US20210009608A1

公开(公告)日：2021-01-14

申请号：US17040192

申请日：2019-03-28

申请人： Michael D. ALTMAN ,  Brandon D. CASH ,  Jared N. CUMMING ,  Duane E. DEMONG ,  Andrew M. HAIDLE ,  James P. JEWELL ,  Matthew A. LARSEN ,  Min LU ,  Ryan D. OTTE ,  Brandon M. TAOKA ,  Benjamin Wesley TROTTER ,  Quang T, TRUONG ,  Merck Sharp & Dohme Corp.

发明人： Michael D. Altman ,  Brandon D. Cash ,  Jared N. Cumming ,  Duane E. DeMong ,  Andrew M. Haidle ,  James P. Jewell ,  Matthew A. Larsen ,  Min Lu ,  Ryan D. Otte ,  Brandon M. Taoka ,  Benjamin Wesley Trotter ,  Quang T. Truong

IPC分类号： C07D513/04 ,  C07D495/04 ,  A61P37/04

摘要： Compounds of general formula (I), and their pharmaceutically acceptable salts, wherein R1, R2, R3, R5, R6, R8, R9, A, X1, X2, and X3 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are compositions comprising such compounds, processes for the synthesis of such compounds, and to uses of such compounds, including administration of such compounds to induce immune response, to induce STING-dependent type I interferon production, and/or to treat a cell proliferation disorder, such as cancer.

公开(公告)号：US11702430B2

公开(公告)日：2023-07-18

申请号：US17040192

申请日：2019-03-28

申请人： Merck Sharp & Dohme LLC ,  Michael D. Altman ,  Brandon D. Cash ,  Jared N. Cumming ,  Duane E. DeMong ,  Andrew M. Haidle ,  James P. Jewell ,  Matthew A. Larsen ,  Min Lu ,  Ryan D. Otte ,  Brandon M. Taoka ,  Benjamin Wesley Trotter ,  Quang T. Truong

发明人： Michael D. Altman ,  Brandon D. Cash ,  Jared N. Cumming ,  Duane E. DeMong ,  Andrew M. Haidle ,  James P. Jewell ,  Matthew A. Larsen ,  Min Lu ,  Ryan D. Otte ,  Brandon M. Taoka ,  Benjamin Wesley Trotter ,  Quang T. Truong

IPC分类号： C07D513/04 ,  C07D495/04 ,  C07D277/64 ,  A61P37/04 ,  A61P35/00

CPC分类号： C07D513/04 ,  A61P37/04 ,  C07D495/04

摘要： Compounds of general formula (I), and their pharmaceutically acceptable salts, wherein R1, R2, R3, R5, R6, R8, R9, A, X1, X2, and X3 are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are compositions comprising such compounds, processes for the synthesis of such compounds, and to uses of such compounds, including administration of such compounds to induce immune response, to induce STING-dependent type I interferon production, and/or to treat a cell proliferation disorder, such as cancer.

公开(公告)号：US20150299125A1

公开(公告)日：2015-10-22

申请号：US14440517

申请日：2013-11-04

申请人： Andrew M. HAIDLE ,  Brandon CASH ,  James P. JEWELL ,  Kerrie SPENCER ,  Michael D. ALTMAN ,  Ryan D. OTTE ,  Alan B. NORTHRUP ,  MERCK SHARP & DOHME CORP.

发明人： Andrew M. Haidle ,  Brandon Cash ,  James P. Jewell ,  Kerrie Spencer ,  Michael D. Altman ,  Ryan D. Otte ,  Alan B. Northrup

IPC分类号： C07D213/74 ,  C07D401/14 ,  C07D405/14

CPC分类号： C07D213/74 ,  C07D401/14 ,  C07D405/14 ,  C07D451/10 ,  C07H13/08

摘要： The present invention provides compounds of Formula (I), which are prodrugs of trans-4-[(1R)-(6-{[4-(difluoromethyl)pyridin-2-yl]amino}-4-methyl-2,3′-bipyridin-6′-yl)-1-hydroxyethyl]cyclohexanecarboxylic acid, a potent inhibitor of Syk. The compounds are useful in the treatment and prevention of diseases mediated by the enzyme, such as asthma, COPD, rheumatoid arthritis and cancer.

摘要翻译： 本发明提供式（I）化合物，其为反式-4 - [（1R） - （6 - {[4-（二氟甲基）吡啶-2-基]氨基} -4-甲基-2,3 “ - 联吡啶-6'-基）-1-羟乙基]环己烷羧酸，Syk的有效抑制剂。 该化合物可用于治疗和预防由酶介导的疾病，例如哮喘，COPD，类风湿性关节炎和癌症。

公开(公告)号：US08551984B2

公开(公告)日：2013-10-08

申请号：US12968608

申请日：2010-12-15

申请人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Michael H. Reutershan ,  Eric Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hua Zhou

发明人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Michael H. Reutershan ,  Eric Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hua Zhou

IPC分类号： C07D417/12 ,  A61K31/497

CPC分类号： C07D417/12 ,  C07D417/14 ,  C07D451/06 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D491/08 ,  C07D495/04 ,  C07F9/65583

摘要： The present invention provides novel pyrimidine amines 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 and rheumatoid arthritis.

摘要翻译： 本发明提供了新颖的式（I）嘧啶胺，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和类风湿性关节炎。

公开(公告)号：US20140243290A1

公开(公告)日：2014-08-28

申请号：US14255480

申请日：2014-04-17

申请人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Sathesh Bhat ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Jean-Francois Fournier ,  Jacques Yves Gauthier ,  Jonathan Grimm ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon D. Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Matthew L. Maddess ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Alessia Petrocchi ,  Michael H. Reutershan ,  Joel S. Robichaud ,  Eric T. Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hyun Chong Woo ,  Hua Zhou

发明人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Sathesh Bhat ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Jean-Francois Fournier ,  Jacques Yves Gauthier ,  Jonathan Grimm ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon D. Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Matthew L. Maddess ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Alessia Petrocchi ,  Michael H. Reutershan ,  Joel S. Robichaud ,  Eric T. Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hyun Chong Woo ,  Hua Zhou

IPC分类号： C07D417/12 ,  C07D495/04 ,  C07D451/06 ,  C07F9/6558 ,  C07D471/08 ,  C07D487/04 ,  C07D471/04 ,  C07D417/14 ,  C07D491/08

CPC分类号： C07D417/12 ,  C07D417/14 ,  C07D451/06 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D491/08 ,  C07D495/04 ,  C07F9/65583

摘要： The present invention provides novel pyrimidine amines 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 and rheumatoid arthritis.

摘要翻译： 本发明提供了新颖的式（I）嘧啶胺，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和类风湿性关节炎。

公开(公告)号：US20120277192A1

公开(公告)日：2012-11-01

申请号：US13516455

申请日：2010-12-15

申请人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Sathesh Bhat ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Jean-Francois Fournier ,  Jacques Yves Gauthier ,  Jonathan Grimm ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Matthew L. Maddess ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Alessia Petrocchi ,  Michael H. Reutershan ,  Joel S. Robichaud ,  Eric Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hyun Chong Woo ,  Hua Zhou

发明人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Sathesh Bhat ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Jean-Francois Fournier ,  Jacques Yves Gauthier ,  Jonathan Grimm ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Matthew L. Maddess ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Alessia Petrocchi ,  Michael H. Reutershan ,  Joel S. Robichaud ,  Eric Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hyun Chong Woo ,  Hua Zhou

IPC分类号： A61K31/506 ,  A61K31/55 ,  A61K31/554 ,  A61K31/551 ,  A61P35/00 ,  C07D417/14 ,  C07F9/6539 ,  C07D417/12 ,  A61P19/02 ,  A61P11/06 ,  A61K31/675 ,  A61K31/5377

CPC分类号： C07D417/12 ,  C07D417/14 ,  C07D451/06 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D491/08 ,  C07D495/04 ,  C07F9/65583

摘要： The present invention provides novel pyrimidine amines 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 and rheumatoid arthritis.

公开(公告)号：US20110245205A1

公开(公告)日：2011-10-06

申请号：US12968608

申请日：2010-12-15

申请人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Sathesh Bhat ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Jean-Francois Fournier ,  Jacques Yves Gauthier ,  Jonathan Grimm ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Matthew L. Maddess ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Alessia Petrocchi ,  Michael H. Reutershan ,  Joel S. Robichaud ,  Eric Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hyun Chong Woo ,  Hua Zhou

发明人： Michael D. Altman ,  Brian M. Andresen ,  Kenneth L. Arrington ,  Sathesh Bhat ,  Jason Burch ,  Kaleen Konrad Childers ,  Bernard Cote ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Kristina Dupont-Gaudet ,  John Michael Ellis ,  Christian Fischer ,  Jean-Francois Fournier ,  Jacques Yves Gauthier ,  Jonathan Grimm ,  Daniel Guay ,  David Joseph Guerin ,  Andrew M. Haidle ,  Solomon Kattar ,  Sandra Lee Knowles ,  Chaomin Li ,  Jongwon Lim ,  Michelle R. Machacek ,  Matthew L. Maddess ,  Alan B. Northrup ,  Brendan M. O'Boyle ,  Ryan D. Otte ,  Alessia Petrocchi ,  Michael H. Reutershan ,  Joel S. Robichaud ,  Eric Romeo ,  Adam J. Schell ,  Tony Siu ,  Kerrie B. Spencer ,  Brandon M. Taoka ,  B. Wesley Trotter ,  Hyun Chong Woo ,  Hua Zhou

IPC分类号： A61K31/675 ,  C07D417/14 ,  A61K31/55 ,  C07D417/12 ,  A61K31/506 ,  C07F9/6558 ,  A61K31/397 ,  A61K31/551 ,  A61K31/553 ,  A61K31/541 ,  C07D413/14 ,  A61K31/5377 ,  A61P11/06 ,  A61P35/00 ,  A61P19/02

CPC分类号： C07D417/12 ,  C07D417/14 ,  C07D451/06 ,  C07D471/04 ,  C07D471/08 ,  C07D487/04 ,  C07D491/08 ,  C07D495/04 ,  C07F9/65583

摘要： The present invention provides novel pyrimidine amines 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 and rheumatoid arthritis.

摘要翻译： 本发明提供了新颖的式（I）嘧啶胺，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和类风湿性关节炎。

公开(公告)号：US09216173B2

公开(公告)日：2015-12-22

申请号：US14349551

申请日：2012-10-01

申请人： Michael D. Altman ,  Corey E. Bienstock ,  John W. Butcher ,  Kaleen Konrad Childers ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  John Michael Ellis ,  Christian Fischer ,  Andrew M. Haidle ,  James P. Jewell ,  Sandra Lee Knowles ,  Alan B. Northrup ,  Ryan D. Otte ,  Scott L. Peterson ,  Graham Frank Smith

发明人： Michael D. Altman ,  Corey E. Bienstock ,  John W. Butcher ,  Kaleen Konrad Childers ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  John Michael Ellis ,  Christian Fischer ,  Andrew M. Haidle ,  James P. Jewell ,  Sandra Lee Knowles ,  Alan B. Northrup ,  Ryan D. Otte ,  Scott L. Peterson ,  Graham Frank Smith

IPC分类号： C07D213/73 ,  A61K31/4439 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D213/81 ,  C07D401/12 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/04 ,  A61K31/444 ,  A61K31/496 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5377

CPC分类号： A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5377 ,  C07D213/81 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/04

摘要： The invention provides certain 2-pyridyl carboxamide-containing compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein A and B 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) kinase.

摘要翻译： 本发明提供了具有式（I）的某些含2-吡啶甲酰胺的化合物或其药学上可接受的盐，其中A和B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）激酶介导的疾病或病症的方法。

公开(公告)号：US09145391B2

公开(公告)日：2015-09-29

申请号：US14116199

申请日：2012-05-04

申请人： Denis Deschenes ,  Michael D. Altman ,  John Michael Ellis ,  Christian Fischer ,  Andrew M. Haidle ,  Solomon D. Kattar ,  Alan B. Northrup ,  Adam J. Schell ,  Graham F. Smith ,  Brandon M. Taoka ,  Corey Bienstock ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Scott Peterson ,  Kerrie B. Spencer ,  James Patrick Jewell ,  Amjad Ali ,  David Jonathan Bennett ,  Qun Dang ,  John Wai

发明人： Denis Deschenes ,  Michael D. Altman ,  John Michael Ellis ,  Christian Fischer ,  Andrew M. Haidle ,  Solomon D. Kattar ,  Alan B. Northrup ,  Adam J. Schell ,  Graham F. Smith ,  Brandon M. Taoka ,  Corey Bienstock ,  Maria Emilia Di Francesco ,  Anthony Donofrio ,  Scott Peterson ,  Kerrie B. Spencer ,  James Patrick Jewell ,  Amjad Ali ,  David Jonathan Bennett ,  Qun Dang ,  John Wai

IPC分类号： C07D213/73 ,  C07D401/14 ,  C07D401/12 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04

CPC分类号： C07D401/14 ,  C07D401/12 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04

摘要： The present invention provides novel pyrimidine amines of formula I which are potent inhibitors of spleen tyrosine kinase, or are prodrugs thereof, and are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD and rheumatoid arthritis and cancer.

摘要翻译： 本发明提供了式I的新型嘧啶胺，其是脾脏酪氨酸激酶的有效抑制剂，或其前药，并且可用于治疗和预防由所述酶介导的疾病，例如哮喘，COPD和类风湿性关节炎和癌症。

公开(公告)号：US09586931B2

公开(公告)日：2017-03-07

申请号：US14431895

申请日：2013-09-24

申请人： Michelle R. Machacek ,  Eric T. Romeo ,  Solomon D. Kattar ,  Matthew Christopher ,  Michael D. Altman ,  Alan B. Northrup ,  John Michael Ellis ,  Brendan O'Boyle ,  Anthony Donofrio ,  Jonathan Grimm ,  Michael H. Reutershan ,  Kaleen Konrad Childers ,  Ryan D. Otte ,  Brandon Cash ,  Yves Ducharme ,  Andrew M. Haidle ,  Kerrie Spencer ,  Dilrukshi Vitharana ,  Lingyun Wu ,  Li Zhang ,  Peng Zhang ,  Christian Beaulieu ,  Daniel Guay

发明人： Michelle R. Machacek ,  Eric T. Romeo ,  Solomon D. Kattar ,  Matthew Christopher ,  Michael D. Altman ,  Alan B. Northrup ,  John Michael Ellis ,  Brendan O'Boyle ,  Anthony Donofrio ,  Jonathan Grimm ,  Michael H. Reutershan ,  Kaleen Konrad Childers ,  Ryan D. Otte ,  Brandon Cash ,  Yves Ducharme ,  Andrew M. Haidle ,  Kerrie Spencer ,  Dilrukshi Vitharana ,  Lingyun Wu ,  Li Zhang ,  Peng Zhang ,  Christian Beaulieu ,  Daniel Guay

IPC分类号： A61K9/10 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D498/04 ,  C07D413/14 ,  C07D239/42 ,  A61K9/00 ,  A61K9/20 ,  A61K9/48 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D471/04

CPC分类号： C07D401/14 ,  A61K9/0019 ,  A61K9/0073 ,  A61K9/0075 ,  A61K9/10 ,  A61K9/2027 ,  A61K9/4858 ,  C07D239/42 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D498/04

摘要： Provided are triazole derivatives of Formula I which are potent inhibitors of spleen tyrosine kinase and pharmaceutical composition. The triazole derivatives are useful in the treatment and prevention of diseases mediated by said enzyme, such as asthma, COPD, rheumatoid arthritis, and cancer.

摘要翻译： 提供式I的三唑衍生物，其是脾脏酪氨酸激酶和药物组合物的有效抑制剂。 三唑衍生物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。