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    ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY
    3.
    发明公开
    ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY 审中-公开
    增强的抗流感病毒药物与抗炎活性物质共轭

    公开(公告)号：EP2841066A1

    公开(公告)日：2015-03-04

    申请号：EP13775664.9

    申请日：2013-04-12

    Applicant: Academia Sinica ,  Wong, Chi-Heuy ,  Fang, Jim-Min ,  Liu, Kung-Cheng ,  Jan, Jia-Tsrong ,  Cheng, Yih-Shyun E. ,  Cheng, Ting-Jen R.

    Inventor： WONG, Chi-Huey ,  FANG, Jim-Min ,  LIU, Kung-Cheng ,  JAN, Jia-Tsrong ,  CHENG, Yih-Shyun, E. ,  CHENG, Ting-Jen, R.

    IPC: A61K31/35 ,  A61K31/36 ,  A61P31/16 ,  A61P29/00

    CPC classification number: A61K47/481 ,  A61K31/351 ,  A61K47/55 ,  C07D309/28

    Abstract: Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

    Abstract translation: 公开了与抗炎剂缀合形成的新型双靶向双功能抗流感药物。 根据本发明的示例性药物包括咖啡酸（CA）荷瘤扎那米韦（ZA）缀合物ZA-7-CA（1）中，ZA-7-CA-酰胺（7）和ZA-7-NAP（43），用于同时抑制 流感病毒神经氨酸酶和抑制促炎细胞因子。 提供了用于制备这些增强的抗流感病毒缀合物药物的合成方法。 合成的双功能ZA缀合物协同作用于保护H1N1或H5N1流感病毒致死性感染的小鼠。 ZA-7-CA，ZA-7-CA-酰胺和ZA-7-Nap缀合物的功效远远大于ZA与抗炎剂的组合疗法。

    ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY
    7.
    发明申请
    ENHANCED ANTI-INFLUENZA AGENTS CONJUGATED WITH ANTI-INFLAMMATORY ACTIVITY 审中-公开
    增强与抗炎活性相关的抗感染药物

    公开(公告)号：WO2013155375A1

    公开(公告)日：2013-10-17

    申请号：PCT/US2013/036308

    申请日：2013-04-12

    Applicant: ACADEMIA SINICA ,  WONG, Chi-Huey ,  FANG, Jim-Min ,  LIU, Kung-Cheng ,  JAN, Jia-Tsrong ,  CHENG, Yih-Shyun, E. ,  CHENG, Ting-Jen, R.

    Inventor： WONG, Chi-Huey ,  FANG, Jim-Min ,  LIU, Kung-Cheng ,  JAN, Jia-Tsrong ,  CHENG, Yih-Shyun, E. ,  CHENG, Ting-Jen, R.

    IPC: A61K31/35 ,  A61K31/36 ,  A61P31/16 ,  A61P29/00

    CPC classification number: A61K47/481 ,  A61K31/351 ,  A61K47/55 ,  C07D309/28

    Abstract: Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti- influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

    Abstract translation: 公开了通过与抗炎剂缀合形成的新型双靶向双功能抗流感药物。 根据本发明的示例性药物包括用于同时抑制的咖啡酸（CA） - 扎尼米韦（ZA）缀合物ZA-7-CA（1），ZA-7-CA-酰胺（7）和ZA-7-Nap（43） 的流感病毒神经氨酸酶和抑制促炎细胞因子。 提供了用于制备这些增强的抗流感病毒缀合物药物的合成方法。 合成双功能ZA缀合物协同作用以保护由H1N1或H5N1流感病毒致死的小鼠。 ZA-7-CA，ZA-7-CA-酰胺和ZA-7-Nap缀合物的功效远远大于ZA与抗炎剂的组合疗法。

    ALPHA-SELECTIVE SIALYL PHOSPHATE DONORS FOR PREPARATION OF SIALOSIDES AND SIALOSIDE ARRAYS FOR INFLUENZA VIRUS DETECTION
    8.
    发明申请
    ALPHA-SELECTIVE SIALYL PHOSPHATE DONORS FOR PREPARATION OF SIALOSIDES AND SIALOSIDE ARRAYS FOR INFLUENZA VIRUS DETECTION 审中-公开
    用于制备用于流感病毒检测的糖尿病和糖尿病病毒颗粒的ALPHA-选择性磷酸二氢钠

    公开(公告)号：WO2010111703A1

    公开(公告)日：2010-09-30

    申请号：PCT/US2010/029058

    申请日：2010-03-29

    Applicant: ACADEMIA SINICA ,  WONG, Chi-Huey ,  WU, Chung-Yi ,  CHENG, Ting-Jen R.

    Inventor： WONG, Chi-Huey ,  WU, Chung-Yi ,  CHENG, Ting-Jen R.

    IPC: C12P19/00

    CPC classification number: A61K39/095 ,  C07H1/00 ,  C07H3/00 ,  C07H9/06 ,  C07H11/00 ,  C07H11/04 ,  C07H13/04

    Abstract: A novel N-acetyl-5- N ,4- O -carbonyl-protected dibutyl sialyl phosphate donor for sialylation of both primary and sterically hindered secondary acceptors to prepare sialosides with high yield and α-selectivity is disclosed. Methods for making disaccharide building blocks comprising α(2→3), α(2→6), α(2→8), α(2→8)/α(2→9) alternate, and α(2→9) sialosides are provided. methods for one-pot synthesis of complex sialosides are disclosed. Libraries of sialosides and methods for using the libraries for detection and receptor binding analysis of surface glycoproteins or pathogens and cancer cells are disclosed. Methods for distinguishing between hemagglutanin (HA) from various strains of influenza are provided.

    Abstract translation: 公开了一种新型的N-乙酰基-5-N，4-O-羰基保护的二丁基唾液酸磷酸盐供体，用于主要和空间位阻二级受体的唾液酸化，以高产率和选择性选择性制备唾液酸苷。 包含（2→3），（2→6），（2〜8），（2〜8）/ a（2〜9）交替和（2〜9） 提供唾液酸苷。 公开了一锅合成唾液酸苷的方法。 公开了唾液酸的文库和使用文库进行表面糖蛋白或病原体和癌细胞的检测和受体结合分析的方法。 提供了用于区分来自各种流感病毒株的血凝素（HA）的方法。

    COMPOSITIONS AND METHODS FOR TREATING INFLAMMATION AND INFLAMMATION-RELATED DISORDERS BY PLECTRANTHUS AMBOINICUS EXTRACTS
    10.
    发明申请
    COMPOSITIONS AND METHODS FOR TREATING INFLAMMATION AND INFLAMMATION-RELATED DISORDERS BY PLECTRANTHUS AMBOINICUS EXTRACTS 审中-公开
    石菖蒲提取物治疗炎症和炎症相关疾病的组合物和方法

    公开(公告)号：WO2009039218A2

    公开(公告)日：2009-03-26

    申请号：PCT/US2008076735

    申请日：2008-09-17

    Applicant: WONG CHI-HUEY ,  CHENG YIH-SHYUN E ,  YU HUI-MING ,  CHENG TING-JEN R ,  LIN KUN-HSIEN ,  HUNG JUNG-TUNG

    Inventor： WONG CHI-HUEY ,  CHENG YIH-SHYUN E ,  YU HUI-MING ,  CHENG TING-JEN R ,  LIN KUN-HSIEN ,  HUNG JUNG-TUNG

    IPC: A61K36/53 ,  A61K31/33 ,  A61K36/18

    CPC classification number: A61K36/53 ,  A61K31/215 ,  A61K31/235

    Abstract: The crude extract of Plectranthus Amboinicus (PA) has anti-inflammatory effects and can inhibit AP-1 binding in vitro. The incubation with PA crude extract resulted in significant inhibition of the LPS-induced expression of IL-6, IL-12, MCP- 1, and RANTES in HUVEC cells. After the crude extract was further fractionated using preparative HPLC, fraction 8, 9, 10 and 11 were identified to inhibit the AP-1 binding activity. The active component of fraction 8 is Mena 987; fraction 9 is Mena 998; fraction 10 is Mena 9102; and fraction 11 is rosmarinic acid and the synthestic rosmarinic acid analogues. Other compounds showed inhibitory activities as well. These compounds have inhibitory effects on AP-1 activity and are useful as preventive or therapeutic agent for diseases in which excessive expression or activities of AP-1 are involved.

    Abstract translation: Plectranthus Amboinicus（PA）的粗提取物具有抗炎作用并且可以在体外抑制AP-1结合。 与PA粗提取物一起温育导致HUVEC细胞中IL-6，IL-12，MCP-1和RANTES的LPS-诱导的表达的显着抑制。 粗制提取物用制备型HPLC进一步分级后，鉴定出级分8,9,10和11以抑制AP-1结合活性。 部分8的活性成分是Mena 987; 部分9是Mena 998; 部分10是梅纳9102; 部分11是迷迭香酸和合成的迷迭香酸类似物。 其他化合物也显示抑制活性。 这些化合物对AP-1活性具有抑制作用，可作为AP-1的过度表达或活性参与的疾病的预防或治疗剂。

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