公开(公告)号：US09527875B2

公开(公告)日：2016-12-27

申请号：US14418147

申请日：2013-07-31

Applicant: Merck Sharp & Dohme Corp.

Inventor： William K. Hagmann ,  Ravi P. Nargund ,  Timothy A. Blizzard ,  Hubert Josien ,  Purakkattle Biju ,  Christopher W. Plummer ,  Qun Dang ,  Bing Li ,  Derun Li ,  Linus S. Lin ,  Mingxiang Cui ,  Bin Hu ,  Jinglai Hao ,  Zhengxia Chen

IPC: C07D417/12 ,  A61K31/4353 ,  C07F9/58 ,  C07D401/14 ,  C07D221/16 ,  C07D401/12 ,  A61K31/435 ,  A61K31/444 ,  A61K45/06 ,  A61K31/4412 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61K31/675 ,  C07D405/12 ,  C07D409/14

CPC classification number: C07F9/58 ,  A61K31/435 ,  A61K31/4412 ,  A61K31/4427 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/513 ,  A61K31/5377 ,  A61K31/675 ,  A61K45/06 ,  C07D221/16 ,  C07D401/12 ,  C07D401/14 ,  C07D405/12 ,  C07D409/14 ,  C07D417/12

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.

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：US20140371138A1

公开(公告)日：2014-12-18

申请号：US14473117

申请日：2014-08-29

Applicant: Merck Sharp & Dohme Corp.

Inventor： Craig A. Coburn ,  John A. McCauley ,  Steven W. Ludmerer ,  Kun Liu ,  Joseph P. Vacca ,  Hao Wu ,  Bin Hu ,  Richard Soll ,  Fei Sun ,  Xinghai Wang ,  Man Yan ,  Chengren Zhang ,  Mingwei Zheng ,  Bin Zhong ,  Jian Zhu

IPC: C07K5/08 ,  A61K38/05 ,  A61K38/06 ,  C07D471/04 ,  A61K31/437 ,  C07K5/06 ,  A61K45/06

CPC classification number: C07D498/04 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/4985 ,  A61K31/506 ,  A61K31/5365 ,  A61K31/5377 ,  A61K31/5383 ,  A61K31/553 ,  A61K38/05 ,  A61K38/06 ,  A61K45/06 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D487/04 ,  C07D498/10 ,  C07K5/06 ,  C07K5/08

Abstract: The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.

Abstract translation: 本发明涉及可用作丙型肝炎病毒（HCV）NS5A抑制剂，这种化合物的合成以及这些化合物用于抑制HCV NS5A活性用于治疗或预防HCV感染的用途的式（I）化合物和 抑制基于细胞的系统中的HCV病毒复制和/或病毒生产。

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：US20150335648A1

公开(公告)日：2015-11-26

申请号：US14761256

申请日：2013-12-31

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Wensheng Yu ,  Ling Tong ,  Joseph A. Kozlowski ,  Oleg Selyutin ,  Lei Chen ,  Jae-Hun Kim ,  Deyou Sha ,  Razia Rizvi ,  Bandarpalle Shankar ,  Bin Hu ,  Bin Zhong ,  Dahai Wang ,  Jinglai Hao ,  Wei Wei ,  Tao Ji ,  Shuai Zan

IPC: A61K31/5365 ,  C07D498/04 ,  C07D513/04 ,  A61K45/06

CPC classification number: A61K31/5365 ,  A61K31/4985 ,  A61K31/7056 ,  A61K31/7072 ,  A61K45/06 ,  C07D498/04 ,  C07D513/04 ,  Y02A50/385 ,  Y02A50/389 ,  A61K2300/00

Abstract: The present invention relates to novel Heterocycle-Substituted Tetracyclic Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, A′, R2 R3, R4 and R are as defined herein. The present invention also relates to compositions comprising at least one Heterocycle-Substituted Tetracyclic Compound, and methods of using the Heterocycle-Substituted Tetracyclic Compounds for treating or preventing HCV infection in a patient.

Abstract translation: 本发明涉及式（I）的新型杂环取代的四环化合物：（I）及其药学上可接受的盐，其中A，A'，R 2 R3，R4和R如本文所定义。 本发明还涉及包含至少一种杂环取代的四环化合物的组合物，以及使用杂环取代的四环化合物治疗或预防患者HCV感染的方法。

公开(公告)号：US10000454B2

公开(公告)日：2018-06-19

申请号：US15310488

申请日：2015-05-19

Applicant: Merck Sharp & Dohme Corp.

Inventor： Tesfaye Biftu ,  Purakkattle Biju ,  Timothy A. Blizzard ,  Zhengxia Chen ,  Matthew J. Clements ,  Mingxiang Cui ,  Jessica L. Frie ,  William K. Hagmann ,  Bin Hu ,  Hubert Josien ,  Anilkumar G. Nair ,  Christopher W. Plummer ,  Cheng Zhu

IPC: C07D221/16 ,  A61K31/435 ,  A61K31/444 ,  C07D401/12 ,  C07D405/12 ,  A61K31/192 ,  A61K31/438 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/538 ,  A61K31/55 ,  A61K45/06 ,  C07C61/39 ,  C07D215/14 ,  C07D401/04 ,  C07D413/12

CPC classification number: C07D221/16 ,  A61K31/192 ,  A61K31/366 ,  A61K31/397 ,  A61K31/435 ,  A61K31/438 ,  A61K31/444 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/4985 ,  A61K31/538 ,  A61K31/55 ,  A61K45/06 ,  C07C61/39 ,  C07C2602/08 ,  C07C2603/12 ,  C07D215/14 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  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：US09932311B2

公开(公告)日：2018-04-03

申请号：US15023124

申请日：2014-09-30

Applicant: Merck Sharp & Dohme Corp.

Inventor： Tesfaye Biftu ,  Purakkattle Biju ,  Steven L. Colletti ,  Mingxiang Cui ,  William K. Hagmann ,  Bin Hu ,  Hubert Josien ,  Nam Fung Kar ,  Anilkumar Nair ,  Ravi Nargund ,  Donald M. Sperbeck ,  Cheng Zhu

IPC: C07D221/16 ,  C07D401/12 ,  C07D405/12 ,  C07D405/14 ,  A61K31/435 ,  A61K31/444 ,  A61K45/06

CPC classification number: C07D221/16 ,  A61K31/435 ,  A61K31/444 ,  A61K45/06 ,  C07D401/12 ,  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.

公开(公告)号：US20170166578A1

公开(公告)日：2017-06-15

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: C07D493/04 ,  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 ,  A61K31/506 ,  C07D213/74 ,  C07D417/04 ,  A61K45/06

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：US20170081287A1

公开(公告)日：2017-03-23

申请号：US15310488

申请日：2015-05-19

Applicant: Tesfaye BIFTU ,  Purakkattle BIJU ,  Timothy A. BLIZZARD ,  Zhengxia CHEN ,  Matthew J. CLEMENTS ,  Mingxiang CUI ,  Jessica L. FRIE ,  William K. HAGMANN ,  Bin HU ,  Hubert JOSIEN ,  Anilkumar G. NAIR ,  Christopher W. PLUMMER ,  Cheng ZHU ,  Merck Sharp & Dohme Corp.

Inventor： Tesfaye Biftu ,  Purakkattle Biju ,  Timothy A. Blizzard ,  Zhengxia Chen ,  Matthew J. Clements ,  Mingxiang Cui ,  Jessica L. Frie ,  William K. Hagmann ,  Bin Hu ,  Hubert Josien ,  Anilkumar G. Nair ,  Christopher W. Plummer ,  Cheng Zhu

IPC: C07D221/16 ,  A61K31/438 ,  C07D405/12 ,  C07D401/12 ,  A61K31/444 ,  C07C61/39 ,  A61K31/192 ,  A61K31/4725 ,  A61K31/4709 ,  A61K31/538 ,  C07D413/12 ,  A61K31/55 ,  C07D215/14 ,  A61K31/47 ,  C07D401/04 ,  A61K45/06

CPC classification number: C07D221/16 ,  A61K31/192 ,  A61K31/366 ,  A61K31/397 ,  A61K31/435 ,  A61K31/438 ,  A61K31/444 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/4725 ,  A61K31/4985 ,  A61K31/538 ,  A61K31/55 ,  A61K45/06 ,  C07C61/39 ,  C07C2602/08 ,  C07C2603/12 ,  C07D215/14 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D413/12 ,  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：US20160257697A1

公开(公告)日：2016-09-08

申请号：US14761259

申请日：2013-12-31

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Ling Tong ,  Wensheng Yu ,  Joseph A. Kozlowski ,  Lei Chen ,  Oleg Selyutin ,  Seong Heon Kim ,  Michael Dwyer ,  Bin Hu ,  Bin Zhong ,  Dahai Wang ,  Jinglai Hao ,  Changmao Shen ,  Zhixin Lei ,  Weijun Wang

IPC: C07D498/04 ,  C07D519/00 ,  A61K45/06 ,  A61K31/7056 ,  A61K31/7072 ,  A61K38/00 ,  A61K31/5365 ,  A61K38/21

CPC classification number: C07D498/04 ,  A61K31/4985 ,  A61K31/5365 ,  A61K31/7056 ,  A61K31/7072 ,  A61K38/005 ,  A61K38/212 ,  A61K45/06 ,  C07D519/00 ,  Y02A50/385 ,  Y02A50/387 ,  Y02A50/389 ,  Y02A50/395 ,  A61K2300/00

Abstract: Thiophene-substituted tetracyclic compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein A, A′, R2, R3, R4 and R5 are as defined herein. The compositions comprising at least one thiophene-substituted tetracyclic compound, and methods of using the thiophene-substituted tetracyclic compounds for treating or preventing HCV infection in a patient are also provided.

Abstract translation: 式（I）的噻吩取代的四环化合物及其药学上可接受的盐，其中A，A'，R 2，R 3，R 4和R 5如本文所定义。 还提供了包含至少一种噻吩取代的四环化合物的组合物，以及使用噻吩取代的四环化合物治疗或预防患者HCV感染的方法。

公开(公告)号：US20160207887A1

公开(公告)日：2016-07-21

申请号：US15023124

申请日：2014-09-30

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Tesfaye Biftu ,  Purakkattle Biju ,  Steven L. Colletti ,  Mingxiang Cui ,  William K. Hagmann ,  Bin Hu ,  Hubert Josien ,  Nam Fung Kar ,  Anilkumar Nair ,  Ravi Nargund ,  Donald M. Sperbeck ,  Cheng Zhu

IPC: C07D221/16 ,  A61K45/06 ,  C07D405/12 ,  A61K31/444 ,  A61K31/435 ,  C07D401/12

CPC classification number: C07D221/16 ,  A61K31/435 ,  A61K31/444 ,  A61K45/06 ,  C07D401/12 ,  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 dyslip idemia, 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，例如混合型或糖尿病型血脂异常，高脂血症，高胆固醇血症， 和高甘油三酯血症。