公开(公告)号：US09006228B2

公开(公告)日：2015-04-14

申请号：US14126685

申请日：2012-06-11

申请人： Michael Miller ,  Andrew Stamford ,  Kallol Basu ,  Harold B. Wood ,  Duane DeMong ,  Wanying Sun ,  Joie Garfunkle ,  Christopher Moyes ,  Zhiyong Hu ,  Ping Liu ,  Scott D. Edmondson ,  Xing Dai ,  Byron Gabriel DuBois

发明人： Michael Miller ,  Andrew Stamford ,  Kallol Basu ,  Harold B. Wood ,  Duane DeMong ,  Wanying Sun ,  Joie Garfunkle ,  Christopher Moyes ,  Zhiyong Hu ,  Ping Liu ,  Scott D. Edmondson ,  Xing Dai ,  Byron Gabriel DuBois

IPC分类号： C07D417/14 ,  C07D211/24 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14 ,  C07D211/22

CPC分类号： C07D211/24 ,  C07D211/22 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/04 ,  C07D413/14 ,  C07D417/14

摘要： 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.

摘要翻译： 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型糖尿病和类似病症。 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：US08912206B2

公开(公告)日：2014-12-16

申请号：US13511062

申请日：2010-11-16

申请人： Santhosh Francis Neelamkavil ,  Andrew Stamford ,  Samuel Chackalamannil ,  William J. Greenlee

发明人： Santhosh Francis Neelamkavil ,  Andrew Stamford ,  Samuel Chackalamannil ,  William J. Greenlee

IPC分类号： C07D491/08 ,  A61K31/505

CPC分类号： C07D491/08

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

摘要翻译： 本发明涉及嘧啶醚衍生物，包含嘧啶醚衍生物的组合物，以及使用嘧啶醚衍生物治疗或预防肥胖，糖尿病，代谢紊乱，心血管疾病或与G- 蛋白偶联受体（GPCR）。

公开(公告)号：US08633231B2

公开(公告)日：2014-01-21

申请号：US13808618

申请日：2011-07-08

申请人： Duane DeMong ,  Michael W. Miller ,  Xing Dai ,  Andrew Stamford

发明人： Duane DeMong ,  Michael W. Miller ,  Xing Dai ,  Andrew Stamford

IPC分类号： A61K31/4178 ,  A61K31/4166 ,  C07D233/36 ,  C07D403/12

CPC分类号： A61K31/4178 ,  A61K31/4166 ,  C07D233/36 ,  C07D233/70 ,  C07D403/12

摘要： The present invention relates to compounds of the general structure shown in Formula (A): (A): and includes pharmaceutically acceptable salts, solvates, esters, prodrugs, tautomers, and isomers of said compounds. Pharmaceutical compositions and methods of treatment are also included.

摘要翻译： 本发明涉及式（A）所示通式结构的化合物：（A）：并且包括所述化合物的药学上可接受的盐，溶剂合物，酯，前体药物，互变异构体和异构体。 还包括药物组合物和治疗方法。

公开(公告)号：US08410122B2

公开(公告)日：2013-04-02

申请号：US13141344

申请日：2009-12-21

申请人： Joel M. Harris ,  Bernard R. Neustadt ,  Andrew Stamford ,  Hong Liu

发明人： Joel M. Harris ,  Bernard R. Neustadt ,  Andrew Stamford ,  Hong Liu

IPC分类号： A61K31/505 ,  A01N43/54

CPC分类号： C07D401/12 ,  C07D401/14

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 metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.

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，糖尿病，代谢紊乱，心血管疾病或与GPCR活性相关的病症的方法 病人。

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：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：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：US20110263624A1

公开(公告)日：2011-10-27

申请号：US13141344

申请日：2009-12-21

申请人： Joel M. Harris ,  Bernard R. Neustadt ,  Andrew Stamford ,  Hong Liu

发明人： Joel M. Harris ,  Bernard R. Neustadt ,  Andrew Stamford ,  Hong Liu

IPC分类号： A61K31/506 ,  A61P3/00 ,  A61P3/10 ,  A61P3/04 ,  C07D401/12 ,  C07D401/14

CPC分类号： C07D401/12 ,  C07D401/14

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 metabolic disorder, a cardiovascular disease or a disorder related to the activity of a GPCR in a patient.

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，糖尿病，代谢紊乱，心血管疾病或与GPCR活性有关的障碍的方法 病人。

公开(公告)号：US20110263570A1

公开(公告)日：2011-10-27

申请号：US13141227

申请日：2009-12-21

申请人： Bernard R. Neustadt ,  Andrew Stamford ,  Jinsong Hao ,  Charles Lee Jayne ,  Yan Xia

发明人： Bernard R. Neustadt ,  Andrew Stamford ,  Jinsong Hao ,  Charles Lee Jayne ,  Yan Xia

IPC分类号： A61K31/55 ,  A61K31/506 ,  C07D401/12 ,  A61P3/00 ,  C07D498/08 ,  A61K31/5386 ,  A61P3/10 ,  A61P3/04 ,  C07D401/14 ,  C07D451/02

CPC分类号： C07D401/14 ,  C07D401/12 ,  C07D471/08 ,  C07D498/08

摘要： The present invention relates to Pyriraidine Derivatives of formula (I), compositions comprising a Pyrimidine Derivative, and methods of using the Pyrimidine 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.

摘要翻译： 本发明涉及式（I）的嘧啶衍生物，包含嘧啶衍生物的组合物，以及使用嘧啶衍生物治疗或预防肥胖症，糖尿病，糖尿病并发症，代谢障碍，心血管疾病或与 G蛋白偶联受体（GPCR）在患者体内的活性。

公开(公告)号：US07910590B2

公开(公告)日：2011-03-22

申请号：US12490884

申请日：2009-06-24

申请人： Ying Huang ,  Guoqing Li ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voigt ,  Jianping Pan

发明人： Ying Huang ,  Guoqing Li ,  Ulrich Iserloh ,  Andrew Stamford ,  Corey Strickland ,  Johannes H. Voigt ,  Jianping Pan

IPC分类号： A61K31/496 ,  A61K31/506

CPC分类号： C04B35/632 ,  C07D207/277 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1 is X is —O—, —C(R 14)2— or —N(R)—; Z is —C(R14)2— or —N(R)—; t is 0, 1, 2 or 3; each R and R2 is independently H, alkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, alkenyl or alkynyl; each R14 is H, alkyl, alkenyl, alkynyl, halo, —CN, haloalkyl, cycloalkyl, cycloalkylalkyl, aryl, heteroaryl, heterocycloalkyl, arylalkyl, heteroarylalkyl, heterocycloalkylalkyl, —OR35, —N(R24)(R25) or —SR35; R41 is alkyl, cycloalkyl, —SO2(alkyl), —C(O)-alkyl, —C(O)-cycloalkyl or -alkyl-NH—C(O)CH3; and the remaining variables are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I and methods of treating cognitive or neurodegenerative diseases with compounds of formula I.Also disclosed are pharmaceutical compositions and methods of treatment comprising compounds of formula I in combination with other agents useful in treating cognitive or neurodegenerative diseases.

摘要翻译： 公开了下式的新化合物或其药学上可接受的盐或溶剂合物，其中R 1是X是-O - ， - C（R 14）2 - 或-N（R） - ; Z是-C（R 14）2 - 或-N（R） - ; t为0,1,2或3; 每个R和R 2独立地为H，烷基，环烷基，环烷基烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，烯基或炔基; 每个R 14是H，烷基，烯基，炔基，卤素，-CN，卤代烷基，环烷基，环烷基烷基，芳基，杂芳基，杂环烷基，芳基烷基，杂芳基烷基，杂环烷基烷基，-OR 35，-N（R 24）（R 25）或-SR 35; R41是烷基，环烷基，-SO2（烷基），-C（O） - 烷基，-C（O） - 环烷基或 - 烷基-NH-C（O）CH3; 其余变量如本说明书中所定义。 还公开了包含式I化合物的药物组合物和用式I化合物治疗认知障碍或神经变性疾病的方法。还公开了药物组合物和治疗方法，其包含式I化合物与用于治疗认知或神经变性的其它药剂 疾病