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：US10047098B2

公开(公告)日：2018-08-14

申请号：US15527975

申请日：2015-11-20

Applicant: Merck Sharp & Dohme Corp.

Inventor： Xing Dai ,  Jared N. Cumming ,  Hong Liu ,  Jack D. Scott

IPC: A61K31/519 ,  C07D491/048 ,  C07D491/052

Abstract: In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminopyrimidinone compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein RN, R1, RA, ring A, m, n, -L1-, ring B, RB, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

公开(公告)号：US20170362248A1

公开(公告)日：2017-12-21

申请号：US15527975

申请日：2015-11-20

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Xing Dai ,  Jared N. Cumming ,  Hong Liu ,  Jack D. Scott

IPC: C07D491/052

CPC classification number: C07D491/052 ,  A61P25/16 ,  A61P25/28

Abstract: In its many embodiments, the present invention provides certain C5-C6-oxacyclic fused iminopyrimidinone compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein RN, R1, RA, ring A, m, n, -L1-, ring B, RB, and p are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

公开(公告)号：US09428475B2

公开(公告)日：2016-08-30

申请号：US14221650

申请日：2014-03-21

Applicant: Merck Sharp & Dohme Corp.

Inventor： Jack D. Scott ,  Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming

IPC: A61K31/549 ,  C07D285/18 ,  A61K31/00 ,  A61K31/54 ,  A61K45/06 ,  C07D403/12 ,  C07D401/14 ,  C07D401/12 ,  C07D403/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D213/89 ,  C07D417/10 ,  C07C309/30 ,  C07D487/04 ,  C07D213/26 ,  A61K31/495 ,  C07D239/14

CPC classification number: A61K31/549 ,  A61K31/00 ,  A61K31/495 ,  A61K31/54 ,  A61K45/06 ,  C07C309/30 ,  C07D213/26 ,  C07D213/89 ,  C07D239/14 ,  C07D285/18 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D417/04 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination nation with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基二嗪二氧化物化合物，包括式（I）：（I）的化合物并包括其立体异构体，以及所述化合物立体异构体的药学上可接受的盐，其中R1，R2，R3，R4，R5 ，R9，环A，环B，m，n，p，-L1-，L2-和L3-是独立选择和如本文所定义的。 令人惊奇地发现本发明的新型亚氨基二嗪二氧化物化合物表现出预期使其作为BACE抑制剂和/或用于治疗和预防与β-淀粉样蛋白（Aβ）生产相关的各种病症的优点的性质。 还公开了包含一种或多种这样的化合物（单独并与一种或多种其它活性剂组合）的药物组合物及其制备和用于治疗与淀粉样蛋白β（Aβ）蛋白（包括阿尔茨海默病）相关的病理学的方法。

公开(公告)号：US09029362B2

公开(公告)日：2015-05-12

申请号：US14221640

申请日：2014-03-21

Applicant: Merck Sharp & Dohme Corp.

Inventor： Jack D. Scott ,  Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming

IPC: A61K31/54 ,  C07C309/30 ,  A61K31/00 ,  A61K45/06 ,  C07D403/12 ,  C07D401/14 ,  C07D401/12 ,  C07D403/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D285/18 ,  C07D213/89 ,  C07D417/10 ,  A61K31/549 ,  C07D213/26 ,  A61K31/495 ,  C07D239/14

CPC classification number: A61K31/549 ,  A61K31/00 ,  A61K31/495 ,  A61K31/54 ,  A61K45/06 ,  C07C309/30 ,  C07D213/26 ,  C07D213/89 ,  C07D239/14 ,  C07D285/18 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D417/04 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, -L2-, and -L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (“Aβ”) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's disease, are also disclosed.

Abstract translation: 在其许多实施方案中，本发明提供了某些亚氨基二嗪二氧化物化合物，包括式（I）化合物：并包括其立体异构体，以及所述化合物立体异构体的药学上可接受的盐，其中R1，R2，R3，R4，R5，R9， 环A，环B，m，n，p，-L 1 - ， - 2 - 和-L 3 - 独立地如本文所定义。 令人惊讶地发现本发明的新型亚氨基二嗪二氧化物化合物表现出预期使其作为BACE抑制剂和/或用于治疗和预防与“淀粉样蛋白”（“A”）生产有关的各种病理学的优点的性质。 还公开了包含一种或多种这样的化合物（单独并与一种或多种其它活性剂组合）的药物组合物，及其制备和用于治疗与淀粉样蛋白β（Aβ）蛋白（包括阿尔茨海默氏病）相关的病理学的方法。

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：US20180230152A1

公开(公告)日：2018-08-16

申请号：US15507577

申请日：2015-08-28

Applicant: Merck Sharp & Dohme Corp.

Inventor： Xing Dai ,  Kallol Basu ,  Duane DeMong ,  Sarah W. Li ,  Michael Miller ,  Jack D. Scott ,  Andrew W. Stamford

IPC: C07D487/04 ,  C07D413/14 ,  C07D403/14 ,  C07D401/14 ,  A61P25/16

CPC classification number: C07D487/04 ,  A61P25/16 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/14

Abstract: The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R9, and A are as defined herein, which are potent inhibitors of LRRK2 kinase and useful in the treatment or prevention of diseases in which the LRRK2 kinase is involved, such as Parkinson's Disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which LRRK-2 kinase is involved.

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.

公开(公告)号：US20170246300A1

公开(公告)日：2017-08-31

申请号：US15516076

申请日：2015-09-28

Applicant: Shuwen HE ,  Jared N. CUMMING ,  Jack D. SCOTT ,  Merck Sharp & Dohme Corp.

Inventor： Shuwen He ,  Jared N. Cumming ,  Jack D. Scott

IPC: A61K45/06 ,  C07D519/06 ,  C07D513/04 ,  C07D417/12 ,  A61K31/54 ,  A61K31/549

CPC classification number: A61K45/06 ,  A61K31/54 ,  A61K31/549 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04 ,  C07D519/00 ,  C07D519/06

Abstract: In its many embodiments, the present invention provides certain C5-C6 fused tricyclic iminothiadiazine compounds, including compounds Formula (I): or a tautomer thereof, and pharmaceutically acceptable salts of said compounds and said tautomers, wherein R1A, R2, R3, RA, ring A, RA, m, -L1-, and RL are as defined herein. The novel compounds of the invention are useful as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including for the possible treatment of Alzheimer's disease, are also disclosed.

公开(公告)号：US09687494B2

公开(公告)日：2017-06-27

申请号：US15250338

申请日：2016-08-29

Applicant: Merck Sharp & Dohme Corp.

Inventor： Jack D. Scott ,  Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming ,  Ulrich Iserloh

IPC: A61K31/506 ,  A61K31/549 ,  A61K31/00 ,  A61K31/54 ,  A61K45/06 ,  C07D403/12 ,  C07D401/14 ,  C07D401/12 ,  C07D403/04 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D495/04 ,  C07D285/18 ,  C07D213/89 ,  C07D417/10 ,  C07C309/30 ,  C07D487/04 ,  C07D213/26 ,  A61K31/495 ,  C07D239/14

CPC classification number: A61K31/549 ,  A61K31/00 ,  A61K31/495 ,  A61K31/54 ,  A61K45/06 ,  C07C309/30 ,  C07D213/26 ,  C07D213/89 ,  C07D239/14 ,  C07D285/18 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D417/04 ,  C07D417/10 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61K2300/00

Abstract: In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): (I) and include stereoisomers thereof, and pharmaceutically acceptable salts of said compounds stereoisomers, wherein each of R1, R2, R3, R4, R5, R9, ring A, ring B, m, n, p, -L1-, L2-, and L3- is selected independently and as defined herein. The novel iminothiadiazine dioxide compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related to β-amyloid (Aβ) production. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers disease, are also disclosed.