公开(公告)号：WO2005007647A1

公开(公告)日：2005-01-27

申请号：PCT/US2004/022327

申请日：2004-07-09

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert, M. ,  SEMPLE, Graeme ,  XIONG, Yifeng ,  SHIN, Young-Jun ,  REN, Albert, S. ,  CALDERON, Imelda ,  CHOI, Jin, Sun, Karoline ,  FIORAVANTI, Beatriz ,  LEHMANN, Juerg ,  BRUCE, Marc, A.

Inventor： JONES, Robert, M. ,  SEMPLE, Graeme ,  XIONG, Yifeng ,  SHIN, Young-Jun ,  REN, Albert, S. ,  CALDERON, Imelda ,  CHOI, Jin, Sun, Karoline ,  FIORAVANTI, Beatriz ,  LEHMANN, Juerg ,  BRUCE, Marc, A.

IPC: C07D401/12

CPC classification number: C07D239/52 ,  C07D239/54 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

Abstract: The present invention relates to certain trisubstituted aryl and heteroaryl derivatives of Formula (I) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

Abstract translation: 本发明涉及作为代谢调节剂的式（I）的某些三取代芳基和杂芳基衍生物。 因此，本发明的化合物可用于预防或治疗代谢紊乱及其并发症，例如糖尿病和肥胖症。

公开(公告)号：WO2004065380A1

公开(公告)日：2004-08-05

申请号：PCT/US2004/001267

申请日：2004-01-14

Applicant: ARENA PHARMACEUTICALS INC. ,  JONES, Robert, M. ,  SEMPLE, Graeme ,  FIORAVANTI, Beatriz ,  PEREIRA, Guilherme ,  CALDERON, Imelda ,  UY, Jane ,  DUVVURI, Kameshwari ,  CHOI, Jin Sun Karoline ,  XIONG, Yifeng ,  DAVE, Vibha

Inventor： JONES, Robert, M. ,  SEMPLE, Graeme ,  FIORAVANTI, Beatriz ,  PEREIRA, Guilherme ,  CALDERON, Imelda ,  UY, Jane ,  DUVVURI, Kameshwari ,  CHOI, Jin Sun Karoline ,  XIONG, Yifeng ,  DAVE, Vibha

IPC: C07D401/14

CPC classification number: C07D213/68 ,  C07D213/79 ,  C07D239/34 ,  C07D239/50 ,  C07D295/096 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/04 ,  C07D405/14 ,  C07D409/14 ,  C07D411/14 ,  C07D413/14 ,  C07D417/14 ,  C07D419/14

Abstract: The present invention relates to certain 1,2,3-trisubstituted aryl and heteroaryl derivatives of Fomula (Ia) that are modulators of metabolism. Accordingly, compounds of the present invention are useful in the prophylaxis or treatment of metabolic disorders and complications thereof, such as, diabetes and obesity.

Abstract translation: 本发明涉及作为代谢调节剂的式（Ia）的某些1,2,3-三取代的芳基和杂芳基衍生物。 因此，本发明化合物可用于预防或治疗代谢紊乱及其并发症，例如糖尿病和肥胖症。

公开(公告)号：WO2012145604A1

公开(公告)日：2012-10-26

申请号：PCT/US2012/034416

申请日：2012-04-20

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M.

Inventor： JONES, Robert M.

IPC: C07D401/14 ,  A61K31/506 ,  A61P3/10

CPC classification number: C07D401/14 ,  A61K31/506 ,  A61K45/06

Abstract: The present invention relates to the GPR119 agonist, 4-(1-(5-ethylpyrimidin-2-yl)piperidin-4-yloxy)-5-fluoro-6-(2-methyl-6-(methylsulfonyl)pyridin-3-yloxy)pyrimidine (Compound 1): and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing the secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

Abstract translation: 本发明涉及GPR119激动剂，4-（1-（5-乙基嘧啶-2-基）哌啶-4-基氧基）-5-氟-6-（2-甲基-6-（甲基磺酰基） 吡啶基氧基）嘧啶（化合物1）及其药学上可接受的盐，溶剂合物和水合物，其可用作单一药剂或与一种或多种另外的药剂如DPP-IV抑制剂，双胍类， α-葡糖苷酶抑制剂，胰岛素类似物，磺酰脲类，SGLT2抑制剂，氯噻嗪，噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如选自以下的病症：GPR119-受体相关病症 ; 通过增加肠降血糖素的分泌而改善的状况; 通过增加血液肠降血糖水平来改善病情; 以低骨量为特征的病症; 神经障碍 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：WO2012145603A1

公开(公告)日：2012-10-26

申请号：PCT/US2012/034415

申请日：2012-04-20

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M.

Inventor： JONES, Robert M.

IPC: C07D401/14 ,  A61K31/506 ,  A61P3/10

CPC classification number: C07D401/14 ,  A61K31/506 ,  A61K45/06

Abstract: The present invention relates to the GPR119 agonist, 1-methylcyclopropyl 4-(5-fluoro-6-(2-methyl-6-(methylsulfonyl)pyridin-3-yloxy)pyrimidin-4-yloxy)piperidine-1-carboxylate (Compound 1):and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing the secretion of an incretin; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

Abstract translation: 本发明涉及GPR119激动剂，4-（5-氟-6-（2-甲基-6-（甲基磺酰基）吡啶-3-基氧基）嘧啶-4-基氧基）哌啶-1-甲酸1-甲基环丙酯（化合物 1）及其药学上可接受的盐，溶剂合物和水合物，其可用作单一药剂或与一种或多种另外的药剂如DPP-IV抑制剂，双胍类，α-葡糖苷酶抑制剂， 胰岛素类似物，磺酰脲类，SGLT2抑制剂，兆奈德，噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如选自以下的病症：GPR119-受体相关病症; 通过增加肠降血糖素的分泌而改善的状况; 通过增加血液肠降血糖水平来改善病情; 以低骨量为特征的病症; 神经障碍 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：WO2012116276A1

公开(公告)日：2012-08-30

申请号：PCT/US2012/026506

申请日：2012-02-24

Applicant: ARENA PHARMACEUTICALS, INC. ,  BLACKBURN, Anthony C. ,  HAN, Sangdon ,  JONES, Robert M. ,  MONTALBAN, Anthony Garrido ,  PAL, Biman B. ,  RUETER, Jaimie Karyn

Inventor： BLACKBURN, Anthony C. ,  HAN, Sangdon ,  JONES, Robert M. ,  MONTALBAN, Anthony Garrido ,  PAL, Biman B. ,  RUETER, Jaimie Karyn

IPC: C07D403/04 ,  A61K31/416 ,  A61P29/00

CPC classification number: C07D403/04 ,  A61K31/497 ,  A61P29/00 ,  C07B2200/13

Abstract: The present invention relates to crystalline forms of (1aS,5aS)-2-(4-oxy-pyrazin-2-yl)- 1a,2,5.5a-tetrahydro- 1 H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid ((S)- 1 - hydroxymcthyl-2.2-dimcthyl-propyl)-amidc (Compound 1) and pharmaceutical compositions thereof that modulate the activity of the cannabinoid CB 2 receptor and are therefore useful in t treatment of CB 2 receptor-mediated disorders, for example, osteoarthritis; pain; hyperalgesia; allodynia; inflammatory hyperalgesia; neuropathic hyperalgesia; acute nociception; osteoporosis; multiple sclerosis-associated spasticity; autoimmune disorders; allergic reactions CNS inflammation for example; atherosclerosis; undesired immune cell activity, and inflammation associated with a disorder selected from: osteoarthritis, anaphylaxis, Behcet's disease, graft rejection, vasculitis, gout, spondylitis, viral disease, bacterial disease, lupus, inflammatory bowel disease, autoimmune hepatitis, and type 1 diabetes mellitus; age-related macular degeneration; cough; leukemia; lymphoma; CNS rumors; prostate cancer; Alzheimer's disease; stroke-induced damage; dementia; amyotrophic lateral sclerosis; and Parkinson's disease.

Abstract translation: 本发明涉及（1aS，5aS）-2-（4-氧 - 吡嗪-2-基）-1a，2,5,5-四氢-1H-2,3-二氮杂 - 环丙烷[a]的结晶形式， （c）-1-羟基辛基-2,2-二甲基丙基） - 酰胺（化合物1）及其药物组合物，其调节大麻素CB2受体的活性，因此可用于治疗CB2受体 介导的疾病，例如骨关节炎; 疼痛; 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炎症例如; 动脉粥样硬化; 不良免疫细胞活性和与选自以下的疾病相关的炎症：骨关节炎，过敏反应，贝切特氏病，移植排斥反应，血管炎，痛风，脊椎炎，病毒性疾病，细菌性疾病，狼疮，炎性肠病，自身免疫性肝炎和1型糖尿病 ; 年龄相关性黄斑变性; 咳嗽; 白血病; 淋巴瘤; CNS传闻 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：WO2011109471A1

公开(公告)日：2011-09-09

申请号：PCT/US2011/026806

申请日：2011-03-02

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M. ,  BUZARD, Daniel J. ,  GHARBAOUI, Tawfik ,  JOHNSON, Benjamin R. ,  KASEM, Michelle ,  SCHRADER, Thomas O. ,  STIRN, Scott

Inventor： JONES, Robert M. ,  BUZARD, Daniel J. ,  GHARBAOUI, Tawfik ,  JOHNSON, Benjamin R. ,  KASEM, Michelle ,  SCHRADER, Thomas O. ,  STIRN, Scott

IPC: C07D487/04 ,  A61K31/407 ,  A61P31/12 ,  A61P37/00

CPC classification number: C07D487/04

Abstract: The present invention relates to salts, processes, and process intermediates useful in the preparation of (R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid of Formula (Ia), salts, and crystalline forms thereof. The compound (R)-2-(9-chloro-7-(4-isopropoxy-3-(trifluoromethyl)benzyloxy)-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetic acid has been identified as an S1P1 receptor modulator that is useful in the treatment of S1P1 receptor-associated disorders, for example, diseases and disorders mediated by lymphocytes, transplant rejection, autoimmune diseases and disorders, inflammatory diseases and disorders (e.g., acute and chronic inflammatory conditions), cancer, and conditions characterized by an underlying defect in vascular integrity or that are associated with angiogenesis such as may be pathologic (e.g., as may occur in inflammation, tumor development, and atherosclerosis).

Abstract translation: 本发明涉及可用于制备（R）-2-（9-氯-7-（4-异丙氧基-3-（三氟甲基）苄氧基）-2,3-二氢-1H- - 吡咯并[1,2-a]吲哚-1-基）乙酸，其盐和结晶形式。 化合物（R）-2-（9-氯-7-（4-异丙氧基-3-（三氟甲基）苄氧基）-2,3-二氢-1H-吡咯并[1,2-a]吲哚-1-基） 乙酸被鉴定为可用于治疗S1P1受体相关疾病的S1P1受体调节剂，例如由淋巴细胞介导的疾病和病症，移植排斥反应，自身免疫性疾病和病症，炎性疾病和病症（例如急性和 慢性炎性病症），癌症和特征在于血管完整性的潜在缺陷或与血管发生相关的病症，例如可能是病理性的（例如，可能发生在炎症，肿瘤发展和动脉粥样硬化中）。

公开(公告)号：WO2011025541A1

公开(公告)日：2011-03-03

申请号：PCT/US2010/002360

申请日：2010-08-27

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M. ,  HAN, Sangdon ,  THORESEN, Lars ,  JUNG, Jae-Kyu ,  STRAH-PLEYNET, Sonja ,  ZHU, Xiuwen ,  XIONG, Yifeng ,  YUE, Dawei

Inventor： JONES, Robert M. ,  HAN, Sangdon ,  THORESEN, Lars ,  JUNG, Jae-Kyu ,  STRAH-PLEYNET, Sonja ,  ZHU, Xiuwen ,  XIONG, Yifeng ,  YUE, Dawei

IPC: C07D231/54 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  A61K31/416 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/661 ,  C07F9/09 ,  A61P29/00 ,  A61P19/02

CPC classification number: C07D231/54 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D413/12 ,  C07D413/14 ,  C07F9/65583

Abstract: 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.

Abstract translation: 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：WO2010011316A1

公开(公告)日：2010-01-28

申请号：PCT/US2009/004265

申请日：2009-07-22

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M. ,  BUZARD, DAniel J. ,  HAN, Sangdon ,  KIM, Sun He ,  LEHMANN, Juerg ,  ULLMAN, Brett ,  MOODY, Jeanne V. ,  ZHU, Xiuwen ,  STIRN, Scott

Inventor： JONES, Robert M. ,  BUZARD, DAniel J. ,  HAN, Sangdon ,  KIM, Sun He ,  LEHMANN, Juerg ,  ULLMAN, Brett ,  MOODY, Jeanne V. ,  ZHU, Xiuwen ,  STIRN, Scott

IPC: C07D209/70 ,  C07D209/88 ,  C07D401/12 ,  C07D403/12 ,  C07D417/12 ,  A61P37/00 ,  A61K31/403

CPC classification number: 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

Abstract: 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.

Abstract translation: 本发明涉及式（Ia）的某些取代的1,2,3,4-四氢环戊并[b]吲哚-3-基）乙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，例如作为激动剂 的S1P1受体。 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。

公开(公告)号：WO2008005576A1

公开(公告)日：2008-01-10

申请号：PCT/US2007/015681

申请日：2007-07-05

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M. ,  LEHMANN, Juerg

Inventor： JONES, Robert M. ,  LEHMANN, Juerg

IPC: C07D401/14 ,  A61K31/506 ,  A61P3/00

CPC classification number: C07D401/14

Abstract: The present invention relates to 4-[6-(6-methanesulfonyl-2-methyl-pyridin-3-ylamino)-5-methyl-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester, pharmaceutically acceptable salts, solvates and hydrates thereof that are modulators of glucose metabolism. Accordingly, compounds of the present invention are useful in the treatment of metabolic-related disorders and complications thereof, such as, diabetes and obesity.

Abstract translation: 本发明涉及4- [6-（6-甲磺酰基-2-甲基 - 吡啶-3-基氨基）-5-甲基 - 嘧啶-4-基氧基] - 哌啶-1-甲酸异丙酯，其药学上可接受的盐， 其是葡萄糖代谢调节剂的溶剂合物和水合物。 因此，本发明的化合物可用于治疗代谢相关疾病及其并发症，例如糖尿病和肥胖症。

公开(公告)号：WO2008005569A2

公开(公告)日：2008-01-10

申请号：PCT/US2007/015670

申请日：2007-07-05

Applicant: ARENA PHARMACEUTICALS, INC. ,  JONES, Robert M. ,  LEHMANN, Juerg ,  SIU-TING WONG, Amy

Inventor： JONES, Robert M. ,  LEHMANN, Juerg ,  SIU-TING WONG, Amy

CPC classification number: C07D401/14

Abstract: The present invention relates to 4-[5-Methoxy-6-(2-methyl-6-[1,2,4]triazol-1-yl-pyridin-3-ylamino)-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester, pharmaceutically acceptable salts, solvates and hydrates thereof that are modulators of glucose metabolism. Accordingly, compounds of the present invention are useful in the treatment of metabolic-related disorders and complications thereof, such as, diabetes and obesity.

Abstract translation: 本发明涉及4- [5-甲氧基-6-（2-甲基-6- [1,2,4]三唑-1-基 - 吡啶-3-基氨基） - 嘧啶-4-基氧基] 1-羧酸异丙酯，其药学上可接受的盐，溶剂化物和水合物，其是葡萄糖代谢的调节剂。 因此，本发明的化合物可用于治疗代谢相关疾病及其并发症，例如糖尿病和肥胖症。