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    Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof
    9.
    发明授权
    Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof 有权
    糖皮质激素受体，AP-1和/或NF-κB活性的调节剂及其用途

    公开(公告)号：US08034940B2

    公开(公告)日：2011-10-11

    申请号：US11835438

    申请日：2007-08-08

    申请人： David S. Weinstein ,  Ping Chen ,  T. G. Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Bingwei Vera Yang ,  Arthur M. Doweyko

    发明人： David S. Weinstein ,  Ping Chen ,  T. G. Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Bingwei Vera Yang ,  Arthur M. Doweyko

    IPC分类号： C07D491/052 ,  A61K31/436

    CPC分类号： C07D417/12 ,  C07D277/46 ,  C07D405/12 ,  C07D417/14 ,  C07D491/04

    摘要： Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R5, R6, R7, and R8; J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted C1-3alkylene, C2-4alkenylene, and substituted C2-4alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R1 to R11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

    摘要翻译： 提供新的非甾体化合物，其可用于治疗与式（I）结构的糖皮质激素受体，AP-1和/或NF-κB活性（包括炎症和免疫疾病）的调节相关的疾病： 其对映异构体，非对映体或其互变异构体或其前药酯或其药学上可接受的盐，其中：Z是杂环或杂芳基; A是5至8元碳环或5至8元杂环; B是环烷基，环烯基，芳基，杂环基或杂芳基环，其中每个环与相邻原子上的A环稠合并任选地被一至四个相同或不同的基团取代，并且独立地选自R5，R6， R7和R8; J1，J2和J3各自出现相同或不同，独立地为-A1QA2-; Q是键，O，S，S（O）或S（O）2; A1和A2相同或不同，并且在每次出现时独立地选自键，C1-3亚烷基，取代的C1-3亚烷基，C2-4亚烯基和取代的C2-4亚烯基，条件是选择A1和A2使得环A为 5-至8-元碳环或杂环; R1至R11如本文所定义。 还提供了使用所述化合物治疗炎性或免疫相关疾病和肥胖症和糖尿病的药物组合物和方法。

    MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF
    10.
    发明申请
    MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-kB ACTIVITY AND USE THEREOF 有权
    GLUCOCORTICOID受体的调节剂，AP-1和/或NF-kB活性及其用途

    公开(公告)号：US20090075995A1

    公开(公告)日：2009-03-19

    申请号：US11835438

    申请日：2007-08-08

    申请人： David S. Weinstein ,  Ping Chen ,  T.G. Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Bingwei Vera Yang ,  Arthur M. Doweyko

    发明人： David S. Weinstein ,  Ping Chen ,  T.G. Murali Dhar ,  Jingwu Duan ,  Hua Gong ,  Bin Jiang ,  Bingwei Vera Yang ,  Arthur M. Doweyko

    IPC分类号： A61K31/5377 ,  A61K31/436 ,  C07D491/052 ,  A61P31/12 ,  A61K31/427 ,  C07D417/12

    CPC分类号： C07D417/12 ,  C07D277/46 ,  C07D405/12 ,  C07D417/14 ,  C07D491/04

    摘要： Novel non-steroidal compounds are provided which are useful in treating diseases associated with modulation of the glucocorticoid receptor, AP-1, and/or NF-κB activity, including inflammatory and immune diseases, having the structure of formula (I): an enantiomer, diastereomer, or tautomer thereof, or a prodrug ester thereof, or a pharmaceutically-acceptable salt thereof, in which: Z is heterocyclo or heteroaryl; A is a 5- to 8-membered carbocyclic ring or a 5- to 8-membered heterocyclic ring; B is a cycloalkyl, cycloalkenyl, aryl, heterocyclo, or heteroaryl ring, wherein each ring is fused to the A ring on adjacent atoms and optionally substituted by one to four groups which are the same or different and are independently selected from R5, R6, R7, and R8; J1, J2, and J3 are at each occurrence the same or different and are independently -A1QA2-; Q is a bond, O, S, S(O), or S(O)2; A1 and A2 are the same or different and are at each occurrence independently selected from a bond, C1-3alkylene, substituted C1-3alkylene, C2-4alkenylene, and substituted C2-4alkenylene, provided that A1 and A2 are chosen so that ring A is a 5- to 8-membered carbocyclic or heterocyclic ring; R1 to R11 are as defined herein. Also provided are pharmaceutical compositions and methods of treating inflammatory- or immune-associated diseases and obesity and diabetes employing said compounds.

    摘要翻译： 提供了新的非甾体化合物，其可用于治疗与式（I）结构的糖皮质激素受体，AP-1和/或NF-κB活性（包括炎症和免疫疾病）调节相关的疾病：对映异构体 ，非对映异构体或其互变异构体，或其前药酯或其药学上可接受的盐，其中：Z是杂环或杂芳基; A是5至8元碳环或5至8元杂环; B是环烷基，环烯基，芳基，杂环基或杂芳基环，其中每个环与相邻原子上的A环稠合并任选地被一至四个相同或不同的基团取代，并且独立地选自R5，R6， R7和R8; J1，J2和J3各自出现相同或不同，独立地为-A1QA2-; Q是键，O，S，S（O）或S（O）2; A1和A2相同或不同，并且在每次出现时独立地选自键，C1-3亚烷基，取代的C1-3亚烷基，C2-4亚烯基和取代的C2-4亚烯基，条件是选择A1和A2使得环A为 5-至8-元碳环或杂环; R1至R11如本文所定义。 还提供了使用所述化合物治疗炎性或免疫相关疾病和肥胖症和糖尿病的药物组合物和方法。