公开(公告)号：US10786488B2

公开(公告)日：2020-09-29

申请号：US16479997

申请日：2018-01-23

申请人： MERCK SHARP & DOHME CORP.

发明人： Tao Yu ,  John A. McCauley ,  Alan Whitehead ,  James M. Apgar ,  Izzat T. Raheem ,  Guizhen Dong ,  Sherman T. Waddell ,  Hong Li

IPC分类号： A61K31/4375 ,  A61K31/427 ,  A61K31/4402 ,  A61K31/47 ,  A61K31/506 ,  A61K31/5365 ,  A61K31/675 ,  A61K31/7068 ,  A61K31/7076 ,  C07D491/147

摘要： The present invention relates to Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein R1 is as defined herein. The present invention also relates to compositions comprising at least one Substituted Quinolizine Derivative, and methods of using the Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.

公开(公告)号：US20160200715A1

公开(公告)日：2016-07-14

申请号：US14912212

申请日：2014-08-18

申请人： Zhiqiang YANG ,  Guizhen DONG ,  Milana MALETIC ,  MERCK SHARP & DOHME CORP.

发明人： Zhiqiang Yang ,  Guizhen Dong ,  Milana Maletic

IPC分类号： C07D413/14 ,  A61K31/444 ,  C07D405/14 ,  A61K31/4439 ,  A61K45/06

CPC分类号： A61K31/60 ,  A61K31/4155 ,  A61K31/4245 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/444 ,  A61K45/06 ,  C07D405/14 ,  C07D413/14 ,  A61K2300/00

摘要： The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof wherein: R1 is W is 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 ASC, secondary prevention of myocardial infarction or stroke, or PAD.

摘要翻译： 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：R1是W，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疾病状态如ASC，二次预防心肌梗塞或中风或PAD。

公开(公告)号：US20160185764A1

公开(公告)日：2016-06-30

申请号：US14912233

申请日：2014-08-18

申请人： MERCK SHARP & DOHME CORP.

发明人： Zhiqiang Yang ,  Fengqi Zhang ,  Guizhen Dong ,  Sandra Lee Knowles ,  Milana Maletic

IPC分类号： C07D405/14 ,  A61K31/444 ,  A61K45/06 ,  C07D405/06 ,  A61K31/443

CPC分类号： C07D405/14 ,  A61K31/4365 ,  A61K31/443 ,  A61K31/444 ,  A61K31/616 ,  A61K45/06 ,  C07D405/06 ,  A61K2300/00

摘要： The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof wherein: R1 is —[C(Ra)(Rb)]x—[C(Rb)(Rb)]y—C(O)NH2, or —N(H)—[(CH2)]z—C(O)—NH2, W is 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 ASC, secondary prevention of myocardial infarction or stroke, or PAD.

摘要翻译： 本发明涉及下式的双环和啶衍生物或其药学上可接受的盐，其中：R 1是 - [C（R a）（R b）] x- [C（R b）（R b）] y -C（O） 或-N（H） - [（CH 2）] z -C（O）-NH 2，W和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疾病状态如ASC，二次预防心肌梗塞或中风或PAD。

公开(公告)号：US20190282579A1

公开(公告)日：2019-09-19

申请号：US16301936

申请日：2017-05-12

申请人： Merck Sharp & Dohme Corp.

发明人： Raphaelle Berger ,  Guizhen Dong ,  Subharekha Raghavan ,  Zhiqiang Yang

IPC分类号： A61K31/519 ,  A61K45/06

摘要： Provided are methods for treating or preventing a fibrotic disease selected from systemic sclerosis, cystic fibrosis, non-alcoholic steatohepatitis, Peyronie's disease, or interstitial lung disease; the method comprising administering a therapeutically effective amount of a compound of Formula (I) (wherein R1, R2, R3, R4, and R5 are as herein described) or a pharmaceutically acceptable salt thereof, to a patient in need of such therapy.

公开(公告)号：US20180015106A1

公开(公告)日：2018-01-18

申请号：US15715446

申请日：2017-09-26

申请人： Merck Sharp & Dohme Corp.

发明人： Zhiqiang Yang ,  Guizhen Dong ,  Milana Maletic

IPC分类号： A61K31/60 ,  C07D405/14 ,  A61K45/06 ,  A61K31/444 ,  A61K31/4439 ,  A61K31/4365 ,  A61K31/4245 ,  C07D413/14 ,  A61K31/4155

CPC分类号： A61K31/60 ,  A61K31/4155 ,  A61K31/4245 ,  A61K31/4365 ,  A61K31/4439 ,  A61K31/444 ,  A61K45/06 ,  C07D405/14 ,  C07D413/14 ,  A61K2300/00

摘要： The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof wherein: R1 is W is 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 ASC, secondary prevention of myocardial infarction or stroke, or PAD.

公开(公告)号：US09353101B2

公开(公告)日：2016-05-31

申请号：US14398165

申请日：2013-04-26

申请人： Merck Sharp & Dohme Corp.

发明人： John J. Acton, III ,  Feng Ye ,  Petr Vachal ,  Deyou Sha ,  James F. Dropinski ,  Lin Chu ,  Debra Ondeyka ,  Alexander J. Kim ,  Vincent J. Colandrea ,  Yi Zang ,  Fengqi Zhang ,  Guizhen Dong

IPC分类号： C07D417/14 ,  C07D413/14 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/444 ,  A61K45/06

CPC分类号： C07D417/14 ,  A61K31/444 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D413/14

摘要： Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and may be useful for raising HDL-cholesterol and reducing LDL-cholesterol in human patients and for treating or preventing atherosclerosis.

摘要翻译： 具有式I结构的化合物，包括化合物的药学上可接受的盐，是CETP抑制剂，可用于提高人类患者的HDL-胆固醇和降低LDL-胆固醇，并用于治疗或预防动脉粥样硬化。

公开(公告)号：US20150111866A1

公开(公告)日：2015-04-23

申请号：US14398165

申请日：2013-04-26

申请人： Merck Sharp & Dohme Corp.

发明人： John J. Acton, III ,  Feng Ye ,  Petr Vachal ,  Deyou Sha ,  James F. Dropinski ,  Lin Chu ,  Debra Ondeyka ,  Alexander J. Kim ,  Vincent J. Colandrea ,  Yi Zang ,  Fengqi Zhang ,  Guizhen Dong

IPC分类号： C07D417/14 ,  A61K45/06 ,  A61K31/5377 ,  A61K31/444 ,  C07D413/14 ,  A61K31/506

CPC分类号： C07D417/14 ,  A61K31/444 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D413/14

摘要： Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and may be useful for raising HDL-cholesterol and reducing LDL-cholesterol in human patients and for treating or preventing atherosclerosis.

摘要翻译： 具有式I结构的化合物，包括化合物的药学上可接受的盐，是CETP抑制剂，可用于提高人类患者的HDL-胆固醇和降低LDL-胆固醇，并用于治疗或预防动脉粥样硬化。

公开(公告)号：US10925876B2

公开(公告)日：2021-02-23

申请号：US16301936

申请日：2017-05-12

申请人： Merck Sharp & Dohme Corp.

发明人： Raphaelle Berger ,  Guizhen Dong ,  Subharekha Raghavan ,  Zhiqiang Yang

IPC分类号： A61K31/519 ,  A61K45/06 ,  C07D519/00 ,  C07D235/00 ,  A61K31/505 ,  C07D249/16

摘要： Provided are methods for treating or preventing a fibrotic disease selected from systemic sclerosis, cystic fibrosis, non-alcoholic steatohepatitis, Peyronie's disease, or interstitial lung disease; the method comprising administering a therapeutically effective amount of a compound of Formula (I) (wherein R1, R2, R3, R4, and R5 are as herein described) or a pharmaceutically acceptable salt thereof, to a patient in need of such therapy.

公开(公告)号：US09701669B2

公开(公告)日：2017-07-11

申请号：US14912233

申请日：2014-08-18

申请人： Merck Sharp & Dohme Corp.

发明人： Zhiqiang Yang ,  Fengqi Zhang ,  Guizhen Dong ,  Sandra Lee Knowles ,  Milana Maletic

IPC分类号： A61K31/4427 ,  C07D405/06 ,  C07D405/14 ,  A61K45/06 ,  A61K31/4365 ,  A61K31/443 ,  A61K31/444 ,  A61K31/616

CPC分类号： C07D405/14 ,  A61K31/4365 ,  A61K31/443 ,  A61K31/444 ,  A61K31/616 ,  A61K45/06 ,  C07D405/06 ,  A61K2300/00

摘要： The present invention relates to bicyclic himbacine derivatives of the formula or a pharmaceutically acceptable salt thereof wherein: R1 is —[C(Ra)(Rb)]x—[C(Rb)(Rb)]y—C(O)NH2, or —N(H)—[(CH2)]z—C(O)—NH2, W is 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 ASC, secondary prevention of myocardial infarction or stroke, or PAD.

公开(公告)号：US20170073355A2

公开(公告)日：2017-03-16

申请号：US14945576

申请日：2015-11-19

申请人： Merck Sharp & Dohme Corp.

发明人： Raphaelle Berger ,  Guizhen Dong ,  Subharekha Raghavan ,  Zhiqiang Yang

IPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06

CPC分类号： C07D519/00 ,  A61K31/519 ,  A61K45/06 ,  C07D487/04

摘要： A compound of Formula I or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of Formula I or a pharmaceutically acceptable salt thereof.

摘要翻译： 或其药学上可接受的盐能够调节身体的环鸟苷酸（“cGMP”）的产生，并且通常适合于治疗和预防与受干扰的cGMP平衡相关的疾病。 本发明还涉及用于制备式I化合物或其药学上可接受的盐的方法，用于治疗和预防上述疾病和用于制备用于该目的的药物以及包含式I化合物的药物组合物 或其药学上可接受的盐。