公开(公告)号：US07569724B2

公开(公告)日：2009-08-04

申请号：US10381791

申请日：2001-09-27

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

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

IPC分类号： C07C239/00

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 formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(═O)— and —C(═O)NR1-; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains 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： 本发明涉及抑制HDAC活性的一些活性氨基甲酸化合物，其具有式（1）其中：A为芳基; Q1是具有至少2个碳原子的骨架的芳基前导基团; J是选自：-NR 1 C（-O） - 和-C（-O）NR 1 - 的酰胺键; R1是酰氨基取代基; 而Q2是酸性引导组; 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。 本发明还涉及包含这种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用途，以抑制HDAC，并且例如抑制增殖性疾病如癌症和牛皮癣。

公开(公告)号：US07880020B2

公开(公告)日：2011-02-01

申请号：US12477493

申请日：2009-06-03

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

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

IPC分类号： C07D333/36 ,  C07D333/22 ,  C07D307/02

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 formula (1) wherein: A is an aryl group; Q1 is an aryl leader group having a backbone of at least 2 carbon atoms; J is an amide linkage selected from: —NR1C(═O)— and —C(═O)NR1—; R1 is an amido substituent; and, Q2 is an acid leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains 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 psorias.

摘要翻译： 本发明涉及抑制HDAC活性的一些活性氨基甲酸化合物，其具有式（1）其中：A为芳基; Q1是具有至少2个碳原子的骨架的芳基前导基团; J是选自：-NR 1 C（= O） - 和-C（= O）NR 1 - 的酰胺键; R1是酰氨基取代基; 而Q2是酸性引导组; 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。 本发明还涉及包含这些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用途，以抑制HDAC，并且例如抑制增殖性疾病如癌症和牛皮癣。

公开(公告)号：US06960685B2

公开(公告)日：2005-11-01

申请号：US10381794

申请日：2001-09-27

申请人： Clare J Watkins ,  Maria Rosario Romero-Martin ,  Paul W Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Daina Lolya ,  Igor Starchenkov ,  Rasma M Bokaldere ,  Valentina Semenikhina ,  C. John Harris ,  James E. S. Duffy

发明人： Clare J Watkins ,  Maria Rosario Romero-Martin ,  Paul W Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Daina Lolya ,  Igor Starchenkov ,  Rasma M Bokaldere ,  Valentina Semenikhina ,  C. John Harris ,  James E. S. Duffy

IPC分类号： A61P17/06 ,  A61P35/00 ,  C07C259/06 ,  C07C323/60 ,  C07C259/04 ,  A61K21/19

CPC分类号： C07C259/06 ,  C07C323/60

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; Q1 is a covalent bond or an aryl leader group; J is an amide linkage selected from: —NR1C(═O)— and —C(═O)NR1—; R1 is an amido substituent; X is an ether heteroatom, and is —O— or —S—; and, R2 and R3 are each independently an ether group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains 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是共价键或芳基前导基团; 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; X是醚杂原子，并且是-O-或-S-; 和R 2和R 3各自独立地是醚基团; 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。 本发明还涉及包含这种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用途，以抑制HDAC，并且例如抑制增殖性疾病如癌症和牛皮癣。

公开(公告)号：US07183298B2

公开(公告)日：2007-02-27

申请号：US10953106

申请日：2004-09-30

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

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

IPC分类号： A01N43/40 ,  A61K31/44

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： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains 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：US06888027B2

公开(公告)日：2005-05-03

申请号：US10381790

申请日：2001-09-27

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

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

IPC分类号： A61K31/341 ,  A61K31/403 ,  A61K31/4406 ,  A61P17/06 ,  A61P35/00 ,  A61P43/00 ,  C07C311/06 ,  C07C311/08 ,  C07C311/10 ,  C07C311/13 ,  C07C311/16 ,  C07C311/17 ,  C07C311/19 ,  C07C311/20 ,  C07C311/21 ,  C07C311/29 ,  C07D209/82 ,  C07D209/88 ,  C07D213/40 ,  C07D213/42 ,  C07D213/65 ,  C07D213/71 ,  C07D307/52 ,  C07D317/58 ,  A01N37/28

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： This invention pertains to certain active carbamic acid compounds which inhibit HDAC activity and which have the following formula: (I) A is an aryl group; Q1 is a covalent bond or an aryl leader group; J is a sulfonamide linkage selected from: —S(═O)2NR1— and —NR1S(═O)2—; R1 is a sulfonamido substituent; and, Q2 is an acid leader group; with the proviso that if J is —S(═O)2NR1—, then Q1 is an aryl leader group; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, chemically protected forms, and prodrugs thereof. The present invention also pertains 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： 本发明涉及抑制HDAC活性的一些活性氨基甲酸化合物，其具有下式：（I）A为芳基; Q 1是共价键或芳基前导基团; J是选自以下的磺酰胺键：-S（-O）2 NR 1 - 和-NR 1 S（-O） > 2 - ; R1是亚磺酰氨基取代基; 而Q 2是酸性引导基团; 条件是如果J是-S（-O）2 NR 1 - ，则Q 1是芳基前导基团; 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。 本发明还涉及包含这种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用途，以抑制HDAC，并且例如抑制增殖性疾病如癌症和牛皮癣。

公开(公告)号：US07629343B2

公开(公告)日：2009-12-08

申请号：US10509732

申请日：2003-04-03

申请人： Clare J. Watkins ,  Maria-Rosario Romero-Martin ,  James Ritchie ,  Paul W Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klara Dikovska ,  Igor Starchenkov ,  Daina Lolya ,  Vija Gailite

发明人： Clare J. Watkins ,  Maria-Rosario Romero-Martin ,  James Ritchie ,  Paul W Finn ,  Ivars Kalvinsh ,  Einars Loza ,  Klara Dikovska ,  Igor Starchenkov ,  Daina Lolya ,  Vija Gailite

IPC分类号： A61K31/497 ,  A61K31/4965 ,  C07D241/04 ,  C07D295/00 ,  C07D401/00 ,  C07D403/00 ,  C07D405/00 ,  C07D409/00 ,  C07D411/00

CPC分类号： C07D213/74 ,  C07D239/42 ,  C07D295/185 ,  C07D295/192 ,  C07D295/26 ,  C07D317/58 ,  C07D333/60

摘要： This invention pertains to certain carbamic acid compounds which inhibit HDAC (histone deacetylase) activity of the following formula: wherein: Cy is independently a cyclyl group; Q1 is independently a covalent bond or cyclyl leader group; the piperazin-1,4-diyl group is optionally substituted; J1 is independently a covalent bond or —C(═; O)—; J2 is independently —C(═O)— or —S(═O)2—; Q2 is independently an acid leader group; wherein: Cy is independently: C3-20carbocyclyl, C3-20heterocyclyl, or C5-20aryl; and is optionally substituted; Q1 is independently: a covalent bond; C1-7alkylene; or C1-7alkylene-X—C1-7alkylene, —X—C1-7alkylene, or C1-7alkylene-X—, wherein X is —O— or —S—; and is optionally substituted; Q2 is independently: C4-8alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or: Q2 is independently: C5-20arylene; C5-20arylene-C1-7alkylene; C1-7alkylene-C5-20arylene; or, C1-7alkylene-C5-20arylene-C1-7alkylene; and is optionally substituted; and has a backbone length of at least 4 atoms; or a pharmaceutically acceptable salt, solvate, amide, ester, ether, chemically protected form, or prodrug thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit HDAC, and in the treatment of conditions mediated by HDAC, cancer, proliferative conditions, psoriasis, etc.

摘要翻译： 本发明涉及抑制下式的HDAC（组蛋白脱乙酰酶）活性的某些氨基甲酸化合物：其中：Cy独立地为环基; Q1独立地是共价键或环状引导基团; 哌嗪-1,4-二基任选被取代; J1独立地是共价键或-C（ - ; O） - ; J2独立地是-C（-O） - 或-S（-O）2 - ; Q2独立为酸性引导基团; 其中：Cy独立地为：C 3-20碳环基，C 3-20杂环基或C 5-20芳基; 并且任选被取代; Q1独立地是共价键; C 1-7亚烷基; 或C 1-7亚烷基-X-C 1-7亚烷基，-X-C 1-7亚烷基或C 1-7亚烷基-X-，其中X是-O-或-S-; 并且任选被取代; Q2独立地为：C4-8亚烷基; 并且任选被取代; 并具有至少4个原子的骨架长度; 或：Q2独立地为：C 5-20亚芳基; C 5-20芳基-C 1-7亚烷基; C 1-7亚烷基-C 5 - 亚芳基; 或C 1-7亚烷基-C 5-20亚芳基-C 1-7亚烷基; 并且任选被取代; 并具有至少4个原子的骨架长度; 或其药学上可接受的盐，溶剂化物，酰胺，酯，醚，化学保护形式或前药。 本发明还涉及包含这些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用途，以抑制HDAC，以及治疗由HDAC，癌症，增殖性病症，牛皮癣等介导的病症 。