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1. 发明授权

US06171576B2 Dopamine transporter imaging agent 失效
标题翻译：多巴胺转运蛋白成像剂
公开(公告)号：US06171576B2
公开(公告)日：2001-01-09
申请号：US08552584
申请日：1995-11-03
申请人： Peter C. Meltzer , Bertha K. Madras , Alan Davison , Paul Blundell , Ashfaq Mahmood , Alun G. Jones
发明人： Peter C. Meltzer , Bertha K. Madras , Alan Davison , Paul Blundell , Ashfaq Mahmood , Alun G. Jones
IPC分类号： A61K5100
CPC分类号： A61K51/0448 , A61K2123/00 , C07C69/753 , C07C2602/44 , C07D451/02
摘要： Radiopharmaceutical compounds are disclosed. A tropane compound is linked through the N atom at the 8-position to a chelating ligand capable of complexing technetium or rhenium to produce a neutral labeled complex that selectively binds to the dopamine transporter. These compounds can be prepared as separate diastereoisomers as well as a mixture of diastereoisomers. Also disclosed are radiopharmaceutical kits for preparing the labeled radiopharmaceutical compounds.
摘要翻译：公开了放射性药物化合物。托烷化合物通过8位的N原子连接到能够络合锝或铼的螯合配体以产生选择性结合多巴胺转运蛋白的中性标记复合物。这些化合物可以制备成单独的非对映异构体以及非对映异构体的混合物。还公开了用于制备标记的放射性药物化合物的放射性药物试剂盒。

2. 发明授权

US07321027B2 Small technetium-99m and rhenium labeled agents and methods for imaging tumors 失效
标题翻译：小锝-99m和铼标记的药剂和肿瘤成像方法
公开(公告)号：US07321027B2
公开(公告)日：2008-01-22
申请号：US10279214
申请日：2002-10-23
申请人： Ashfaq Mahmood , Matthias Friebe , Cristina Bolzati , Alun G. Jones , Alan Davison
发明人： Ashfaq Mahmood , Matthias Friebe , Cristina Bolzati , Alun G. Jones , Alan Davison
IPC分类号： C07F13/00
CPC分类号： C07D295/13 , A61K51/0478 , C07C323/41 , C07F13/005 , C07K5/06026
摘要： The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tumors, e.g., carcinomas, melanomas and other tumors. In another embodiment, the invention relates to methods of imaging tumors using radiolabeled metal complexes. Preferred radiolabeled complexes for imaging tumors include technetium and rhenium complexes. The high tumor uptake and significant tumor/nontumor ratios of the technetium complexes of the invention indicate that such small technetium-99m-based molecular probes can be developed as in-vivo diagnostic agents for melanoma and its metastases. In yet another embodiment, the invention relates to methods of treatment of tumors using a radiolabeled metal complex as a radiopharmaceutical agent to treat the tumor.
摘要翻译：本发明涉及适用于肿瘤例如癌，黑素瘤和其他肿瘤的成像或治疗性治疗的化合物及其相关的锝和铼络合物。在另一个实施方案中，本发明涉及使用放射性标记的金属络合物成像肿瘤的方法。用于成像肿瘤的优选放射性标记复合物包括锝和铼络合物。本发明的锝络合物的高肿瘤摄取和显着的肿瘤/非肿瘤比率表明，这种基于锝-99m的小分子探针可以作为黑色素瘤及其转移的体内诊断剂开发。在另一个实施方案中，本发明涉及使用放射性标记的金属络合物作为放射性药物治疗肿瘤的方法治疗肿瘤。

3. 发明申请

US20080226550A1 SMALL TECHNETIUM-99M AND RHENIUM LABELED AGENTS AND METHODS FOR IMAGING TUMORS 审中-公开
标题翻译：小技术-99M和氙标签代理和成像肿瘤的方法
公开(公告)号：US20080226550A1
公开(公告)日：2008-09-18
申请号：US12017328
申请日：2008-01-21
申请人： Ashfaq Mahmood , Matthias Friebe , Cristina Bolzati , Alun G. Jones , Alan Davison
发明人： Ashfaq Mahmood , Matthias Friebe , Cristina Bolzati , Alun G. Jones , Alan Davison
IPC分类号： A61K51/04 , C07F5/00 , C07D211/00 , A61P35/00 , C07D295/00
CPC分类号： C07D295/13 , A61K51/0478 , C07C323/41 , C07F13/005 , C07K5/06026
摘要： The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tumors, e.g., carcinomas, melanomas and other tumors. In another embodiment, the invention relates to methods of imaging tumors using radiolabeled metal complexes. Preferred radiolabeled complexes for imaging tumors include technetium and rhenium complexes. The high tumor uptake and significant tumor/nontumor ratios of the technetium complexes of the invention indicate that such small technetium-99m-based molecular probes can be developed as in-vivo diagnostic agents for melanoma and its metastases. In yet another embodiment, the invention relates to methods of treatment of tumors using a radiolabeled metal complex as a radiopharmaceutical agent to treat the tumor.
摘要翻译：本发明涉及适用于肿瘤例如癌，黑素瘤和其他肿瘤的成像或治疗性治疗的化合物及其相关的锝和铼络合物。在另一个实施方案中，本发明涉及使用放射性标记的金属络合物成像肿瘤的方法。用于成像肿瘤的优选放射性标记复合物包括锝和铼络合物。本发明的锝络合物的高肿瘤摄取和显着的肿瘤/非肿瘤比率表明，这种基于锝-99m的小分子探针可以作为黑色素瘤及其转移的体内诊断剂开发。在另一个实施方案中，本发明涉及使用放射性标记的金属络合物作为放射性药物治疗肿瘤的方法治疗肿瘤。

4. 发明申请

US20060159617A1 Small technetium-99m and rhenium labeled agents and methods for imaging tissues, organs and tumors 审中-公开
标题翻译：小锝-99m和铼标记的试剂和成像组织，器官和肿瘤的方法
公开(公告)号：US20060159617A1
公开(公告)日：2006-07-20
申请号：US10534225
申请日：2003-11-08
申请人： Ashfaq Mahmood , Zhen Cheng , Alun Jones , Alan Davison
发明人： Ashfaq Mahmood , Zhen Cheng , Alun Jones , Alan Davison
IPC分类号： A61K51/00 , C07F13/00 , C07F5/00 , C07D211/26
CPC分类号： C07C323/41 , A61K51/0455 , A61K51/0478 , C07C323/25 , C07D211/14 , C07D211/52 , C07D211/58 , C07F13/005
摘要： The present invention relates to compounds and related technetium and rhenium complexes thereof which are suitable for imaging or therapeutic treatment of tissues, organs, or tumors. In another embodiment, the invention relates the methods of imaging tissues, organs or tumors using radiolabeled metal complexes, particularly tissues, organs, or tumors which express certain receptors to which the compounds or complexes of the invention have an affinity. The present invention also relates to methods of treating cancer, particularly those cancer lines which express certain receptors to which the compounds or complexes of the invention have an affinity. In yet another embodiment, the present invention provides methods of imaging and/or inhibiting receptors or neuroreceptors using compounds or complexes of the invention which have an affinity for the receptor or neuroreceptor to be imaged and/or inhibited.
摘要翻译：本发明涉及适用于组织，器官或肿瘤的成像或治疗性治疗的化合物及其相关锝和铼络合物。在另一个实施方案中，本发明涉及使用放射性标记的金属络合物，特别是表达本发明的化合物或复合物具有亲和力的某些受体的组织，器官或肿瘤来成像组织，器官或肿瘤的方法。本发明还涉及治疗癌症的方法，特别是那些表达本发明化合物或复合物具有亲和力的某些受体的那些癌症系。在另一个实施方案中，本发明提供使用对受体或神经受体成像和/或抑制的亲和力的本发明化合物或复合物成像和/或抑制受体或神经受体的方法。

5. 发明授权

US4707544A Metal-isonitrile adducts for preparing radionuclide complexes for labelling and imaging agents 失效
标题翻译：用于制备用于标记和成像剂的放射性核素复合物的金属 - 异腈加合物
公开(公告)号：US4707544A
公开(公告)日：1987-11-17
申请号：US675540
申请日：1984-11-28
申请人： Alun G. Jones , Alan Davison , Michael J. Abrams
发明人： Alun G. Jones , Alan Davison , Michael J. Abrams
IPC分类号： G01N33/60 , A61K51/04 , C07F3/06 , C07F9/00 , C07F11/00 , C07F13/00 , C07F15/00 , G01N33/58 , A61K43/00 , A61K49/00 , C07C121/20 , C07F1/08
CPC分类号： C07F13/00 , A61K51/0476 , C07F3/06 , A61K2123/00
摘要： A method for preparing a coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta is disclosed. The method comprises preparing a soluble metal adduct of said isonitrile ligand by admixing said ligand with a salt of a displaceable metal having a complete d-electron shell selected from the group consisting of Zn, Ga, Cd, In, Sn, Hg, Tl, Pb and Bi to form a soluble metal-isonitrile salt, and admixing said metal isonitrile salt with a salt comprising said radioactive metal in a suitable solvent to displace said displaceable metal with the radioactive metal thereby forming said coordination. The complex is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.
摘要翻译：公开了制备诸如Tc，Ru，Co，Pt，Fe，Os，Ir，W，Re，Cr，Mo，Mn，Ni，Rh，Pd，Nb和Ta之类的异腈配体和放射性核素的配位络合物的方法。该方法包括通过将所述配体与可选择的金属的盐混合制备所述异腈配体的可溶性金属加合物，所述可置换金属的盐具有选自Zn，Ga，Cd，In，Sn，Hg，Tl， Pb和Bi以形成可溶性金属 - 异腈盐，并将所述金属异腈盐与包含所述放射性金属的盐在合适的溶剂中混合，以用放射性金属置换所述可置换金属，从而形成所述配位。该复合物可用作标记脂质体或囊泡的诊断剂，以及选择的含有脂质膜的活细胞如血凝块，心肌组织，胆囊组织等。

6. 发明授权

US4746505A Technetium radiodiagnostic fatty acids derived from bisamide bisthiol ligands 失效
标题翻译：来自双酰胺二硫醇配体的锝放射性诊断脂肪酸
公开(公告)号：US4746505A
公开(公告)日：1988-05-24
申请号：US727582
申请日：1985-04-26
申请人： Alun G. Jones , John Lister-James , Alan Davison
发明人： Alun G. Jones , John Lister-James , Alan Davison
IPC分类号： A61K51/00 , A61K51/04 , C07C67/00 , C07C313/00 , C07C323/41 , C07C323/60 , C07C325/00 , C07C327/36 , C07F13/00 , A61K43/00 , A61K49/00 , A61K49/02 , C07C149/23
CPC分类号： C07F13/005 , A61K51/04 , A61K2123/00
摘要： A bisamide-bisthiol ligand containing fatty acid substituted thiol useful for producing Tc-labelled radiodiagnostic imaging agents is described. The ligand forms a complex with the radionuclide .sup.99m Tc suitable for administration as a radiopharmaceutical to obtain images of the heart for diagnosis of myocardial disfunction.
摘要翻译：描述了含有用于制备Tc-标记的放射诊断显像剂的含有脂肪酸取代的硫醇的双酰胺 - 二硫醇配体。配体与放射性核素99mTc形成复合物，适合作为放射性药物的给药，以获得用于心肌功能障碍诊断的心脏图像。

7. 发明授权

US4872561A Carboxy, carboalkoxy and carbamile substituted isonitrile radionuclide complexes 失效
标题翻译：羧基，烷氧羰基和氨基甲酰取代的异腈核苷配合物
公开(公告)号：US4872561A
公开(公告)日：1989-10-10
申请号：US139289
申请日：1987-12-29
申请人： Alun G. Jones , Alan Davison , James Kronauge , Michael J. Abrams
发明人： Alun G. Jones , Alan Davison , James Kronauge , Michael J. Abrams
IPC分类号： A61K51/00 , A61K51/04 , C07F13/00
CPC分类号： C07F13/005 , C07C251/00 , A61K2123/00
摘要： A coordination complex comprising a radionuclide selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt and Re and an isonitrile ligand of the formula:(CNX)R,where X is a lower alkyl group having 1 to 4 carbon atoms, wherein R is selected from the group consisting of COOR.sup.1 and CONR.sup.2 R.sup.3 where R.sup.1 can be H, a pharmaceutically acceptable cation, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms. R.sup.2, and R.sup.3 can be H, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, and R.sup.2 and R.sup.3 can be the same of different is disclosed. Kits that can be used to form these complexes are also disclosed.
摘要翻译：包含选自Tc，Ru，Co，Pt和Re的放射性同位素的放射性核素的配位络合物和式（CNX）R的异腈配体，其中X是具有1至4个碳原子的低级烷基其中R选自COOR1和CONR2R3，其中R1可以是H，药学上可接受的阳离子或具有1至4个碳原子的取代或未取代的烷基。 R2和R3可以是H，或者取代或未取代的具有1至4个碳原子的烷基，R2和R3可以是不同的。还可以公开可用于形成这些络合物的试剂盒。

8. 发明授权

US4452774A Isonitrile radionuclide complexes for labelling and imaging agents 失效
标题翻译：异丙腈放射性核素复合物用于标记和成像剂
公开(公告)号：US4452774A
公开(公告)日：1984-06-05
申请号：US373511
申请日：1982-04-30
申请人： Alun G. Jones , Alan Davison , Michael J. Abrams
发明人： Alun G. Jones , Alan Davison , Michael J. Abrams
IPC分类号： A61K20060101 , A61K51/00 , A61K51/12 , C07C20060101 , C07C291/10 , C07F1/08 , C07F13/00 , C12Q20060101 , G01N20060101 , G01N33/60 , A61K43/00 , A61K49/00 , C07C121/20
CPC分类号： A61K51/1234 , A61K51/025 , C07C251/00 , C07F13/005 , A61K2123/00
摘要： A coordination complex of an isonitrile ligand and radionuclide such as Tc, Ru, Co, Pt, Fe, Os, Ir, W, Re, Cr, Mo, Mn, Ni, Rh, Pd, Nb and Ta, is useful as a diagnostic agent for labelling liposomes or vesicles, and selected living cells containing lipid membranes, such as blood clots, myocardial tissue, gall bladder tissue, etc.
摘要翻译：异氰酸酯配体和放射性核素如Tc，Ru，Co，Pt，Fe，Os，Ir，W，Re，Cr，Mo，Mn，Ni，Rh，Pd，Nb和Ta的配位络合物可用作诊断用于标记脂质体或囊泡的试剂，以及选择的含有脂质膜的活细胞，例如血块，心肌组织，胆囊组织等。

9. 发明授权

US4826961A Method for preparing radiopharmaceutical complexes 失效
标题翻译：放射性药物复合物的制备方法
公开(公告)号：US4826961A
公开(公告)日：1989-05-02
申请号：US6562
申请日：1987-01-22
申请人： Alun G. Jones , Alan Davison , Michael J. Abrams
发明人： Alun G. Jones , Alan Davison , Michael J. Abrams
IPC分类号： A61K51/04 , C07F3/06 , C07F13/00 , A61K49/00
CPC分类号： C07F13/00 , A61K51/0476 , C07F3/06 , A61K2123/00
摘要： A method for preparing radiopharmaceutical complexes that are substantially free of the reaction materials used to produce the radiopharmaceutical complex is disclosed. The method involves admixing in a suitable first solvent in a container a target seeking ligand or salt or metal adduct thereof, a radionuclide label, and a reducing agent for said radionuclide, thereby forming said radiopharmaceutical complex; coating the interior walls of the container with said pharmaceutical complex; discarding the solvent containing by-products and unreacted starting reaction materials; and removing the radiopharmaceutical complex from said walls by dissolving it in a second solvent, thereby obtaining said radiopharmaceutical complex substantially free of by-products and unreacted starting materials.
摘要翻译：公开了一种制备基本上不含用于制备放射性药物复合物的反应材料的放射性药物复合物的方法。该方法包括在合适的第一溶剂中在适当的第一溶剂中混合目的物，寻找配体或其盐或金属加成物，放射性核素标记和用于所述放射性核素的还原剂，从而形成所述放射性药物复合物; 用所述药物复合物涂覆容器的内壁; 丢弃含有副产物和未反应的起始反应物质的溶剂; 并通过将其溶解在第二溶剂中从所述壁中除去放射性药物复合物，从而获得基本上不含副产物和未反应起始物质的所述放射性药物复合物。

10. 发明授权

US4735793A Carboxy, carboalkoxy and carbamile substituted isonitrile radionuclide complexes 失效
标题翻译：羧基，烷氧羰基和氨基甲酰取代的异腈核苷配合物
公开(公告)号：US4735793A
公开(公告)日：1988-04-05
申请号：US771284
申请日：1985-08-30
申请人： Alun G. Jones , Alan Davison , James Kronauge , Michael J. Abrams
发明人： Alun G. Jones , Alan Davison , James Kronauge , Michael J. Abrams
IPC分类号： C07B59/00 , A61K31/28 , A61K31/282 , A61K33/24 , A61K51/00 , A61K51/04 , C07B31/00 , C07C67/00 , C07C325/00 , C07C395/00 , C07F13/00 , C07F15/00 , C07F15/06 , A61K43/00 , A61K49/02 , C07C119/02
CPC分类号： C07F13/005 , A61K51/0476 , C07C251/00 , A61K2123/00
摘要： A coordination complex comprising a radionuclide selected from the class consisting of radioactive isotopes of Tc, Ru, Co, Pt and Re and an isonitrile ligand of the formula:(CNX)R,where X is a lower alkyl group having 1 to 4 carbon atoms, wherein R is selected from the group consisting of COOR.sup.1 and CONR.sup.2 R.sup.3 where R.sup.1 can be H, a pharmaceutically acceptable cation, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, R.sup.2, and R.sup.3 can be H, or a substituted or unsubstituted alkyl group having 1 to 4 carbon atoms, and R.sup.2 and R.sup.3 can be the same or different is disclosed. Kits that can be used to form these complexes are also disclosed.
摘要翻译：包含选自Tc，Ru，Co，Pt和Re的放射性同位素的放射性核素的配位络合物和式（CNX）R的异腈配体，其中X是具有1至4个碳原子的低级烷基其中R选自COOR1和CONR2R3，其中R1可以是H，药学上可接受的阳离子或具有1至4个碳原子的取代或未取代的烷基，R 2和R 3可以是H，或者取代或未取代的具有1至4个碳原子的烷基，R2和R3可以相同或不同。还可以公开可用于形成这些络合物的试剂盒。

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