公开(公告)号：US20220363707A1

公开(公告)日：2022-11-17

申请号：US17266521

申请日：2019-08-05

申请人： Merck Sharp & Dohme Corp. ,  MSD International GmbH

发明人： Michelle Machacek ,  David Witter ,  Craig Gibeau ,  Chunhui Huang ,  Shuhei Kawamura ,  David L. Sloman ,  Phieng Siliphaivanh ,  Ryan Quiroz ,  Murray Wan ,  Sebastian Schneider ,  Charles S. Yeung ,  Michael H. Reutershan ,  Timothy J. Henderson ,  Jean-Laurent Paparin ,  Houcine Rahali ,  Jonathan M. E. Hughes ,  Sulagna Sanyal ,  Yingchun Ye ,  David A. Candito ,  Patrick S. Fier ,  Steven M. Silverman

IPC分类号： C07H19/14 ,  C07D487/04 ,  A61P35/00

摘要： The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.

公开(公告)号：US10793557B2

公开(公告)日：2020-10-06

申请号：US16372103

申请日：2019-04-01

申请人： Merck Sharp & Dohme Corp.

发明人： Michael D. Altman ,  Brandon D. Cash ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  Duane E. DeMong ,  Andrew Marc Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Matthew A. Larsen ,  Jongwon Lim ,  Min Lu ,  Ryan D. Otte ,  Benjamin Wesley Trotter

IPC分类号： C07D409/12 ,  C07D417/10 ,  C07D498/04 ,  C07D495/04 ,  C07D277/64 ,  C07D417/12 ,  C07D333/56 ,  A61P35/00

摘要： Compounds of general formula (I), of general formula (II), of general formula (III), of general formula (IV), of general formula (V), of general formula (VI), and their pharmaceutically acceptable salts, wherein all variables 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：US20180230178A1

公开(公告)日：2018-08-16

申请号：US15752144

申请日：2016-08-11

申请人： Michael D. ALTMAN ,  Brian ANDRESEN ,  Wonsuk CHANG ,  Matthew Lloyd CHILDERS ,  Jared N. CUMMING ,  Andrew Marc HAIDLE ,  Timothy J. HENDERSON ,  James P. JEWELL ,  Min LU ,  Alan B. NORTHRUP ,  Ryan D. OTTE ,  Tony SIU ,  Benjamin Wesley TROTTER ,  Quang T TRUONG ,  Merck Sharp & Dohme Corp.

发明人： Michael D. Altman ,  Brian Andresen ,  Wonsuk Chang ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  Andrew Marc Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Min Lu ,  Alan B. Northrup ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Quang T. Truong

IPC分类号： C07H21/04 ,  C07H21/02 ,  C07H19/23 ,  C07H19/20 ,  A61P35/00

摘要： A class of polycyclic compounds of general formula (II), of general formula (II′), or of general formula (II″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3a, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US10981902B2

公开(公告)日：2021-04-20

申请号：US16621943

申请日：2018-06-22

申请人： Merck Sharp & Dohme Corp. ,  MERCK R&D (CHINA) CO., LTD.

发明人： Jianming Bao ,  Timothy J. Henderson ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Meng Na ,  Michael T. Rudd ,  David M. Tellers ,  Ling Tong

IPC分类号： C07D413/14 ,  C07D471/04 ,  C07D487/04

摘要： The present invention is directed to 5-(pyridine-3-yl)oxaxole 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.

公开(公告)号：US10730849B2

公开(公告)日：2020-08-04

申请号：US16513417

申请日：2019-07-16

申请人： MERCK SHARP & DOHME CORP.

发明人： Michael D. Altman ,  Brandon D. Cash ,  Wonsuk Chang ,  Jared N. Cumming ,  Andrew M. Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Matthew A. Larsen ,  Rui Liang ,  Jongwon Lim ,  Min Lu ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Sriram Tyagarajan

IPC分类号： C07D333/60 ,  C07D333/62 ,  C07D409/12 ,  C07D498/04

摘要： Compounds of general formula (Ia), compounds of general formula (Ia′), compounds of general formula (Ib), compounds of general formula (Ib′), compounds of general formula (I), compounds of general formula (I′), and their pharmaceutically acceptable salts, wherein R1, R2, R3, R4, R5, R6, R8, R9, 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 processes for the synthesis and use of compounds of the disclosure.

公开(公告)号：US10703738B2

公开(公告)日：2020-07-07

申请号：US16513409

申请日：2019-07-16

申请人： MERCK SHARP & DOHME CORP.

发明人： Michael D. Altman ,  Brandon D. Cash ,  Wonsuk Chang ,  Jared N. Cumming ,  Andrew M. Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Matthew A. Larsen ,  Rui Liang ,  Jongwon Lim ,  Min Lu ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Sriram Tyagarajan

IPC分类号： C07D333/60 ,  C07D333/62 ,  C07D409/12 ,  C07D498/04

摘要： Compounds of general formula (Ia), compounds of general formula (Ia′), compounds of general formula (Ib), compounds of general formula (Ib′), compounds of general formula (I), compounds of general formula (I′), and their pharmaceutically acceptable salts, wherein R1, R2, R3, R4, R5, R6, R8, R9, 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 processes for the synthesis and use of compounds of the disclosure.

公开(公告)号：US20190337917A1

公开(公告)日：2019-11-07

申请号：US16513409

申请日：2019-07-16

申请人： MERCK SHARP & DOHME CORP.

发明人： Michael D. Altman ,  Brandon D. Cash ,  Wonsuk Chang ,  Jared N. Cumming ,  Andrew M. Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Matthew A. Larsen ,  Rui Liang ,  Jongwon Lim ,  Min Lu ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Sriram Tyagarajan

IPC分类号： C07D333/60 ,  C07D498/04 ,  C07D333/62 ,  C07D409/12

摘要： Compounds of general formula (Ia), compounds of general formula (Ia′), compounds of general formula (Ib), compounds of general formula (Ib′), compounds of general formula (I), compounds of general formula (I′), and their pharmaceutically acceptable salts, wherein R1, R2, R3, R4, R5, R6, R8, R9, 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 processes for the synthesis and use of compounds of the disclosure.

公开(公告)号：US20180237469A1

公开(公告)日：2018-08-23

申请号：US15886578

申请日：2018-02-01

申请人： Merck Sharp & Dohme Corp.

发明人： Michael D. Altman ,  Brian Andresen ,  Wonsuk Chang ,  Matthew Lloyd Childers ,  Jared N. Cumming ,  Andrew Marc Haidle ,  Timothy J. Henderson ,  James P. Jewell ,  Rui Liang ,  Jongwon Lim ,  Hong Liu ,  Min Lu ,  Alan B. Northrup ,  Ryan D. Otte ,  Tony Siu ,  Benjamin Wesley Trotter ,  Quang T. Truong ,  Shawn P. Walsh ,  Kake Zhao

IPC分类号： C07H21/04 ,  C07H19/23 ,  C07H21/00 ,  C07H19/20 ,  A61K39/39 ,  C07H21/02 ,  A61K31/7076 ,  A61K31/708 ,  A61K31/706 ,  A61K31/7084 ,  A61K31/7064

摘要： A class of polycyclic compounds of general formula (I), of general formula (I′), or of general formula (I″), wherein Base1, Base2, Y, Ya, Xa, Xa1, Xb, Xb1, Xc, Xc1, Xd, Xd1, R1, R1a, R2, R2a, R3, R4, R4a, R5, R6, R6a, R7, R7a, R8, and R8a are defined herein, that may be useful as inductors of type I interferon production, specifically as STING active agents, are provided. Also provided are processes for the synthesis and use of compounds.

公开(公告)号：US20160214997A1

公开(公告)日：2016-07-28

申请号：US14914843

申请日：2014-08-25

申请人： Amjad ALI ,  Gioconda V. GALLO ,  Timothy J. HENDERSON ,  Rongze KUANG ,  Yeon-Hee LIM ,  Michael Man-Chu LO ,  Edward METZGER ,  Manuel de Lera RUIZ ,  Andrew STAMFORD ,  Paul TEMPEST ,  Brent WHITEHEAD ,  Heping WU ,  MERCK SHARP & DOHME CORP.

发明人： Ali Amjad ,  Gioconda V. Gallo ,  Timothy J. Henderson ,  Rongze Kuang ,  Yeon-Hee Lim ,  Michael Man-Chu Lo ,  Edward Metzger ,  Manuel de Lera Ruiz ,  Andrew Stamford ,  Paul Tempest ,  Brent Whitehead ,  Heping Wu

IPC分类号： C07D519/00 ,  C07D491/147

CPC分类号： C07D519/00 ,  C07D491/147

摘要： The present invention is directed to 2,2-difluorodioxolo compounds that are antagonists of A2A receptor. The present invention is also directed to uses of the 2,2-difluorodioxolo compounds described herein in the potential treatment or prevention of neurological disorders and diseases in which A2A receptor are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds and to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which A2A receptors are involved.

摘要翻译： 本发明涉及作为A2A受体拮抗剂的2,2-二氟二氧代己基化合物。 本发明还涉及本文所述的2,2-二氟二氧代环戊基化合物在涉及A2A受体的神经障碍和疾病的潜在治疗或预防中的用途。 本发明还涉及包含这些化合物的药物组合物以及这些药物组合物用于预防或治疗其中涉及A2A受体的疾病的用途。

公开(公告)号：US11046714B2

公开(公告)日：2021-06-29

申请号：US14914843

申请日：2014-08-25

申请人： Merck Sharp & Dohme Corp. ,  Ali Amjad ,  Gioconda V. Gallo ,  Timothy J. Henderson ,  Rongze Kuang ,  Yeon-Hee Lim ,  Michael Man-Chu Lo ,  Edward Metzger ,  Manuel de Lera Ruiz ,  Andrew Stamford ,  Paul Tempest ,  Brent Whitehead ,  Heping Wu

发明人： Ali Amjad ,  Gioconda V. Gallo ,  Timothy J. Henderson ,  Rongze Kuang ,  Yeon-Hee Lim ,  Michael Man-Chu Lo ,  Edward Metzger ,  Manuel de Lera Ruiz ,  Andrew Stamford ,  Paul Tempest ,  Brent Whitehead ,  Heping Wu

IPC分类号： C07D519/00 ,  C07D491/147

摘要： The present invention is directed to 2,2-difluorodioxolo compounds that are antagonists of A2A receptor. The present invention is also directed to uses of the 2,2-difluorodioxolo compounds described herein in the potential treatment or prevention of neurological disorders and diseases in which A2A receptor are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds and to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which A2A receptors are involved.