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1. 发明申请

WO2010111303A2 IMAGING AGENTS FOR DETECTING NEUROLOGICAL DISORDERS 审中-公开
标题翻译：用于检测神经疾病的成像剂
公开(公告)号：WO2010111303A2
公开(公告)日：2010-09-30
申请号：PCT/US2010028360
申请日：2010-03-23
申请人： SIEMENS MEDICAL SOLUTIONS , GANGADHARMATH UMESH B , KOLB HARTMUTH C , SCOTT PETER J H , WALSH JOSEPH C , ZHANG WEI , SZARDENINGS ANNA KATRIN , SINHA ANJANA , CHEN GANG , WANG ERIC , MOCHARLA VANI P , YU CHUL , LIU CHANGHUI , CASHION DANIEL KURT , KASI DHANALAKSHMI
发明人： GANGADHARMATH UMESH B , KOLB HARTMUTH C , SCOTT PETER J H , WALSH JOSEPH C , ZHANG WEI , SZARDENINGS ANNA KATRIN , SINHA ANJANA , CHEN GANG , WANG ERIC , MOCHARLA VANI P , YU CHUL , LIU CHANGHUI , CASHION DANIEL KURT , KASI DHANALAKSHMI
IPC分类号： A61K51/04 , C07B59/00 , C07D215/00 , C07D235/04 , C07D263/52 , C07D277/62
CPC分类号： A61K51/0455 , A61K51/04 , A61K51/0453 , A61K51/0459 , A61K51/0463 , C07B59/002 , C07D215/06 , C07D235/14 , C07D277/62 , C07D401/04 , C07D403/06 , C07D413/10 , C07D413/14 , C07D487/04
摘要： Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering ti a patient in need compounds of formula (I) capable of binding to tau proteins and ß-amyloid peptides are presented herein. The invention also relates to methods of imaging Aß and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disoders.
摘要翻译：式（I）的成像剂和用于检测神经障碍的方法包括给予需要能够结合tau蛋白和β-淀粉样蛋白肽的式（I）化合物的化合物。本发明还涉及成像Aβ和tau聚集体的方法，包括引入可检测量的包含放射性标记的式（I）化合物的药物制剂，并检测患者中与淀粉样蛋白沉积物和/或tau蛋白相关的标记化合物。这些方法和组合使得AD和其他神经系统解剖器的临床前诊断和监测进展。

2. 发明申请

WO2013028664A1 PSMA IMAGING AGENTS 审中-公开
标题翻译： PSMA成像代理
公开(公告)号：WO2013028664A1
公开(公告)日：2013-02-28
申请号：PCT/US2012/051674
申请日：2012-08-21
申请人： SIEMENS MEDICAL SOLUTIONS USA, INC. , WANG, Eric , KOLB, Hartmuth C. , SZARDENINGS, Anna Katrin , LIU, Changhui , WALSH, Joseph C. , CHEN, Gang , SINHA, Anjana , KASI, Dhanalakshmi , YU, Chul , GANGADHARMATH, Umesh B. , ZHANG, Wei , ZHAO, Tieming , MOCHARLA, Vani P.
发明人： WANG, Eric , KOLB, Hartmuth C. , SZARDENINGS, Anna Katrin , LIU, Changhui , WALSH, Joseph C. , CHEN, Gang , SINHA, Anjana , KASI, Dhanalakshmi , YU, Chul , GANGADHARMATH, Umesh B. , ZHANG, Wei , ZHAO, Tieming , MOCHARLA, Vani P.
IPC分类号： A61K51/08 , C07K5/02 , C07K5/06 , C07D223/16 , A61P35/00
CPC分类号： C07K5/0215 , A61K38/00 , A61K51/0453 , A61K51/088 , C07D207/16 , C07D209/48 , C07D213/81 , C07D213/82 , C07D233/78 , C07D233/96 , C07D239/60 , C07D249/04 , C07D249/06 , C07D251/30 , C07D263/34 , C07D277/56 , C07D401/12 , C07D403/06 , C07D403/12 , C07D405/12 , C07K5/06026 , C07K5/06113
摘要： Compounds for targeting and agents for imaging, Prostate-specific membrane antigen (PSMA) are disclosed. Methods of synthesizing compounds and imaging agents, as well as methods for imaging PSMA are also disclosed. The imaging agents disclosed are suitable for PET and SPECT imaging.
摘要翻译：公开了靶向化合物和成像剂，前列腺特异性膜抗原（PSMA）。还公开了合成化合物和成像剂的方法以及PSMA成像方法。所公开的成像剂适用于PET和SPECT成像。

3. 发明申请

WO2010111303A3 IMAGING AGENTS FOR DETECTING NEUROLOGICAL DISORDERS 审中-公开
公开(公告)号：WO2010111303A3
公开(公告)日：2010-09-30
申请号：PCT/US2010/028360
申请日：2010-03-23
申请人： SIEMENS MEDICAL SOLUTIONS USA, INC. , GANGADHARMATH, Umesh, B. , KOLB, Hartmuth, C. , SCOTT, Peter, J.H. , WALSH, Joseph, C. , ZHANG, Wei , SZARDENINGS, Anna, Katrin , SINHA, Anjana , CHEN, Gang , WANG, Eric , MOCHARLA, Vani, P. , YU, Chul , LIU, Changhui , CASHION, Daniel, Kurt , KASI, Dhanalakshmi
发明人： GANGADHARMATH, Umesh, B. , KOLB, Hartmuth, C. , SCOTT, Peter, J.H. , WALSH, Joseph, C. , ZHANG, Wei , SZARDENINGS, Anna, Katrin , SINHA, Anjana , CHEN, Gang , WANG, Eric , MOCHARLA, Vani, P. , YU, Chul , LIU, Changhui , CASHION, Daniel, Kurt , KASI, Dhanalakshmi
IPC分类号： A61K51/04 , C07D215/00 , C07D235/04 , C07D263/52 , C07D277/62 , C07B59/00
摘要： Imaging agents of formula (I) and methods for detecting neurological disorders comprising administering ti a patient in need compounds of formula (I) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Aβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formula (I) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disoders.

4. 发明申请

WO2013176698A1 CARBOLINE AND CARBAZOLE BASED IMAGING AGENTS FOR DETECTING NEUROLOGICAL DYSFUNCTION 审中-公开
标题翻译：基于CARBOLINE和CARBAZOLE的成像剂用于检测神经性功能障碍
公开(公告)号：WO2013176698A1
公开(公告)日：2013-11-28
申请号：PCT/US2012/061912
申请日：2012-10-25
申请人： ELI LILLY AND COMPANY , SZARDENINGS, Anna Katrin , KOLB, Hartmuth C. , WALSH, Joseph C. , CHEN, Gang , GANGADHARMATH, Umesh B. , KASI, Dhanalakshmi , LIU, Changhui , SINHA, Anjana , WANG, Eric , YU, Chul , ZHANG, Wei , CHEN, Kai , MOCHARLA, Vani P. , SCOTT, Peter J.H.
发明人： SZARDENINGS, Anna Katrin , KOLB, Hartmuth C. , WALSH, Joseph C. , CHEN, Gang , GANGADHARMATH, Umesh B. , KASI, Dhanalakshmi , LIU, Changhui , SINHA, Anjana , WANG, Eric , YU, Chul , ZHANG, Wei , CHEN, Kai , MOCHARLA, Vani P. , SCOTT, Peter J.H.
IPC分类号： C07D209/88 , C07D403/12 , C07D471/04 , C07D471/14 , A61K51/04 , A61K49/10 , C07B59/00
CPC分类号： C07D209/88 , C07B59/002 , C07D209/80 , C07D403/12 , C07D471/04 , C07D471/14
摘要： Disclosed here in are compounds and methods of diagnosing Alzheimer's Disease or a predisposition thereto in a mammal, the method comprising administering to the mammal a diagnostically effective amount of a radiolabeled compound, allowing the com¬ pound to distribute into the brain tissue, and imaging the brain tissue, wherein an increase in binding of the compound to the brain tissue compared to a normal control level of binding indicates that the mammal mal is suffering from or is at risk of developing Alzheimer's Disease. The claimed compounds have the structure of formula (I) wherein: L is N or CR5, M is N or CR6; P is N or CR7; and Q is N or CR8; X is a bond or is Cl-14alkyl, wherein at least one carbon is optionally replaced by C(O), 0, S, S02, or NH, NH-Cl-8alkyl, and wherein at least one H of Cl-8alkyl is optionally replaced by halo, OH, Cl-6alkyl; wherein at least one halo is optionally replaced with a radionuclide or a fluorescent tag. The other variables are as defined in the claims.
摘要翻译：本文公开了在哺乳动物中诊断阿尔茨海默氏病或其倾向的化合物和方法，所述方法包括向哺乳动物施用诊断有效量的放射性标记化合物，允许该组分分布于脑组织中，并使脑成像组织，其中与正常对照水平的结合相比，化合物与脑组织的结合增加表明哺乳动物的马曾患有或有发展为阿尔茨海默病的风险。所要求保护的化合物具有式（I）的结构，其中：L是N或CR 5，M是N或CR 6; P为N或CR7; Q为N或CR8; X是一个键或是C 1-4烷基，其中至少一个碳任选地被C（O），O，S，SO 2或NH，NH-C 1-8烷基取代，并且其中至少一个C 1-8烷基的H 任选被卤素，OH，C 1-6烷基取代; 其中至少一个卤素任选被放射性核素或荧光标记替代。其他变量如权利要求中所定义。

5. 发明申请

WO2011119565A1 IMAGING AGENTS FOR DETECTING NEUROLOGICAL DISORDERS 审中-公开
标题翻译：用于检测神经疾病的成像剂
公开(公告)号：WO2011119565A1
公开(公告)日：2011-09-29
申请号：PCT/US2011/029368
申请日：2011-03-22
申请人： SIEMENS MEDICAL SOLUTIONS USA, INC. , CASHION, Daniel, Kurt , CHEN, Gang , KASI, Dhanalakshmi , KOLB, Hartmuth C. , LIU, Changhui , SINHA, Anjana , SZARDENINGS, Anna, Katrin , WANG, Eric , YU, Chul , ZHANG, Wei , GANGADHARMATH, Umesh, B. , WALSH, Joseph, C.
发明人： CASHION, Daniel, Kurt , CHEN, Gang , KASI, Dhanalakshmi , KOLB, Hartmuth C. , LIU, Changhui , SINHA, Anjana , SZARDENINGS, Anna, Katrin , WANG, Eric , YU, Chul , ZHANG, Wei , GANGADHARMATH, Umesh, B. , WALSH, Joseph, C.
IPC分类号： C07D235/04 , C07D401/02 , A61K31/4184 , A61K31/4353 , A61P25/00
CPC分类号： C07D235/04 , A61K51/04 , C07B59/002 , C07D215/06 , C07D235/14 , C07D277/62 , C07D401/02 , C07D401/04 , C07D403/06 , C07D413/10 , C07D413/14 , C07D471/04 , C07D487/04
摘要： Imaging agents of formulas (I)-(V) and methods for detecting neurological disorders comprising administering to a patient in need compounds of formulas (I)-(V) capable of binding to tau proteins and β-amyloid peptides are presented herein. The invention also relates to methods of imaging Αβ and tau aggregates comprising introducing a detectable quantity of pharmaceutical formulation comprising a radiolabeled compound of formulas (I)-(V) and detecting the labeled compound associated with amyloid deposits and/or tau proteins in a patient. These methods and compositions enable preclinical diagnosis and monitoring progression of AD and other neurological disorders. Formula (V) or a pharmaceutically acceptable salt thereof, and stereoisomers thereof, wherein: X 25 -X 28 are each independently CH, CR 11 , or N; X 29 is CH, N, O or S; X 30 is CH, C, or N; X 31-34 are each independently CH, CR 12 , CR 13 or N; RII-RU are each independently H, halogen, hydroxy, nitro, cyano, ammo, alkyl, alkylaryl, alkylamino, alkylamine, arylamine, arylamino, alkoxy,— (O-CH 2 - CH 2 ) n -, alkenyL alkynyl, aryloxy, NRl0COOalkyl, NRl0 COOaryU NRW COalkyl, NR 10 CO aryl, COOalkyl, COOaryl, COalkyl, COaryl, aryl, cycloalkyl, cycloalkylamino, cycloalkylamine, bicyclic, saturated heterocycle and unsaturated heterocycle, wherein at least one carbon of R 11 -R 13 is optionally replaced with N, Q, S, triazole, or halo, and, wherein at least one hydrogen is optionally replaced with halo, amine, amino, alkoxy, nitro, alkyl, alkenyL alkynyl, aryloxy, alkylaryl, alkylamino, alkylamine, NRioCOOalkyl, NR 10 COOaryl, NR 10 COalkyl, NR,0 CO aryl, COOalkyl, COOaryl, COalkyl, COaryl, aryl, cycloalkyl, cycloalkylamino, cycloalkylamine, bicyclic saturated heterocycle and unsaturated heterocycle, a leaving group, CN, OH or a radioactive isotope.
摘要翻译：式（I） - （V）的成像剂和用于检测神经障碍的方法包括向需要的患者施用能够结合tau蛋白和β-淀粉样肽的式（I） - （V）化合物。本发明还涉及成像β和tau聚集体的方法，包括引入可检测量的包含放射性标记的式（I） - （V）化合物的药物制剂，并检测与淀粉样蛋白沉积物和/或tau蛋白相关的标记化合物患者。这些方法和组合使得临床前诊断和监测AD和其他神经障碍的进展。式（V）或其药学上可接受的盐及其立体异构体，其中：X25-X28各自独立地为CH，CR11或N; X29是CH，N，O或S; X30是CH，C或N; X31-34各自独立地为CH，CR12，CR13或N; RII-RU各自独立地为H，卤素，羟基，硝基，氰基，氨基，烷基，烷基芳基，烷基氨基，烷基胺，芳基胺，芳基氨基，烷氧基， - （O-CH 2 -CH 2）n - 烯基炔基，芳氧基，NR 10 COO烷基， NR10 COOaryU NRW CO烷基，NR10CO芳基，COO烷基，COO芳基，CO烷基，芳基，芳基，环烷基，环烷基氨基，环烷基胺，双环，饱和杂环和不饱和杂环，其中R11-R13的至少一个碳任选被N，Q，烷基，烯基炔基，芳氧基，烷基芳基，烷基氨基，烷基胺，NROCOO烷基，NR10 COO芳基，NR10CO烷基，NR 芳基，环烷基，环烷基氨基，环烷基胺，双环饱和杂环和不饱和杂环，离去基团，CN，OH或放射性同位素。

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