公开(公告)号：US10201533B2

公开(公告)日：2019-02-12

申请号：US15725407

申请日：2017-10-05

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Tao Yu ,  Yonglian Zhang ,  Sherman Tim Waddell ,  John M. Sanders ,  Thomas H. Graham ,  Hong Li

IPC: C07D491/00 ,  A61K31/44 ,  A61K31/4375 ,  C07D455/02 ,  A61K31/427 ,  A61K31/4402 ,  A61K31/444 ,  A61K31/4745 ,  A61K31/505 ,  A61K31/513 ,  A61K31/52 ,  A61K31/635 ,  A61K31/675 ,  C07D455/00 ,  C07D455/04 ,  C07D471/14 ,  C07D491/147 ,  A61K45/06 ,  C07D519/00

Abstract: The present invention relates to Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R1, R2, R3, R4, R5, R9 and R10 are 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：US20180051043A1

公开(公告)日：2018-02-22

申请号：US15560896

申请日：2016-03-25

Applicant: Merck Sharp & Dohme Corp.

Inventor： Tao Yu ,  Sherman T. Waddell ,  John A. McCauley ,  Thomas H. Graham ,  Hong Li ,  Izzat Raheem ,  Jay A. Grobler

IPC: C07F9/6561 ,  A61K31/683 ,  A61K31/675

CPC classification number: C07F9/6561 ,  A61K31/427 ,  A61K31/4402 ,  A61K31/505 ,  A61K31/513 ,  A61K31/52 ,  A61K31/635 ,  A61K31/675 ,  A61K31/683 ,  A61K2300/00

Abstract: The present invention relates to Phosphate Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R1, R2, R3, R4, R5, R9 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Phosphate Substituted Quinolizine Derivative, and methods of using the Phosphate Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.

公开(公告)号：US20160075724A1

公开(公告)日：2016-03-17

申请号：US14875438

申请日：2015-10-05

Applicant: Merck Sharp & Dohme Corp.

Inventor： Amjad Ali ,  Joann M. Napolitano ,  Qiaolin Deng ,  Zhijian Lu ,  Peter J. Sinclair ,  Gayle E. Hallet ,  Christopher F. Thompson ,  Nazia Quraishi ,  Cameron J. Smith ,  Julianne A. Hunt ,  Adrian A. Dowst ,  Yi-Heng Chen ,  Hong Li

IPC: C07F7/10 ,  C07D413/04 ,  C07D233/32 ,  C07D417/10 ,  C07D285/06 ,  C07D207/26 ,  C07D233/52 ,  C07D413/10 ,  C07D263/22 ,  C07D401/04

CPC classification number: C07F7/10 ,  A61K31/4015 ,  A61K31/4166 ,  A61K31/4168 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61K31/433 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D207/26 ,  C07D207/27 ,  C07D233/32 ,  C07D233/38 ,  C07D233/50 ,  C07D233/52 ,  C07D263/04 ,  C07D263/20 ,  C07D263/22 ,  C07D263/24 ,  C07D263/26 ,  C07D285/06 ,  C07D285/10 ,  C07D401/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/10 ,  C07D417/04 ,  C07D417/10

Abstract: Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: In the compounds of Formula I, B or R2 is a phenyl group which has an ortho aryl, heterocyclic, benzoheterocyclic or benzocycloalkyl substituent, and one other position on the 5-membered ring has an aromatic, heterocyclic, cycloalkyl, benzoheterocyclic or benzocycloalkyl substituent connected directly to the ring or attached to the ring through a —CH2—.

Abstract translation: 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，可用于升高HDL-胆固醇，降低LDL-胆固醇，以及用于治疗或预防动脉粥样硬化。在式I化合物中，B或 R2是具有邻芳基，杂环，苯并杂环或苯并环烷基取代基的苯基，并且在5元环上的另一个位置具有直接连接到环上或连接到环上的芳族，杂环，环烷基，苯并杂环或苯并环烷基取代基 通过-CH2-。

公开(公告)号：US20150307591A1

公开(公告)日：2015-10-29

申请号：US14653620

申请日：2013-12-19

Applicant: MERCK SHARP & DOHME CORP.

Inventor： Rebecca A. Chmielowski ,  Collette Cutler ,  Hong Li ,  Thomas O. Linden

IPC: C07K14/775 ,  C07K1/20

CPC classification number: C07K14/775 ,  C07K1/20

Abstract: Provided are methods of refolding and purifying lipoproteins on a chromatography column. In particular methods of refolding ApoL1 polypeptides using a hydrophobic interaction column (HIC). The present invention provides methods for the purification of an active form of a human lipoprotein, such as ApoL1. More particularly, the present invention relates to a method for renaturing an inclusion body of proteins expressed in a large quantity in E. coli into an active form using a hydrophobic interaction column and removal of impurities, e.g., endotoxins.

Abstract translation: 提供了在色谱柱上重新折叠和纯化脂蛋白的方法。 特别是使用疏水相互作用柱（HIC）重新折叠ApoL1多肽的方法。 本发明提供了纯化人脂蛋白（例如ApoL1）的活性形式的方法。 更具体地说，本发明涉及一种使用疏水相互作用柱将大量表达大量蛋白质的包涵体复性为活性形式的方法，并除去杂质例如内毒素。

公开(公告)号：US10786488B2

公开(公告)日：2020-09-29

申请号：US16479997

申请日：2018-01-23

Applicant: MERCK SHARP & DOHME CORP.

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

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

Abstract: 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：US10081647B2

公开(公告)日：2018-09-25

申请号：US15560896

申请日：2016-03-25

Applicant: Merck Sharp & Dohme Corp.

Inventor： Tao Yu ,  Sherman T. Waddell ,  John A. McCauley ,  Thomas H. Graham ,  Hong Li ,  Izzat Raheem ,  Jay A. Grobler

IPC: A61K31/675 ,  C07F9/6561 ,  A61K31/683

CPC classification number: C07F9/6561 ,  A61K31/427 ,  A61K31/4402 ,  A61K31/505 ,  A61K31/513 ,  A61K31/52 ,  A61K31/635 ,  A61K31/675 ,  A61K31/683 ,  A61K2300/00

Abstract: The present invention relates to Phosphate Substituted Quinolizine Derivatives of Formula (I): and pharmaceutically acceptable salts or prodrug thereof, wherein X, Y, R1, R2, R3, R4, R5, R9 and R10 are as defined herein. The present invention also relates to compositions comprising at least one Phosphate Substituted Quinolizine Derivative, and methods of using the Phosphate Substituted Quinolizine Derivatives for treating or preventing HIV infection in a subject.

公开(公告)号：US09717714B2

公开(公告)日：2017-08-01

申请号：US14653445

申请日：2013-12-17

Applicant: Merck Sharp & Dohme Corp.

Inventor： Debra Ondeyka ,  Xiaoxia Qian ,  Petr Vachal ,  Sriram Tyagarajan ,  Cameron J. Smith ,  Hong Li ,  Jianming Bao

IPC: A61K31/4439 ,  A61K31/423 ,  A61K31/444 ,  A61K31/506 ,  A61K31/5377 ,  C07D413/14 ,  C07D413/06 ,  C07D263/52 ,  A61K45/06

CPC classification number: A61K31/423 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D263/52 ,  C07D413/06 ,  C07D413/14

Abstract: 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. The chemical compounds that are disclosed cholesterol ester transfer protein (CETP) and are expected to have utility in raising HDL-C, lowering LDL-C, and in the treatment and prevention of atherosclerosis.

公开(公告)号：US20140221383A1

公开(公告)日：2014-08-07

申请号：US14252256

申请日：2014-04-14

Applicant: Merck Sharp & Dohme Corp.

Inventor： Amjad Ali ,  Joann M. Napolitano ,  Qiaolin Deng ,  Zhijian Lu ,  Peter J. Sinclair ,  Gayle E. Hallet ,  Christopher F. Thompson ,  Nazia Quraishi ,  Cameron J. Smith ,  Julianne A. Hunt ,  Adrian A. Dowst ,  Yi-Heng Chen ,  Hong Li

IPC: C07D417/04 ,  A61K31/497 ,  A61K31/506 ,  A61K31/4439 ,  A61K31/433 ,  A61K31/427 ,  A61K31/421 ,  A61K31/4166 ,  A61K31/4168 ,  A61K31/4015 ,  C07D413/04 ,  C07D285/10 ,  C07D417/10 ,  C07D263/26 ,  C07D233/38 ,  C07D233/50 ,  C07D207/27 ,  C07D413/10 ,  A61K31/422 ,  A61K45/06 ,  A61K31/501

CPC classification number: C07F7/10 ,  A61K31/4015 ,  A61K31/4166 ,  A61K31/4168 ,  A61K31/421 ,  A61K31/422 ,  A61K31/427 ,  A61K31/433 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D207/26 ,  C07D207/27 ,  C07D233/32 ,  C07D233/38 ,  C07D233/50 ,  C07D233/52 ,  C07D263/04 ,  C07D263/20 ,  C07D263/22 ,  C07D263/24 ,  C07D263/26 ,  C07D285/06 ,  C07D285/10 ,  C07D401/04 ,  C07D413/04 ,  C07D413/06 ,  C07D413/10 ,  C07D417/04 ,  C07D417/10

Abstract: Compounds having the structures of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis: In the compounds of Formula I, B or R2 is a phenyl group which has an ortho aryl, heterocyclic, benzoheterocyclic or benzocycloalkyl substituent, and one other position on the 5-membered ring has an aromatic, heterocyclic, cycloalkyl, benzoheterocyclic or benzocycloalkyl substituent connected directly to the ring or attached to the ring through a —CH2—.

Abstract translation: 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，可用于升高HDL-胆固醇，降低LDL-胆固醇，以及用于治疗或预防动脉粥样硬化。在式I化合物中，B或 R2是具有邻芳基，杂环，苯并杂环或苯并环烷基取代基的苯基，并且在5元环上的另一个位置具有直接连接到环上或连接到环上的芳族，杂环，环烷基，苯并杂环或苯并环烷基取代基 通过-CH2-。

公开(公告)号：US20190365727A1

公开(公告)日：2019-12-05

申请号：US16479997

申请日：2018-01-23

Applicant: MERCK SHARP & DOHME CORP.

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

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

Abstract: 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：US10351558B2

公开(公告)日：2019-07-16

申请号：US15550862

申请日：2016-02-12

Applicant: Merck Sharp & Dohme Corp. ,  Dongfang Meng ,  Hong Li ,  Meng Yang ,  Manuel de Lera Ruiz ,  Sunita V. Dewnani ,  Tianying Jian ,  Dann L. Parker, Jr. ,  Ting Zhang ,  Louis-Charles Campeau ,  Harold B. Wood ,  Jiayi Xu ,  Richard Berger ,  Jane Yang Wu ,  Robert K. Orr ,  Shawn P. Walsh ,  Bart Harper

Inventor： Dongfang Meng ,  Hong Li ,  Meng Yang ,  Manuel de Lera Ruiz ,  Sunita V. Dewnani ,  Tianying Jian ,  Dann L. Parker, Jr. ,  Ting Zhang ,  Louis-Charles Campeau ,  Harold B. Wood ,  Jiayi Xu ,  Richard Berger ,  Jane Yang Wu ,  Robert K. Orr ,  Shawn P. Walsh ,  Bart Harper

IPC: C07D471/04 ,  C07D403/12 ,  C07D417/14 ,  A61P9/00 ,  C07D413/14 ,  C07D471/14 ,  C07D498/04 ,  C07D513/04

Abstract: The present invention provides a compound of Formula I and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for treating or preventing unstable angina, refractory angina, myocardial infarction, transient ischemic attacks, atrial fibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis, disseminated intravascular coagulation, ocular build up of fibrin, and reocclusion or restenosis of recanalized vessels. The compounds are selective Factor IXa inhibitors.