公开(公告)号：US20170197964A1

公开(公告)日：2017-07-13

申请号：US15323985

申请日：2015-07-09

Applicant: Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Ian Davies ,  Fa-Xiang Ding ,  Jinglong Jiang ,  Shuzhi Dong ,  Xin Gu

IPC: C07D471/10 ,  A61K31/444 ,  A61K45/06 ,  A61K31/438

CPC classification number: C07D471/10 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

公开(公告)号：US20200375987A1

公开(公告)日：2020-12-03

申请号：US16769670

申请日：2018-12-20

Applicant: Alexander PASTERNAK ,  Shuzhi DONG ,  Jack D. SCOTT ,  Haiqun TANG ,  Zhiqiang ZHAO ,  Dexi YANG ,  Li XIAO ,  Xin GU ,  Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Shuzhi Dong ,  Jack D. Scott ,  Haiqun Tang ,  Zhiqiang Zhao ,  Dexi Yang ,  Li Xiao ,  Xin Gu ,  Jinlong Jiang

IPC: A61K31/4985 ,  C07D487/04 ,  C07D471/04 ,  A61K31/4439 ,  A61K31/519 ,  A61K31/4188 ,  C07D513/04 ,  C07D403/10 ,  A61K31/4178 ,  A61K31/407 ,  A61K31/496 ,  A61K31/165 ,  A61K31/7048 ,  A61K31/546 ,  A61P31/04

Abstract: The present invention relates to metallo-β-lactamase inhibitor compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein RA, R1, and Z 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：US20170275283A1

公开(公告)日：2017-09-28

申请号：US15505277

申请日：2015-10-26

Applicant: Alexander PASTERNAK ,  Fa-Xiang DING ,  Shuzhi DONG ,  Jinlong JIANG ,  Haifeng TANG ,  Xin GU ,  Reynalda K. DEJESUS ,  Jessica FRIE ,  Qinghong FU ,  Takao SUZUKI ,  Zhifa PU ,  Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Fa-Xiang Ding ,  Shuzhi Dong ,  Jinlong Jiang ,  Haifeng Tang ,  Xin Gu ,  Reynalda K. DeJesus ,  Jessica Frie ,  Qinghong Fu ,  Takao Suzuki ,  Zhifa Pu

IPC: C07D471/10 ,  C07D498/10 ,  A61K31/5386 ,  A61K45/06 ,  A61K31/435 ,  A61K31/537 ,  C07D498/20 ,  A61K31/553 ,  A61K31/499 ,  A61K31/55

CPC classification number: C07D471/10 ,  A61K31/401 ,  A61K31/41 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/435 ,  A61K31/4422 ,  A61K31/499 ,  A61K31/537 ,  A61K31/5386 ,  A61K31/55 ,  A61K31/553 ,  A61K45/06 ,  C07D487/10 ,  C07D498/10 ,  C07D498/20 ,  A61K2300/00

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

公开(公告)号：US20160333021A1

公开(公告)日：2016-11-17

申请号：US15110431

申请日：2015-01-16

Applicant: Merck Sharp & Dohme Corp.

Inventor： Mihir Mandal ,  Haifeng Tang ,  Li Xiao ,  Jing Su ,  Guoqing Li ,  Shu-Wei Yang ,  Weidong Pan ,  Haiqun Tang ,  Reynalda DeJesus ,  Jacqueline Hicks ,  Matthew Lombardo ,  Hong Chu ,  William Hagmann ,  Alex Pasternak ,  Xin Gu ,  Jinlong Jiang ,  Shuzhi Dong ,  Fa-Xiang Ding ,  Clare London ,  Dipshikha Biswas ,  Katherine Young ,  David N. Hunter ,  Zhiqiang Zhao ,  Dexi Yang

IPC: C07D491/048 ,  A61K31/41 ,  A61K45/06 ,  A61K31/407 ,  A61K31/197 ,  C07D405/12 ,  A61K31/5377 ,  C07D403/10 ,  A61K31/4192 ,  A61K31/496 ,  C07D401/10 ,  A61K31/454 ,  A61K31/4439 ,  C07D409/10 ,  C07D417/10 ,  A61K31/427 ,  C07D405/14 ,  C07D413/10 ,  A61K31/422 ,  A61K31/506 ,  A61K31/497 ,  A61K31/4178 ,  A61K31/501 ,  A61K31/4155 ,  C07D471/04 ,  A61K31/437 ,  C07D417/14 ,  C07D401/14 ,  C07D487/04 ,  A61K31/5025 ,  A61K31/4245 ,  A61K31/541 ,  C07D401/04 ,  C07D413/14 ,  A61K31/55 ,  C07D471/10 ,  C07D257/04

CPC classification number: C07D491/048 ,  A61K31/197 ,  A61K31/407 ,  A61K31/41 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4192 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61K45/06 ,  C07D257/04 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D405/10 ,  C07D405/12 ,  C07D405/14 ,  C07D409/10 ,  C07D413/10 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  C07D451/04 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  Y02A50/473 ,  A61K2300/00

Abstract: The present invention relates to compounds of formula (I) that are metallo-β-lactamase inhibitors, the synthesis of such compounds, and the use of such compounds for use with β-lactam antibiotics for overcoming resistance.

公开(公告)号：US20160024091A1

公开(公告)日：2016-01-28

申请号：US14774390

申请日：2014-03-10

Applicant: Alexander PASTERNAK ,  Fa-Xiang DING ,  Shuzhi DONG ,  Haifeng TANG ,  Jinlong JIANG ,  Cangming YANG ,  Dipshikha BISWAS ,  MERCK SHARP & DOHME CORP.

Inventor： Alexander Pasternak ,  Fa-Xiang Ding ,  Shuzhi Dong ,  Dipshikha Biswas ,  Haifeng Tang ,  Jinlong Jiang ,  Cangming Yang ,  Xin Gu

IPC: C07D471/10 ,  A61K31/444 ,  A61K31/506 ,  A61K31/435 ,  A61K31/5386 ,  A61K31/501 ,  C07D471/20 ,  A61K31/4995 ,  C07D498/20 ,  A61K45/06 ,  A61K31/497

CPC classification number: C07D471/10 ,  A61K31/24 ,  A61K31/401 ,  A61K31/403 ,  A61K31/405 ,  A61K31/407 ,  A61K31/41 ,  A61K31/417 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/435 ,  A61K31/4422 ,  A61K31/444 ,  A61K31/472 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/4995 ,  A61K31/501 ,  A61K31/506 ,  A61K31/519 ,  A61K31/5386 ,  A61K31/55 ,  A61K31/551 ,  A61K31/554 ,  A61K31/585 ,  A61K31/675 ,  A61K45/06 ,  C07D471/20 ,  C07D498/20 ,  A61K2300/00

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

Abstract translation: 本发明提供式I化合物及其药学上可接受的盐，它们是ROMK（Kir1.1）通道的抑制剂。 这些化合物可以用作利尿剂和/或利尿钠剂，并且用于治疗和预防包括心血管疾病如高血压，心力衰竭和慢性肾脏疾病以及与过量的盐和水保留有关的病症的医学病症。

公开(公告)号：US08952166B2

公开(公告)日：2015-02-10

申请号：US13951096

申请日：2013-07-25

Applicant: Merck Sharp & Dohme Corp.

Inventor： Fa-Xiang Ding ,  Shuzhi Dong ,  Jessica Frie ,  Xin Gu ,  Jinlong Jiang ,  Alexander Pasternak ,  Haifeng Tang ,  Zhicai Wu ,  Yang Yu ,  Takao Suzuki

IPC: C07D471/10 ,  C07D307/88 ,  C07D498/20 ,  C07D519/00 ,  C07D471/20 ,  A61K31/438 ,  A61K31/46 ,  A61K31/435 ,  A61K31/4995 ,  A61K31/5386 ,  A61K45/06 ,  C07D451/00

CPC classification number: C07D498/20 ,  A61K31/435 ,  A61K31/46 ,  A61K31/4995 ,  A61K31/5386 ,  A61K45/06 ,  C07D451/00 ,  C07D471/10 ,  C07D471/20 ,  C07D519/00

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and conditions associated with excessive salt and water retention.

Abstract translation: 本发明提供式I化合物及其药学上可接受的盐，它们是ROMK（Kir1.1）通道的抑制剂。 该化合物可以用作利尿剂和/或利尿钠剂，并且用于治疗和预防包括心血管疾病如高血压，心力衰竭以及与过量盐和水滞留有关的病症的医学病症。

公开(公告)号：US11207312B2

公开(公告)日：2021-12-28

申请号：US16631673

申请日：2018-07-12

Applicant: Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Shuzhi Dong ,  Jack D. Scott ,  Haiqun Tang ,  Zhiqiang Zhao ,  Dexi Yang ,  Xin Gu ,  Jinlong Jiang ,  Li Xiao

IPC: A61K31/454 ,  A61P31/04 ,  A61K31/198 ,  A61K31/407 ,  A61K31/41 ,  A61K31/438 ,  A61K31/439 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/55 ,  A61K31/551 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D403/14 ,  C07D405/14 ,  C07D413/10 ,  C07D471/08 ,  C07D471/10 ,  C07D498/10

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：US10227331B2

公开(公告)日：2019-03-12

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: C07D403/10 ,  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: (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.

公开(公告)号：US09926317B2

公开(公告)日：2018-03-27

申请号：US15323985

申请日：2015-07-09

Applicant: Merck Sharp & Dohme Corp.

Inventor： Alexander Pasternak ,  Ian Davies ,  Fa-Xiang Ding ,  Jinglong Jiang ,  Shuzhi Dong ,  Xin Gu

IPC: C07D471/10 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

CPC classification number: C07D471/10 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

Abstract: The present invention provides compounds of Formula I and the pharmaceutically acceptable salts thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention.

公开(公告)号：US09839629B2

公开(公告)日：2017-12-12

申请号：US15101481

申请日：2014-12-19

Applicant: Merck Sharp & Dohme Corp.

Inventor： Shuzhi Dong ,  Alexander Pasternak ,  Xin Gu ,  Qinghong Fu ,  Jinlong Jiang ,  Fa-Xiang Ding ,  Haifeng Tang ,  Reynalda K. DeJesus ,  Takao Suzuki

IPC: C07D471/10 ,  C07D498/10 ,  A61K31/4545 ,  A61K31/537 ,  A61K31/4745 ,  A61K31/435 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  C07D519/00 ,  A61K31/437 ,  A61K31/438 ,  A61K31/444 ,  A61K45/06

CPC classification number: A61K31/435 ,  A61K31/437 ,  A61K31/438 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/537 ,  A61K45/06 ,  C07D471/10 ,  C07D498/10 ,  C07D519/00 ,  A61K2300/00

Abstract: Novel spirocyclic compounds of formula I: and pharmaceutically acceptable salts thereof are disclosed as inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure and chronic kidney disease and conditions associated with excessive salt and water retention. Pharmaceutical compositions and methods of treatment are also included.