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1. 发明申请

US20190076552A1 Precursor of a histone deacetylase inhibitor PET imaging compound for tracking cerebral neurodegenerative and tumor diseases 审中-公开
公开(公告)号：US20190076552A1
公开(公告)日：2019-03-14
申请号：US15698672
申请日：2017-09-08
申请人： Ming-Hsin Li , Chyng-Yann Shiue , Han-Chih Chang , Chun-Fang Feng
发明人： Ming-Hsin Li , Chyng-Yann Shiue , Han-Chih Chang , Chun-Fang Feng
IPC分类号： A61K49/00 , G06T7/00 , G01T1/29 , A61K51/00 , G06T7/40
摘要： Method provided for labeling a nuclear medicine for imaging tracing, comprising a labeling precursor of the HDAC inhibitor BNL-26 (C22H23N3O) and the derivatives that are separated into two classes. The first class comprises a BNL-26 (C22H23N3O) and derivatives BNL-26a (C21H21N3O), BNL-26b (C22H22N2O), and other compounds of the labeling precursors which are categorized into two parts, the first part includes BNL-26-CH2CH2OTs (C31H33N3O4S), BNL-26a-CH2CH2OTs (C30H31N3O4S), and BNL-26b-CH2CH2OTs (C31H32N2O4S), which provides labeling precursor through —CH2CH2OTs structure, and the second part includes pre-BNL-26 (C28H34N3O3B), pre-BNL-26a (C27H32N3O3B), pre-BNL-26b (C28H33N2O3B), which provides labeling precursor through 4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl structure. The second class includes BNL-26 (C22H23N3O) indole/indoline, which provides a series of derivative labeling precursors derived from a secondary amide bond.

2. 发明授权

US10005727B2 Compound and analogues for tracing histone acetylation inhibitors PET imaging for diagnosis and treatment of tumors 有权
公开(公告)号：US10005727B2
公开(公告)日：2018-06-26
申请号：US15286596
申请日：2016-10-06
申请人： Ming-Hsin Li , Chyng-Yann Shiue , Han-Chih Chang , Chun-Fang Feng
发明人： Ming-Hsin Li , Chyng-Yann Shiue , Han-Chih Chang , Chun-Fang Feng
IPC分类号： C07D209/04 , C07D401/12 , C07D401/14
CPC分类号： C07D209/04 , C07D209/08 , C07D401/12 , C07D401/14
摘要： The present invention relates to a group of compounds for nuclear medicine imaging through F-18 labeled histone acetylation inhibitors (HDACi) of indole or indoline benzoyl amine and its derivatives, and provides a series of nuclear medicine imaging agents that bind with HDAC overexpression in vivo for diagnosis of malignant tumors discovered in the nuclear medicine imaging tracing.

3. 发明申请

US20180099933A1 Compound and analogues for tracing histone acetylation inhibitors PET imaging for diagnosis and treatment of tumors 有权
公开(公告)号：US20180099933A1
公开(公告)日：2018-04-12
申请号：US15286596
申请日：2016-10-06
申请人： MING-HSIN LI , Chyng-Yann Shiue , Han-Chih Chang , Chun-Fang Feng
发明人： MING-HSIN LI , Chyng-Yann Shiue , Han-Chih Chang , Chun-Fang Feng
IPC分类号： C07D209/04 , C07D401/12 , C07D401/14
CPC分类号： C07D209/04 , C07D209/08 , C07D401/12 , C07D401/14
摘要： The present invention relates to a group of compounds for nuclear medicine imaging through F-18 labeled histone acetylation inhibitors (HDACi) of indole or indoline benzoyl amine and its derivatives, and provides a series of nuclear medicine imaging agents that bind with HDAC overexpression in vivo for diagnosis of malignant tumors discovered in the nuclear medicine imaging tracing.

4. 发明授权

US09603950B1 Compounds of imaging agent with HDAC inhibitor for treatment of Alzheimer syndrome and method of synthesis thereof 有权
公开(公告)号：US09603950B1
公开(公告)日：2017-03-28
申请号：US14922159
申请日：2015-10-25
申请人： Ming-Hsin Li , Chyng-Yann Shiue , Han-Chih Chang , Han-Hsiang Chu
发明人： Ming-Hsin Li , Chyng-Yann Shiue , Han-Chih Chang , Han-Hsiang Chu
IPC分类号： C07C237/40 , C07C231/12 , A61K51/04 , C07C233/80
CPC分类号： A61K51/04 , C07B59/001 , C07B2200/05 , C07C233/80 , C07C237/40
摘要： A method of synthesizing a compound of imaging agent with HDAC (histone deacetylase) inhibitor consists of two parts, the first part of the method is to provide the inhibitor of HDAC with a compound of imaging agent that includes HDAC inhibitor BNL-26 (C22H23N3O) and its analogs to be labeled with radionuclide F-18, producing a series of new nuclear medicine tracers: BNL-26-CH2CH218F, BNL-26a-CH2CH218FF, BNL-26b-CH2CH218F, BNL-26c-CH2CH218F and BNL-26d-CH2CH218F. These nuclear medicine with imaging agents can be used as a tracer in vivo binding to over-expression HDAC and produce a HDAC nuclear medicine imaging effect to serve for clinical diagnosis. The second part of the method is to provide a slightly adjusted a structural framework of BNL-26 and use pyridine to substitute the benzene ring of the BNL-26 structure, and then synthesize with other substituent to produce a series of additional 30 more HDAC inhibitors, named from Iner-1 to Iner-30 compounds.

5. 发明申请

US20050026974A1 Detection of hypoxia 审中-公开
标题翻译：检测缺氧
公开(公告)号：US20050026974A1
公开(公告)日：2005-02-03
申请号：US10927696
申请日：2004-08-27
申请人： Cameron Koch , Alexander Kachur , Sydney Evans , Chyng-Yann Shiue , Ian Baird , Kirsten Skov , William Dolbier , An-Rong Li , Brian James
发明人： Cameron Koch , Alexander Kachur , Sydney Evans , Chyng-Yann Shiue , Ian Baird , Kirsten Skov , William Dolbier , An-Rong Li , Brian James
IPC分类号： C07D233/91 , C07D277/38 , C07K16/44 , A61K31/426
CPC分类号： C07D233/91 , C07K16/44
摘要： Novel nitroaromatic compounds and immunogenic conjugates comprising a novel nitroaromatic compound and a carrier protein are disclosed. The invention further presents monoclonal antibodies highly specific for the claimed nitroaromatic compounds, the compounds' protein conjugates, the compounds' reductive byproducts, and adducts formed between the compounds and mammalian hypoxic cell tissue proteins. The invention is further directed to methods for detecting tissue hypoxia using immunohistological techniques, non-invasive nuclear medicinal methods, or nuclear magnetic resonance. Diagnostic kits useful in practicing the methods of claimed invention are also provided.
摘要翻译：公开了包含新型硝基芳族化合物和载体蛋白质的新型硝基芳族化合物和免疫原性缀合物。本发明还提供对所要求保护的硝基芳族化合物，化合物的蛋白质缀合物，化合物的还原副产物以及化合物和哺乳动物缺氧细胞组织蛋白质之间形成的加合物高度特异性的单克隆抗体。本发明还涉及使用免疫组织化学技术，非侵入性核医学方法或核磁共振来检测组织缺氧的方法。还提供了可用于实践所要求保护的发明的方法的诊断试剂盒。

6. 发明授权

US06252087B1 Nitroaromatic compounds for the detection of hypoxia 失效
标题翻译：用于检测缺氧的硝基芳族化合物
公开(公告)号：US06252087B1
公开(公告)日：2001-06-26
申请号：US09123300
申请日：1998-07-28
申请人： Cameron J. Koch , Alexander V. Kachur , Sydney M. Evans , Chyng-Yann Shiue , Ian R. Baird , Kirsten A. Skov , William R. Dolbier, Jr. , An-Rong Li , Brian R. James
发明人： Cameron J. Koch , Alexander V. Kachur , Sydney M. Evans , Chyng-Yann Shiue , Ian R. Baird , Kirsten A. Skov , William R. Dolbier, Jr. , An-Rong Li , Brian R. James
IPC分类号： C07D23391
CPC分类号： C07D233/91 , A61K49/001 , C07K16/44
摘要： Nitroaromatic compounds and immunogenic conjugates comprising a novel nitroaromatic compound and a carrier protein are disclosed. The invention further presents monoclonal antibodies highly specific for the claimed nitroaromatic compounds, the compounds' protein conjugates, the compounds' reductive byproducts, and adducts formed between the compounds and mammalian hypoxic cell tissue proteins. The invention is further directed to methods for detecting tissue hypoxia using immunohistological techniques, non-invasive nuclear medicinal methods, or nuclear magnetic resonance. Diagnostic kits useful in practicing the methods of claimed invention are also provided.
摘要翻译：公开了包含新型硝基芳族化合物和载体蛋白质的硝基芳族化合物和免疫原性缀合物。本发明还提供对所要求保护的硝基芳族化合物，化合物的蛋白质缀合物，化合物的还原副产物以及化合物和哺乳动物缺氧细胞组织蛋白质之间形成的加合物高度特异性的单克隆抗体。本发明还涉及使用免疫组织化学技术，非侵入性核医学方法或核磁共振来检测组织缺氧的方法。还提供了可用于实践所要求保护的发明的方法的诊断试剂盒。

7. 依法登记的发明

USH1209H No-carrier-added (18F)-N-methylspiroperidol 失效
公开(公告)号：USH1209H
公开(公告)日：1993-07-06
申请号：US784149
申请日：1985-10-04
申请人： Chyng-Yann Shiue , Joanna S. Fowler , Alfred P. Wolf
发明人： Chyng-Yann Shiue , Joanna S. Fowler , Alfred P. Wolf
IPC分类号： A61K51/04
CPC分类号： A61K51/0455 , A61K2123/00
摘要： There is disclosed a radioligand labeled with a positron emitting radionuclide suitable for dynamic study in living humans with positron emission transaxial tomography. [.sup.18 F]-N-methylspiroperidol, exhibiting extremely high affinity for the dopamine receptors, provides enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to provide [.sup.18 F]-N-methylspiroperidol as a radioligand superior to known radioligands for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for this material is disclosed.

8. 发明授权

US4871527A No-carrier-added [.sup.18 F]-N-fluoroalkylspiroperidols 失效
标题翻译：无载体添加[18 F] -N-氟烷基螺环脂醇
公开(公告)号：US4871527A
公开(公告)日：1989-10-03
申请号：US43824
申请日：1987-04-29
申请人： Chyng-Yann Shiue , Alfred P. Wolf , Lan-Qin Bai , Ren-Tui Teng
发明人： Chyng-Yann Shiue , Alfred P. Wolf , Lan-Qin Bai , Ren-Tui Teng
IPC分类号： A61K51/04
CPC分类号： C07B59/002 , A61K51/0455 , A61K2123/00
摘要： There is disclosed radioligands labeled with the position emitting radionuclide [.sup.18 F] suitable for dynamic study in living humans with position emission transaxial tomography. These new [.sup.18 F]-N-fluoroalkylspiroperidols, wherein the alkyl group contains from 2-6 carbon atoms, exhibit extremely high affinity for the dopamine receptors and provide enhanced uptake and retention in the brain concomitant with reduced radiation burden. These characteristics all combine to make these new radioligands useful for mapping dopamine receptors in normal and disease states in the living brain. Additionally, a new synthetic procedure for these radioligands as well as a new procedure for preparing the radiolabeled alkyl halide alkylating reagents are also disclosed.
摘要翻译：公开了放射性核素标记的放射性核素[18F]的位置，适用于活体位置发射横轴断层扫描的动态研究。这些新的[18 F] -N-氟烷基螺环脂醇，其中烷基含有2-6个碳原子，对多巴胺受体表现出非常高的亲和力，并且随着减少的辐射负担而提供增强的大脑摄取和保留。这些特征都结合起来，使这些新的放射性配体可用于在活体大脑的正常和疾病状态下测定多巴胺受体。此外，还公开了这些放射性配体的新合成方法以及制备放射性标记的烷基卤烷基化试剂的新方法。

9. 发明授权

US06864393B2 Fluorinated phenyl thiophenyl derivatives and their use for imaging serotonin transporters 有权
公开(公告)号：US06864393B2
公开(公告)日：2005-03-08
申请号：US10388363
申请日：2003-03-14
申请人： Hank F. Kung , Chyng-Yann Shiue , Shunichi Oya , Seok Rye Choi , Grace G. Shiue , Ping Fang
发明人： Hank F. Kung , Chyng-Yann Shiue , Shunichi Oya , Seok Rye Choi , Grace G. Shiue , Ping Fang
摘要： This invention relates to novel fluorinated phenyl thiphenyl (also named diarylsulfide) derivatives and their use in Positron Emission Tomagraphy (PET) imaging of Serotonin Transporters (SERTS). The present invention also provides diagnostic compositions comprising the novel compounds of the present invention, and a pharmaceutically acceptable carrier or diluent. The invention further provides a method of imaging SERTS, comprising introducing into a patient a detectable quantity of a labeled compound of the present invetion, or a pharmaceutically acceptable salt, ester, amide or prodrug thereof.

10. 发明授权

US4617386A Process for the production of .sup.18 F-2-deoxy-2-fluoro-D-glucose 失效
标题翻译：制备18 F-2-脱氧-2-氟-D-葡萄糖的方法
公开(公告)号：US4617386A
公开(公告)日：1986-10-14
申请号：US488311
申请日：1983-04-25
申请人： David R. Elmaleh , Shlomo Levy , Chyng-Yann Shiue , Alfred P. Wolf
发明人： David R. Elmaleh , Shlomo Levy , Chyng-Yann Shiue , Alfred P. Wolf
IPC分类号： C07H5/02 , C07H15/04 , C07H1/00
CPC分类号： C07H5/02 , C07H15/04
摘要： Process for the production of 2-deoxy-2-fluoro-D-glucose and the corresponding .sup.18 F-compound in which methyl 4,6-O-benzylidine-3-O-methyl-2-O-trifluoromethanesulfonyl-.beta.-D-mannopyranoside is reacted with a triflating reagent, the resulting compound reacted with CsHF.sub.2, RbF or the corresponding .sup.18 F-compounds, and thereafter the alkyl groups removed by hydrolysis.
摘要翻译：制备2-脱氧-2-氟-D-葡萄糖的方法和相应的18F-化合物，其中甲基4,6-O-亚苄基-3-O-甲基-2-O-三氟甲磺酰基-β-D-吡喃甘露糖苷与三氟甲烷试剂反应，所得化合物与CsHF 2，RbF或相应的18 F化合物反应，然后通过水解除去烷基。

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