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1. 发明授权

US07445765B2 Radiopharmaceutical for diagnostic imaging containing a technetium-99m nitride heterocomplex 失效
标题翻译：用于包含锝-99m氮化物异复合物的诊断成像的放射性药物
公开(公告)号：US07445765B2
公开(公告)日：2008-11-04
申请号：US10332707
申请日：2001-07-25
申请人： Adriano Duatti , Cristina Bolzati , Licia Uccelli , Alessandra Boschi , Fiorenzo Refosco , Francesco Tisato
发明人： Adriano Duatti , Cristina Bolzati , Licia Uccelli , Alessandra Boschi , Fiorenzo Refosco , Francesco Tisato
IPC分类号： A61K49/00
CPC分类号： A61K51/02 , A61K51/0476
摘要： A radiopharmaceutical for diagnostic imaging containing as an active ingredient a technetium-99m nitride heterocomplex comprising technetium-99m nitride and two different ligands coordinated therewith, i.e., a bisphosphinoamine compound as a π electron acceptor and a bidentate ligand as a π electron donor and represented by the following formula (I): [99mTc(N)(PNP)(XY)]+ (I)wherein 99mTc(N) is technetium-99m nitride, PNP is a bisphosphinoamine compound and XY is a bidentate ligand, is markedly accumulated in heart and adrenal glands and hence is useful for radiodiagnostic imaging of heart and adrenal glands.
摘要翻译：用于诊断成像的放射性药物，其包含锝-99m氮化物异复合物作为活性成分，其包含锝-99m氮化物和与其配位的两种不同配体，即作为pi电子受体的双膦胺化合物和作为pi电子供体的二齿配体，以下式（I）：其中99m Tc（N（N））其中99m Tc（N）（PNP）（XY））是锝-99m氮化物，PNP是双膦胺化合物，XY是双齿配体，明显地积聚在心脏和肾上腺中，因此可用于心脏和肾上腺的放射诊断成像。

2. 发明申请

US20080267868A1 Radiopharmaceutical for diagnostic imaging containing a technetium-99m nitride heterocomplex 审中-公开
标题翻译：用于包含锝-99m氮化物异复合物的诊断成像的放射性药物
公开(公告)号：US20080267868A1
公开(公告)日：2008-10-30
申请号：US11889127
申请日：2007-08-09
申请人： Adriano Duatti , Cristina Bolzati , Licia Uccelli , Alessandra Boschi , Fiorenzo Refosco , Francesco Tisato
发明人： Adriano Duatti , Cristina Bolzati , Licia Uccelli , Alessandra Boschi , Fiorenzo Refosco , Francesco Tisato
IPC分类号： A61K51/00
CPC分类号： A61K51/02 , A61K51/0476
摘要： A process for diagnostic imaging of heart or adrenal glands of a human being comprises administering to the human being a radiopharmaceutical containing as an active ingredient a technetium-99m nitride heterocomplex comprising technetium-99m nitride and two different ligands coordinated therewith, i.e., a bisphosphinoamine compound and a bidentate ligand and represented by the formula (1): [99mTc(N)(PNP)(XY)]+. In this formula, 99mTc(N) is technetium-99m nitride, PNP is a bisphosphinoamine compound and XY is a bidentate ligand as described in the specification. The compound of the formula is markedly accumulated in heart and adrenal glands and hence is used for radiodiagnostic imaging of heart and adrenal glands.
摘要翻译：用于人的心脏或肾上腺的诊断成像的方法包括向人体施用含有作为活性成分的锝-99m氮化物异复合物的放射性药物，其包含锝-99m的氮化物和与其配位的两种不同的配体，即双膦胺化合物和二齿配体，由式（1）表示：[99m Tc（N）（PNP）（XY）] + SUP。在该式中，99m Tc（N）是锝-99m的氮化物，PNP是双膦胺化合物，并且XY是如说明书中所述的二齿配体。该配方的化合物显着积累在心脏和肾上腺，因此用于心脏和肾上腺的放射诊断成像。

3. 发明授权

US06270745B1 Radioactive transition metal nitride heterocomplex 有权
标题翻译：放射性过渡金属氮化物杂复合物
公开(公告)号：US06270745B1
公开(公告)日：2001-08-07
申请号：US09331237
申请日：1999-06-17
申请人： Adriano Duatti , Cristina Bolzati , Licia Uccelli , Fiorenzo Refosco , Francesco Tisato
发明人： Adriano Duatti , Cristina Bolzati , Licia Uccelli , Fiorenzo Refosco , Francesco Tisato
IPC分类号： A61K5100
CPC分类号： C07F13/005 , A61K51/0476 , A61K51/0478 , C07F9/5004
摘要： The present invention provides a single radioactive transition metal nitride heterocomplex which permits labeling of a physiologically active substance such as a peptide, hormone or the like without impairing the activity of the substance. The radioactive transition metal nitride heterocomplex of the present invention is represented by the following formula (I): (M≡N)XY (I) wherein a radioactive transition metal M is radioactive technetium or radioactive rhenium, N is a nitrogen atom, X is a diphosphine compound or a diarsine compound, and Y is a bindentate ligand having a combination of electron-donating atoms.
摘要翻译：本发明提供了一种单一的放射性过渡金属氮化物异复合体，其允许在不损害物质活性的情况下标记生理活性物质如肽，激素等。本发明的放射性过渡金属氮化物异构复合体由下式（I）表示：其中放射性过渡金属M为放射性锝或放射性铼，N为氮原子，X为二膦化合物或胂系化合物， Y是具有给电子原子的组合的结合配体。

4. 发明授权

US07396523B2 Radioactive transition metal-imido hetero-diphosphine complexes, their preparation and radiopharmaceutical compositions thereof 失效
标题翻译：放射性过渡金属 - 亚氨基杂二膦配合物，它们的制备和放射性药物组合物
公开(公告)号：US07396523B2
公开(公告)日：2008-07-08
申请号：US10533988
申请日：2003-10-31
申请人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
发明人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07F13/005 , A61K51/0489 , C07B2200/05 , C07F9/5004
摘要： The present invention provides radioactive metal heterocomplexes of formula (I): [(Me═N—R)L1L2]+Z (I), wherein Me, R, L1 L2 and Z− have the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium- or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L1, which allows the formation of substitution-inert [(Me═N—R)L1] moieties. Such moieties are fixed in an intermediate [(Me═N—R)Y2L1)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand L2 to give the final [(Me═N—R)L1L2]+Z− heterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the L2 framework or the imido R group.
摘要翻译：本发明提供式（I）的放射性金属异复合物：[（Me-NR）L 1 L 2 + Z（I），其中Me，R，L ^{1 2＆lt; 2＆gt;和Z - - 具有说明书中指出的含义。络合物包括三价放射性金属 - 亚氨基，通常是锝或铼 - 酰亚胺基，其通过存在辅助三齿异二膦配体L 1 1强烈稳定，这允许形成取代 -inert [（Me-NR）L 1]部分。这些部分被固定在含有两个不稳定的，定形的Y（Y）的中间体[（Me-NR）Y 2 L 1 L 1）+ / 配体，其中Y优选为卤化物基团。后者容易被二齿配体L 2替代，得到最终的[（Me-NR）L 1 L 2 L 2 O 2 + - 异复合物。本发明的配合物可用于制备放射性药物：事实上，赋予生物寻靶特性的生物活性片段可以在L 2框架或亚氨基R基团上引入。}

5. 发明授权

US08182789B2 Intermediate compound of technetium nitride complex for radiodiagnostic imaging 失效
标题翻译：用于放射诊断成像的氮化钇络合物的中间体化合物
公开(公告)号：US08182789B2
公开(公告)日：2012-05-22
申请号：US12160920
申请日：2006-01-20
申请人： Francesco Tisato , Fiorenzo Refosco , Cristina Bolzati , Stefania Agostini , Marina Porchia , Mario Cavazza-Ceccato , Shinji Tokunaga
发明人： Francesco Tisato , Fiorenzo Refosco , Cristina Bolzati , Stefania Agostini , Marina Porchia , Mario Cavazza-Ceccato , Shinji Tokunaga
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07F9/5004 , A61K51/0489 , C07F9/4009 , C07F13/005
摘要： A bisphosphonoamine compound represented by the following formula (I): wherein R1, R2, R3, R4 and R5 are independently an alkyl group having 1 to 6 carbon atoms, and n is an integer of 1 to 6, is extremely useful as an intermediate for preparing a technetium nitride complex for radiodiagnostic imaging.
摘要翻译：由下式（I）表示的双膦酰胺化合物：其中R1，R2，R3，R4和R5独立地为具有1至6个碳原子的烷基，n为1至6的整数，作为中间体是非常有用的用于制备用于放射诊断成像的锝氮化物络合物。

6. 发明申请

US20080267869A1 RADIOACTIVE TRANSITION METAL-IMIDO HETERO-DIPHOSPHINE COMPLEXES, THEIR PREPARATION AND RADIOPHARMACEUTICAL COMPOSITIONS THEREOF 失效
标题翻译：放射性转移金属 - 咪唑类异双膦酸酯复合物，其制备及放射性能组合物
公开(公告)号：US20080267869A1
公开(公告)日：2008-10-30
申请号：US12144370
申请日：2008-06-23
申请人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
发明人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
IPC分类号： A61K51/04 , C07F3/00
CPC分类号： C07F13/005 , A61K51/0489 , C07B2200/05 , C07F9/5004
摘要： The present invention provides radioactive metal heterocomplexes of formula (I): [(Me=N—R)L1L2]+Z− (I), wherein Me, R, L1 L2 and Z− have the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium- or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L1, which allows the formation of substitution-inert [(Me=N—R)L1] moieties. Such moieties are fixed in an intermediate [(Me=N—R)Y2L1)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand L2 to give the final [(Me=N—R)L1L2]+ Z−heterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the L2 framework or the imido R group.
摘要翻译：本发明提供了式（I）的放射性金属异复合物：[（Me = NR）L 1 L 2] + Z - （I ），其中Me，R，L 1，L 2，Z 2和Z 2具有说明书中指出的含义。络合物包括三价放射性金属 - 亚氨基，通常是锝或铼 - 酰亚胺基，其通过存在辅助三齿异二膦配体L 1 1强烈稳定，这允许形成取代 -inert [（Me = NR）L 1]部分。这些部分固定在含有两个不稳定的，定形的Y（Y）的中间体[（Me = NR）Y 2 L 1 L 1 - 配体，其中Y优选为卤化物基团。后者容易被二齿配体L 2替代，得到最终的[（Me = NR）L 1 L 2 L 2 + - 异复合物。本发明的配合物可用于制备放射性药物：事实上，赋予生物寻靶特性的生物活性片段可以在L 2框架或亚氨基R基团上引入。

7. 发明授权

US07771704B2 Radioactive transition metal-imido hetero-diphosphine complexes, their preparation and radiopharmaceutical compositions thereof 失效
标题翻译：放射性过渡金属 - 亚氨基杂二膦配合物，它们的制备和放射性药物组合物
公开(公告)号：US07771704B2
公开(公告)日：2010-08-10
申请号：US12144370
申请日：2008-06-23
申请人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
发明人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
IPC分类号： A61K51/00 , A61M36/14
CPC分类号： C07F13/005 , A61K51/0489 , C07B2200/05 , C07F9/5004
摘要： The present invention provides radioactive metal heterocomplexes of formula (I): [(Me=N—R)L1L2]+Z− wherein Me, R, L1L2 and Z− have the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium-or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L1, which allows the formation of substitution-inert [(Me=N—R)L1] moieties. Such moieties are fixed in an intermediate [(Me=N—R)Y2L1)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand L2 to give the final [(Me=N—R)L1L2]+ Z−heterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the L2 framework or the imido R group.
摘要翻译：本发明提供式（I）的放射性金属异复合物：[（Me = N-R）L1L2] + Z-其中Me，R，L1L2和Z-具有说明书中所示的含义。络合物包括三价放射性金属 - 亚氨基，通常是锝或铼 - 亚胺基，其通过存在辅助三齿异二膦配体L1而稳定，其允许形成取代惰性的[（Me = N- R）L1]部分。这些部分固定在含有两个不稳定的，定位的Y配体的中间体[（Me = N-R）Y2L1）] +化合物中，其中Y优选为卤素基团。后者容易被二齿配体L2替代，得到最终的[（Me = N-R）L1L2] + Z-异构复合物。本发明的复合物可用于制备放射性药物：事实上，赋予生物靶标特性的生物活性片段可以引入到L2骨架或亚胺基R基团上。

8. 发明申请

US20100160615A1 INTERMEDIATE COMPOUND OF TECHNETIUM NITRIDE COMPLEX FOR RADIODIAGNOSTIC IMAGING 失效
标题翻译：放射线成像技术硝酸复合物的中间化合物
公开(公告)号：US20100160615A1
公开(公告)日：2010-06-24
申请号：US12160920
申请日：2006-01-20
申请人： Francesco Tisato , Fiorenzo Refosco , Cristina Bolzati , Stefania Agostini , Marina Porchia , Mario Cavazza-Ceccato , Shinji Tokunaga
发明人： Francesco Tisato , Fiorenzo Refosco , Cristina Bolzati , Stefania Agostini , Marina Porchia , Mario Cavazza-Ceccato , Shinji Tokunaga
IPC分类号： C07F13/00 , C07F9/28
CPC分类号： C07F9/5004 , A61K51/0489 , C07F9/4009 , C07F13/005
摘要： A bisphosphonoaminc compound represented by the following formula (I): wherein R1, R2, R3, R4 and R5 are independently an alkyl group having 1 to 6 carbon atoms, and n is an integer of 1 to 6, is extremely useful as an intermediate for preparing a technetium nitride complex for radiodiagnostic imaging.
摘要翻译：由下式（I）表示的双膦酰氨基化合物：其中R1，R2，R3，R4和R5独立地是具有1至6个碳原子的烷基，n是1至6的整数，作为中间体是非常有用的用于制备用于放射诊断成像的锝氮化物络合物。

9. 发明申请

US20060120957A1 Radioactive transition metal-imido hetero-diphosphine complexes, their preparation and radiopharmaceutical compositions thereof 失效
标题翻译：放射性过渡金属 - 亚氨基杂二膦配合物，它们的制备和放射性药物组合物
公开(公告)号：US20060120957A1
公开(公告)日：2006-06-08
申请号：US10533988
申请日：2003-10-31
申请人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
发明人： Francesco Tisato , Cristina Bolzati , Marina Porchia , Fiorenzo Refosco
IPC分类号： A61K51/00 , C07F5/00
CPC分类号： C07F13/005 , A61K51/0489 , C07B2200/05 , C07F9/5004
摘要： The present invention provides radioactive metal heterocomplexes of formula (I): [(Me═N—R)L1L2]+Z. (I), wherein Me, R, L1 L2 and Z− have the meanings indicated in the description. The complexes include a trivalent radioactive metal-imido group, typically a technetium- or rhenium-imido group, strongly stabilized by the presence of an ancillary tridentate hetero-diphosphine ligand L1, which allows the formation of substitution-inert [(Me═N—R)L1] moieties. Such moieties are fixed in an intermediate [(Me═N—R)Y2L1)]+ compound which contains two labile, cispositioned, Y ligands, where Y is preferably an halide group. The latter are easily replaced by a bidentate ligand L2 to give the final [(Me═N—R)L1L2]+Z−heterocomplexes. The complexes of the invention are useful for the preparation of radiopharmaceuticals: in fact, a bioactive fragment which confers biological target-seeking properties can be introduced either on the L2 framework or the imido R group.
摘要翻译：本发明提供式（I）的放射性金属异复合物：[（Me-N-R）L 1 L 2 + Z。（I），其中Me，R，L 1，L 2和Z 2具有说明书中指出的含义。络合物包括三价放射性金属 - 亚氨基，通常是锝或铼 - 酰亚胺基，其通过存在辅助三齿异二膦配体L 1 1强烈稳定，这允许形成取代 -inert [（Me-NR）L 1]部分。这些部分被固定在含有两个不稳定的，定形的Y（Y）的中间体[（Me-NR）Y 2 L 1 L 1）+ / 配体，其中Y优选为卤化物基团。后者容易被二齿配体L 2替代，得到最终的[（Me-NR）L 1 L 2 L 2 O 2 + - 异复合物。本发明的配合物可用于制备放射性药物：事实上，赋予生物寻靶特性的生物活性片段可以在L 2框架或亚氨基R基团上引入。

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