公开(公告)号：EP2292593A3

公开(公告)日：2011-05-25

申请号：EP10010651.7

申请日：2001-09-27

申请人： TopoTarget UK Limited

发明人： Watkins, Clare, J. ,  Romero-Martin, Maria-Rosario ,  Moore, Kathryn, G. ,  Richie, James ,  Finn, Paul, W. ,  Kalvinsh, Ivars ,  Loza, Einars ,  Dikovska, Klara ,  Gailite, Vija ,  Vorona, Maxim ,  Piskunova, Irina ,  Starchenkov, Igor ,  Andrianov, Victor ,  Harris, C., John ,  Duffy, James, E., S.

IPC分类号： C07C311/21 ,  C07D317/58 ,  C07D307/52 ,  C07D213/65 ,  C07D213/42 ,  C07D209/88 ,  A61K31/44 ,  A61K31/40 ,  A61K31/36 ,  A61K31/34 ,  A61P35/00 ,  A61P17/06

CPC分类号： C07D213/40 ,  C07C311/06 ,  C07C311/13 ,  C07C311/16 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07C2602/08 ,  C07D209/88 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58

摘要： The present invention relates to compounds of the following formula, and pharmaceutically acceptable salts and solvates thereof, wherein: A is C 5-20 heteroaryl or C 5-20 carboaryl, and is optionally substituted; Q 1 is: a covalent bond, a saturated aliphatic C 1-7 alkylene group and is optionally substituted, or a partially unsaturated aliphatic C 2-7 alkylene group and is optionally substituted; R 1 is hydrogen, C 1-7 alkyl, or C 5-20 aryl; and, Q 2 is -(CH 2 ) n - where n is 4, 5, 6, or 7. The present invention also relates to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

公开(公告)号：EP2083005A1

公开(公告)日：2009-07-29

申请号：EP09004388.6

申请日：2001-09-27

申请人： TopoTarget UK Limited

发明人： Watkins, Clare J. ,  Romero-Martin, Maria-Rosario ,  Moore, Kathryn G. ,  Ritchie, James ,  Finn, Paul W ,  Kalvinsh, Ivars ,  Loza, Einars ,  Starchenkov, Igor ,  Dikovska, Klara ,  Bokaldere, Rasma Melita ,  Gailite, Vija ,  Vorona, Maxim ,  Andrianov, Victor ,  Lolya, Daina ,  Semenikhina, Valentina ,  Amolins, Andris ,  Harris, John C ,  Duffy, James E S

IPC分类号： C07D207/40 ,  C07D209/14 ,  C07D213/06 ,  C07D233/04 ,  C07D233/08 ,  C07D235/24 ,  C07D307/34 ,  C07D333/24 ,  C07D333/60 ,  A61K31/426 ,  A61K31/381 ,  A61K31/38 ,  A61K31/277 ,  A61K31/198 ,  A61K31/195 ,  A61K31/16 ,  A61P31/20

CPC分类号： C07D207/337 ,  A61K31/16 ,  A61K31/195 ,  A61K31/198 ,  A61K31/277 ,  A61K31/38 ,  A61K31/381 ,  A61K31/426 ,  C07C233/49 ,  C07C233/83 ,  C07C235/34 ,  C07C237/36 ,  C07C255/57 ,  C07C259/06 ,  C07C259/08 ,  C07C2603/18 ,  C07D207/40 ,  C07D207/404 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/22 ,  C07D213/06 ,  C07D213/55 ,  C07D213/56 ,  C07D233/04 ,  C07D233/08 ,  C07D235/14 ,  C07D235/24 ,  C07D271/06 ,  C07D307/34 ,  C07D307/54 ,  C07D317/60 ,  C07D333/24 ,  C07D333/60 ,  C07D403/12 ,  Y02A50/411

摘要： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula:

wherein: A is an aryl group; Q 1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: -NR 1 (=O)- and -C(=O)NR 1 -; R 1 is an amido substituent; and, Q 2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, and ethers thereof, for use in the treatment of a fibroproliferative disorder; liver fibrosis; smooth muscle proliferative disorder; atherosclerosis; restenosis; a neurodegenative disease; Alzheimer's; Parkinson's; Huntington's chorea; amyotropic lateral sclerosis; spino-cerebellar degeneration; an inflammatory disease; osteoarthritis; rheumatoid arthritis; a diseases involving angiogenesis; diabetic retinopathy; a haematopoietic disorder; anaemia; sickle cell anaemia; thalassaeimia; a fungal infection; a parasitic infection; trypanosomiasis; helminthiasis; a protozoal infection; a bacterial infection; a viral infection; a condition treatable by immune modulation; multiple sclerosis; autoimmune diabetes; lupus; atopic dermatitis; an allergy; asthma; allergic rhinitis; or inflammatory bowel disease.

摘要翻译： 本发明涉及抑制HDAC活性的某些活性氨基甲酸化合物，其具有下式：其中：A为芳基; Q 1是具有至少2个碳原子的主链的芳基前导基团; J是选自：-NR 1（= O） - 和-C（= O）NR 1 - 的酰胺键; R 1是酰氨基取代基; Q 2是酸性引导基团; 和其药学上可接受的盐，溶剂合物，酰胺，酯和醚，用于治疗纤维增生性疾病; 肝纤维化; 平滑肌增生障碍; 动脉粥样硬化; 再狭窄; 神经退行性疾病 老年痴呆症; 帕金森氏; 亨廷顿舞蹈 肌萎缩性侧索硬化; 脊髓小脑变性; 炎性疾病; 骨关节炎; 类风湿关节炎; 涉及血管生成的疾病 糖尿病性视网膜病变; 造血障碍 贫血; 镰状细胞性贫血 thalassaeimia; 真菌感染; 寄生虫感染; 锥虫病; 蠕虫病; 原生动物感染; 细菌感染; 病毒感染; 通过免疫调节治疗的病症; 多发性硬化症 自身免疫性糖尿病 狼疮; 特应性皮炎; 过敏; 哮喘; 过敏性鼻炎; 或炎症性肠病。

公开(公告)号：EP1598067B1

公开(公告)日：2009-05-06

申请号：EP05015737.9

申请日：2001-09-27

申请人： TopoTarget UK Limited

发明人： Watkins, Clare J. ,  Romero-Martin, Maria-Rosario ,  Moore, Kathryn G. ,  Ritchie, James ,  Finn, Paul W. ,  Kalvinsh, Ivars Latvian Inst. of Org. Synthesis ,  Loza, Einars Latvian Inst. of Org. Synthesis ,  Starchenkov, Igor Latvian Inst. of Org. Synthesis ,  Dikovska, Klara Latvian Inst. of Org. Synthesis ,  Bokaldere, Rasma Melita ,  Gailite, Vija Latvian Inst. of Org. Synthesis ,  Vorona, Maxim Latvian Inst. of Org. Synthesis ,  Andrianov, Victor Latvian Inst. of Org. Synthesis ,  Lolya, Daina Latvian Inst. of Org. Synthesis ,  Semenikhina, Valentina ,  Amolins, Andris Latvian Inst. of Org. Synthesis ,  Harris, John C. BioFocus Discovery ,  Duffy, James, E. S.

IPC分类号： A61K31/426 ,  A61K31/381 ,  A61K31/38 ,  A61K31/277 ,  A61K31/198 ,  A61K31/195 ,  A61K31/16 ,  A61P31/20

CPC分类号： C07D207/337 ,  A61K31/16 ,  A61K31/195 ,  A61K31/198 ,  A61K31/277 ,  A61K31/38 ,  A61K31/381 ,  A61K31/426 ,  C07C233/49 ,  C07C233/83 ,  C07C235/34 ,  C07C237/36 ,  C07C255/57 ,  C07C259/06 ,  C07C259/08 ,  C07C2603/18 ,  C07D207/40 ,  C07D207/404 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/22 ,  C07D213/06 ,  C07D213/55 ,  C07D213/56 ,  C07D233/04 ,  C07D233/08 ,  C07D235/14 ,  C07D235/24 ,  C07D271/06 ,  C07D307/34 ,  C07D307/54 ,  C07D317/60 ,  C07D333/24 ,  C07D333/60 ,  C07D403/12 ,  Y02A50/411

摘要： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: wherein: A is an aryl group; Q is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: -NR C(=O)- and -C(=O)NR -; R is an amido substituent; and, Q is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof, for use in the treatment of parasitic infections, such as malaria.

公开(公告)号：EP2292593A2

公开(公告)日：2011-03-09

申请号：EP10010651.7

申请日：2001-09-27

申请人： TopoTarget UK Limited

发明人： Watkins, Clare, J. ,  Romero-Martin, Maria-Rosario ,  Moore, Kathryn, G. ,  Richie, James ,  Finn, Paul, W. ,  Kalvinsh, Ivars ,  Loza, Einars ,  Dikovska, Klara ,  Gailite, Vija ,  Vorona, Maxim ,  Piskunova, Irina ,  Starchenkov, Igor ,  Andrianov, Victor ,  Harris, C., John ,  Duffy, James, E., S.

IPC分类号： C07C311/21 ,  C07D317/58 ,  C07D307/52 ,  C07D213/65 ,  C07D213/42 ,  C07D209/88 ,  A61K31/44 ,  A61K31/40 ,  A61K31/36 ,  A61K31/34 ,  A61P35/00 ,  A61P17/06

CPC分类号： C07D213/40 ,  C07C311/06 ,  C07C311/13 ,  C07C311/16 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07C2602/08 ,  C07D209/88 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58

摘要： The present invention relates to compounds of the following formula, and pharmaceutically acceptable salts and solvates thereof, wherein: A is C 5-20 heteroaryl or C 5-20 carboaryl, and is optionally substituted; Q 1 is: a covalent bond, a saturated aliphatic C 1-7 alkylene group and is optionally substituted, or a partially unsaturated aliphatic C 2-7 alkylene group and is optionally substituted; R 1 is hydrogen, C 1-7 alkyl, or C 5-20 aryl; and, Q 2 is -(CH 2 ) n - where n is 4, 5, 6, or 7. The present invention also relates to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and, e.g., to inhibit proliferative conditions, such as cancer and psoriasis.

摘要翻译： 本发明涉及下式的化合物及其药学上可接受的盐和溶剂合物，其中：A是C 5-20杂芳基或C 5-20碳芳基，并且任选被取代; Q1是：共价键，饱和脂肪族C 1-7亚烷基并且任选被取代，或者部分不饱和脂肪族C 2-7亚烷基并且被任选取代; R1是氢，C1-7烷基或C5-20芳基; 并且Q 2是 - （CH 2）n - ，其中n是4,5,6或7.本发明还涉及包含此类化合物的药物组合物，以及这些化合物和组合物在体外和体内的应用， 抑制HDAC，并且例如抑制增殖性疾病如癌症和牛皮癣。

公开(公告)号：EP1598067A1

公开(公告)日：2005-11-23

申请号：EP05015737.9

申请日：2001-09-27

申请人： TopoTarget UK Limited

发明人： Watkins, Clare J. ,  Romero-Martin, Maria-Rosario ,  Moore, Kathryn G. ,  Ritchie, James ,  Finn, Paul W. ,  Kalvinsh, Ivars Latvian Inst. of Org. Synthesis ,  Loza, Einars Latvian Inst. of Org. Synthesis ,  Starchenkov, Igor Latvian Inst. of Org. Synthesis ,  Dikovska, Klara Latvian Inst. of Org. Synthesis ,  Bokaldere, Rasma Melita ,  Gailite, Vija Latvian Inst. of Org. Synthesis ,  Vorona, Maxim Latvian Inst. of Org. Synthesis ,  Andranov, Victor Latvian Inst. of Org. Synthesis ,  Lolya, Daina Latvian Inst. of Org. Synthesis ,  Semenikhina, Valentina ,  Amolins, Andris Latvian Inst. of Org. Synthesis ,  Harris, John C. ,  Duffy, James, E. S.

IPC分类号： A61K31/426 ,  A61K31/381 ,  A61K31/38 ,  A61K31/277 ,  A61K31/198 ,  A61K31/195 ,  A61K31/16 ,  A61P31/20

CPC分类号： C07D207/337 ,  A61K31/16 ,  A61K31/195 ,  A61K31/198 ,  A61K31/277 ,  A61K31/38 ,  A61K31/381 ,  A61K31/426 ,  C07C233/49 ,  C07C233/83 ,  C07C235/34 ,  C07C237/36 ,  C07C255/57 ,  C07C259/06 ,  C07C259/08 ,  C07C2603/18 ,  C07D207/40 ,  C07D207/404 ,  C07D209/14 ,  C07D209/16 ,  C07D209/18 ,  C07D209/22 ,  C07D213/06 ,  C07D213/55 ,  C07D213/56 ,  C07D233/04 ,  C07D233/08 ,  C07D235/14 ,  C07D235/24 ,  C07D271/06 ,  C07D307/34 ,  C07D307/54 ,  C07D317/60 ,  C07D333/24 ,  C07D333/60 ,  C07D403/12 ,  Y02A50/411

摘要： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula:
wherein: A is an aryl group; Q 1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: -NR 1 C(=O)- and -C(=O)NR 1 -; R 1 is an amido substituent; and, Q 2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof, for use in the treatment of parasitic infections, such as malaria.

摘要翻译： 本发明涉及某些抑制HDAC活性的活性氨基甲酸化合物，具有下式：其中：A为芳基; Q 1是具有至少2个碳原子的主链的芳基前导基团; J是选自以下的酰胺键：-NR 1 C（= O） - 和-C（= O）NR 1 - ; R 1是酰氨基取代基; 而Q 2是酸性引导基团; 和其药学上可接受的盐，溶剂合物，酰胺，酯，醚，化学保护形式及其前药，用于治疗寄生虫感染如疟疾。