公开(公告)号：US09840512B2

公开(公告)日：2017-12-12

申请号：US14767815

申请日：2014-02-20

Applicant: Merck Sharp & Dohme Corp.

Inventor： Linda L. Brockunier ,  Helen Chen ,  Harry R. Chobanian ,  Matthew J. H. Clements ,  Alejandro Crespo ,  Duane E. DeMong ,  Yan Guo ,  William K. Hagmann ,  Karen M. Marcantonio ,  Michael Miller ,  Barbara Pio ,  Christopher W. Plummer ,  Dong Xiao

IPC: C07D311/04 ,  C07D311/28 ,  C07D491/052 ,  C07D493/04 ,  C07D201/00 ,  C07D405/14 ,  C07D319/20 ,  C07D405/04 ,  C07D405/06 ,  C07D405/10 ,  C07D413/10 ,  C07D417/04 ,  C07D491/048 ,  A61K31/352 ,  A61K31/416 ,  A61K31/422 ,  A61K31/427 ,  A61K31/436 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/497 ,  A61K31/538 ,  A61K45/06

CPC classification number: C07D493/04 ,  A61K31/352 ,  A61K31/416 ,  A61K31/422 ,  A61K31/427 ,  A61K31/436 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/497 ,  A61K31/538 ,  A61K45/06 ,  C07D201/00 ,  C07D311/04 ,  C07D311/28 ,  C07D319/20 ,  C07D405/04 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D413/10 ,  C07D417/04 ,  C07D491/048 ,  C07D491/052

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：US09834563B2

公开(公告)日：2017-12-05

申请号：US15039607

申请日：2014-12-17

Applicant: Merck Sharp & Dohme Corp.

Inventor： William K. Hagmann ,  Bing Li ,  Jason W. Szewczyk ,  Bowei Wang ,  Dann Parker ,  Timothy Blizzard ,  Hubert Josien ,  Purakkattle Biju ,  Harry Chobanian ,  Candido Gude ,  Ravi P. Nargund ,  Barbara Pio ,  Qun Dang ,  Linus S. Lin ,  Bin Hu ,  Mingxiang Cui ,  Zhengxia Chen ,  Meibi Dai ,  Zaihong Zhang ,  Ying Lv ,  Lili Tian

IPC: A61K31/506 ,  C07D493/04 ,  A61K45/06 ,  C07D213/64 ,  A61K31/44 ,  C07D409/12 ,  A61K31/4436 ,  C07D401/04 ,  A61K31/4545 ,  C07D471/04 ,  A61K31/437 ,  C07D405/12 ,  A61K31/4433 ,  C07D401/12 ,  A61K31/4439 ,  A61K31/443 ,  C07D239/34 ,  A61K31/505 ,  C07D451/06 ,  A61K31/46 ,  C07D221/20 ,  A61K31/438 ,  C07D213/74 ,  C07D417/04

CPC classification number: C07D493/04 ,  A61K31/437 ,  A61K31/438 ,  A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/4545 ,  A61K31/46 ,  A61K31/505 ,  A61K31/506 ,  A61K45/06 ,  C07D213/64 ,  C07D213/74 ,  C07D221/20 ,  C07D239/34 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D417/04 ,  C07D451/06 ,  C07D471/04

Abstract: The present invention relates to a compound represented by formula (I): and pharmaceutically acceptable salts thereof. The compounds of formula I 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：US20160207922A1

公开(公告)日：2016-07-21

申请号：US14908222

申请日：2014-07-28

Applicant: Merck Sharp & Dohme Corp.

Inventor： Haifeng Tang ,  Barbara Pio ,  Jinlong Jiang ,  Alexander Pasternak ,  Shuzhi Dong ,  Ronald Dale Ferguson, II ,  Zack Zhiqiang Guo ,  Harry Chobanian ,  Jessica Frie ,  Yan Guo ,  Zhicai Wu ,  Yang Yu ,  Ming Wang

IPC: C07D471/10 ,  A61K45/06 ,  A61K31/435 ,  A61K31/506 ,  A61K31/5386 ,  C07D451/00 ,  A61K31/46 ,  A61K31/497 ,  C07D498/10 ,  A61K31/444 ,  A61K31/501

CPC classification number: C07D471/10 ,  A61K31/435 ,  A61K31/444 ,  A61K31/46 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5386 ,  A61K45/06 ,  C07D451/00 ,  C07D493/04 ,  C07D498/10

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：US20160002255A1

公开(公告)日：2016-01-07

申请号：US14767815

申请日：2014-02-20

Applicant: Linda L. BROCKUNIER ,  Helen CHEN ,  Harry R. CHOBANIAN ,  Matthew J. CLEMENTS ,  Alejandro CRESPO ,  Duane E. DEMONG ,  Yan GUO ,  William K. HAGMANN ,  Karen M. MARCANTONIO ,  Michael MILLER ,  Barbara PIO ,  Christopher W. PLUMMER ,  Dong XIAO ,  MERCK SHARP & DOHME CORP.

Inventor： Linda L. Brockunier ,  Helen Chen ,  Harry R. Chobanian ,  Matthew J. H. Clements ,  Alejandro Crespo ,  Duane E. DeMong ,  Yan Guo ,  William K. Hagmann ,  Karen M. Marcantonio ,  Michael Miller ,  Barbara Pio ,  Christopher W. Plummer ,  Dong Xiao

IPC: C07D493/04 ,  A61K31/352 ,  C07D405/04 ,  A61K31/4433 ,  C07D311/28 ,  C07D417/04 ,  A61K31/427 ,  C07D491/052 ,  A61K31/436 ,  C07D405/14 ,  A61K31/444 ,  C07D413/10 ,  A61K31/422 ,  C07D405/10 ,  A61K31/416 ,  A61K31/497 ,  A61K31/538 ,  A61K45/06 ,  C07D311/04

CPC classification number: C07D493/04 ,  A61K31/352 ,  A61K31/416 ,  A61K31/422 ,  A61K31/427 ,  A61K31/436 ,  A61K31/4433 ,  A61K31/444 ,  A61K31/497 ,  A61K31/538 ,  A61K45/06 ,  C07D201/00 ,  C07D311/04 ,  C07D311/28 ,  C07D319/20 ,  C07D405/04 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D413/10 ,  C07D417/04 ,  C07D491/048 ,  C07D491/052

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：US20140296225A1

公开(公告)日：2014-10-02

申请号：US14353410

申请日：2012-10-22

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Haifeng Tang ,  Barbara Pio ,  Nardos Teumelsan ,  Alexander Pasternak ,  Reynalda DeJesus

IPC: C07D413/10 ,  A61K31/495 ,  C07D403/10 ,  A61K31/496 ,  C07D407/10 ,  C07D401/06 ,  C07D241/04 ,  A61K45/06

CPC classification number: C07D413/10 ,  A61K31/495 ,  A61K31/496 ,  A61K45/06 ,  C07D241/04 ,  C07D241/08 ,  C07D401/06 ,  C07D403/06 ,  C07D403/10 ,  C07D405/06 ,  C07D405/14 ,  C07D407/10 ,  C07D413/06 ,  C07D413/14

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：US20140288088A1

公开(公告)日：2014-09-25

申请号：US14353418

申请日：2012-10-22

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Haifeng Tang ,  Barbara Pio ,  Harry R. Chobanian

IPC: C07D405/14 ,  A61K31/496 ,  C07D409/14 ,  C07D417/14 ,  C07D495/04 ,  C07D405/06 ,  A61K45/06

CPC classification number: C07D405/14 ,  A61K31/495 ,  A61K31/496 ,  A61K45/06 ,  C07D241/04 ,  C07D405/06 ,  C07D409/14 ,  C07D417/14 ,  C07D495/04 ,  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.

公开(公告)号：US20140235628A1

公开(公告)日：2014-08-21

申请号：US14344681

申请日：2012-09-10

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Shawn Walsh ,  Alexander Pasternak ,  Brian Cato ,  Paul E. Finke ,  Jessica Frie ,  Qinghong Fu ,  Dooseop Kim ,  Barbara Pio ,  Aurash Shahripour ,  Zhi-Cai Shi ,  Haifeng Tang

IPC: C07D401/10 ,  C07D211/28 ,  C07D487/04 ,  C07D405/14 ,  C07D211/48 ,  C07D471/08 ,  C07D211/62 ,  C07D413/14

CPC classification number: C07D401/10 ,  C07D211/28 ,  C07D211/48 ,  C07D211/62 ,  C07D403/10 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14 ,  C07D471/08 ,  C07D487/04

Abstract: This invention relates to compounds having structural Formula I: and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kir1.1). The compounds of Formula I 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: 本发明涉及具有结构式I的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。 式I的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保持引起的疾病，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：US11174248B2

公开(公告)日：2021-11-16

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: A61K31/506 ,  C07D403/14 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D498/04 ,  C07D498/10 ,  C07D519/00

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：US11072602B2

公开(公告)日：2021-07-27

申请号：US16461569

申请日：2017-12-01

Applicant: Merck Sharp & Dohme Corp. ,  Michael Miller ,  Harry R. Chobanian ,  Shuwen He ,  Jinsong Hao ,  Barbara Pio

Inventor： Michael Miller ,  Harry R. Chobanian ,  Shuwen He ,  Jinsong Hao ,  Barbara Pio

IPC: C07D405/14 ,  C07D311/04 ,  C07D405/06 ,  C07D451/02 ,  C07D471/08 ,  C07D471/10 ,  C07D491/08 ,  A61K31/366 ,  A61K31/397 ,  A61K31/4985 ,  A61K45/06

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：US10968232B2

公开(公告)日：2021-04-06

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 ,  A61P3/10 ,  C07D311/96 ,  C07D405/12

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.