公开(公告)号：US10357481B2

公开(公告)日：2019-07-23

申请号：US15579878

申请日：2016-06-27

Applicant: MERCK SHARP & DOHME CORP. ,  Gregori J. Morriello ,  Lehua Chang ,  Ashley Forster ,  Yili Chen ,  Michael P. Dwyer ,  Zack Zhiqiang Guo ,  Ming Wang ,  Shimin Xu ,  Yingjian Bo ,  Jianmin Fu

Inventor： Gregori J. Morriello ,  Lehua Chang ,  Ashley Forster ,  Yili Chen ,  Michael P. Dwyer ,  Zack Zhiqiang Guo ,  Ming Wang ,  Shimin Xu ,  Yingjian Bo ,  Jianmin Fu

IPC: A61K31/4196 ,  C07D471/04 ,  C07D487/04 ,  A61P25/28 ,  A61P25/22 ,  A61P25/18 ,  A61P25/16 ,  A61P25/06 ,  A61K31/52

Abstract: The present invention is directed to substituted triazolo bicyclic compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

公开(公告)号：US20180169072A1

公开(公告)日：2018-06-21

申请号：US15579878

申请日：2016-06-27

Applicant: Gregori J. MORRIELLO ,  Lehua CHANG ,  Ashley FORSTER ,  Yili CHEN ,  Michael P. DWYER ,  Zack Zhiqiang GUO ,  Ming WANG ,  Shimin XU ,  Yingjian BO ,  Jianmin FU ,  MERCK SHARP & DOHME CORP.

Inventor： Gregori J. MORRIELLO ,  Lehua CHANG ,  Ashley FORSTER ,  Yili CHEN ,  Michael P. DWYER ,  Zack Zhiqiang GUO ,  Ming WANG ,  Shimin XU ,  Yingjian BO ,  Jianmin FU

IPC: A61K31/4196 ,  A61K31/52 ,  A61P25/06 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/28

CPC classification number: A61K31/4196 ,  A61K31/52 ,  A61P25/06 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/28 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention is directed to substituted triazolo bicyclic compounds of formula I which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 2 (PDE2). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis, Parkinson's disease, Parkinson's disease dementia (PDD), or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.

公开(公告)号：US20140057893A1

公开(公告)日：2014-02-27

申请号：US14110332

申请日：2012-04-05

Applicant: Scott Edmondson ,  Zhiqiang Guo ,  Harold B. Wood ,  Andrew W. Stamford ,  Michael W. Miller ,  Duane E. DeMong ,  Gregori J. Morriello ,  Rajan Anand ,  Vincent J. Colandrea ,  Megan Macala ,  Milana Maletic ,  Cheng Zhu ,  Yuping Zhu ,  Wanying Sun ,  Kake Zhao ,  Yong Huang ,  Joel M. Harris ,  Lehua Chang ,  Nam Fung Kar ,  Zhiyong Hu ,  Liping Wang ,  Bowei Wang ,  Ping Liu ,  Jason W. Szewczyk ,  William B. Geiss

Inventor： Scott Edmondson ,  Zhiqiang Guo ,  Harold B. Wood ,  Andrew W. Stamford ,  Michael W. Miller ,  Duane E. DeMong ,  Gregori J. Morriello ,  Rajan Anand ,  Vincent J. Colandrea ,  Megan Macala ,  Milana Maletic ,  Cheng Zhu ,  Yuping Zhu ,  Wanying Sun ,  Kake Zhao ,  Yong Huang ,  Joel M. Harris ,  Lehua Chang ,  Nam Fung Kar ,  Zhiyong Hu ,  Liping Wang ,  Bowei Wang ,  Ping Liu ,  Jason W. Szewczyk ,  William B. Geiss

IPC: C07D513/04 ,  C07D413/14 ,  C07D413/04 ,  C07D498/04 ,  C07D405/04 ,  C07D471/04 ,  C07D487/04 ,  C07D401/12 ,  C07D211/22

CPC classification number: C07D513/04 ,  A61K9/4858 ,  C07D211/22 ,  C07D401/12 ,  C07D405/04 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D498/04

Abstract: Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included

Abstract translation: 公开了取代的式I的环丙基化合物及其药学上可接受的盐可用于治疗或预防2型糖尿病和类似病状。 该化合物可用作G蛋白偶联受体GPR-119的激动剂。 还包括药物组合物和治疗方法

公开(公告)号：US20130289003A1

公开(公告)日：2013-10-31

申请号：US13881929

申请日：2011-10-25

Applicant: Amjad Ali ,  Michael Man-Chu Lo ,  Robert K. Baker ,  Zhiqiang Guo ,  Brent Whitehead ,  Timothy J. Henderson ,  Edward Metzger ,  Lin Yan ,  Shrenik K. Shah ,  James Dellureficio ,  Jun Wang

Inventor： Amjad Ali ,  Michael Man-Chu Lo ,  Robert K. Baker ,  Zhiqiang Guo ,  Brent Whitehead ,  Timothy J. Henderson ,  Edward Metzger ,  Lin Yan ,  Shrenik K. Shah ,  James Dellureficio ,  Jun Wang

IPC: C07D207/12 ,  C07D205/04 ,  C07D413/10 ,  C07D403/10 ,  C07D307/20 ,  C07D309/12 ,  C07D211/44 ,  C07D401/04

CPC classification number: C07D211/44 ,  A61K31/655 ,  C07D205/04 ,  C07D207/12 ,  C07D207/16 ,  C07D207/273 ,  C07D307/20 ,  C07D309/12 ,  C07D401/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/10 ,  C07D413/04 ,  C07D413/10 ,  C07D417/04

Abstract: A compound having the structure: useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy.

Abstract translation: 具有以下结构的化合物：用于治疗高血压，肺动脉高压（PAH），充血性心力衰竭，由过度保水引起的病症，心血管疾病，糖尿病，氧化应激，内皮功能障碍，肝硬化，先兆子痫，骨质疏松症或肾病。

公开(公告)号：US08361994B2

公开(公告)日：2013-01-29

申请号：US13412032

申请日：2012-03-05

Applicant: Amjad Ali ,  Michael Man-Chu Lo ,  Zhiqiang Guo ,  Brent Whitehead ,  Timothy J. Henderson ,  Lin Yan ,  Shrenik K. Shah

Inventor： Amjad Ali ,  Michael Man-Chu Lo ,  Zhiqiang Guo ,  Brent Whitehead ,  Timothy J. Henderson ,  Lin Yan ,  Shrenik K. Shah

IPC: C07D205/04 ,  C07D207/12 ,  C07D211/44 ,  C07D309/10 ,  C07D401/02 ,  C07D401/04 ,  C07D401/14 ,  C07D403/02 ,  A61K31/655 ,  A61P9/12

CPC classification number: C07D211/46 ,  C07D207/12 ,  C07D207/273 ,  C07D207/48 ,  C07D211/96 ,  C07D223/08 ,  C07D309/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/04 ,  C07D403/10 ,  C07D405/12

Abstract: A compound having the structure useful for treating hypertension, Pulmonary Arterial Hypertension (PAH), congestive heart failure, conditions resulting from excessive water retention, cardiovascular disease, diabetes, oxidative stress, endothelial dysfunction, cirrhosis, pre-eclampsia, osteoporosis or nephropathy.

Abstract translation: 具有用于治疗高血压，肺动脉高压（PAH），充血性心力衰竭，由过度保水引起的病症，心血管疾病，糖尿病，氧化应激，内皮功能障碍，肝硬化，先兆子痫，骨质疏松症或肾病的结构的化合物。

公开(公告)号：US07462625B2

公开(公告)日：2008-12-09

申请号：US11520022

申请日：2006-09-11

Applicant: Yun-Fei Zhu ,  Chen Chen ,  Fabio C. Tucci ,  Zhiqiang Guo ,  Timothy D. Gross ,  Martin Rowbottom ,  R. Scott Struthers

Inventor： Yun-Fei Zhu ,  Chen Chen ,  Fabio C. Tucci ,  Zhiqiang Guo ,  Timothy D. Gross ,  Martin Rowbottom ,  R. Scott Struthers

IPC: C07D239/46 ,  A61K31/505 ,  A61K31/506 ,  A61P35/00 ,  A61P5/04 ,  A61P15/08 ,  C07D239/47 ,  C07D239/56

CPC classification number: C07D239/54 ,  A61K31/513 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D413/04 ,  C07D413/06 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04 ,  C07D491/08 ,  C07D498/08 ,  C07D513/04

Abstract: GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein A, Q, R1, R2, R3a, R3b, R4, R5, R6 and n are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了具有用于治疗男性和女性中各种性激素相关病症的GnRH受体拮抗剂。 本发明的化合物具有以下结构：其中A，Q，R 1，R 2，R 3a，R 3b，R 4，R 5，R 6和n如本文所定义，包括其立体异构体，前药和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US07419983B2

公开(公告)日：2008-09-02

申请号：US11627204

申请日：2007-01-25

Applicant: Zhiqiang Guo ,  Yongsheng Chen ,  Dongpei Wu ,  Chen Chen ,  Warren Wade ,  Wesley J. Dwight ,  Charles Q. Huang ,  Fabio C. Tucci

Inventor： Zhiqiang Guo ,  Yongsheng Chen ,  Dongpei Wu ,  Chen Chen ,  Warren Wade ,  Wesley J. Dwight ,  Charles Q. Huang ,  Fabio C. Tucci

IPC: C07D239/54 ,  A61K31/513

CPC classification number: C07D239/54 ,  C07D239/52 ,  C07D403/12 ,  C07D405/04

Abstract: GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R1c, R2a, R2b, R3, R4, R5, R6 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了具有用于治疗男性和女性中各种性激素相关病症的GnRH受体拮抗剂。 本发明的化合物具有以下结构：其中R 1a，R 1b，R 1c，R 2a， R 2b，R 3，R 4，R 5，R 6和R 6，和 X如本文所定义，包括其立体异构体，前药和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US20070015778A1

公开(公告)日：2007-01-18

申请号：US11446583

申请日：2006-06-02

Applicant: Yun-Fei Zhu ,  Collin Regan ,  Jaimie Rueter ,  Zhiqiang Guo ,  Yongsheng Chen ,  Charles Huang

Inventor： Yun-Fei Zhu ,  Collin Regan ,  Jaimie Rueter ,  Zhiqiang Guo ,  Yongsheng Chen ,  Charles Huang

IPC: A61K31/513 ,  C07D239/52

CPC classification number: C07D239/54 ,  C07D401/06

Abstract: GnRH receptor antagonists are disclosed that have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1a, R1b, R2a, R2b, R3, R4, R5, R6, R7 and X are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了具有用于治疗男性和女性中各种性激素相关病症的GnRH受体拮抗剂。 本发明的化合物具有以下结构：其中R 1a，R 1b，R 2a，R 2b， R 3，R 4，R 5，R 6，R 7和R 7， X如本文所定义，包括其立体异构体，前药和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US20050075339A1

公开(公告)日：2005-04-07

申请号：US10705762

申请日：2003-11-10

Applicant: Joseph Pontillo ,  Zhiqiang Guo ,  Dongpei Wu

Inventor： Joseph Pontillo ,  Zhiqiang Guo ,  Dongpei Wu

IPC: C07D253/06 ,  A61K31/53 ,  A61P1/12 ,  A61P5/02 ,  A61P13/08 ,  A61P15/00 ,  A61P15/08 ,  A61P15/18 ,  A61P17/00 ,  A61P17/02 ,  A61P25/20 ,  A61P35/00 ,  A61P43/00 ,  C07D253/075 ,  C07D401/04 ,  C07D409/04 ,  C07D43/02

CPC classification number: C07D253/075 ,  C07D401/04 ,  C07D409/04

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein R1, R2, R3a, R3b, R4, R5, and n are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.

Abstract translation: 公开了GnRH受体拮抗剂，其可用于治疗男性和女性中各种性激素相关病症。 本发明的化合物具有以下结构：其中R1，R2，R3a，R3b，R4，R5和n如本文所定义，包括其立体异构体，前药和药学上可接受的盐。 还公开了含有本发明化合物与药学上可接受的载体组合的组合物，以及涉及其在有需要的受试者中拮抗促性腺激素释放激素的方法。

公开(公告)号：US06750350B2

公开(公告)日：2004-06-15

申请号：US10211972

申请日：2002-08-02

Applicant: Chen Chen ,  Dongpei Wu ,  Zhiqiang Guo ,  Martin Rowbottom

Inventor： Chen Chen ,  Dongpei Wu ,  Zhiqiang Guo ,  Martin Rowbottom

IPC: C07D21174

CPC classification number: C07D213/64 ,  C07D401/12

Abstract: GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure: wherein A, R1, R2, R3a, R3b, R4, R5, R6, and n are as defined herein, including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.