公开(公告)号：US10119972B2

公开(公告)日：2018-11-06

申请号：US15666242

申请日：2017-08-01

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Jiun-Jie Shie

IPC: C07D311/02 ,  G01N33/58 ,  C07F5/02 ,  C07K7/08 ,  G01N21/64 ,  C07D309/14

Abstract: Provided are azido-BODIPY compounds of formula (I), cyclooctyne-based fluorogenic probes of formula (IV), and activity-based probes of formula (VI). These compounds undergo azide-alkyne cycloadditions (AAC) with to form triazolyl products. The provided compounds are useful for detection and imaging of alkyne-, or azide-containing molecules. Methods for detection and imaging biomolecules using compounds of the present disclosure are disclosed.

公开(公告)号：US09547009B2

公开(公告)日：2017-01-17

申请号：US14422939

申请日：2013-08-21

Applicant: Academia Sinica

Inventor： Chi-Huey Wong ,  Jim-Min Fang ,  Jiun-Jie Shie

IPC: G01N33/58 ,  C07D413/06 ,  C07D311/78 ,  C07D491/04 ,  C07D493/04 ,  C07D405/14 ,  C07D311/94 ,  C07D405/06 ,  C07D495/04 ,  C07D513/04 ,  A61K49/00

CPC classification number: G01N33/582 ,  A61K49/0032 ,  C07D311/78 ,  C07D311/94 ,  C07D405/06 ,  C07D405/14 ,  C07D413/06 ,  C07D491/04 ,  C07D493/04 ,  C07D495/04 ,  C07D513/04

Abstract: Provided are benzocyclooctyne compounds of formula (I). These compounds undergo strain-promoted azide-alkyne cyclo additions (SPAAC) without presence of toxic metal catalysts. The provided compounds are useful for diagnosis and imaging of azide-containing molecules. Methods for detection and imaging biomolecules using compounds of the present disclosure are disclosed.

Abstract translation: 提供式（I）的苯并环辛烯化合物。 这些化合物在不存在有毒金属催化剂的情况下经历应变促进的叠氮炔 - 环加成（SPAAC）。 所提供的化合物可用于含叠氮化物分子的诊断和成像。 公开了使用本公开的化合物检测和成像生物分子的方法。

公开(公告)号：US09115116B2

公开(公告)日：2015-08-25

申请号：US14160515

申请日：2014-01-21

Applicant: Academia Sinica ,  National Taiwan University

Inventor： Jung-Hsin Lin ,  Ching-Chow Chen ,  Jim-Min Fang ,  Jhih-Bin Chen ,  Ting-Rong Chern ,  Tzu-Tang Wei

IPC: C07D207/32 ,  C07D309/10 ,  A61K31/4192 ,  A61K31/351 ,  C07D405/12 ,  C07D309/30 ,  C07F7/18

CPC classification number: C07D405/12 ,  C07D309/30 ,  C07F7/1804

Abstract: Disclosed herein are novel compounds of formula (I), and uses thereof. The compounds of Formula (I) are inhibitors of histone deacetylases (HDACs) and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR). Also provided are methods of using the compounds of Formula (I) for inhibiting the activity of HDACs and HMGR, treating diseases associated with HDACs or HMGR (e.g., cancer, hypercholesterolemia, an acute or chronic inflammatory disease, autoimmune disease, allergic disease, pathogen infection, neurodegenerative disease, or a disease associated with oxidative stress,

Abstract translation: 本文公开了新的式（I）化合物及其用途。 式（I）的化合物是组蛋白脱乙酰酶（HDAC）和3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶（HMGR）的抑制剂。 还提供了使用式（I）化合物抑制HDAC和HMGR活性的方法，治疗与HDAC或HMGR相关的疾病（例如，癌症，高胆固醇血症，急性或慢性炎性疾病，自身免疫性疾病，过敏性疾病，病原体 感染，神经变性疾病或与氧化应激相关的疾病，

公开(公告)号：US10301348B2

公开(公告)日：2019-05-28

申请号：US15031711

申请日：2014-10-22

Applicant: Academia Sinica

Inventor： Jim-Min Fang ,  Yun-Lian Lin ,  Jung-Hsin Lin ,  Chun-Jung Lin ,  Yijuang Chern ,  Nai-Kuei Huang ,  Hung-Li Wang ,  Benjamin Pang-hsien Tu ,  Chih-Cheng Chen

IPC: C07H19/167 ,  C07H19/16 ,  C07D473/34 ,  A61K31/7076

Abstract: Compounds for use in prevention and treatment of neurodegenerative disease and pain are disclosed. In one embodiment of the invention, the compound is selected from the group consisting of N6-[(3-halothien-2-yl)methyl]adenosine, N6-[(4-halothien-2-yl)methyl]adenosine, and N6-[(5-halothien-2-yl)methyl]adenosine. In another embodiment of the invention, the compound is selected from the group consisting of N6-[(2-bromothien-3-yl)methyl]adenosine, N6-[(4-bromothien-3-yl)methyl]adenosine, N6-[(5-bromothien-3-yl)methyl]adenosine N6-[(2-chlorothien-3-yl)methyl]adenosine, N6-[(4-chlorothien-3-yl)methyl]adenosine, and N6-[(5-chlorothien-3-yl)methyl]adenosine. Also disclosed are methods of making and using the same.

公开(公告)号：US20160264613A1

公开(公告)日：2016-09-15

申请号：US15031711

申请日：2014-10-22

Applicant: Academia Sinica

Inventor： Jim-Min Fang ,  Yun-Lian LIn ,  Jung-Hsin Lin ,  Chun-Jung Lin ,  Yijuang Chem ,  Nai-Kuei Huang ,  Hung-Li Wang ,  Benjamin Pang-hsien Tu ,  Chih-Cheng Chen

IPC: C07H19/16

CPC classification number: C07H19/16 ,  A61K31/7076 ,  C07D473/34 ,  C07H19/167 ,  Y02P20/582

Abstract: Compounds for use in prevention and treatment of neurodegenerative disease and pain are disclosed. In one embodiment of the invention, the compound is selected from the group consisting of N6-[(3-halothien-2-yl)methyl]adenosine, N6-[(4-halothien-2-yl)methyl]adenosine, and N6-[(5-halothien-2-yl)methyl]adenosine. In another embodiment of the invention, the compound is selected from the group consisting of N6-[(2-bromothien-3-yl)methyl]adenosine, N6-[(4-bromothien-3-yl)methyl]adenosine, N6-[(5-bromothien-3-yl)methyl]adenosine N6-[(2-chlorothien-3-yl)methyl]adenosine, N6-[(4-chlorothien-3-yl)methyl]adenosine, and N6-[(5-chlorothien-3-yl)methyl]adenosine. Also disclosed are methods of making and using the same.

Abstract translation: 公开了用于预防和治疗神经变性疾病和疼痛的化合物。 在本发明的一个实施方案中，该化合物选自N6 - [（3-卤代噻吩-2-基）甲基]腺苷，N6 - [（4-卤代噻吩-2-基）甲基]腺苷和N6 - [（5-卤代噻吩-2-基）甲基]腺苷。 在本发明的另一个实施方案中，该化合物选自N6 - [（2-溴噻吩-3-基）甲基]腺苷，N6 - [（4-溴噻吩-3-基）甲基]腺苷，N6- [（5-溴噻吩-3-基）甲基]腺苷N6 - [（2-氯噻吩-3-基）甲基]腺苷，N6 - [（4-氯噻吩-3-基）甲基]腺苷和N6 - [ 5-氯噻吩-3-基）甲基]腺苷。 还公开了制造和使用它们的方法。

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。

公开(公告)号：US12129273B2

公开(公告)日：2024-10-29

申请号：US18227782

申请日：2023-07-28

Applicant: Academia Sinica

Inventor： Chih-Cheng Chen ,  Jim-Min Fang ,  Cheng-Han Lee ,  Jen-Yao Chang

IPC: C07H19/16 ,  A61K31/7076 ,  A61K38/04 ,  A61K47/55 ,  A61P29/00

CPC classification number: C07H19/16 ,  A61K31/7076 ,  A61K38/046 ,  A61K47/55 ,  A61P29/00

Abstract: Compounds for use in prevention and/or treatment of pain are disclosed. The compounds are derived by conjugation of N6-(4-hydroxybenzyl)adenosine and analogous compounds with amino acids or peptides. In one embodiment of the invention, the compound is 5′-glycylcarbonyl-N6-(4-hydroxybenzyl)adenosine (I-a1). In another embodiment of the invention, the compound is 5′-deoxy-5′-(N′-glycylureido)-N6-(4-hydroxybenzyl)adenosine (I-d1). Also disclosed are methods of making and using the same.

公开(公告)号：US11753432B2

公开(公告)日：2023-09-12

申请号：US16481042

申请日：2018-01-26

Applicant: Academia Sinica

Inventor： Chih-Cheng Chen ,  Jim-Min Fang ,  Cheng-Han Lee ,  Jen-Yao Chang

IPC: C07H19/16 ,  A61K47/55 ,  A61P29/00 ,  A61K31/7076 ,  A61K38/04

CPC classification number: C07H19/16 ,  A61K31/7076 ,  A61K38/046 ,  A61K47/55 ,  A61P29/00

Abstract: Compounds for use in prevention and/or treatment of pain are disclosed. The compounds are derived by conjugation of N6-(4-hydroxybenzyl)adenosine and analogous compounds with amino acids or peptides. In one embodiment of the invention, the compound is 5′-O-(glycine-N-carbonyl-N6-(4-hydroxybenzyl)adenosine (I-a1). In another embodiment of the invention, the compound is 5-deoxy-5′-(glycine-N-amido)-N6-(4-hydroxybenzyl)adenosine (I-d1). Also disclosed are methods of making and using the same.

公开(公告)号：US20180369249A1

公开(公告)日：2018-12-27

申请号：US16075202

申请日：2017-02-03

Applicant: Academia Sinica ,  National Taiwan University

Inventor： Chi-Huey Wong ,  Pan-Chyr Yang ,  Jim-Min Fang ,  Szu-Hua Pan ,  Ting-Jen R. Cheng ,  Ling-Wei Li

IPC: A61K31/522 ,  A61K35/00

Abstract: The present disclosure provides compounds of Formulas (I′) and (I), and pharmaceutically acceptable salts thereof. The compounds described herein may be useful in treating and/or preventing proliferative diseases (e.g., cancer). Also provided in the present disclosure are pharmaceutical compositions, kits, and uses thereof for treating proliferative diseases.

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.