公开(公告)号：US20210188818A1

公开(公告)日：2021-06-24

申请号：US16755177

申请日：2018-10-08

Applicant: Merck Sharp & Dohme Corp.

Inventor： John Acton ,  David Annunziato Candito ,  J. Michael Ellis ,  Peter H. Fuller ,  Hakan Gunaydin ,  Blair T. Lapointe ,  Weiguo Liu ,  Joey L. Methot ,  Santhosh F. Neelamkavil ,  Barbara Pio ,  Vladimir Simov ,  Harold B. Wood

IPC: C07D403/14 ,  C07D401/14 ,  C07D498/10 ,  C07D498/04 ,  C07D413/14 ,  C07D519/00 ,  C07D405/14

Abstract: The present invention is directed to substituted certain reversed indazole compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1A, R1B, X, Y, RZ and R2 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 and other diseases and disorders described herein. 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：US09340530B2

公开(公告)日：2016-05-17

申请号：US14383176

申请日：2013-02-27

Applicant: Merck, Sharp & Dohme Corp.

Inventor： Mihir Mandal ,  Timothy A. Blizzard ,  Helen Chen ,  Harry Chobanian ,  Yan Guo ,  Barbara Pio ,  Zhicai Wu ,  Tesfaye Biftu ,  William J. Greenlee ,  Johnny Zhaoning Zhu

IPC: A61K31/44 ,  C07D401/06 ,  C07D417/14 ,  C07D405/06 ,  A61K45/06 ,  A61K31/365 ,  A61K31/4365 ,  A61K31/443 ,  A61K31/4439 ,  A61K31/616 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  A61K31/444

CPC classification number: C07D405/06 ,  A61K31/365 ,  A61K31/4365 ,  A61K31/443 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/616 ,  A61K45/06 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  A61K2300/00

Abstract: The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof, wherein: X is —O—, —N(R), —C(R8)(R9) or —C(O)—; and Y is —O—, —N(R), —C(R8)(R9) or —C(O)— and the remaining variables are described herein. The compounds of the invention are effective inhibitors of the PAR-1 receptor. The inventive compounds may be used for the treatment or prophylaxis of disease states such as ACS, secondary prevention of myocardial infarction or stroke, or PAD.

Abstract translation: 本发明涉及下式的双环烟肼衍生物或其药学上可接受的盐，其中：X是-O - ， - N（R），-C（R 8）（R 9）或-C（O） - ; 并且Y是-O - ， - N（R），-C（R 8）（R 9）或-C（O） - ，其余变量在本文中描述。 本发明的化合物是PAR-1受体的有效抑制剂。 本发明化合物可用于治疗或预防诸如ACS，二级预防心肌梗塞或中风或PAD的疾病状态。

公开(公告)号：US20140336177A1

公开(公告)日：2014-11-13

申请号：US14364908

申请日：2012-12-11

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Barbara Pio ,  Alexander Pasternak ,  Aurash Shahripour ,  Haifeng Tang ,  Shawn Walsh

IPC: C07D513/04 ,  A61K31/5383 ,  A61K45/06 ,  A61K31/542 ,  C07D487/04 ,  A61K31/4985 ,  C07D498/04 ,  A61K31/553

CPC classification number: C07D513/04 ,  A61K31/401 ,  A61K31/41 ,  A61K31/4178 ,  A61K31/4422 ,  A61K31/4985 ,  A61K31/5383 ,  A61K31/542 ,  A61K31/553 ,  A61K31/585 ,  A61K31/675 ,  A61K45/06 ,  C07D487/04 ,  C07D498/04 ,  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 act as diuretics and natriuretics and are valuable pharmaceutically active compounds for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension and conditions resulting from 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。 该化合物作为利尿剂和利尿钠，并且是用于治疗和预防包括心血管疾病如高血压在内的医学病症和由于过量的盐和水保留引起的病症的有价值的药物活性化合物。

公开(公告)号：US10059667B2

公开(公告)日：2018-08-28

申请号：US15110894

申请日：2015-02-03

Applicant: MERCK SHARP & DOHME CORP. ,  Harry Chobanian ,  Duane DeMong ,  Yan Guo ,  Zhiyong Hu ,  Michael Miller ,  Barbara Pio ,  Christopher W. Plummer ,  Dong Xiao ,  Cangming Yang ,  Rui Zhang

Inventor： Harry Chobanian ,  Duane DeMong ,  Yan Guo ,  Zhiyong Hu ,  Michael Miller ,  Barbara Pio ,  Christopher W. Plummer ,  Dong Xiao ,  Cangming Yang

IPC: C07D211/42 ,  A61K45/06 ,  A61K31/366 ,  A61K31/397 ,  A61K31/40 ,  A61K31/44 ,  C07D231/20 ,  A61K31/4985 ,  C07D401/04 ,  C07D239/52 ,  C07C217/52 ,  C07D205/04 ,  C07D491/056 ,  C07D265/30 ,  C07D207/08 ,  C07D207/10 ,  C07D207/12 ,  C07D209/52 ,  C07D209/54 ,  C07D211/22 ,  C07D213/30 ,  C07D213/64 ,  C07D213/65 ,  C07D213/69 ,  C07D307/86 ,  C07D307/88 ,  C07C59/72 ,  C07D205/12 ,  C07D213/647

CPC classification number: C07D211/42 ,  A61K31/366 ,  A61K31/397 ,  A61K31/40 ,  A61K31/44 ,  A61K31/4985 ,  A61K45/06 ,  C07C59/72 ,  C07C217/52 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07D205/04 ,  C07D205/12 ,  C07D207/08 ,  C07D207/10 ,  C07D207/12 ,  C07D209/52 ,  C07D209/54 ,  C07D211/22 ,  C07D213/30 ,  C07D213/64 ,  C07D213/647 ,  C07D213/65 ,  C07D213/69 ,  C07D231/20 ,  C07D239/52 ,  C07D265/30 ,  C07D307/86 ,  C07D307/88 ,  C07D401/04 ,  C07D491/056 ,  A61K2300/00

Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

公开(公告)号：US20170217920A1

公开(公告)日：2017-08-03

申请号：US15328908

申请日：2015-08-03

Applicant: Merck Sharp & Dohme Corp.

Inventor： Harry Chobanian ,  Duane DeMong ,  Yan Guo ,  Barbara Pio ,  Christopher W. Plummer

IPC: C07D335/06 ,  C07D213/64 ,  C07D311/04

Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

公开(公告)号：US20160332968A1

公开(公告)日：2016-11-17

申请号：US15110894

申请日：2015-02-03

Applicant: Harry CHOBANIAN ,  Duane DEMONG ,  Yan Guo ,  Zhiyong Hu ,  Barbara PIO ,  Christopher PLUMMER ,  Dong XIAO ,  Cangming YANG ,  Rui ZHANG ,  Merck Sharp & Dohme Corp. ,  Michael MILLER

Inventor： Harry Chobanian ,  Duane DeMong ,  Yan Guo ,  Zhiyong Hu ,  Michael Miller ,  Barbara Pio ,  Christopher W. Plummer ,  Dong Xiao ,  Michael Yang

IPC: C07D211/42 ,  C07D211/22 ,  C07D205/04 ,  C07D209/54 ,  C07D209/52 ,  C07D207/12 ,  C07D205/12 ,  C07C217/52 ,  C07D401/04 ,  C07D265/30 ,  C07C59/72 ,  C07D213/64 ,  C07D213/69 ,  C07D239/52 ,  C07D231/20 ,  C07D307/88 ,  C07D491/056 ,  C07D307/86 ,  C07D213/30 ,  C07D213/647 ,  C07D207/08

CPC classification number: C07D211/42 ,  A61K31/366 ,  A61K31/397 ,  A61K31/40 ,  A61K31/44 ,  A61K31/4985 ,  A61K45/06 ,  C07C59/72 ,  C07C217/52 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/10 ,  C07D205/04 ,  C07D205/12 ,  C07D207/08 ,  C07D207/10 ,  C07D207/12 ,  C07D209/52 ,  C07D209/54 ,  C07D211/22 ,  C07D213/30 ,  C07D213/64 ,  C07D213/647 ,  C07D213/65 ,  C07D213/69 ,  C07D231/20 ,  C07D239/52 ,  C07D265/30 ,  C07D307/86 ,  C07D307/88 ,  C07D401/04 ,  C07D491/056 ,  A61K2300/00

Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

Abstract translation: 结构式（I）的新型化合物及其药学上可接受的盐是G蛋白偶联受体40（GPR40）的激动剂，可用于治疗，预防和抑制G蛋白偶联受体 受体40.本发明的化合物可用于治疗2型糖尿病，以及通常与该疾病相关的病症，包括肥胖症和脂质疾病，例如混合或糖尿病性血脂异常，高脂血症，高胆固醇血症和 高甘油三酯血症

公开(公告)号：US20160304515A1

公开(公告)日：2016-10-20

申请号：US15101467

申请日：2014-12-16

Applicant: Harry CHOBANIAN ,  Barbara PIO ,  Yan GUO ,  Fa-Xiang DING ,  Shuzhi DONG ,  Shawn P. WALSH ,  Jinlong JIANG ,  Dooseop KIM ,  MERCK SHARP & DOHME CORP.

Inventor： Harry Chobanian ,  Barbara Pio ,  Yan Guo ,  Fa-Xiang Ding ,  Shuzhi Dong ,  Shawn P. Walsh ,  Jinlong Jiang ,  Dooseop Kim

IPC: C07D471/04 ,  A61K45/06 ,  A61K31/55 ,  C07D487/04 ,  A61K31/4985 ,  C07D498/04 ,  A61K31/519 ,  A61K31/437

CPC classification number: C07D471/04 ,  A61K31/401 ,  A61K31/4178 ,  A61K31/424 ,  A61K31/437 ,  A61K31/4422 ,  A61K31/496 ,  A61K31/4965 ,  A61K31/4985 ,  A61K31/519 ,  A61K31/55 ,  A61K31/585 ,  A61K45/06 ,  C07D487/04 ,  C07D498/04 ,  A61K2300/00

Abstract: The present invention provides compounds of Formula (I) (Formula (I)) including 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：US09139585B2

公开(公告)日：2015-09-22

申请号：US14353804

申请日：2012-10-25

Applicant: Merck Sharp & Dohme Corp.

Inventor： Shawn P. Walsh ,  Alexander Pasternak ,  Reynalda K. DeJesus ,  Haifeng Tang ,  Barbara Pio ,  Aurash Shahripour ,  Kevin M. Belyk ,  Harry R. Chobanian ,  Yan Guo ,  Jessica L. Frie ,  Zhi-Cai Shi ,  Helen Chen ,  Timothy A. Blizzard ,  Brian Cato

IPC: A61K31/496 ,  C07D405/12 ,  C07D405/14 ,  C07D471/08 ,  C07D498/08 ,  C07D487/18 ,  C07D487/08 ,  C07D491/08 ,  C07D409/14

CPC classification number: C07D471/08 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D487/08 ,  C07D487/18 ,  C07D491/08 ,  C07D498/08

Abstract: This invention relates to compounds of Formula I-VI having the following general structure: and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir1.1). The compounds are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure.

Abstract translation: 本发明涉及具有以下一般结构的式I-VI化合物及其药学上可接受的盐，它们是肾外
膜（ROMK）通道（Kir1.1）的抑制剂。 这些化合物可用作利尿剂和利尿钠，因此可用于治疗和预防由过度的盐和水分滞留引起的疾病，包括心血管疾病如高血压和慢性和急性心力衰竭。

公开(公告)号：US20150025046A1

公开(公告)日：2015-01-22

申请号：US14383176

申请日：2013-02-27

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Mihir Mandal ,  Timothy A. Blizzard ,  Helen Chen ,  Harry Chobanian ,  Yan Guo ,  Barbara Pio ,  Zhicai Wu ,  Tesfaye Biftu ,  William J. Greenlee ,  Johnny Zhaoning Zhu

IPC: C07D405/06 ,  A61K45/06 ,  C07D405/14 ,  C07D401/06 ,  A61K31/4439 ,  C07D413/14 ,  A61K31/444 ,  A61K31/443 ,  C07D417/14

CPC classification number: C07D405/06 ,  A61K31/365 ,  A61K31/4365 ,  A61K31/443 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/616 ,  A61K45/06 ,  C07D401/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  A61K2300/00

Abstract: The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof, wherein: X is —O—, —N(R), —C(R8)(R9) or —C(O)—; and Y is —O—, —N(R), —C(R8)(R9) or —C(O)— and the remaining variables are described herein. The compounds of the invention are effective inhibitors of the PAR-1 receptor. The inventive compounds may be used for the treatment or prophylaxis of disease states such as ACS, secondary prevention of myocardial infarction or stroke, or PAD.

Abstract translation: 本发明涉及下式的双环烟肼衍生物或其药学上可接受的盐，其中：X是-O - ， - N（R），-C（R 8）（R 9）或-C（O） - ; 并且Y是-O - ， - N（R），-C（R 8）（R 9）或-C（O） - ，其余变量在本文中描述。 本发明的化合物是PAR-1受体的有效抑制剂。 本发明化合物可用于治疗或预防诸如ACS，二级预防心肌梗塞或中风或PAD的疾病状态。

公开(公告)号：US20190337961A1

公开(公告)日：2019-11-07

申请号：US16465156

申请日：2017-12-15

Applicant: Merck Sharp & Dohme Corp.

Inventor： Michael Miller ,  Harry R. Chobanian ,  Shuwen He ,  Jinsong Hao ,  Barbara Pio ,  Yan Guo ,  Dong Xiao

IPC: C07D491/107 ,  C07D311/96 ,  C07D405/12 ,  A61P3/10

Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.