公开(公告)号：US20100292233A1

公开(公告)日：2010-11-18

申请号：US12863637

申请日：2009-01-22

申请人： Robert M. Jones ,  Daniel J. Buzard ,  Andrew M. Kawasaki ,  Luis A. Lopez ,  Jeanne V. Moody ,  Lars Thoresen ,  Brett Ullman

发明人： Robert M. Jones ,  Daniel J. Buzard ,  Andrew M. Kawasaki ,  Luis A. Lopez ,  Jeanne V. Moody ,  Lars Thoresen ,  Brett Ullman

IPC分类号： A61K31/4245 ,  C07D487/04 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/5377 ,  A61P37/00 ,  A61P35/00 ,  A61P29/00 ,  A61P17/06 ,  A61P1/04 ,  A61P3/10 ,  A61P9/10 ,  A61P17/10 ,  A61P31/00 ,  A61P31/12

CPC分类号： C07D487/04

摘要： The present invention relates to certain (1,2,4-oxadiazol-3-yl)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl carboxylic acid derivatives of Formula (Ia) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1 associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, sepsis, myocardial infarction, ischemic stroke, acne, microbial infections or diseases and viral infections or diseases.

摘要翻译： 本发明涉及式（Ia）的某些（1,2,4-恶二唑-3-基）-2,3-二氢-1H-吡咯并[1,2-a]吲哚-1-基羧酸衍生物和 其药学上可接受的盐，其表现出有用的药理学性质，例如作为S1P1受体的激动剂。 本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物和组合物治疗S1P1相关病症的方法，例如牛皮癣，类风湿性关节炎，克罗恩病，移植排斥反应，多发性硬化 ，系统性红斑狼疮，溃疡性结肠炎，I型糖尿病，败血症，心肌梗死，缺血性中风，痤疮，微生物感染或疾病以及病毒感染或疾病。

公开(公告)号：US20140018371A1

公开(公告)日：2014-01-16

申请号：US14007759

申请日：2012-03-30

申请人： Robert M. Jones ,  Sangdon Han ,  Juerg Lehmann ,  Lars Thoresen

发明人： Robert M. Jones ,  Sangdon Han ,  Juerg Lehmann ,  Lars Thoresen

IPC分类号： A61K31/506 ,  C07D413/04 ,  A61K31/454 ,  C07D401/12 ,  A61K45/06 ,  A61K31/497 ,  C07D401/14 ,  C07D211/24 ,  C07D401/06 ,  A61K31/445 ,  A61K31/4545

CPC分类号： A61K31/506 ,  A61K31/445 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/497 ,  A61K45/06 ,  C07D211/22 ,  C07D211/24 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D413/04 ,  C07D413/06

摘要： The present invention relates to compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as a single agent or in combination with one or more pharmaceutical agents, such as, an inhibitor of DPP-IV, a biguanide, or an alpha-glucosidase inhibitor, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

摘要翻译： 本发明涉及式（Ia）化合物及其药学上可接受的盐，溶剂合物和水合物，其可用作单一试剂或与一种或多种药剂组合使用，例如DPP-IV抑制剂， 双胍或α-葡糖苷酶抑制剂，用于治疗例如选自以下的病症：GPR119-受体相关病症; 通过增加血液肠降血糖水平来改善病情; 代谢相关疾病; 2型糖尿病; 肥胖; 和相关的并发症。

公开(公告)号：US20080070867A1

公开(公告)日：2008-03-20

申请号：US11814239

申请日：2006-01-17

申请人： Zacharia Cheruvallath ,  Joseph Semple ,  Vasanthakumar Rajappan ,  Darryl Rideout ,  Venkatachalapathi Yalamoori ,  Chung-Ying Tsai ,  Feiyue Wu ,  Lars Thoresen ,  Mark Shenderovich

发明人： Zacharia Cheruvallath ,  Joseph Semple ,  Vasanthakumar Rajappan ,  Darryl Rideout ,  Venkatachalapathi Yalamoori ,  Chung-Ying Tsai ,  Feiyue Wu ,  Lars Thoresen ,  Mark Shenderovich

IPC分类号： A61K31/675 ,  A61P3/10 ,  C07F9/02

CPC分类号： C07F9/65583 ,  C07F9/6506 ,  C07F9/65068 ,  C07F9/65586

摘要： Compounds and compositions are provided for modulating the activity of protein tyrosine phosphatases. The compounds for use in the compositions and methods provided herein have formulae (I) Protein tyrosine phosaphatase, including PTB-IB, mediated diseases and disorders include diabetes including Type 1 and Type 2 diabetes (and associated complications such as hypertension, ischemic diseases of the large and small blood vessels, blindness, circulatory problems, kidney failure and atherosclerosis), syndrome X, metabolic syndrome, glucose intolerance, insulin resistance, obesity, cancer, and neurodegenerative diseases.

摘要翻译： 提供化合物和组合物用于调节蛋白酪氨酸磷酸酶的活性。 用于本文提供的组合物和方法的化合物具有式（I）蛋白酪氨酸磷酸酶，包括PTB-IB，介导的疾病和病症包括糖尿病，包括1型和2型糖尿病（以及相关并发症，例如高血压，缺血性疾病 大，小血管，失明，循环问题，肾功能衰竭和动脉粥样硬化），综合征X，代谢综合征，葡萄糖不耐受，胰岛素抵抗，肥胖，癌症和神经变性疾病。

公开(公告)号：US08778950B2

公开(公告)日：2014-07-15

申请号：US13392074

申请日：2010-08-27

申请人： Robert M. Jones ,  Sangdon Han ,  Lars Thoresen ,  Jae-Kyu Jung ,  Sonja Strah-Pleynet ,  Xiuwen Zhu ,  Yifeng Xiong ,  Dawei Yue

发明人： Robert M. Jones ,  Sangdon Han ,  Lars Thoresen ,  Jae-Kyu Jung ,  Sonja Strah-Pleynet ,  Xiuwen Zhu ,  Yifeng Xiong ,  Dawei Yue

IPC分类号： A61K31/4965 ,  A01N43/56 ,  A61K31/415 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00 ,  C07D413/00 ,  C07D417/00 ,  C07D419/00 ,  C07D231/54 ,  C07D487/00

CPC分类号： C07D231/54 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07F9/65583

摘要： The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

摘要翻译： 本发明涉及某些式Ia化合物及其药物组合物，其调节大麻素CB2受体的活性。 本发明还涉及某些式Ia化合物及其药物组合物，其调节CB1受体和CB2受体的活性。 本发明的化合物及其药物组合物涉及可用于治疗以下疼痛的方法：疼痛，例如骨和关节疼痛，肌肉疼痛，牙痛，偏头痛和其他头痛疼痛，炎性疼痛，神经性疼痛，疼痛发生于 与骨关节炎相关的治疗和疼痛的不利影响; 痛觉过敏 异常性疼痛 炎性痛觉过敏; 神经性痛觉过敏; 急性伤害感受 骨质疏松症 多发性硬化相关性痉挛状态; 自身免疫性疾病 过敏反应; CNS炎症; 动脉粥样硬化 不良免疫细胞活性和炎症; 年龄相关性黄斑变性; 咳嗽; 白血病; 淋巴瘤 CNS肿瘤; 前列腺癌; 阿尔茨海默氏病; 中风引起的损伤; 痴呆; 肌萎缩性侧索硬化和帕金森病。

公开(公告)号：US08415484B2

公开(公告)日：2013-04-09

申请号：US13060477

申请日：2009-08-26

申请人： Robert M. Jones ,  Daniel J. Buzard ,  Andrew M. Kawasaki ,  Sun Hee Kim ,  Lars Thoresen ,  Juerg Lehmann ,  Xiuwen Zhu

发明人： Robert M. Jones ,  Daniel J. Buzard ,  Andrew M. Kawasaki ,  Sun Hee Kim ,  Lars Thoresen ,  Juerg Lehmann ,  Xiuwen Zhu

IPC分类号： C07D403/02 ,  C07D487/00 ,  C07D471/14 ,  C07D487/12 ,  C07D401/00 ,  C07D403/14 ,  A61K31/44 ,  A61K31/415 ,  A61K31/40

CPC分类号： C07D487/04 ,  C07D471/04

摘要： The present invention relates to certain substituted tricyclic acid derivatives of Formula (I) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, myocardial ischemia-reperfusion injury, hypertensive nephropathy, glomerulosclerosis, gastritis, polymyositis, thyroiditis, vitiligo, hepatitis, biliary cirrhosis, microbial infections and associated diseases, viral infections and associated diseases, diseases and disorders mediated by lymphocytes, auto immune diseases, inflammatory diseases, and cancer.

摘要翻译： 本发明涉及某些取代的式（I）的三环酸衍生物及其药学上可接受的盐，其表现出有用的药理学性质，例如作为S1P1受体的激动剂。 本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物和组合物治疗S1P1相关病症的方法，例如牛皮癣，类风湿性关节炎，克罗恩病，移植排斥反应，多发性 硬化症，系统性红斑狼疮，溃疡性结肠炎，I型糖尿病，痤疮，心肌缺血再灌注损伤，高血压肾病，肾小球硬化，胃炎，多发性肌炎，甲状腺炎，白癜风，肝炎，胆汁性肝硬化，微生物感染和相关疾病，病毒感染和相关疾病 ，由淋巴细胞介导的疾病和病症，自身免疫疾病，炎性疾病和癌症。

公开(公告)号：US20110160243A1

公开(公告)日：2011-06-30

申请号：US13060477

申请日：2009-08-26

申请人： Robert M. Jones ,  Daniel J. Buzard ,  Andrew M. Kawasaki ,  Sun Hee Kim ,  Lars Thoresen ,  Juerg Lehmann ,  Xiuwen Zhu

发明人： Robert M. Jones ,  Daniel J. Buzard ,  Andrew M. Kawasaki ,  Sun Hee Kim ,  Lars Thoresen ,  Juerg Lehmann ,  Xiuwen Zhu

IPC分类号： A61K31/437 ,  C07D487/04 ,  C07D471/04 ,  A61K31/407 ,  A61K31/4188 ,  A61K31/4439 ,  A61K31/4155 ,  A61P29/00 ,  A61P17/06 ,  A61P37/06 ,  A61P25/28 ,  A61P3/10 ,  A61P13/12 ,  A61P9/10 ,  A61P17/10 ,  A61P1/00 ,  A61P31/00 ,  A61P31/12

CPC分类号： C07D487/04 ,  C07D471/04

摘要： The present invention relates to certain substituted tricyclic acid derivatives of Formula (I) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the S1P1 receptor. Also provided by the present invention are pharmaceutical compositions containing compounds of the invention, and methods of using the compounds and compositions of the invention in the treatment of S1P1-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, myocardial ischemia-reperfusion injury, hypertensive nephropathy, glomerulosclerosis, gastritis, polymyositis, thyroiditis, vitiligo, hepatitis, biliary cirrhosis, microbial infections and associated diseases, viral infections and associated diseases, diseases and disorders mediated by lymphocytes, auto immune diseases, inflammatory diseases, and cancer.

摘要翻译： 本发明涉及某些取代的式（I）的三环酸衍生物及其药学上可接受的盐，其表现出有用的药理学性质，例如作为S1P1受体的激动剂。 本发明还提供了含有本发明化合物的药物组合物，以及使用本发明化合物和组合物治疗S1P1相关病症的方法，例如牛皮癣，类风湿性关节炎，克罗恩病，移植排斥反应，多发性 硬化症，系统性红斑狼疮，溃疡性结肠炎，I型糖尿病，痤疮，心肌缺血再灌注损伤，高血压肾病，肾小球硬化，胃炎，多发性肌炎，甲状腺炎，白癜风，肝炎，胆汁性肝硬化，微生物感染和相关疾病，病毒感染和相关疾病 ，由淋巴细胞介导的疾病和病症，自身免疫疾病，炎性疾病和癌症。

公开(公告)号：US20060009517A1

公开(公告)日：2006-01-12

申请号：US11221245

申请日：2005-09-06

申请人： Stephen Webber ,  Stacie Canan-Koch ,  Jayashree Tikhe ,  Lars Thoresen

发明人： Stephen Webber ,  Stacie Canan-Koch ,  Jayashree Tikhe ,  Lars Thoresen

IPC分类号： A61K31/277

CPC分类号： C07D471/06 ,  A61K31/277 ,  A61K31/4375 ,  C07D487/06

摘要： Compounds of the formula below are poly(ADP-ribosyl)transferase (PARP) inhibitors, and are useful as therapeutics in treatment of cancers and the amelioration of the effects of stroke, head trauma, and neurodegenerative disease. As cancer therapeutics, the compounds of the invention may be used, e.g., in combination with cytotoxic agents and/or radiation.

公开(公告)号：US09597340B2

公开(公告)日：2017-03-21

申请号：US14001132

申请日：2012-02-24

申请人： Jayant Thatte ,  Anthony C. Blackburn ,  Sangdon Han ,  Robert M. Jones ,  Jae-Kyu Jung ,  Antonio Garrido Montalban ,  Biman B. Pal ,  Jaimie Karyn Rueter ,  Sonja Strah-Pleynet ,  Lars Thoresen ,  Yifeng Xiong ,  Dawei Yue ,  Xiuwen Zhu

发明人： Jayant Thatte ,  Anthony C. Blackburn ,  Sangdon Han ,  Robert M. Jones ,  Jae-Kyu Jung ,  Antonio Garrido Montalban ,  Biman B. Pal ,  Jaimie Karyn Rueter ,  Sonja Strah-Pleynet ,  Lars Thoresen ,  Yifeng Xiong ,  Dawei Yue ,  Xiuwen Zhu

IPC分类号： A61K31/4439 ,  A61K31/675 ,  A61K31/416 ,  A61K45/06 ,  A61K31/497

CPC分类号： A61K31/675 ,  A61K31/416 ,  A61K31/4439 ,  A61K31/497 ,  A61K45/06 ,  A61K2300/00

摘要： Provided are certain methods useful in the treatment of cancer comprising administering a compound of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor;

公开(公告)号：US20150126477A1

公开(公告)日：2015-05-07

申请号：US14001132

申请日：2012-02-24

申请人： Jayant Thatte ,  Anthony C. Blackburn ,  Sangdon Han ,  Robert M. Jones ,  Jae-Kyu Jung ,  Antonio Garrido Montalban ,  Biman B. Pal ,  Jaimie Karyn Rueter ,  Sonja Strah-Pleynet ,  Lars Thoresen ,  Yifeng Xiong ,  Dawei Yue ,  Xiuwen Zhu

发明人： Jayant Thatte ,  Anthony C. Blackburn ,  Sangdon Han ,  Robert M. Jones ,  Jae-Kyu Jung ,  Antonio Garrido Montalban ,  Biman B. Pal ,  Jaimie Karyn Rueter ,  Sonja Strah-Pleynet ,  Lars Thoresen ,  Yifeng Xiong ,  Dawei Yue ,  Xiuwen Zhu

IPC分类号： A61K31/675 ,  A61K31/4439 ,  A61K31/497 ,  A61K45/06 ,  A61K31/416

CPC分类号： A61K31/675 ,  A61K31/416 ,  A61K31/4439 ,  A61K31/497 ,  A61K45/06 ,  A61K2300/00

摘要： Provided are certain methods useful in the treatment of cancer comprising administering a compound of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor;

摘要翻译： 提供某些方法可用于治疗癌症，包括施用式Ia化合物及其药物组合物，其调节大麻素CB2受体的活性;

公开(公告)号：US20130165412A1

公开(公告)日：2013-06-27

申请号：US13616918

申请日：2012-09-14

申请人： Robert M. Jones ,  Sangdon Han ,  Lars Thoresen ,  Jae-Kyu Jung ,  Sonja Strah-Pleynet ,  Xiuwen Zhu ,  Yifeng Xiong ,  Dawei Yue

发明人： Robert M. Jones ,  Sangdon Han ,  Lars Thoresen ,  Jae-Kyu Jung ,  Sonja Strah-Pleynet ,  Xiuwen Zhu ,  Yifeng Xiong ,  Dawei Yue

IPC分类号： C07F9/6558 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  C07D413/14 ,  C07D231/54 ,  C07D403/04

CPC分类号： C07D231/54 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07F9/65583

摘要： The present invention relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB2 receptor. The present invention further relates to certain compounds of Formula Ia and pharmaceutical compositions thereof that modulate the activities of both the CB1 receptor and the CB2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: pain, for example bone and joint pain, muscle pain, dental pain, migraine and other headache pain, inflammatory pain, neuropathic pain, pain that occurs as an adverse effect of therapeutics and pain associated with osteoarthritis; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions; CNS inflammation; atherosclerosis; undesired immune cell activity and inflammation; age-related macular degeneration; cough; leukemia; lymphoma; CNS tumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis, and Parkinson's disease.

摘要翻译： 本发明涉及某些式Ia化合物及其药物组合物，其调节大麻素CB2受体的活性。 本发明还涉及某些式Ia化合物及其药物组合物，其调节CB1受体和CB2受体的活性。 本发明的化合物及其药物组合物涉及可用于治疗以下疼痛的方法：疼痛，例如骨和关节疼痛，肌肉疼痛，牙痛，偏头痛和其他头痛疼痛，炎性疼痛，神经性疼痛，疼痛发生于 与骨关节炎相关的治疗和疼痛的不利影响; 痛觉过敏 异常性疼痛 炎性痛觉过敏; 神经性痛觉过敏; 急性伤害感受 骨质疏松症 多发性硬化相关性痉挛状态; 自身免疫性疾病 过敏反应; CNS炎症; 动脉粥样硬化 不良免疫细胞活性和炎症; 年龄相关性黄斑变性; 咳嗽; 白血病; 淋巴瘤 CNS肿瘤; 前列腺癌; 阿尔茨海默氏病; 中风引起的损伤; 痴呆; 肌萎缩性侧索硬化和帕金森病。