公开(公告)号：WO2009055520A3

公开(公告)日：2009-10-29

申请号：PCT/US2008080861

申请日：2008-10-23

Applicant: GEN ELECTRIC ,  AMARASINGHE KANDE KANKANANAMAL ,  RISHEL MICHAEL JAMES ,  DINN SEAN RICHARD ,  JOHNSON BRUCE FLETCHER

Inventor： AMARASINGHE KANDE KANKANANAMAL ,  RISHEL MICHAEL JAMES ,  DINN SEAN RICHARD ,  JOHNSON BRUCE FLETCHER

IPC: A61K51/04

CPC classification number: C07D471/04 ,  A61K51/0455

Abstract: The present invention provides novel fluorinated ether compounds related to dihydrotetrabenazine and intermediates useful in the preparation of such fluorinated ether compounds. The fluorinated ether compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluorinated ether compounds are shown to possess high affinity for VMAT-2, a biomarker implicated inter alia in human diabetes. The fluorinated ether compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabeled fluorinated ether compounds are useful as probes for the discovery of PET imaging agents.

Abstract translation: 本发明提供了与二氢丁苯那嗪有关的新型氟化醚化合物和用于制备这种氟化醚化合物的中间体。 氟化醚化合物以外消旋形式和对映体富集形式提供，并且可以包含氟-18和氟19中的一种或两种。氟化醚化合物显示对VMAT-2具有高亲和力，VMAT-2特别涉及人类糖尿病中的生物标志物 。 包含氟-18基团的氟化醚化合物可用作靶向VMAT-2生物标志物的PET成像剂。 非放射性标记的氟化醚化合物可用作发现PET成像剂的探针。

公开(公告)号：WO2010141704A2

公开(公告)日：2010-12-09

申请号：PCT/US2010037237

申请日：2010-06-03

Applicant: GEN ELECTRIC ,  TAN HEHIR CRISTINA ABUCAY ,  SICLOVAN TIBERIU MIRCEA ,  BARNHARDT NICOLE EVELYN ,  FISH KENNETH MICHAEL ,  CARTER RANDALL LEE ,  JOHNSON BRUCE FLETCHER ,  ZHANG RONG

Inventor： TAN HEHIR CRISTINA ABUCAY ,  SICLOVAN TIBERIU MIRCEA ,  BARNHARDT NICOLE EVELYN ,  FISH KENNETH MICHAEL ,  CARTER RANDALL LEE ,  JOHNSON BRUCE FLETCHER ,  ZHANG RONG

IPC: A61K49/10

CPC classification number: A61K49/10

Abstract: The present invention relates to methods for myelin basic protein detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the agent, and determining myelination in the subject by detecting binding to myelin basic protein. Methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using an agent with specific binding to myelin basic protein are also provided as is a kit containing the agent or its derivatives for use in detecting myelin basic protein.

Abstract translation: 本发明涉及髓鞘碱性蛋白检测的方法，包括鉴定患有髓磷脂相关神经病的风险或被诊断的受试者，通过胃肠外给药该试剂，以及通过检测与髓磷脂碱性蛋白的结合来测定受试者的髓鞘形成。 还提供了检测髓磷脂的方法以及使用特异性结合髓磷脂碱性蛋白的药剂对样品中局部浓度的定量测量，其中包含用于检测髓磷脂碱性蛋白质的试剂或其衍生物的试剂盒。

公开(公告)号：WO2009073677A1

公开(公告)日：2009-06-11

申请号：PCT/US2008/085304

申请日：2008-12-03

Applicant: GENERAL ELECTRIC COMPANY ,  AMARASINGHE, Kande Kankananamalage Dayarathna ,  RISHEL, Michael James ,  DINN, Sean Richard ,  JOHNSON, Bruce Fletcher

Inventor： AMARASINGHE, Kande Kankananamalage Dayarathna ,  RISHEL, Michael James ,  DINN, Sean Richard ,  JOHNSON, Bruce Fletcher

IPC: C07D471/04 ,  C07D455/06 ,  A61K31/4353

CPC classification number: C07D455/06

Abstract: The present invention provides novel fluoroalkyl tetrabenazine carbinol compounds. The fluoroalkyl tetrabenazine carbinol compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluoroalkyl tetrabenazine carbinol compounds are shown to possess high affinity for VMAT-2, a biomarker implicated in human diabetes. The fluoroalkyl tetrabenazine carbinol compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled fluoroalkyl tetrabenazine carbinol compounds are useful as probes for the discovery of PET imaging agents.

Abstract translation: 本发明提供新的氟代烷基四苯并嗪甲醇化合物。 氟烷基四苯并嗪甲醇化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的一种或两种。氟烷基丁苯那嗪甲醇化合物显示对VMAT-2具有高亲和力，VMAT-2是涉及人类糖尿病的生物标记 。 包含氟-18基团的氟代烷基四苯并嗪甲醇化合物可用作靶向VMAT-2生物标志物的PET显像剂。 非放射性氟烷基丁苯那嗪甲醇化合物可用作发现PET成像剂的探针。

公开(公告)号：WO2008154243A1

公开(公告)日：2008-12-18

申请号：PCT/US2008/065738

申请日：2008-06-04

Applicant: GENERAL ELECTRIC COMPANY ,  RISHEL, Michael James ,  AMARASINGHE, Kande Kankananamalage Dayarathna ,  DINN, Sean Richard ,  JOHNSON, Bruce Fletcher

Inventor： RISHEL, Michael James ,  AMARASINGHE, Kande Kankananamalage Dayarathna ,  DINN, Sean Richard ,  JOHNSON, Bruce Fletcher

IPC: C07D217/00 ,  C07D217/24 ,  C07D455/00

CPC classification number: C07D455/06 ,  C07D217/16 ,  C07D217/18 ,  Y02P20/55

Abstract: A method of preparing a tetrabenazine compound (TBZ compound) having structure I comprising the steps of reacting a nucleophilic alkenyl species with aldehyde compound II and oxidizing the resultant allylic alcohol to provide enone III. The protecting group P 1 on the tetrahydroisoquinoline nitrogen is removed and the resultant deprotected intermediate is induced to undergo an amino cyclization reaction to provide a product TBZ compound having structure I. The method may be used to prepare either enantiomeric form of tetrabenazine; (+)-tetrabenazine or (-)-tetrabenazine. Alternatively the method may be adapted to provide a mixture enriched in one tetrabenazine enantiomer, a racemic mixture, or a diastereomeric mixture of tetrabenazine compounds. In addition, the present invention provides novel synthetic intermediate compositions which may be used to prepare either or both enantiomers of tetrabenazine, derivatives of tetrabenazine, and analogs of tetrabenazine.

Abstract translation: 制备具有结构I的丁苯那嗪化合物（TBZ化合物）的方法包括以下步骤：使亲核烯基物质与醛化合物II反应并氧化得到的烯丙基醇以提供烯酮III。 除去四氢异喹啉氮上的保护基P1，将所得脱保护的中间体诱导进行氨基环化反应，得到具有结构I的产物TBZ化合物。该方法可用于制备对映体形式的丁苯那嗪; （+） - 丁苯那嗪或（ - ） - 丁苯那嗪。 或者，该方法可以适于提供富集一种四苯并嗪对映异构体，外消旋混合物或丁苯那嗪化合物的非对映体混合物的混合物。 此外，本发明提供了新的合成中间体组合物，其可用于制备丁苯那嗪，丁苯那敏衍生物和丁苯那嗪类似物的任一种或两种对映异构体。

公开(公告)号：WO2005023317A1

公开(公告)日：2005-03-17

申请号：PCT/US2004/021600

申请日：2004-07-06

Applicant: GENERAL ELECTRIC COMPANY ,  JOHNSON, Bruce, Fletcher ,  SICLOVAN, Tiberiu, Mircea

Inventor： JOHNSON, Bruce, Fletcher ,  SICLOVAN, Tiberiu, Mircea

IPC: A61K51/04

CPC classification number: A61K51/04

Abstract: Compounds that include a targeting moiety bound to a regioselective leaving group are useful for preparing imaging agents. The imaging agents can be isolated from by­products derived from the leaving group based on differences in the chemical attributes (e.g., net charge or polarity) of the molecules or physical attributes of the molecules through the use of a solid support. Methods of producing an imaging agent include the steps of providing a compound that includes a targeting moiety bound to a support via a linker group that contains a site for regioselective substitution of a detectable species, contacting the compound with a solution containing the detectable species, and recovering the imaging agent. Kits which include a first container (5) having therein a solution (31) containing a detectable species and a second container (2) having therein a compound that includes a targeting moiety bound to a support (30) via a leaving group that contains a site for regioselective substitution of the detectable species are also useful for preparing imaging agents.

Abstract translation: 包含与区域选择性离去基团结合的靶向部分的化合物可用于制备成像剂。 基于通过使用固体支持物的分子的化学属性（例如，净电荷或极性）或分子的物理属性的差异，可以从衍生自离去基团的副产物中分离成像剂。 制备显影剂的方法包括以下步骤：提供化合物，其包括通过连接基团与支持物结合的靶向部分，该接头基团含有用于可检测物质的区域选择性取代的位点，使化合物与含有可检测物质的溶液接触，以及 恢复成像剂。 包括其中具有含有可检测物质的溶液（31）的第一容器（5）和其中具有化合物的第二容器（2），所述第二容器包含通过离去基团与支持物（30）结合的靶向部分，所述离去基团含有 可检测物种的区域选择性取代的位点也可用于制备成像剂。

公开(公告)号：WO2013039754A1

公开(公告)日：2013-03-21

申请号：PCT/US2012/053861

申请日：2012-09-06

Applicant: GENERAL ELECTRIC COMPANY ,  WEBSTER, Jack Mathew ,  JOHNSON, Bruce Fletcher ,  LEE, Brian Duh-Lan ,  PABBA, Chittari ,  RISHEL, Michael James

Inventor： WEBSTER, Jack Mathew ,  JOHNSON, Bruce Fletcher ,  LEE, Brian Duh-Lan ,  PABBA, Chittari ,  RISHEL, Michael James

IPC: A61K51/04 ,  A61K101/02

CPC classification number: A61K51/0406 ,  C07B59/001

Abstract: Imaging agents are described that comprise labeled substrates capable of being introduced into cells via the cystine/glutamate antiporter. The substrates may be used for imaging or detecting oxidative stress in cells by introducing the labeled agents into cells via the cystine/glutamate antiporter and subsequent detection.

Abstract translation: 描述了包含能够通过胱氨酸/谷氨酸反向转运体引入细胞的标记底物的成像剂。 通过将标记的试剂通过胱氨酸/谷氨酸反转录酶引入细胞并随后检测，底物可用于成像或检测细胞中的氧化应激。

公开(公告)号：WO2010141704A3

公开(公告)日：2010-12-09

申请号：PCT/US2010/037237

申请日：2010-06-03

Applicant: GENERAL ELECTRIC COMPANY ,  TAN HEHIR, Cristina, Abucay ,  SICLOVAN, Tiberiu, Mircea ,  BARNHARDT, Nicole, Evelyn ,  FISH, Kenneth, Michael ,  CARTER, Randall, Lee ,  JOHNSON, Bruce, Fletcher ,  ZHANG, Rong

Inventor： TAN HEHIR, Cristina, Abucay ,  SICLOVAN, Tiberiu, Mircea ,  BARNHARDT, Nicole, Evelyn ,  FISH, Kenneth, Michael ,  CARTER, Randall, Lee ,  JOHNSON, Bruce, Fletcher ,  ZHANG, Rong

IPC: A61K49/10

Abstract: The present invention relates to methods for myelin basic protein detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the agent, and determining myelination in the subject by detecting binding to myelin basic protein. Methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using an agent with specific binding to myelin basic protein are also provided as is a kit containing the agent or its derivatives for use in detecting myelin basic protein.

公开(公告)号：WO2009070552A1

公开(公告)日：2009-06-04

申请号：PCT/US2008/084601

申请日：2008-11-25

Applicant: GENERAL ELECTRIC COMPANY ,  RISHEL, Michael James ,  JOHNSON, Bruce Fletcher ,  AMARASINGHE, Kande Kankananamalage Dayarathna ,  DINN, Sean Richard

Inventor： RISHEL, Michael James ,  JOHNSON, Bruce Fletcher ,  AMARASINGHE, Kande Kankananamalage Dayarathna ,  DINN, Sean Richard

IPC: C07D471/04 ,  A61K49/00 ,  A61K51/04 ,  C07F7/18 ,  A61K31/4745

CPC classification number: C07D471/04 ,  A61K51/0455 ,  C07B2200/05

Abstract: The present invention provides novel alpha-fluoroalkyl compounds having structure I and the corresponding dihydrotetrabenazine compounds IV and intermediates useful in the preparation of such compounds. The alpha-fluoroalkyl compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine- 18 and fluorine 19. The alpha-fluoroalkyl compounds are shown to possess high affinity for VMAT-2, a biomarker implicated, for example, in human diabetes. The alpha-fluoroalkyl compounds comprising a fluorine- 18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabled alpha-tluoroalkyl compounds are useful as probes for the discovery of PET imaging agents.

Abstract translation: 本发明提供具有结构I和相应的二氢丁苯那嗪化合物IV的新型α-氟烷基化合物和可用于制备这些化合物的中间体。 α-氟烷基化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。所示的α-氟代烷基化合物对VMAT-2具有高亲和力，VMAT-2是涉及的生物标志物，例如 ，在人类糖尿病。 包含氟-18基团的α-氟烷基化合物可用作靶向VMAT-2生物标志物的PET成像剂。 非放射性α-三氟烷基化合物可用作发现PET成像剂的探针。

公开(公告)号：WO2009055520A2

公开(公告)日：2009-04-30

申请号：PCT/US2008/080861

申请日：2008-10-23

Applicant: GENERAL ELECTRIC COMPANY ,  AMARASINGHE, Kande Kankananamalage Dayarathna ,  RISHEL, Michael James ,  DINN, Sean Richard ,  JOHNSON, Bruce Fletcher

Inventor： AMARASINGHE, Kande Kankananamalage Dayarathna ,  RISHEL, Michael James ,  DINN, Sean Richard ,  JOHNSON, Bruce Fletcher

IPC: A61K51/04

CPC classification number: C07D471/04 ,  A61K51/0455

Abstract: The present invention provides novel fluorinated ether compounds related to dihydrotetrabenazine and intermediates useful in the preparation of such fluorinated ether compounds. The fluorinated ether compounds are provided in both racemic and enantiomerically enriched forms and may comprise either or both of fluorine-18 and fluorine 19. The fluorinated ether compounds are shown to possess high affinity for VMAT-2, a biomarker implicated inter alia in human diabetes. The fluorinated ether compounds comprising a fluorine-18 group are useful as PET imaging agents targeting the VMAT-2 biomarker. The non-radiolabeled fluorinated ether compounds are useful as probes for the discovery of PET imaging agents.

Abstract translation: 本发明提供了与二氢丁苯那嗪有关的新型氟化醚化合物和可用于制备这种氟化醚化合物的中间体。 氟化醚化合物以外消旋和对映异构体富集的形式提供，并且可以包含氟-18和氟19中的任一种或两者。显示氟化醚化合物对于VMAT-2具有高亲和力，VMAT-2特别涉及人类糖尿病 。 包含氟-18基团的氟化醚化合物可用作靶向VMAT-2生物标志物的PET显像剂。 非放射性标记的氟化醚化合物可用作发现PET成像剂的探针。

公开(公告)号：WO2007044001A1

公开(公告)日：2007-04-19

申请号：PCT/US2005/036191

申请日：2005-10-06

Applicant: GENERAL ELECTRIC COMPANY ,  SICLOVAN, Tiberiu, Mircea ,  SYUD, Faisal, Ahmed ,  JOHNSON, Bruce, Fletcher

Inventor： SICLOVAN, Tiberiu, Mircea ,  SYUD, Faisal, Ahmed ,  JOHNSON, Bruce, Fletcher

IPC: C07B59/00 ,  C07K7/06

CPC classification number: C07K1/006 ,  C07B59/00 ,  C07K1/1077

Abstract: A method of labeling amino acid-containing compounds and derivatives thereof with a halide moiety comprises reacting a nucleophilic moiety on such compounds with a halogenated electrophilic compound. Radioactive halide-labeled amino acid­-containing compounds can be targeted to diseased sites and provide a means to diagnose and/or treat the disease.

Abstract translation: 用卤化物部分标记含氨基酸的化合物及其衍生物的方法包括使这些化合物上的亲核部分与卤代亲电子化合物反应。 放射性卤化物标记的含氨基酸的化合物可以靶向病变部位，并提供诊断和/或治疗疾病的手段。