公开(公告)号：US10017504B2

公开(公告)日：2018-07-10

申请号：US15523252

申请日：2015-10-27

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Nigel Liverton ,  Scott D. Kuduk ,  Douglas Beshore ,  Yunfu Luo ,  Na Meng ,  Tingting Yu

IPC: C07D413/04 ,  C07D413/14 ,  C07D417/04 ,  C07D417/14 ,  A61K31/4525 ,  A61K31/4535 ,  A61K31/4545 ,  A61K31/454 ,  A61K31/506

CPC classification number: C07D413/14 ,  C07D413/04 ,  C07D417/04 ,  C07D417/14

Abstract: The present invention is directed to piperidine isoxazole and isothiazole orexin compounds which are antagonists of orexin receptors. Such compounds are of the general structural formula I: wherein the variables are defined herein. 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 orexin 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 prevention or treatment of such diseases in which orexin receptors are involved.

公开(公告)号：US20170210732A1

公开(公告)日：2017-07-27

申请号：US15329634

申请日：2015-07-23

Applicant: Merck Sharp & Dohme Corp.

Inventor： Weiguo Liu ,  Scott D. Edmondson ,  Zhuyan Guo ,  Sung-Sau So ,  Anthony K. Ogawa ,  Rongze Kuang ,  Heping Wu ,  Amjad Ali ,  Ying-Duo Gao ,  Yu Jiang ,  Chunsing Li ,  Tingting Yu

IPC: C07D409/14 ,  C07D401/06 ,  C07D401/14 ,  C07D417/14 ,  C07D413/14

CPC classification number: C07D409/14 ,  A61P7/02 ,  C07D401/06 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

公开(公告)号：US20160108048A1

公开(公告)日：2016-04-21

申请号：US14895406

申请日：2014-06-02

Applicant: Craig A. COBURN ,  Milana MALETIC ,  Yunfu LUO ,  Zhiqi QI ,  Chunsing LI ,  Tingting YU ,  Richard SOLL ,  MERCK SHARP & DOHME CORP.

Inventor： Craig A. Coburn ,  Milana Maletic ,  Yunfu Luo ,  Zhiqi Qi ,  Chunsing Li ,  Tingting Yu ,  Richard Soll

IPC: C07D487/04 ,  A61K31/4545 ,  C07D498/04 ,  A61K31/5383 ,  A61K31/4985 ,  A61K45/06 ,  A61K31/496 ,  A61K31/551 ,  C07D405/14 ,  C07D401/06 ,  C07D413/14 ,  C07D401/14 ,  A61K31/454

CPC classification number: C07D487/04 ,  A61K31/4375 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/513 ,  A61K31/5365 ,  A61K31/5383 ,  A61K31/55 ,  A61K31/551 ,  A61K45/06 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04 ,  C07D498/04 ,  A61K2300/00

Abstract: The present invention relates to Imidazole Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Y, R1 and R2 are as defined herein. The present invention also relates to compositions comprising at least one Imidazole Derivative, and methods of using the Imidazole Derivatives for inhibiting CYP450 3A. Inhibition of CYP450 3A can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.

Abstract translation: 本发明涉及式（I）的咪唑衍生物及其药学上可接受的盐，其中A，B，Y，R 1和R 2如本文所定义。 本发明还涉及包含至少一种咪唑衍生物的组合物，以及使用咪唑衍生物抑制CYP450A 3A的方法。 CYP450 3A的抑制可用于改善由CYP450 3A4代谢的药物的药代动力学。

公开(公告)号：US10745377B2

公开(公告)日：2020-08-18

申请号：US15036268

申请日：2014-11-07

Applicant: MERCK SHARP & DOHME CORP. ,  Craig A. Coburn ,  Milana M. Maletic ,  Yunfu Luo ,  Zhiqi Qi ,  Tingting Yu ,  Richard Soll

Inventor： Craig A. Coburn ,  Milana M. Maletic ,  Yunfu Luo ,  Zhiqi Qi ,  Tingting Yu ,  Richard Soll

IPC: A61K31/4178 ,  A61K31/4439 ,  A61K31/4436 ,  A61K31/443 ,  A61K31/551 ,  A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  C07D401/06 ,  C07D401/14 ,  C07D401/04 ,  C07D403/06 ,  C07D403/14 ,  C07D409/06 ,  C07D413/04 ,  C07D417/04 ,  A61K45/06 ,  A61K31/454 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  C07D249/08 ,  C07D233/61 ,  A61P31/18 ,  C07D213/14 ,  C07D471/04 ,  A61K31/4545 ,  C07D471/10

Abstract: The present invention relates to piperidine or piperazine linked imidazole and triazole derivatives, compositions comprising said compounds, alone or in combination with other drugs, and methods of using the compounds for improving the pharmacokinetics of a drug. The compounds of the invention are useful in human and veterinary medicine for inhibiting CYP3A4 and for improving the pharmacokinetics of a therapeutic compound that is metabolized by CYP3A4.

公开(公告)号：US10308645B2

公开(公告)日：2019-06-04

申请号：US15523251

申请日：2015-09-27

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Nigel Liverton ,  Scott D. Kuduk ,  Yunfu Luo ,  Na Meng ,  Tingting Yu

IPC: C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D417/04

Abstract: The present invention is directed to piperidine oxadiazole and thiadiazole orexin compounds which are antagonists of orexin receptors. 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 orexin 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 prevention or treatment of such diseases in which orexin receptors are involved.

公开(公告)号：US09981969B2

公开(公告)日：2018-05-29

申请号：US14895406

申请日：2014-06-02

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Craig A. Coburn ,  Milana Maletic ,  Yunfu Luo ,  Zhiqi Qi ,  Chunsing Li ,  Tingting Yu ,  Richard Soll

IPC: C07D487/04 ,  C07D401/14 ,  C07D413/14 ,  A61K31/4985 ,  A61K31/5365 ,  C07D401/06 ,  C07D471/04 ,  C07D498/04 ,  A61K45/06 ,  A61K31/4375 ,  A61K31/4545 ,  A61K31/513 ,  A61K31/55 ,  C07D405/14 ,  A61K31/454 ,  A61K31/496 ,  A61K31/5383 ,  A61K31/551

CPC classification number: C07D487/04 ,  A61K31/4375 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/513 ,  A61K31/5365 ,  A61K31/5383 ,  A61K31/55 ,  A61K31/551 ,  A61K45/06 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D471/04 ,  C07D498/04 ,  A61K2300/00

Abstract: The present invention relates to Imidazole Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Y, R1 and R2 are as defined herein. The present invention also relates to compositions comprising at least one Imidazole Derivative, and methods of using the Imidazole Derivatives for inhibiting CYP450 3A. Inhibition of CYP450 3A can be used to improve the pharmacokinetics of a drug that is metabolized by CYP450 3A4.

公开(公告)号：US09975888B2

公开(公告)日：2018-05-22

申请号：US15036274

申请日：2014-11-07

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Craig A. Coburn ,  Milana M. Maletic ,  Yunfu Luo ,  Zhiqi Qi ,  Chun Sing Li ,  Tingting Yu

IPC: C07D417/14 ,  C07D417/12 ,  C07D487/04 ,  C07D401/12 ,  C07D405/14 ,  C07D403/10 ,  C07D401/14 ,  A61K45/06 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/4985 ,  C07D409/14 ,  C07D471/04 ,  A61K31/4178 ,  A61K31/5377

CPC classification number: C07D417/14 ,  A61K31/4178 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  A61K2300/00

Abstract: The present invention relates to aryl linked imidazole and triazole derivatives, compositions comprising said compounds, alone or in combination with other drugs, and methods of using the compounds for improving the pharmacokinetics of a drug. The compounds of the invention are useful in human and veterinary medicine for inhibiting CYP3A4 and for improving the pharmacokinetics of a therapeutic compound that is metabolized by CYP3A4.

公开(公告)号：US09868727B2

公开(公告)日：2018-01-16

申请号：US15329634

申请日：2015-07-23

Applicant: Merck Sharp & Dohme Corp.

Inventor： Weiguo Liu ,  Scott D. Edmondson ,  Zhuyan Guo ,  Sung-Sau So ,  Anthony K. Ogawa ,  Rongze Kuang ,  Heping Wu ,  Amjad Ali ,  Ying-Duo Gao ,  Yu Jiang ,  Chunsing Li ,  Tingting Yu

IPC: C07D409/14 ,  C07D417/14 ,  C07D413/14 ,  C07D401/14 ,  C07D401/06 ,  A61K31/4439 ,  A61K31/444

CPC classification number: C07D409/14 ,  A61P7/02 ,  C07D401/06 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention provides a compound of Formula (I) and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing thromboses, embolisms, hypercoagulability or fibrotic changes. The compounds are selective Factor XIa inhibitors or dual inhibitors of Factor XIa and plasma kallikrein.

公开(公告)号：US09695163B2

公开(公告)日：2017-07-04

申请号：US14910548

申请日：2014-08-04

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Nigel Liverton ,  Douglas C. Beshore ,  Scott D. Kuduk ,  Yunfu Luo ,  Na Meng ,  Tingting Yu

IPC: C07D417/14 ,  C07D417/04

CPC classification number: C07D417/14 ,  C07D417/04

Abstract: The present invention is directed to thiazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the thiazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.

公开(公告)号：US09828368B2

公开(公告)日：2017-11-28

申请号：US14910552

申请日：2014-08-04

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Nigel Liverton ,  Douglas C. Beshore ,  Scott D. Kuduk ,  Yunfu Luo ,  Na Meng ,  Tingting Yu

IPC: C07D417/14 ,  C07D417/04 ,  C07D413/14 ,  C07D413/04

CPC classification number: C07D413/14 ,  C07D413/04 ,  C07D417/14

Abstract: The present invention is directed to oxazole compounds which are antagonists of orexin receptors. The present invention is also directed to uses of the oxazole compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The present invention is also directed to pharmaceutical compositions comprising these compounds. The present invention is also directed to uses of these pharmaceutical compositions in the prevention or treatment of such diseases in which orexin receptors are involved.