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：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：US20200087375A1

公开(公告)日：2020-03-19

申请号：US16495703

申请日：2018-03-19

Applicant: Merck Sharp & Dohme Corp.

Inventor： Danqing Feng ,  David N. Hunter ,  Pei Huo ,  Ahmet Kekec ,  Songnian Lin ,  Christopher R. Moyes ,  Ravi Nargund ,  Brenda Pipik ,  Dmitri A. Pissarnitski ,  Lin Yan ,  Zhiqiang Zhao ,  Yuping Zhu

IPC: C07K14/62 ,  A61K47/61 ,  A61K47/54

Abstract: An insulin conjugate comprising or consisting of a tri-valent sugar cluster is described. In particular aspects, the insulin conjugate displays a pharmacokinetic (PK) and/or pharmacodynamic (PD) profile that is responsive to the systemic concentrations of a saccharide such as glucose or alpha-methylmannose even when administered to a subject in need thereof in the absence of an exogenous multivalent saccharide-binding molecule such as Con A.

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：US20210177981A1

公开(公告)日：2021-06-17

申请号：US16771819

申请日：2018-12-13

Applicant: Merck Sharp & Dohme Corp. ,  SmartCells,Inc.

Inventor： Lin Yan ,  Pei Huo ,  Ahmet Kekec ,  Yuping Zhu ,  Dmitri Pissarnitski ,  Danqing D. Feng ,  Chris Moyes ,  Zhiqiang Zhao ,  David N. Hunter ,  Songnian Lin ,  Thomas M. Lancaster ,  Benjamin Chen

IPC: A61K47/61 ,  A61K47/54 ,  A61P3/10

Abstract: The present disclosure provides conjugates which comprise an insulin molecule conjugated via a conjugate framework to one or more separate ligands that include a first saccharide, and wherein the conjugate framework also comprises a fatty chain (e.g., a C8-30 fatty chain). In certain embodiments, a conjugate is characterized in that, when the conjugate is administered to a mammal, at least one pharmacokinetic (PK) and/or pharmacodynamic (PD) property of the conjugate is sensitive to serum concentration of a second saccharide. In certain embodiments, a conjugate is also characterized by having a protracted PK profile. Exemplary conjugates and sustained release formulations are provided in addition to methods of use and preparation.

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：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：US20140296311A1

公开(公告)日：2014-10-02

申请号：US14354992

申请日：2012-10-26

Applicant: MERCK SHARP & DOHME CORP.

Inventor： William Greenlee ,  Dmitri Pissarnitski ,  Zhiqiang Zhao ,  Zhaoning Zhu

IPC: C07D413/10

CPC classification number: C07D413/10 ,  C07D413/14

Abstract: Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and use of the compounds in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.

Abstract translation: 本文公开了式（I）的化合物及其药学上可接受的盐，其中每个取代基被给出如说明书和权利要求书中所阐述的定义。 还公开了含有式（I）化合物的药物组合物和该化合物在治疗神经变性疾病或病症如阿尔茨海默病中的用途。

公开(公告)号：US20200281913A1

公开(公告)日：2020-09-10

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

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：US20190144432A1

公开(公告)日：2019-05-16

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 ,  A61K31/198 ,  C07D403/12 ,  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 ,  A61K31/407 ,  A61K31/5025 ,  A61K31/517 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/14 ,  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 ,  C07D487/04 ,  A61K31/506 ,  C07D471/04 ,  C07D417/14 ,  C07D417/10 ,  C07D413/10 ,  C07D407/14 ,  C07D403/14 ,  C07D401/10 ,  C07D413/14 ,  A61K31/41

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: 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.