公开(公告)号：US08361959B2

公开(公告)日：2013-01-29

申请号：US13121725

申请日：2009-09-30

申请人： Andrew Stamford ,  Michael W. Miller ,  Duane Eugene DeMong ,  William J. Greenlee ,  Joseph A. Kozlowski ,  Brian J. Lavey ,  Michael K. C. Wong ,  Wensheng Yu ,  Xing Dai ,  De-Yi Yang ,  Guowei Zhou

发明人： Andrew Stamford ,  Michael W. Miller ,  Duane Eugene DeMong ,  William J. Greenlee ,  Joseph A. Kozlowski ,  Brian J. Lavey ,  Michael K. C. Wong ,  Wensheng Yu ,  Xing Dai ,  De-Yi Yang ,  Guowei Zhou

IPC分类号： A61F7/10 ,  A61K31/4184 ,  C07D235/02

CPC分类号： C07D235/02 ,  A61K31/4184 ,  A61K45/06 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/12 ,  C07D491/10 ,  A61K2300/00

摘要： The present invention relates to compounds of the general formula: (I) wherein ring A, ring B, R1, R3, Z, L1, and L2 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and to methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.

摘要翻译： 本发明涉及以下通式的化合物：（I）其中环A，环B，R 1，R 3，Z，L 1和L 2彼此独立地并且如本文所定义，包含该化合物的组合物，和 涉及使用该化合物作为胰高血糖素受体拮抗剂并用于治疗或预防2型糖尿病及与之有关的病症的方法。

公开(公告)号：US20120232108A1

公开(公告)日：2012-09-13

申请号：US13377598

申请日：2010-06-15

申请人： Xianhai Huang ,  Zhaoning Zhu ,  William J. Greenlee ,  Anandan Palani ,  Robert G. Aslanian

发明人： Xianhai Huang ,  Zhaoning Zhu ,  William J. Greenlee ,  Anandan Palani ,  Robert G. Aslanian

IPC分类号： A61K31/437 ,  A61P25/28 ,  C07D471/04

CPC分类号： C07D471/04

摘要： This invention provides novel compounds that are modulators of gamma secretase. The compounds have the Formula I: Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of Formula I.

公开(公告)号：US08236805B2

公开(公告)日：2012-08-07

申请号：US12564678

申请日：2009-09-22

申请人： Eric J. Gilbert ,  Michael W. Miller ,  Jack D. Scott ,  Andrew W. Stamford ,  William J. Greenlee ,  Jay Weinstein

发明人： Eric J. Gilbert ,  Michael W. Miller ,  Jack D. Scott ,  Andrew W. Stamford ,  William J. Greenlee ,  Jay Weinstein

IPC分类号： A61K31/497 ,  C07D403/00

CPC分类号： C07D241/04 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D403/06 ,  C07D403/10 ,  C07D403/12 ,  C07D405/04 ,  C07D405/06 ,  C07D405/08 ,  C07D405/12 ,  C07D409/04 ,  C07D409/06 ,  C07D409/12 ,  C07D409/14 ,  C07D413/06 ,  C07D413/12 ,  C07D417/06 ,  C07D417/10

摘要： Compounds of Formula (I): or pharmaceutically acceptable salts, solvates, or esters thereof, are useful in treating diseases or conditions mediated by CB1 receptors, such as metabolic syndrome and obesity, neuroinflammatory disorders, cognitive disorders and psychosis, addiction (e.g., smoking cessation), gastrointestinal disorders, and cardiovascular conditions.

摘要翻译： 式（I）化合物或其药学上可接受的盐，溶剂合物或酯可用于治疗由CB1受体介导的疾病或病症，例如代谢综合征和肥胖症，神经炎症性疾病，认知障碍和精神病，成瘾（例如吸烟 停止），胃肠道疾病和心血管疾病。

公开(公告)号：US08183252B2

公开(公告)日：2012-05-22

申请号：US12693874

申请日：2010-01-26

申请人： Zhaoning Zhu ,  Zhong-Yue Sun ,  Andrew Stamford ,  William J. Greenlee ,  Jared N. Cumming ,  Lingyan Wang ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Ying Huang ,  Guoqing Li ,  Jianping Pan

发明人： Zhaoning Zhu ,  Zhong-Yue Sun ,  Andrew Stamford ,  William J. Greenlee ,  Jared N. Cumming ,  Lingyan Wang ,  Ulrich Iserloh ,  Xiaoxiang Liu ,  Ying Huang ,  Guoqing Li ,  Jianping Pan

IPC分类号： A01N43/54 ,  A61K31/505 ,  C07D239/02

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 W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method 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.

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：US08148363B2

公开(公告)日：2012-04-03

申请号：US12993607

申请日：2009-05-18

申请人： Martin C. Clasby ,  William J. Greenlee ,  Yan Xia ,  Tin-Yau Chan ,  Mariappan V. Chelliah ,  Samuel Chackalamannil ,  Haiyan Pu ,  Keith A. Eagen ,  Henry Vaccaro ,  Brian A. McKittrick ,  Liyuan Wang ,  Xiaobang Gao

发明人： Martin C. Clasby ,  William J. Greenlee ,  Yan Xia ,  Tin-Yau Chan ,  Mariappan V. Chelliah ,  Samuel Chackalamannil ,  Haiyan Pu ,  Keith A. Eagen ,  Henry Vaccaro ,  Brian A. McKittrick ,  Liyuan Wang ,  Xiaobang Gao

IPC分类号： A61K31/55 ,  A61K31/4184 ,  A61K31/5377 ,  A61K31/4192 ,  A61K31/454 ,  A61K31/4439 ,  A61K31/422 ,  A61K31/506 ,  A61K31/496 ,  A61P7/02 ,  C07D403/14 ,  C07D413/14 ,  C07D403/04 ,  C07D401/14

CPC分类号： C07D487/04 ,  C07D231/18 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D413/04 ,  C07D413/14

摘要： The present invention relates to novel heterocyclic compounds of Formulae I-III; as disclosed herein or a pharmaceutically acceptable salt, solvate, ester, prodrug or stereoisomer thereof. Also disclosed are pharmaceutical compositions comprising said compounds, and methods for using said compounds for treating or preventing a thromboembolic disorder.

摘要翻译： 本发明涉及式I-III的新型杂环化合物; 如本文所公开的或其药学上可接受的盐，溶剂化物，酯，前药或立体异构体。 还公开了包含所述化合物的药物组合物，以及使用所述化合物治疗或预防血栓栓塞性疾病的方法。

公开(公告)号：US20110313008A1

公开(公告)日：2011-12-22

申请号：US13145025

申请日：2010-01-21

申请人： Hubert B. Josien ,  John W. Clader ,  Andrew Stamford ,  William J. Greenlee ,  Michael John Mayer ,  Jason L. Davis ,  Ming Min Hsia ,  Shuangyi Wan

发明人： Hubert B. Josien ,  John W. Clader ,  Andrew Stamford ,  William J. Greenlee ,  Michael John Mayer ,  Jason L. Davis ,  Ming Min Hsia ,  Shuangyi Wan

IPC分类号： A61K31/426 ,  A61P3/10 ,  A61P3/00 ,  C07D277/04

CPC分类号： C07D417/04 ,  C07D277/34

摘要： This invention provides for certain pentafluorosulpholane-containing compounds of the formula or a pharmaceutically acceptable salt, ester, solvate or prodrug thereof, wherein the variables are defined herein; the inventive compounds are agonists of the G-protein coupled receptor 40 (GPR40, also known as free fatty acid receptor FFAR). This invention further relates to pharmaceutical compositions containing these compounds, and the use of these compounds to regulate insulin levels in a mammal. The compounds may be used, for example in the prevention and treatment of Type 2 diabetes mellitus and in the prevention and treatment of conditions related to Type 2 diabetes mellitus, such as insulin resistance, obesity and lipid disorders.

摘要翻译： 本发明提供了具有下式的某些五氟丁烷化合物或其药学上可接受的盐，酯，溶剂合物或前药，其中变量在本文中定义; 本发明化合物是G蛋白偶联受体40（GPR40，也称为游离脂肪酸受体FFAR）的激动剂。 本发明还涉及含有这些化合物的药物组合物，以及这些化合物在哺乳动物体内调节胰岛素水平的用途。 该化合物可用于例如预防和治疗2型糖尿病以及预防和治疗与2型糖尿病相关的病症，例如胰岛素抵抗，肥胖症和脂质疾病。

公开(公告)号：US20110218194A1

公开(公告)日：2011-09-08

申请号：US13108454

申请日：2011-05-16

申请人： Zhaoning Zhu ,  Brian A. Mckittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X. H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachel C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

发明人： Zhaoning Zhu ,  Brian A. Mckittrick ,  Zhong-Yue Sun ,  Yuanzan C. Ye ,  Johannes H. Voight ,  Corey Strickland ,  Elizabeth M. Smith ,  Andrew Stamford ,  William J. Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared N. Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy X. H. Le ,  Kurt W. Saionz ,  Suresh D. Babu ,  Rachel C. Hunter ,  Michelle L. Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

IPC分类号： A61K31/5395 ,  C07D273/04 ,  C07D413/10 ,  A61P9/00 ,  A61P33/02 ,  A61P31/10 ,  A61P25/28 ,  A61P25/00

CPC分类号： C07D233/46 ,  C07D233/70 ,  C07D233/88 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D401/04 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/10 ,  C07D409/04 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method 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.

公开(公告)号：US20110166167A1

公开(公告)日：2011-07-07

申请号：US13003716

申请日：2009-07-15

申请人： Santhosh Francis Neelamkavil ,  Craig D. Boyle ,  Bernard R. Neustadt ,  Samuel Chackalamannil ,  William J. Greenlee

发明人： Santhosh Francis Neelamkavil ,  Craig D. Boyle ,  Bernard R. Neustadt ,  Samuel Chackalamannil ,  William J. Greenlee

IPC分类号： A61K31/519 ,  C07D519/00 ,  A61P3/10

CPC分类号： C07D519/00

摘要： The present invention relates to Bicyclic Heterocycle Derivatives, compositions comprising a Bicyclic Heterocycle Derivative, and methods of using the Bicyclic Heterocycle Derivatives for treating or preventing obesity, diabetes, a diabetic complication, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of a G protein-coupled receptor (GPCR) in a patient. The compounds are of structure (I).

摘要翻译： 本发明涉及双环杂环衍生物，包含双环杂环衍生物的组合物，以及使用双环杂环衍生物治疗或预防肥胖症，糖尿病，糖尿病并发症，代谢紊乱，心血管疾病或与该活动相关的病症的方法 的G蛋白偶联受体（GPCR）。 化合物为结构（I）。

公开(公告)号：US20110065634A1

公开(公告)日：2011-03-17

申请号：US12992771

申请日：2009-05-13

申请人： William J. Greenlee ,  Andrew Stamford ,  Michael W. Miller ,  Duane Eugene DeMong

发明人： William J. Greenlee ,  Andrew Stamford ,  Michael W. Miller ,  Duane Eugene DeMong

IPC分类号： A61K38/28 ,  C07D231/18 ,  A61K31/415 ,  C07D231/22 ,  C07D231/38 ,  C07D401/12 ,  A61K31/41 ,  C07D231/12 ,  A61K38/22 ,  A61K31/7004 ,  A61P3/00

CPC分类号： C07D231/22 ,  C07D231/38

摘要： The present invention relates to compounds of general formula (I), wherein ring A, ring B, R1, R2, R3, Z, and L1 are selected independently of each other and are as defined herein, to compositions comprising the compounds, and methods of using the compounds as glucagon receptor antagonists and for the treatment or prevention of type 2 diabetes and conditions related thereto.

摘要翻译： 本发明涉及通式（I）的化合物，其中环A，环B，R 1，R 2，R 3，Z和L 1彼此独立地并且如本文所定义，包含该化合物的组合物和方法 使用该化合物作为胰高血糖素受体拮抗剂并用于治疗或预防2型糖尿病及与此有关的病症。