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：US20070054863A1

公开(公告)日：2007-03-08

申请号：US11433783

申请日：2006-05-11

申请人： Arnold Satterthwait ,  Xiao-kun Zhang ,  Xiuwen Zhu ,  Siva Kolluri

发明人： Arnold Satterthwait ,  Xiao-kun Zhang ,  Xiuwen Zhu ,  Siva Kolluri

IPC分类号： A61K38/10 ,  A61K38/08 ,  C07K7/06 ,  C07K7/08

CPC分类号： G01N33/6872 ,  A61K38/00 ,  C07K14/4747 ,  C07K14/70567

摘要： Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing or preventing apoptosis are described, together with methods for identifying molecules that induce or prevent apoptosis through interaction with Bcl-2-family members. Methods for treatment of proliferative diseases and neurodegenerative diseases using the modulators of Bcl-2 and related family members are also disclosed.

摘要翻译： 鉴定了调节抗凋亡蛋白如Bcl-2和相关Bcl-2家族成员功能的化合物。 这些化合物具有将Bcl-2家族成员蛋白的活性从抗凋亡转化为促凋亡的能力。 描述诱导或预防凋亡的方法，以及用于鉴定通过与Bcl-2家族成员相互作用诱导或预防凋亡的分子的方法。 还公开了使用Bcl-2和相关家族成员的调节剂治疗增殖性疾病和神经变性疾病的方法。

公开(公告)号：US20100292145A1

公开(公告)日：2010-11-18

申请号：US12815893

申请日：2010-06-15

申请人： Arnold Satterthwait ,  Xiao-kun Zhang ,  Xiuwen Zhu ,  Siva Kolluri

发明人： Arnold Satterthwait ,  Xiao-kun Zhang ,  Xiuwen Zhu ,  Siva Kolluri

IPC分类号： A61K38/18 ,  C12N5/071 ,  A61P35/00

CPC分类号： G01N33/6872 ,  A61K38/00 ,  C07K14/4747 ,  C07K14/70567

摘要： Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing or preventing apoptosis are described, together with methods for identifying molecules that induce or prevent apoptosis through interaction with Bcl-2-family members. Methods for treatment of proliferative diseases and neurodegenerative diseases using the modulators of Bcl-2 and related family members are also disclosed.

摘要翻译： 鉴定了调节抗凋亡蛋白如Bcl-2和相关Bcl-2家族成员功能的化合物。 这些化合物具有将Bcl-2家族成员蛋白的活性从抗凋亡转化为促凋亡的能力。 描述诱导或预防凋亡的方法，以及用于鉴定通过与Bcl-2家族成员相互作用诱导或预防凋亡的分子的方法。 还公开了使用Bcl-2和相关家族成员的调节剂治疗增殖性疾病和神经变性疾病的方法。

公开(公告)号：US07745574B2

公开(公告)日：2010-06-29

申请号：US11433783

申请日：2006-05-11

申请人： Arnold Satterthwait ,  Xiao-kun Zhang ,  Xiuwen Zhu ,  Siva Kolluri

发明人： Arnold Satterthwait ,  Xiao-kun Zhang ,  Xiuwen Zhu ,  Siva Kolluri

IPC分类号： C07K14/00 ,  A61K38/16

CPC分类号： G01N33/6872 ,  A61K38/00 ,  C07K14/4747 ,  C07K14/70567

摘要： Compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified. These compounds have the ability to convert the activity of Bcl-2-family member proteins from anti-apoptotic to pro-apoptotic. Methods for inducing or preventing apoptosis are described, together with methods for identifying molecules that induce or prevent apoptosis through interaction with Bcl-2-family members. Methods for treatment of proliferative diseases and neurodegenerative diseases using the modulators of Bcl-2 and related family members are also disclosed.

摘要翻译： 鉴定了调节抗凋亡蛋白如Bcl-2和相关Bcl-2家族成员功能的化合物。 这些化合物具有将Bcl-2家族成员蛋白的活性从抗凋亡转化为促凋亡的能力。 描述诱导或预防凋亡的方法，以及用于鉴定通过与Bcl-2家族成员相互作用诱导或预防凋亡的分子的方法。 还公开了使用Bcl-2和相关家族成员的调节剂治疗增殖性疾病和神经变性疾病的方法。

公开(公告)号：US09944606B2

公开(公告)日：2018-04-17

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 ,  C07D413/14 ,  C07D231/54 ,  C07D403/04 ,  C07D413/12 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14

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.

公开(公告)号：US20140206649A1

公开(公告)日：2014-07-24

申请号：US14001131

申请日：2012-02-24

申请人： Jayant Thatte ,  Anthony C. Blackburn ,  Sangdon Han ,  Robert M. Jones ,  Jae-Kyu Jung ,  Anthony 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 ,  Anthony 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 ,  A61K31/416 ,  A61K31/4439 ,  A61K45/06 ,  A61K31/497

CPC分类号： A61K31/497 ,  A61K31/13 ,  A61K31/416 ,  A61K31/4439 ,  A61K31/485 ,  A61K31/675 ,  A61K45/06 ,  C07D231/54 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07F9/65583

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

摘要翻译： 提供有用于治疗疼痛的某些方法，包括施用式Ia化合物及其调节大麻素CB 2受体活性的药物组合物;

公开(公告)号：US08580841B2

公开(公告)日：2013-11-12

申请号：US13055333

申请日：2009-07-22

申请人： Robert M Jones ,  Daniel J Buzard ,  Sangdon Han ,  Sun Hee Kim ,  Juerg Lehmann ,  Brett Ullman ,  Jeanne V Moody ,  Xiuwen Zhu ,  Scott Stirn

发明人： Robert M Jones ,  Daniel J Buzard ,  Sangdon Han ,  Sun Hee Kim ,  Juerg Lehmann ,  Brett Ullman ,  Jeanne V Moody ,  Xiuwen Zhu ,  Scott Stirn

IPC分类号： A61K31/403

CPC分类号： C07D209/94 ,  A61K31/137 ,  A61K31/198 ,  A61K31/404 ,  A61K31/433 ,  A61K31/4439 ,  A61K31/497 ,  C07C211/27 ,  C07C229/26 ,  C07C255/03 ,  C07C279/14 ,  C07D209/70 ,  C07D209/88 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D417/12 ,  Y02A50/475

摘要： The present invention relates to certain substituted 1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic 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 receptor-associated disorders, for example, psoriasis, rheumatoid arthritis, Crohn's disease, transplant rejection, multiple sclerosis, systemic lupus erythematosus, ulcerative colitis, type I diabetes, acne, microbial infections or diseases and viral infections or diseases.

摘要翻译： 本发明涉及式（Ia）的某些取代的1,2,3,4-四氢环戊二烯并[b]吲哚-3-基）乙酸衍生物及其药学上可接受的盐，它们具有有用的药理学性质，例如： S1P1受体的激动剂。 本发明还提供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受体相关疾病例如牛皮癣，类风湿性关节炎，克罗恩病，移植排斥反应的方法， 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，微生物感染或疾病以及病毒感染或疾病。