公开(公告)号：US08178513B2

公开(公告)日：2012-05-15

申请号：US12480391

申请日：2009-06-08

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voigt ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X. H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voigt ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X. H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter

IPC分类号： A01N57/00 ,  A01N43/54 ,  A01N43/40 ,  A61K31/675 ,  A61K31/44 ,  A61K31/445 ,  C07D239/02 ,  C07D233/00 ,  C07D239/24 ,  C07D401/00

CPC分类号： C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  A61K31/4184 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/5377 ,  A61K31/655 ,  A61K45/06 ,  C07D233/46 ,  C07D233/70 ,  C07D235/02 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D295/15 ,  C07D401/04 ,  C07D401/06 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/06 ,  C07D405/10 ,  C07D405/14 ,  C07D407/06 ,  C07D409/04 ,  C07D409/06 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06 ,  Y02A50/411

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W, U, X, R1, R2, R3, and R4 are as defined herein, and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of using such compounds to inhibit aspartyl protease and to treat a variety of disease or disorders, including cardiovascular diseases, cognitive and neurodegenerative diseases. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic antagonist

摘要翻译： 公开了式I化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂化物，其中W，U，X，R 1，R 2，R 3和R 4如本文所定义，并且药物组合物包含式I化合物 还公开了使用这些化合物抑制天冬氨酰蛋白酶和治疗各种疾病或病症（包括心血管疾病，认知和神经变性疾病）的方法。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱拮抗剂组合治疗认知或神经变性疾病的方法

公开(公告)号：US20110009392A1

公开(公告)日：2011-01-13

申请号：US12671806

申请日：2008-08-04

申请人： Zhaoning Zhu ,  William J. Greenlee ,  John P. Caldwell ,  Robert D. Mazzola, JR. ,  Brian McKittrick ,  Chad E. Bennett ,  Xianhai Huang ,  Hubert B. Josien ,  Duane A. Burnett

发明人： Zhaoning Zhu ,  William J. Greenlee ,  John P. Caldwell ,  Robert D. Mazzola, JR. ,  Brian McKittrick ,  Chad E. Bennett ,  Xianhai Huang ,  Hubert B. Josien ,  Duane A. Burnett

IPC分类号： A61K31/55 ,  C07D487/04 ,  C07D235/02 ,  C07D498/04 ,  C07D491/04 ,  A61K31/4188 ,  A61K31/519 ,  A61K31/535 ,  A61K31/4353 ,  A61K31/435 ,  A61K31/47 ,  A61K31/505 ,  A61K31/397 ,  A61K31/4406 ,  A61K38/16 ,  A61P25/28

CPC分类号： C07D487/04 ,  C07D217/24 ,  C07D498/04

摘要： In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

公开(公告)号：US10329289B2

公开(公告)日：2019-06-25

申请号：US15386009

申请日：2016-12-21

申请人： Jianming Bao ,  Xiaolei Gao ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Debra L. Ondeyka ,  Andrew W. Stamford ,  Fengqi Zhang

发明人： Jianming Bao ,  Xiaolei Gao ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Debra L. Ondeyka ,  Andrew W. Stamford ,  Fengqi Zhang

IPC分类号： C07D471/04 ,  C07F9/22 ,  C07D519/00 ,  C07D491/048 ,  C07D471/08 ,  C07D491/052 ,  A61K31/437 ,  A61P25/00

摘要： The present invention is directed to 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US20140378416A1

公开(公告)日：2014-12-25

申请号：US14345114

申请日：2012-09-11

申请人： Michael P. Dwyer ,  Kartik M. Keertikar ,  Qingbei Zeng ,  Robert D. Mazzola, JR. ,  Wensheng Yu ,  Haiqun Tang ,  Seong Heon Kim ,  Ling Tong ,  Stuart B. Rosenblum ,  Joseph A. Kozlowski ,  Anilkumar Gopinadhan Nair

发明人： Michael P. Dwyer ,  Kartik M. Keertikar ,  Qingbei Zeng ,  Robert D. Mazzola, JR. ,  Wensheng Yu ,  Haiqun Tang ,  Seong Heon Kim ,  Ling Tong ,  Stuart B. Rosenblum ,  Joseph A. Kozlowski ,  Anilkumar Gopinadhan Nair

IPC分类号： C07F7/10 ,  A61K45/06 ,  A61K31/695

CPC分类号： C07F7/10 ,  A61K31/695 ,  A61K45/06 ,  A61K2201/094 ,  A61K2300/00 ,  C07F7/0816

摘要： The present invention relates to novel Silyl-Containing Heterocyclic Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, C, D, E, F and L are as defined herein. The present invention also relates to compositions comprising at least one Silyl-Containing Heterocyclic Compound, and methods of using the Silyl-Containing Heterocyclic Compounds for treating or preventing HCV infection in a patient.

摘要翻译： 本发明涉及式（I）的新的含甲硅烷基的杂环化合物及其药学上可接受的盐，其中A，B，C，D，E，F和L如本文所定义。 本发明还涉及包含至少一种含甲硅烷基的杂环化合物的组合物，以及使用含有甲硅烷基的杂环化合物治疗或预防患者HCV感染的方法。

公开(公告)号：US08691831B2

公开(公告)日：2014-04-08

申请号：US13416140

申请日：2012-03-09

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy X. E. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey A. Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey O. Strickland ,  Elizabeth M. Smith ,  Andrew W. Stamford ,  William J. Greenlee ,  Robert D. Mazzola, Jr. ,  John P. Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Tao Guo ,  Thuy X. E. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachael C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse ,  Ying Huang ,  Guoqing Li ,  Jianping Pan ,  Jeffrey A. Misiaszek ,  Gaifa Lai ,  Jingqi Duo ,  Chuanxing Qu ,  Yuefei Shao

IPC分类号： A01N43/54 ,  A61K31/505

CPC分类号： C07D233/88 ,  A61K31/4168 ,  A61K31/4178 ,  C07D239/22 ,  C07D401/06 ,  C07D401/10 ,  C07D403/06 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/10 ,  C07D417/14 ,  C07D495/10

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein each variable in Formula I are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed are methods of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

摘要翻译： 公开了式I化合物或其立体异构体，互变异构体或其药学上可接受的盐或溶剂化物，其中式I中的每个变量如说明书中所定义; 以及包含式I化合物的药物组合物。还公开了抑制天冬氨酰蛋白酶的方法，特别是治疗心血管疾病，认知和神经退行性疾病的方法，以及抑制人类免疫缺陷病毒，plasmepins，组织蛋白酶D和 原生动物酶。 还公开了使用式I化合物与胆碱酯酶抑制剂或毒蕈碱m1激动剂或m2拮抗剂组合治疗认知或神经变性疾病的方法。

公开(公告)号：US20110053918A1

公开(公告)日：2011-03-03

申请号：US12665551

申请日：2008-06-27

申请人： Zhaoning Zhu ,  William J. Greenlee ,  Robert D. Mazzola, JR. ,  Jun Qin ,  Xianhai Huang ,  Anandan Palani

发明人： Zhaoning Zhu ,  William J. Greenlee ,  Robert D. Mazzola, JR. ,  Jun Qin ,  Xianhai Huang ,  Anandan Palani

IPC分类号： A61K31/541 ,  C07D239/70 ,  C07D239/24 ,  C07D233/56 ,  C07D403/12 ,  C07D401/10 ,  C07D279/02 ,  C07D413/10 ,  C07D265/36 ,  C07D241/36 ,  A61K31/4353 ,  A61K31/519 ,  A61K31/505 ,  A61K31/4166 ,  A61K31/4439 ,  A61K31/5355 ,  A61K31/538 ,  A61K31/497 ,  A61P25/28 ,  A61P9/10 ,  A61P25/00

CPC分类号： C07D487/04 ,  C07D401/10 ,  C07D403/10 ,  C07D413/10 ,  C07D417/10 ,  C07D471/04

摘要： In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

公开(公告)号：US11149036B2

公开(公告)日：2021-10-19

申请号：US16621959

申请日：2018-06-22

申请人： John J. Acton, III ,  Merck Sharp & Dohme Corp. ,  MSD R&D (China) Co., Ltd. ,  Jianming Bao ,  Qiaolin Deng ,  Melissa Egbertson ,  Ronald Ferguson, II ,  Xiaolei Gao ,  Scott Timothy Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Meng Na ,  Michael T. Rudd ,  Oleg Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang

发明人： John J. Acton, III ,  Jianming Bao ,  Qiaolin Deng ,  Melissa Egbertson ,  Ronald Ferguson, II ,  Xiaolei Gao ,  Scott Timothy Harrison ,  Sandra L. Knowles ,  Chunsing Li ,  Michael Man-Chu Lo ,  Robert D. Mazzola, Jr. ,  Zhaoyang Meng ,  Meng Na ,  Michael T. Rudd ,  Oleg Selyutin ,  David M. Tellers ,  Ling Tong ,  Fengqi Zhang

IPC分类号： C07D471/04 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D491/048 ,  C07D498/04

摘要： The present invention is directed to pyrazol-4-yl-pyridine compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.

公开(公告)号：US08357682B2

公开(公告)日：2013-01-22

申请号：US12598704

申请日：2008-05-05

申请人： Zhaoning Zhu ,  William J. Greenlee ,  Zhong-Yue Sun ,  Gioconda Gallo ,  Theodros Asberom ,  Xianhai Huang ,  Xiaohong Zhu ,  Mark D. McBriar ,  Dmitri A. Pissarnitski ,  Zhiqiang Zhao ,  Ruo Xu ,  Hongmei Li ,  Anandan Palani ,  Johannes H. Voigt ,  Robert D. Mazzola, Jr. ,  John Clader ,  Hubert Josien ,  Jun Qin

发明人： Zhaoning Zhu ,  William J. Greenlee ,  Zhong-Yue Sun ,  Gioconda Gallo ,  Theodros Asberom ,  Xianhai Huang ,  Xiaohong Zhu ,  Mark D. McBriar ,  Dmitri A. Pissarnitski ,  Zhiqiang Zhao ,  Ruo Xu ,  Hongmei Li ,  Anandan Palani ,  Johannes H. Voigt ,  Robert D. Mazzola, Jr. ,  John Clader ,  Hubert Josien ,  Jun Qin

IPC分类号： C07D413/10 ,  C07D413/14 ,  C07D498/10 ,  A61K31/395 ,  A61K31/4245 ,  A61K31/4439

CPC分类号： C07D413/10 ,  C07D413/14 ,  C07D498/04 ,  C07D498/10 ,  C07D498/20

摘要： The present invention provides a novel class of heterocyclic compounds of Formula (I) as modulators of gamma secretase, wherein the definitions of the variables of Formula (I) are defined herein, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

摘要翻译： 本发明提供了一类新颖的式（I）杂环化合物作为γ-分泌酶的调节剂，其中式（I）变量的定义在本文中定义，制备此类化合物的方法，含有一种或多种此类化合物的药物组合物 制备包含一种或多种此类化合物的药物制剂的方法，以及使用这些化合物或药物组合物治疗，预防，抑制或改善与中枢神经系统相关的一种或多种疾病的方法。

公开(公告)号：US20100247514A1

公开(公告)日：2010-09-30

申请号：US12598704

申请日：2008-05-05

申请人： Zhaoning Zhu ,  William J. Greenlee ,  Zhong-Yue Sun ,  Gioconda Gallo ,  Theodros Asberom ,  Xianhai Huang ,  Xiaohong Zhu ,  Mark D. McBriar ,  Dmitri A. Pissarnitski ,  Zhiqiang Zhao ,  Ruo Xu ,  Hongmei Li ,  Anandan Palani ,  Johannes H. Voigt ,  Robert D. Mazzola, JR. ,  John Clader ,  Hubert Josien ,  Jun Qin

发明人： Zhaoning Zhu ,  William J. Greenlee ,  Zhong-Yue Sun ,  Gioconda Gallo ,  Theodros Asberom ,  Xianhai Huang ,  Xiaohong Zhu ,  Mark D. McBriar ,  Dmitri A. Pissarnitski ,  Zhiqiang Zhao ,  Ruo Xu ,  Hongmei Li ,  Anandan Palani ,  Johannes H. Voigt ,  Robert D. Mazzola, JR. ,  John Clader ,  Hubert Josien ,  Jun Qin

IPC分类号： A61K39/395 ,  C07D413/10 ,  A61K31/4245 ,  C07D413/14 ,  A61K31/4439 ,  C07D498/10 ,  A61K31/438 ,  C07D498/04 ,  A61K31/437 ,  A61K31/5365 ,  A61P25/28 ,  A61P25/00 ,  A61K31/397 ,  A61P9/00

CPC分类号： C07D413/10 ,  C07D413/14 ,  C07D498/04 ,  C07D498/10 ,  C07D498/20

摘要： In its many embodiments, the present invention provides a novel class of heterocyclic compounds as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

摘要翻译： 在其许多实施方案中，本发明提供了一类新颖的杂环化合物作为γ-分泌酶的调节剂，制备这些化合物的方法，含有一种或多种这样的化合物的药物组合物，制备包含一种或多种这类化合物的药物制剂的方法和方法 使用这些化合物或药物组合物治疗，预防，抑制或改善与中枢神经系统相关的一种或多种疾病。

公开(公告)号：US20190315762A1

公开(公告)日：2019-10-17

申请号：US16471675

申请日：2017-12-18

申请人： Xiaolei GAO ,  Sandra L. KNOWLES ,  Chun-sing LI ,  Michael Man-Chu LO ,  Robert D. MAZZOLA, JR. ,  Ling TONG ,  Merck Sharp & Dohme Corp.

发明人： Xiaolei GAO ,  Sandra L. KNOWLES ,  Chunsing LI ,  Michael Man-Chu LO ,  Robert D. MAZZOLA, Jr. ,  Ling TONG

IPC分类号： C07D491/052 ,  C07D471/04 ,  C07D498/04 ,  C07D491/048

摘要： The present invention is directed to 6,6-fused heteroarylpiperidine ether compounds which are allosteric modulators of the M4 muscarinic acetylcholine receptor. The present invention is also directed to uses of the compounds described herein in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which M4 muscarinic acetylcholine receptors are involved. The present invention is also directed to compositions comprising these compounds. The present invention is also directed to uses of these compositions in the potential prevention or treatment of such diseases in which M4 muscarinic acetylcholine receptors are involved.