公开(公告)号：US10780092B2

公开(公告)日：2020-09-22

申请号：US16301935

申请日：2017-05-11

Applicant: Merck Sharp & Dohme Corp. ,  Alan Whitehead ,  Olga Ornoski ,  Subharekha Raghavan ,  Raphaelle Berger ,  Joie Garfunkle ,  Zhiqiang Yang ,  Gang Ji ,  Falong Jiang ,  Jianmin Fu

Inventor： Alan Whitehead ,  Olga Ornoski ,  Subharekha Raghavan ,  Raphaelle Berger ,  Joie Garfunkle ,  Zhiqiang Yang ,  Gang Ji ,  Falong Jiang ,  Jianmin Fu

IPC: C07D487/04 ,  C07D519/00 ,  A61K31/519 ,  A61P9/12

Abstract: The invention provides certain fused pyrazine compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, R1, R3, R4a, R5a, R5b, R6, and the subscript t are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases or disorders which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and disorders and for preparing pharmaceuticals for this purpose.

公开(公告)号：US10100064B2

公开(公告)日：2018-10-16

申请号：US15318483

申请日：2015-06-09

Applicant: Merck Sharp & Dohme Corp.

Inventor： Meredeth Ann McGowan ,  Kin Chiu Fong ,  Neville John Anthony ,  Hua Zhou ,  Jason D. Katz ,  Lihu Yang ,  Chaomin Li ,  Yuan Tian ,  Changwei Mu ,  Baijun Ye ,  Feng Shi ,  Xiaoli Zhao ,  Jianmin Fu ,  Yabin Li

IPC: C07D473/30 ,  C07D473/34 ,  C07D519/00 ,  A61K31/52

Abstract: The instant invention provides compounds of formula (I) which are PI3K-delta inhibitors, and as such are useful for the treatment of PI3K-delta-mediated diseases such as inflammation, asthma, COPD and cancer.

公开(公告)号：US20180244656A1

公开(公告)日：2018-08-30

申请号：US15737351

申请日：2016-06-24

Applicant: Merck Sharp & Dohme Corp.

Inventor： Frank Bennett ,  Jinlong Jiang ,  Alexander Pasternak ,  Shuzhi Dong ,  Xin Gu ,  Jack D. Scott ,  Haiqun Tang ,  Zhiqiang Zhao ,  Yuhua Huang ,  Dexi Yang ,  Katherine Young ,  Li Xiao ,  Zhibo Zhang ,  Jianmin Fu

IPC: C07D403/10 ,  A61K31/4184 ,  C07D401/10 ,  A61K31/4709 ,  A61K31/416 ,  C07D413/10 ,  A61K31/423 ,  C07D417/10 ,  A61K31/428 ,  C07D417/14 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/454 ,  C07D471/04 ,  C07D495/08 ,  C07D487/10 ,  A61K31/541 ,  C07D493/04 ,  C07D493/08 ,  C07D453/02 ,  C07D403/14 ,  C07D405/14 ,  A61K31/41 ,  A61K31/4245 ,  A61K31/4192 ,  A61K31/421 ,  A61K31/4196 ,  A61K31/198 ,  A61K31/431 ,  A61K31/546 ,  A61K31/4545 ,  A61K31/439 ,  A61K31/407 ,  A61P31/04

CPC classification number: C07D403/10 ,  A61K31/198 ,  A61K31/407 ,  A61K31/41 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/4192 ,  A61K31/4196 ,  A61K31/421 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/428 ,  A61K31/431 ,  A61K31/437 ,  A61K31/4375 ,  A61K31/439 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/546 ,  A61K45/06 ,  A61P31/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  C07D453/02 ,  C07D471/04 ,  C07D487/04 ,  C07D487/10 ,  C07D493/04 ,  C07D493/08 ,  C07D495/08

Abstract: The present invention relates to metallo-beta-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and R1 are as defined herein. The present invention also relates to compositions which comprise a metallo-beta-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta-lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

公开(公告)号：US09884048B2

公开(公告)日：2018-02-06

申请号：US15531759

申请日：2015-12-10

Applicant: Merck Sharp & Dohme Corp.

Inventor： Phieng Siliphaivanh ,  Joey Methot ,  Kathryn Ann Lipford ,  Danielle Molinari ,  David L. Sloman ,  David Witter ,  Hua Zhou ,  Christopher Boyce ,  Xianhai Huang ,  Jongwon Lim ,  David Guerin ,  Ganesh Babu Karunakaran ,  Raman Kumar Bakshi ,  Ziping Liu ,  Jianmin Fu ,  Zhilong Wan ,  Wei Liu

IPC: A61K31/437 ,  A61K31/4545 ,  A61K31/444 ,  C07D471/04 ,  C07D519/00

CPC classification number: A61K31/437 ,  A61K31/444 ,  A61K31/4545 ,  C07D471/04 ,  C07D519/00

Abstract: The present invention provides a compound of Formula (I) or the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are ERK2 inhibitors. The invention also provides a pharmaceutical composition comprising an effective amount of at least one compound of Formula (I) and a pharmaceutically acceptable carrier. The invention also provides a pharmaceutical composition comprising an effective amount of at least one compound of Formula (I) and an effective amount of at least one other pharmaceutically active ingredient (such as, for example, a chemotherapeutic agent), and a pharmaceutically acceptable carrier.

公开(公告)号：US09777035B2

公开(公告)日：2017-10-03

申请号：US14669398

申请日：2015-03-26

Applicant: Merck Sharp & Dohme Corp.

Inventor： Vinay M. Girijavallabhan ,  David B. Olsen ,  Zhibo Zhang ,  Jianmin Fu ,  Bing-Yu Tang

IPC: A61K31/7064 ,  A61K45/06 ,  C07H19/12 ,  C07H19/14 ,  C07H19/06 ,  C07D487/04

CPC classification number: C07H19/14 ,  A61K31/7064 ,  A61K45/06 ,  C07D487/04 ,  C07H19/06 ,  C07H19/12

Abstract: The present invention is directed to 4′-substituted nucleoside derivatives of Formula I and their use in the inhibition of HIV reverse transcriptase, 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 and/or ARC.

公开(公告)号：US10544130B2

公开(公告)日：2020-01-28

申请号：US16244876

申请日：2019-01-10

Applicant: Merck Sharp & Dohme Corp.

Inventor： Frank Bennett ,  Jinlong Jiang ,  Alexander Pasternak ,  Shuzhi Dong ,  Xin Gu ,  Jack D. Scott ,  Haiqun Tang ,  Zhiqiang Zhao ,  Yuhua Huang ,  Dexi Yang ,  Katherine Young ,  Li Xiao ,  Zhibo Zhang ,  Jianmin Fu

IPC: C07D403/10 ,  C07D403/12 ,  C07D413/14 ,  C07D401/10 ,  C07D403/14 ,  C07D407/14 ,  C07D413/10 ,  C07D417/10 ,  C07D417/14 ,  C07D471/04 ,  A61P31/04 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/428 ,  A61K31/437 ,  A61K31/4375 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/14 ,  C07D487/04 ,  A61K31/198 ,  A61K31/407 ,  A61K31/41 ,  A61K31/4192 ,  A61K31/4196 ,  A61K31/421 ,  A61K31/4245 ,  A61K31/431 ,  A61K31/439 ,  A61K31/496 ,  A61K31/541 ,  A61K31/546 ,  C07D405/14 ,  C07D453/02 ,  C07D487/10 ,  C07D493/04 ,  C07D493/08 ,  C07D495/08

Abstract: The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and R1 are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.

公开(公告)号：US10428076B2

公开(公告)日：2019-10-01

申请号：US16019964

申请日：2018-06-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Raphaelle Berger ,  Yi-Heng Chen ,  Guoqing Li ,  Joie Garfunkle ,  Hong-Dong Li ,  Shouwu Miao ,  Subharekha Raghavan ,  Cameron J. Smith ,  John Stelmach ,  Alan Whitehead ,  Rui Zhang ,  Yong Zhang ,  Jianmin Fu ,  Gang Ji ,  Falong Jiang

IPC: C07D487/04 ,  C07D519/00 ,  A61K31/519 ,  A61K45/06

Abstract: The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

公开(公告)号：US20180305366A1

公开(公告)日：2018-10-25

申请号：US16019964

申请日：2018-06-27

Applicant: Merck Sharp & Dohme Corp.

Inventor： Raphaelle Berger ,  Yi-Heng Chen ,  Guoqing Li ,  Joie Garfunkle ,  Hong-Dong Li ,  Shouwu Miao ,  Subharekha Raghavan ,  Cameron J. Smith ,  John Stelmach ,  Alan Whitehead ,  Rui Zhang ,  Yong Zhang ,  Jianmin Fu ,  Gang Ji ,  Falong Jiang

IPC: C07D487/04 ,  A61K31/519 ,  C07D519/00 ,  A61K45/06

CPC classification number: C07D487/04 ,  A61K31/519 ,  A61K45/06 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P9/12 ,  C07D519/00

Abstract: The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

公开(公告)号：US10030027B2

公开(公告)日：2018-07-24

申请号：US15384429

申请日：2016-12-20

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Raphaelle Berger ,  Yi-Heng Chen ,  Guoqing Li ,  Joie Garfunkle ,  Hong-Dong Li ,  Shouwu Miao ,  Subharekha Raghavan ,  Cameron J. Smith ,  John Stelmach ,  Alan Whitehead ,  Rui Zhang ,  Yong Zhang ,  Jianmin Fu ,  Gang Ji ,  Falong Jiang

IPC: C07D487/04 ,  C07D519/00 ,  A61K45/06 ,  A61K31/519

Abstract: The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R1, R2, R4, Ra, and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

公开(公告)号：US20180179190A1

公开(公告)日：2018-06-28

申请号：US15737334

申请日：2016-06-24

Applicant: Merck Sharp &Dohme Corp.

Inventor： Frank Bennett ,  Jinlong Jiang ,  Alexander Pasternak ,  Shuzhi Dong ,  Xin Gu ,  Jack D. Scott ,  Haiqun Tang ,  Zhiqiang Zhao ,  Yuhua Huang ,  David Hunter ,  Dexi Yang ,  Katherine Young ,  Li Xiao ,  Zhibo Zhang ,  Jianmin Fu ,  Yunfeng Bai ,  Zhixiang Zheng ,  Xu Zhang

IPC: C07D403/14 ,  A61K45/06 ,  A61K31/4184 ,  C07D401/14 ,  A61K31/454 ,  C07D471/04 ,  A61K31/437 ,  A61K31/4545 ,  C07D487/04 ,  A61K31/5025 ,  C07D403/10 ,  A61K31/416 ,  A61K31/4439 ,  C07D417/14 ,  A61K31/428 ,  A61K31/4375 ,  C07D413/14 ,  A61K31/423 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/517 ,  A61K31/506 ,  A61K31/498 ,  A61K31/5377 ,  A61P31/04

CPC classification number: C07D403/10 ,  A61K31/198 ,  A61K31/407 ,  A61K31/41 ,  A61K31/416 ,  A61K31/4184 ,  A61K31/4192 ,  A61K31/4196 ,  A61K31/421 ,  A61K31/423 ,  A61K31/4245 ,  A61K31/428 ,  A61K31/431 ,  A61K31/437 ,  A61K31/4375 ,  A61K31/439 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/498 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/517 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/546 ,  A61K45/06 ,  A61P31/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D407/14 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  C07D453/02 ,  C07D471/04 ,  C07D487/04 ,  C07D487/10 ,  C07D493/04 ,  C07D493/08 ,  C07D495/08

Abstract: The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: (I) and pharmaceutically acceptable salts thereof, wherein Z, RA, X1, X2 and RB are as defined herein. The present invention also relates to compositions which comprise a metallo-β-lactamase inhibitor compound of the invention or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, optionally in combination with a beta lactam antibiotic and/or a beta-lactamase inhibitor. The invention further relates to methods for treating a bacterial infection comprising administering to a patient a therapeutically effective amount of a compound of the invention, in combination with a therapeutically effective amount of one or more β-lactam antibiotics and optionally in combination with one or more beta-lactamase inhibitor compounds. The compounds of the invention are useful in the methods described herein for overcoming antibiotic resistance.