公开(公告)号：US10130714B2

公开(公告)日：2018-11-20

申请号：US13836356

申请日：2013-03-15

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Kung-Cheng Liu ,  Jia-Tsrong Jan ,  Yih-Shyun E. Cheng ,  Ting-Jen R. Cheng

IPC: A61K31/351 ,  C07D309/28 ,  A61K47/55 ,  A61K47/48

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.

公开(公告)号：US09914956B2

公开(公告)日：2018-03-13

申请号：US14422310

申请日：2013-08-16

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Yih-Shyun E. Cheng ,  Charng-Sheng Tsai

IPC: C12Q1/70 ,  C12Q1/40 ,  C12N9/96 ,  C08B37/00 ,  C12Q1/34 ,  C12Q1/04 ,  C07H13/04 ,  C07H13/12 ,  C07H5/00 ,  C12N9/24

CPC classification number: C12Q1/40 ,  C07H5/00 ,  C07H13/04 ,  C07H13/12 ,  C12N9/2402 ,  C12Q1/04 ,  C12Q1/34 ,  C12Q1/70 ,  C12Y302/01018 ,  G01N2333/11

Abstract: Provided herein are novel irreversible sialidase inhibitors. These compounds can be conjugated with a detectable tagging moiety such as azide-annexed biotin via CuAAC for isolation and identification of sialidases. The provided compounds and the corresponding detectable conjugates are useful for detecting sialidase-containing pathogens and imaging in situ sialidase activities under physiological conditions.

公开(公告)号：US20150225766A1

公开(公告)日：2015-08-13

申请号：US14422310

申请日：2013-08-16

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Yih-Shyun E. Cheng ,  Charng-Sheng Tsai

IPC: C12Q1/40 ,  C12Q1/70 ,  C07H5/00 ,  C12N9/24

CPC classification number: C12Q1/40 ,  C07H5/00 ,  C07H13/04 ,  C07H13/12 ,  C12N9/2402 ,  C12Q1/04 ,  C12Q1/34 ,  C12Q1/70 ,  C12Y302/01018 ,  G01N2333/11

Abstract: Provided herein are novel irreversible sialidase inhibitors. These compounds can be conjugated with a detectable tagging moiety such as azide-annexed biotin via CuAAC for isolation and identification of sialidases. The provided compounds and the corresponding detectable conjugates are useful for detecting sialidase-containing pathogens and imaging in situ sialidase activities under physiological conditions.

Abstract translation: 本文提供了新的不可逆唾液酸酶抑制剂。 这些化合物可以通过CuAAC与可检测的标记部分如叠氮化物附着的生物素缀合，用于分离和鉴定唾液酸酶。 提供的化合物和相应的可检测的缀合物可用于检测含唾液酸酶的病原体并在生理条件下成像原位唾液酸酶活性。

公开(公告)号：US20130274229A1

公开(公告)日：2013-10-17

申请号：US13836356

申请日：2013-03-15

Applicant: ACADEMIA SINICA

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Kung-Cheng Liu ,  Jia-Tsrong Jan ,  Yih-Shyun E. Cheng ,  Ting-Jen R. Cheng

IPC: A61K47/48

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

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。 提供了制备这些增强型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。