公开(公告)号：US11993602B2

公开(公告)日：2024-05-28

申请号：US17266474

申请日：2019-08-05

Applicant: Merck Sharp & Dohme LLC ,  David Witter ,  Shuhei Kawamura ,  Michelle Machacek ,  Ryan Quiroz ,  Michael H. Reutershan ,  Sebastian Schneider ,  Phieng Siliphaivanh ,  Yingchun Ye ,  Charles S. Yeung

Inventor： David Witter ,  Shuhei Kawamura ,  Michelle Machacek ,  Ryan Quiroz ,  Michael H. Reutershan ,  Sebastian Schneider ,  Phieng Siliphaivanh ,  Yingchun Ye ,  Charles S. Yeung

IPC: C07D487/04 ,  C07D519/00

CPC classification number: C07D487/04 ,  C07D519/00

Abstract: The present invention provides a compound of Formula (I) Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

公开(公告)号：US20120115885A1

公开(公告)日：2012-05-10

申请号：US13384946

申请日：2010-07-19

Applicant: Pablo De Leon ,  Melissa Egbertson ,  Ivory D. Hills ,  Adam Wayne Johnson ,  Michelle Machacek

Inventor： Pablo De Leon ,  Melissa Egbertson ,  Ivory D. Hills ,  Adam Wayne Johnson ,  Michelle Machacek

IPC: A61K31/4709 ,  C07D409/04 ,  C07D215/22 ,  A61K31/4704 ,  A61P25/18 ,  C07D401/12 ,  A61P25/22 ,  A61P25/00 ,  A61P25/16 ,  C07D409/14 ,  A61K31/506

CPC classification number: A61K31/47 ,  C07D215/22 ,  C07D215/227 ,  C07D401/14 ,  C07D409/04 ,  C07D409/14

Abstract: The present invention is directed to quinolinone compounds 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 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2（PDE2）相关的中枢神经系统疾病的治疗剂的喹啉酮化合物。 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。

公开(公告)号：US20090306071A1

公开(公告)日：2009-12-10

申请号：US12227959

申请日：2007-06-05

Applicant: Jonathan R. Young ,  Andrew Haidle ,  Paul Tempest ,  Michelle Machacek

Inventor： Jonathan R. Young ,  Andrew Haidle ,  Paul Tempest ,  Michelle Machacek

IPC: A61K31/5377 ,  A61K31/497 ,  A61K31/4745 ,  C07D471/04

CPC classification number: C07D471/04

Abstract: The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Abstract translation: 本发明提供抑制四种已知的哺乳动物JAK激酶（JAK1，JAK2，JAK3和TYK2）和PDK1的化合物。 本发明还提供了包含这种抑制化合物的组合物和通过向需要治疗骨髓增生性疾病或癌症的患者施用化合物来抑制JAK1，JAK2，JAK3 TYK2和PDK1的活性的方法。

公开(公告)号：US20210309688A1

公开(公告)日：2021-10-07

申请号：US17266507

申请日：2019-08-05

Applicant: Jongwon Lim ,  Michelle Machacek ,  Michael H. Reutershan ,  Sebastian Schneider ,  Merck Sharp & Dohme Corp.

Inventor： Jongwon Lim ,  Michelle Machacek ,  Michael H. Reutershan ,  Sebastian Schneider

IPC: C07H19/167 ,  C07D473/34 ,  C07D471/04

Abstract: The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

公开(公告)号：US07763634B2

公开(公告)日：2010-07-27

申请号：US12227959

申请日：2007-06-05

Applicant: Jonathan R. Young ,  Andrew Haidle ,  Paul Tempest ,  Michelle Machacek

Inventor： Jonathan R. Young ,  Andrew Haidle ,  Paul Tempest ,  Michelle Machacek

IPC: A61K31/4745 ,  C07D471/02

CPC classification number: C07D471/04

Abstract: The instant invention provides for tetracyclic compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Abstract translation: 本发明提供抑制四种已知的哺乳动物JAK激酶（JAK1，JAK2，JAK3和TYK2）和PDK1的四环化合物。 本发明还提供了包含这种抑制化合物的组合物和通过向需要治疗骨髓增生性疾病或癌症的患者施用化合物来抑制JAK1，JAK2，JAK3 TYK2和PDK1的活性的方法。

公开(公告)号：US08344144B2

公开(公告)日：2013-01-01

申请号：US12999342

申请日：2009-06-08

Applicant: Michelle Machacek ,  Gabriela de Almeida ,  Jonathan B. Grimm ,  Rachel N. MacCoss ,  Eric Romeo ,  Tony Siu ,  Catherine White ,  Kevin Wilson

Inventor： Michelle Machacek ,  Gabriela de Almeida ,  Jonathan B. Grimm ,  Rachel N. MacCoss ,  Eric Romeo ,  Tony Siu ,  Catherine White ,  Kevin Wilson

IPC: C07D471/02 ,  A61K31/395

CPC classification number: C07D513/04 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

Abstract: The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3, TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

Abstract translation: 本发明提供抑制四种已知的哺乳动物JAK激酶（JAK1，JAK2，JAK3和TYK2）和PDK1的化合物。 本发明还提供了包含这种抑制化合物的组合物和通过将该化合物施用于需要治疗骨髓增生性疾病或癌症的患者的JAK1，JAK2，JAK3，TYK2和PDK1的活性的方法。

公开(公告)号：US20100256097A1

公开(公告)日：2010-10-07

申请号：US12665045

申请日：2008-06-16

Applicant: Michael Altman ,  Matthew Christopher ,  Jonathan B. Grimm ,  Andrew Haidle ,  Kaleen Konrad ,  Jongwon Lim ,  Rachel N. MacCoss ,  Michelle Machacek ,  Ekundayo Osimboni ,  Ryan D. Otte ,  Tony Siu ,  Kerrie Spencer ,  Brandon Taoka ,  Paul Tempest ,  Kevin Wilson ,  Hyan Chong Woo ,  Jonathan Young ,  Anna Zabierek

Inventor： Michael Altman ,  Matthew Christopher ,  Jonathan B. Grimm ,  Andrew Haidle ,  Kaleen Konrad ,  Jongwon Lim ,  Rachel N. MacCoss ,  Michelle Machacek ,  Ekundayo Osimboni ,  Ryan D. Otte ,  Tony Siu ,  Kerrie Spencer ,  Brandon Taoka ,  Paul Tempest ,  Kevin Wilson ,  Hyan Chong Woo ,  Jonathan Young ,  Anna Zabierek

IPC: A61K31/675 ,  C07D409/14 ,  A61K31/4439 ,  A61K31/4436 ,  C07D413/14 ,  A61K31/5377 ,  C07D409/12 ,  A61K31/501 ,  C07F9/28 ,  C07D417/14 ,  A61K31/541

CPC classification number: C07D409/12 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14 ,  C07D498/10 ,  C07F9/65586 ,  C07F9/65685

Abstract: The instant invention provides for compounds that inhibit the four known mammalian JAK kinases (JAK1, JAK2, JAK3 and TYK2) and PDK1. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting the activity of JAK1, JAK2, JAK3 TYK2 and PDK1 by administering the compound to a patient in need of treatment for myeloproliferative disorders or cancer.

公开(公告)号：US20060293358A1

公开(公告)日：2006-12-28

申请号：US11473273

申请日：2006-06-22

Applicant: Christopher Dinsmore ,  Ana Gabarda Ortega ,  David Guerin ,  James Jewell ,  Jason Katz ,  Jongwon Lim ,  Michelle Machacek ,  Ryan Otte ,  Jonathan Young

Inventor： Christopher Dinsmore ,  Ana Gabarda Ortega ,  David Guerin ,  James Jewell ,  Jason Katz ,  Jongwon Lim ,  Michelle Machacek ,  Ryan Otte ,  Jonathan Young

IPC: A61K31/473 ,  C07D221/02

CPC classification number: C07D471/04 ,  C07D221/16 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D413/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  C07D487/04 ,  C07D491/10 ,  C07D491/113 ,  C07F7/1804

Abstract: The present invention relates to 5H-benzo[4,5]cyclohepta[1,2-b]pyridine compounds, that are useful for treating cellular proliferative diseases, for treating disorders associated with MET activity, and for inhibiting the receptor tyrosine kinase MET. The invention also related to compositions which comprise these compounds, and methods of using them to treat cancer in mammals.

公开(公告)号：US20210309687A1

公开(公告)日：2021-10-07

申请号：US17266515

申请日：2019-08-05

Applicant: Michelle MACHACEK ,  David WITTER ,  Chunhui HUANG ,  Shuhei KAWAMURA ,  Sebastian SCHNEIDER ,  Mrray WAN ,  Merck Sharp & Dohme Corp.

Inventor： Michelle Machacek ,  David Witter ,  Chunhui Huang ,  Shuhei Kawamura ,  Sebastian Schneider ,  Murray Wan

IPC: C07H19/14 ,  A61P35/00

Abstract: The present invention provides a compound of formula (I) Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, 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：US20150368247A1

公开(公告)日：2015-12-24

申请号：US14764616

申请日：2014-02-04

Applicant: Matthew P. CHRISTOPHER ,  Francesc Xavier FRADERA LLINAS ,  Michelle MACHACEK ,  Michelle MARTINEZ ,  Michael Hale REUTERSHAN ,  Manami SHIZUKA ,  Binyuan SUN ,  Christopher Francis THOMPSON ,  Wesley B. TROTTER ,  Matthew E. VOSS ,  Liping YANG ,  Merck Sharp & Dohme Corp.

Inventor： Matthew P. Christopher ,  Francesc Xavier Fradera Llinas ,  Michelle Machacek ,  Michelle Martinez ,  Michael Hale Reutershan ,  Manami Shizuka ,  Binyuan Sun ,  Christopher Francis Thompson ,  B. Wesley Trotter ,  Matthew E. Voss ,  Liping Yang

IPC: C07D473/34 ,  C07D473/00 ,  C07D473/30

CPC classification number: C07D473/34 ,  C07D473/00 ,  C07D473/30

Abstract: The present invention provides 2,6,7 substituted purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and potential methods of treating cancer using the same.

Abstract translation: 本发明提供2,6,7本文所述的取代嘌呤或其药学上可接受的盐。 代表性化合物可用作HDM2蛋白的抑制剂。 还公开了包含上述化合物的药物组合物和使用其治疗癌症的潜在方法。