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    Carbamic acid compounds comprising a piperazine linkage as HDAC inhibitors
    9.
    发明授权
    Carbamic acid compounds comprising a piperazine linkage as HDAC inhibitors 失效
    包含哌嗪键的氨基甲酸化合物作为HDAC抑制剂

    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 。