公开(公告)号：US20140023667A1

公开(公告)日：2014-01-23

申请号：US14009654

申请日：2012-04-02

申请人： Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming

发明人： Andrew W. Stamford ,  Eric J. Gilbert ,  Jared N. Cumming

IPC分类号： C07D513/04 ,  A61K45/06 ,  A61K31/549

CPC分类号： C07D513/04 ,  A61K31/549 ,  A61K45/06

摘要： In its many embodiments, the present invention provides certain iminothiadiazine dioxide compounds, including compounds Formula (I): and tautomers and stereoisomers thereof, and pharmaceutically acceptable salts of said compounds, said tautomeros and said stereoisomers, wherein each of W, Z, R1H, R2, R3, R4, ring A, ring B, m, n, p, and -L1- is as defined herein. The novel compounds of the invention have surprisingly been found to exhibit properties which are expected to render them advantageous as BACE inhibitors and/or for the treatment and prevention of various pathologies related thereto. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use, including Alzheimer's disease, are also disclosed.

摘要翻译： 在其许多实施方案中，本发明提供了某些亚氨基二嗪二氧化物化合物，包括式（I）化合物及其互变异构体和立体异构体，以及所述化合物，所述互变异构体和所述立体异构体的药学上可接受的盐，其中W，Z，R 1 H， R2，R3，R4，环A，环B，m，n，p和-L1-如本文所定义。 令人惊奇地发现本发明的新化合物表现出预期使其作为BACE抑制剂和/或用于治疗和预防与之相关的各种病症的优点。 还公开了包含一种或多种这样的化合物（单独和与一种或多种其它活性剂组合）的药物组合物及其制备和使用方法，包括阿尔茨海默氏病。

公开(公告)号：US08415353B2

公开(公告)日：2013-04-09

申请号：US12920928

申请日：2009-03-03

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

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

IPC分类号： A61K31/495

CPC分类号： C07D241/44 ,  C07D401/12 ,  C07D403/04 ,  C07D405/12 ,  C07D413/04 ,  C07D417/04 ,  C07D417/12

摘要： Compounds of the Formula (I), where W represents CH or N; and Q represents —CN, —C(═NOH)NH2, —CONHR1 or various herein described heterocyclic radicals; as well as pharmaceutically acceptable salts, solvates, esters and prodrugs thereof are adenosine A2a receptor antagonists and, therefore, are useful in the treatment of central nervous system diseases, in particular Parkinson's disease.

摘要翻译： 式（I）的化合物，其中W表示CH或N; 和Q表示-CN，-C（= NOOH）NH 2，-CONHR1或本文所述的各种杂环基; 以及其药学上可接受的盐，溶剂合物，酯和前药是腺苷A2a受体拮抗剂，因此可用于治疗中枢神经系统疾病，特别是帕金森病。

公开(公告)号：US20120195881A1

公开(公告)日：2012-08-02

申请号：US13391441

申请日：2010-10-06

申请人： Ulrich Iserloh ,  Andrew W. Stamford ,  Jared N. Cumming

发明人： Ulrich Iserloh ,  Andrew W. Stamford ,  Jared N. Cumming

IPC分类号： A61K39/395 ,  A61K38/00 ,  A61K31/513 ,  C07D405/04 ,  A61P29/00 ,  A61P25/28 ,  A61P25/16 ,  A61P25/00 ,  A61P3/10 ,  A61P31/04 ,  A61K39/00 ,  C07D239/22

CPC分类号： C07D239/22 ,  C07D405/04

摘要： In its many embodiments, the present invention provides certain pentafluorosulfur imino heterocyclic compounds, including compounds Formula (a) and pharmaceutically acceptable salts thereof. Compounds of Formula (a) have the general structure: (a) wherein each variable is selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds (alone and in combination with one or more other active agents), and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimers Disease, are also disclosed.

摘要翻译： 在其许多实施方案中，本发明提供某些五氟硫亚氨基杂环化合物，包括式（a）化合物及其药学上可接受的盐。 式（a）的化合物具有通式结构：（a）其中每个变量是独立选择的，如本文所定义。 还公开了包含一种或多种这样的化合物（单独并与一种或多种其它活性剂组合）的药物组合物及其制备和用于治疗与包括阿尔茨海默病在内的淀粉样蛋白β（A＆bgr））蛋白相关的病理学的方法。

公开(公告)号：US20110280867A1

公开(公告)日：2011-11-17

申请号：US13191978

申请日：2011-07-27

申请人： Zhaoning Zhu ,  Andrew W. Stamford ,  Brian McKittrick

发明人： Zhaoning Zhu ,  Andrew W. Stamford ,  Brian McKittrick

IPC分类号： A61K39/395 ,  A61K31/55 ,  C07D409/04 ,  A61P25/28 ,  A61P25/00 ,  A61P9/00 ,  C07D498/04 ,  A61K31/5517 ,  C07D487/04

CPC分类号： C07D409/04 ,  C07D487/04

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 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. 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Ar，R 1，R 2，R 3，R 4和R 5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：US08012960B2

公开(公告)日：2011-09-06

申请号：US12794858

申请日：2010-06-07

申请人： Zhaoning Zhu ,  Andrew W. Stamford ,  Brian McKittrick

发明人： Zhaoning Zhu ,  Andrew W. Stamford ,  Brian McKittrick

IPC分类号： C07D487/04 ,  C07D498/04 ,  A61K31/18

CPC分类号： C07D409/04 ,  C07D487/04

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein Ar, R1, R2, R3, R4 and R5 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. 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Ar，R 1，R 2，R 3，R 4和R 5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：US20110110927A1

公开(公告)日：2011-05-12

申请号：US12988464

申请日：2009-04-21

申请人： Andrew W. Stamford ,  Zhaoning Zhu ,  Mihirbaran Mandal ,  Xiaoxiang Liu

发明人： Andrew W. Stamford ,  Zhaoning Zhu ,  Mihirbaran Mandal ,  Xiaoxiang Liu

IPC分类号： A61K39/395 ,  C07D471/04 ,  A61K31/519 ,  A61P25/28 ,  A61P25/00

CPC分类号： C07D487/04

摘要： In its many embodiments, the present invention provides provides certain thiophenyl-substituted 2-imino-3-methyl pyrrolo pyrimidone compounds, including compounds (or tautomers or a pharmaceutically acceptable salts thereof) having the structural Formula (III): wherein R2, R3, R4, R5, R6, R7, R8, and R9 are each selected independently and as defined herein. Pharmaceutical compositions comprising one or more such compounds, and methods for their preparation and use in treating pathologies associated with amyloid beta (Aβ) protein, including Alzheimer's Disease, are also disclosed.

摘要翻译： 在其许多实施方案中，本发明提供某些噻吩基取代的2-亚氨基-3-甲基吡咯并嘧啶酮化合物，包括具有结构式（III）的化合物（或其互变异构体或其药学上可接受的盐）：其中R2，R3， R 4，R 5，R 6，R 7，R 8和R 9各自独立地如本文所定义。 还公开了包含一种或多种这样的化合物的药物组合物，及其制备和用于治疗与淀粉样蛋白β（A＆bgr））蛋白质（包括阿尔茨海默氏病）相关的病理学的方法。

公开(公告)号：US20110003825A1

公开(公告)日：2011-01-06

申请号：US12861347

申请日：2010-08-23

申请人： Ying Huang ,  Guoqing Li ,  Andrew W. Stamford

发明人： Ying Huang ,  Guoqing Li ,  Andrew W. Stamford

IPC分类号： A61K31/495 ,  C07D233/32 ,  C07D401/12 ,  C07D405/12 ,  C07D403/12 ,  C07D413/12 ,  C07D417/12 ,  A61K31/4152 ,  A61K31/4439 ,  A61K31/501 ,  A61K31/422 ,  A61K31/427 ,  A61K31/496 ,  A61P25/28 ,  A61P25/00

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

摘要： Disclosed are novel compounds of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein R1, R2, R3, R4 and X are as defined in the specification. Also disclosed are pharmaceutical compositions comprising the compounds of formula I.Also disclosed are methods of treating cognitive or neurodegenerative diseases such as Alzheimer's disease.Also disclosed are methods of treating a cognitive or neurodegenerative disease comprising administering to a patient I need of such treatment a combination of at least one compound of formula I and at least one compound selected from the group consisting of β-secretase inhibitors other than those of formula I, HMG-CoA reductase inhibitors, gamma-secretase inhibitors, non-steroidal anti-inflammatory agents, N-methyl-D-aspartate receptor antagonists, cholinesterase inhibitors and anti-amyloid antibodies.

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化物，其中R1，R2，R3，R4和X如说明书中所定义。 还公开了包含式I化合物的药物组合物。还公开了治疗认知或神经变性疾病如阿尔茨海默病的方法。 还公开了治疗认知或神经退行性疾病的方法，包括向需要这种治疗的患者施用至少一种式I化合物和至少一种选自除了那些的那些之外的其他化合物 式I，HMG-CoA还原酶抑制剂，γ-分泌酶抑制剂，非甾体抗炎剂，N-甲基-D-天冬氨酸受体拮抗剂，胆碱酯酶抑制剂和抗淀粉样蛋白抗体。

公开(公告)号：US20100190687A1

公开(公告)日：2010-07-29

申请号：US12596341

申请日：2008-04-17

申请人： Craig D. Boyle ,  Santhosh Francis Neelamkavil ,  Samuel Chackalamannil ,  Bernard R. Neustadt ,  Jinsong Hao ,  Unmesh G. Shah ,  Joel M. Harris ,  Hong Liu ,  Andrew W. Stamford

发明人： Craig D. Boyle ,  Santhosh Francis Neelamkavil ,  Samuel Chackalamannil ,  Bernard R. Neustadt ,  Jinsong Hao ,  Unmesh G. Shah ,  Joel M. Harris ,  Hong Liu ,  Andrew W. Stamford

IPC分类号： A61K38/28 ,  C07D487/04 ,  A61K31/519 ,  A61K31/55 ,  A61K38/22 ,  A61P3/10 ,  A61P3/04

CPC分类号： C07D401/04 ,  C07D487/04

摘要： The present invention relates to Pyrimidinone Derivatives, compositions comprising a Pyrimidinone Derivative, and methods of using the Pyrimidinone Derivatives for treating or preventing obesity, diabetes, a metabolic disorder, a cardiovascular disease or a disorder related to the activity of G protein-coupled receptor 119 (“GPR119”) in a patient.

摘要翻译： 本发明涉及嘧啶酮衍生物，包含嘧啶酮衍生物的组合物，以及使用嘧啶酮衍生物治疗或预防与G蛋白偶联受体119的活性相关的肥胖症，糖尿病，代谢紊乱，心血管疾病或病症的方法 （“GPR119”）。

公开(公告)号：US06667319B2

公开(公告)日：2003-12-23

申请号：US10202239

申请日：2002-07-24

申请人： Andrew W. Stamford ,  Ying Huang ,  Guoqing Li

发明人： Andrew W. Stamford ,  Ying Huang ,  Guoqing Li

IPC分类号： A61K314468

CPC分类号： C07D409/14 ,  C07D211/58 ,  C07D211/96 ,  C07D401/12 ,  C07D401/14

摘要： The present invention discloses compounds which, are novel receptor antagonists for NPY Y5 as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such NPY Y5 receptor antagonists as well as methods of using them to treat obesity, metabolic disorders, eating disorders such as hyperphagia, and diabetes.

摘要翻译： 本发明公开了作为NPY Y5的新型受体拮抗剂的化合物及其制备方法。 在另一个实施方案中，本发明公开了包含这种NPY Y5受体拮抗剂的药物组合物以及使用它们治疗肥胖，代谢紊乱，进食障碍如食欲过盛和糖尿病的方法。

公开(公告)号：US06632828B2

公开(公告)日：2003-10-14

申请号：US10200966

申请日：2002-07-23

申请人： Andrew W. Stamford ,  Craig D. Boyle ,  Ying Huang

发明人： Andrew W. Stamford ,  Craig D. Boyle ,  Ying Huang

IPC分类号： A61K314545

CPC分类号： C07D233/64 ,  C07D233/88 ,  C07D401/04 ,  C07D401/06 ,  C07D401/10 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D417/12

摘要： Compounds of the formula I or a pharmaceutically acceptable salt, solvate or N-oxide thereof, wherein X is ═CH— or ═N—; Y is H, halogen, trihaloalkyl, alkyl, alkenyl, cycloalkyl, cycloalkyl, SH, —S-alkyl, or —CN. R is alkyl, —CF3, cycloalkyl, heterocycloalkyl, heterocycloalkyl-alkyl, heteroarylalky or adamantyl, or optionally substituted phenyl, phenoxyalkyl, phenylthioalkyl, pyridyl, thienyl, thiazolyl, pyrazinyl, 1,2,5,6-tetrahydropyridine or  wherein R10 and R11 are hydrogen, alkyl or together form a cycloalkyl, are disclosed, as well as pharmaceutical compositions and methods of using said compounds in the treatment of eating disorders and diabetes.

摘要翻译： 式I化合物或其药学上可接受的盐，溶剂化物或N-氧化物，其中X为= CH-或= N-; Y为H，卤素，三卤代烷基，烷基，烯基，环烷基， 环烷基，SH，-S-烷基或-CN。R是烷基，-CF 3，环烷基，杂环烷基，杂环烷基 - 烷基，杂芳基烷基或金刚烷基， 或任选取代的苯基，苯氧基烷基，苯硫基烷基，吡啶基，噻吩基，噻唑基，吡嗪基，1,2,5,6-四氢吡啶，或其中R“H”> 10 SP> 是氢，烷基或一起形成环烷基，以及使用所述化合物治疗进食障碍和糖尿病的药物组合物和方法。