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1. 发明申请

WO2007090022A2 NOVEL COMPOUNDS FOR TARGETING ENDOTHELIAL CELLS, COMPOSITIONS CONTAINING THE SAME AND METHODS FOR THEIR USE 审中-公开
标题翻译：用于靶向内皮细胞的新化合物，包含其的组合物及其使用方法
公开(公告)号：WO2007090022A2
公开(公告)日：2007-08-09
申请号：PCT/US2007/061019
申请日：2007-01-25
申请人： BRACCO INTERNATIONAL B.V. , VON WRONSKI, Mathew, A. , MARINELLI, Edmund, R. , NUNN, Adrian, D. , PILLAI, Radhakrishna , RAMALINGAM, Kondareddiar , TWEEDLE, Michael, F. , LINDER, Karen, E. , NANJAPPAN, Palaniappa , RAJU, Natarajan
发明人： VON WRONSKI, Mathew, A. , MARINELLI, Edmund, R. , NUNN, Adrian, D. , PILLAI, Radhakrishna , RAMALINGAM, Kondareddiar , TWEEDLE, Michael, F. , LINDER, Karen, E. , NANJAPPAN, Palaniappa , RAJU, Natarajan
IPC分类号： C07K7/08 , A61K49/14
CPC分类号： A61K49/0067 , A61K38/00 , A61K47/6923 , A61K47/6929 , A61K49/0056 , A61K49/14 , A61K49/223 , A61K51/088 , B82Y5/00 , B82Y10/00 , B82Y30/00 , C07K7/06
摘要： The present invention provides compounds for targeting endothelial cells, tumor cells or other cells that express the NP-I receptor, compositions containing the same and methods for their use. Additionally, the present invention includes diagnostic, therapeutic and radiotherapeutic compositions useful for visualization, therapy or radiotherapy.
摘要翻译：本发明提供用于靶向表达NP-1受体的内皮细胞，肿瘤细胞或其他细胞的化合物，其含有该组合物的组合物及其使用方法。另外，本发明包括可用于可视化，治疗或放射治疗的诊断，治疗和放射治疗组合物。

2. 发明申请

WO2006096207A2 METHODS FOR PREPARING MULTIVALENT CONSTRUCTS FOR THERAPEUTIC AND DIAGNOSTIC APPLICATIONS 审中-公开
标题翻译：制备治疗和诊断应用的多种结构的方法
公开(公告)号：WO2006096207A2
公开(公告)日：2006-09-14
申请号：PCT/US2005/028127
申请日：2005-08-09
申请人： BRACCO INTERNATIONAL B.V. , FAN, Hong , MARINELLI, Edmund , NANJAPPAN, Palaniappa , PILLAI, Radhakrishna , SWENSON, Rolf, e.
发明人： FAN, Hong , MARINELLI, Edmund , NANJAPPAN, Palaniappa , PILLAI, Radhakrishna , SWENSON, Rolf, e.
IPC分类号： A61K51/00 , A61K49/00
CPC分类号： A61K51/088 , A61K47/60 , A61K47/64 , A61K49/0043 , A61K49/0056 , A61K49/223 , B82Y5/00 , C07K7/08 , C07K7/64
摘要： Methods for the preparation of multivalent constructs for therapeutic and diagnostic applications are provided. More specifically, novel methods for preparing multivalent constructs comprising the formula A-B-C-D-E-B’F for therapeutic and diagnostic applications are provided which use a novel linker D comprising, in various embodiments, a dicarboxylic acid derivative such as e.g ., a glutaric acid bis N-hydroxysuccinimidyl ester or a derivative thereof; or a diamine derivative. The remaining components in the multivalent construct A-B-C-D-E-B’F are defined as follows; A is a peptide, B is a first branching group, C is an optional first spacer, E is an optional second spacer which may be the same as or different from said first spacer C, B’ is an optional second branching group which may be the same as or different from said first branching group B, and F is a second peptide which may be the same as or different from said first peptide A.
摘要翻译：提供了用于治疗和诊断应用的多价构建体的制备方法。更具体地，提供了用于制备包含用于治疗和诊断应用的式ABCDE-B'F的多价构建体的新方法，其使用新的接头D，其在各种实施方案中包括二羧酸衍生物，例如戊二酸双-N- 羟基琥珀酰亚胺酯或其衍生物; 或二胺衍生物。多价构建体A-B-C-D-E-B'F中的其余组分定义如下： A是肽，B是第一支化基团，C是任选的第一间隔基，E是可选的第二间隔基，其可以与所述第一间隔物C相同或不同，B'是任选的第二支化基团，其可以是与所述第一支化基团B相同或不同，F是可以与所述第一肽A相同或不同的第二肽。

3. 发明申请

WO1998028259A1 A PROCESS FOR THE PREPARATION OF AN INTERMEDIATE USEFUL IN THE SYNTHESIS OF IODINATED CONTRAST MEDIA 审中-公开
标题翻译：制备适用于碘化对比介质合成的中间体的方法
公开(公告)号：WO1998028259A1
公开(公告)日：1998-07-02
申请号：PCT/EP1997007026
申请日：1997-12-15
申请人： BRACCO INTERNATIONAL B.V. , VILLA, Marco , PAIOCCHI, Maurizio
发明人： BRACCO INTERNATIONAL B.V.
IPC分类号： C07C231/02
CPC分类号： C07C231/02
摘要： A process for the preparation of the compound L-5-(2-acetoxypropionylamino)-2,4,6-triiodoisophthaloyl dichloride by reacting 5-amino-2,4,6-triiodoisophthaloyl dichloride with L-2-acetoxyproprionyl chloride in N,N-dimethylacetamide as a solvent, characterized in that a catalytic amount of water is added to the reaction mixture.
摘要翻译：通过使5-氨基-2,4,6-三碘间苯二酰氯与L-2-乙酰氧基丙酰氯在N中反应制备化合物L-5-（2-乙酰氧基丙酰基氨基）-2,4,6-三碘间苯二酰氯的方法， N-二甲基乙酰胺作为溶剂，其特征在于向反应混合物中加入催化量的水。

4. 发明申请

WO1995027705A1 AROMATIC AMIDE COMPOUNDS AND METAL CHELATES THEREOF 审中-公开
标题翻译：芳香族化合物及其金属螯合物
公开(公告)号：WO1995027705A1
公开(公告)日：1995-10-19
申请号：PCT/IB1995000238
申请日：1995-04-06
申请人： BRACCO INTERNATIONAL B.V.
发明人： BRACCO INTERNATIONAL B.V. , RANGANATHAN, Ramachadran, S. , MARINELLI, Edmund, R. , PILLAI, Radhakrishna , TWEEDLE, Michael, F.
IPC分类号： C07D257/02
CPC分类号： A61K49/122 , A61K49/085 , A61K49/106 , C07D257/02 , Y10S436/806 , Y10S514/836 , Y10T436/24
摘要： Novel aromatic amide compounds comprising a ligand nucleus containing at least one aminocarboxylate, aminophosphonate and/or aminohydroxamate chelating group, substituted with a substituted aromatic amide group of the formula (1), wherein R is (a), (b) or -[(CH2)2-Y]-R13, salts and/or multimers thereof, and metal chelates, particularly useful for MRI of the hepatobiliary system.
摘要翻译：新颖的芳族酰胺化合物，其包含由至少一个氨基羧酸盐，氨基膦酸盐和/或氨基羟肟酸盐螯合基团的配体核团，其被式（1）的取代芳族酰胺基团取代，其中R是（a），（b）或 - [ CH2）2-Y] -R13，其盐和/或多聚体，以及金属螯合物，特别适用于肝胆系统的MRI。

5. 发明申请

WO1995016469A1 MULTILAYER LYOPHILE FOR PREPARING RADIOPHARMACEUTICALS 审中-公开
标题翻译：用于制备放射线显微镜的多层LYOPHILE
公开(公告)号：WO1995016469A1
公开(公告)日：1995-06-22
申请号：PCT/IB1994000390
申请日：1994-12-05
申请人： BRACCO INTERNATIONAL B.V.
发明人： BRACCO INTERNATIONAL B.V. , NOWOTNIK, David, P.
IPC分类号： A61K51/12
CPC分类号： A61K51/0497 , A61K51/1258
摘要： The present invention is directed to a stable multilayer lyophile having a radioligand in a first layer and at least one other layer having at least one component which is chemically incompatible with the radioligand in the first layer. The invention also comprises an optional interface layer. The multilayer lyophile provides a number of advantages. First, it allows incompatible ingredients to be contained in separate layers in a single vial. Secondly, it is easier to use because less manipulation is required as compared to a multicontainer kit. Thirdly, less raw materials are required for manufacture because only one package, one label, etc., is needed. Finally, there is increased manufacturing efficiency because only one freeze drying run is needed to prepare the product.
摘要翻译：本发明涉及在第一层中具有放射性配体的稳定的多层冻干制品和至少一种具有至少一种在第一层中与放射性配体化学不相容的组分的其它层。本发明还包括可选接口层。多层冻干提供了许多优点。首先，它允许不相容的成分包含在单个小瓶中的单独层中。其次，使用更容易，因为与多容器套件相比，需要较少的操作。第三，制造需要较少的原材料，因为只需要一个包装，一个标签等。最后，提高制造效率，因为只需要一次冷冻干燥来制备产品。

6. 发明申请

WO2009076388A3 TARGETING VECTOR-PHOSPHOLIPID CONJUGATES 审中-公开
公开(公告)号：WO2009076388A3
公开(公告)日：2009-06-18
申请号：PCT/US2008/086136
申请日：2008-12-10
申请人： BRACCO INTERNATIONAL B.V. , BUSSAT, Philippe , CHERKAOUI, Samir , FAN, Hong (Helen) , LAMY, Bernard , NANJAPPAN, Palaniappa , PILLAI, Radhakrishna, K. , POCHON, Sibylle , SONG, Bo , SWENSON, Rolf, E.
发明人： BUSSAT, Philippe , CHERKAOUI, Samir , FAN, Hong (Helen) , LAMY, Bernard , NANJAPPAN, Palaniappa , PILLAI, Radhakrishna, K. , POCHON, Sibylle , SONG, Bo , SWENSON, Rolf, E.
IPC分类号： A61K49/22 , A61B8/00 , C07K14/00
摘要： Peptide vectors having high KDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.

7. 发明申请

WO2007067979A2 TARGETING VECTOR-PHOSPHOLIPID CONJUGATES 审中-公开
标题翻译：靶向载体 - 磷脂结合体
公开(公告)号：WO2007067979A2
公开(公告)日：2007-06-14
申请号：PCT/US2006/061793
申请日：2006-12-08
申请人： BRACCO INTERNATIONAL B.V. , BUSSAT, Philippe , CHERKAOUI, Samir , FAN, Hong (Helen) , LAMY, Bernard , NANJAPPAN, Palaniappa , PILLAI, Radhakrishna, K. , POCHON, Sibylle , SONG, Bo , SWENSON, Rolf, E.
发明人： BUSSAT, Philippe , CHERKAOUI, Samir , FAN, Hong (Helen) , LAMY, Bernard , NANJAPPAN, Palaniappa , PILLAI, Radhakrishna, K. , POCHON, Sibylle , SONG, Bo , SWENSON, Rolf, E.
IPC分类号： A61K38/10 , C07K7/08
CPC分类号： C07K14/00 , A61K47/544 , A61K49/223 , Y02A50/58
摘要： Peptide vectors having high KLDR binding affinity and processes for making such vectors are provided. The peptide vectors may be conjugated to phospholipids and included in ultrasound contrast agent compositions. Such ultrasound contrast agents are particularly useful in therapeutic and diagnostic methods, such as in imaging KDR-containing tissue and in the evaluation and treatment of angiogenic processes associated with neoplastic conditions. The present invention also provides processes for the large scale production of highly pure dimeric and monomeric peptide phospholipid conjugates as well as precursor materials used to form the conjugates. The present invention further provides processes for the large scale production of highly pure peptide phospholipid conjugates which contain very low levels of TFA.
摘要翻译：提供了具有高KLDR结合亲和力的肽载体和用于制备此类载体的方法。肽载体可以与磷脂结合并包含在超声造影剂组合物中。这样的超声造影剂在治疗和诊断方法中是特别有用的，例如在成像含KDR组织和评估和治疗与肿瘤病症相关的血管生成过程中。本发明还提供大规模生产高纯度二聚体和单体肽磷脂共轭物以及用于形成缀合物的前体材料的方法。本发明还提供了大规模生产含有非常低水平的TFA的高纯度肽磷脂缀合物的方法。

8. 发明申请

WO2002062810A2 LINKABLE SIALYL LEWIS X ANALOGS 审中-公开
标题翻译：可连接的SIALYL LEWIS X模拟
公开(公告)号：WO2002062810A2
公开(公告)日：2002-08-15
申请号：PCT/US2001/044590
申请日：2001-11-29
申请人： BRACCO INTERNATIONAL B.V. , RANGANATHAN, Ramachandra , RAMALINGAM, Kondareddiar , PILLAI, Radhakrishna , MARINELLI, Edmund, R. , SWENSON, Rolf
发明人： RANGANATHAN, Ramachandra , RAMALINGAM, Kondareddiar , PILLAI, Radhakrishna , MARINELLI, Edmund, R. , SWENSON, Rolf
IPC分类号： C07H
CPC分类号： C07H15/04 , A61K49/0002 , C07H7/02 , C07H15/00
摘要： Disclosed herein is a class of linkable tetrasaccharide compounds that includes the amino phenyl glycoside of sialyl Lewis X (SLe X ) and related analogs. These compounds have conjugatable nucleophilic groups, making them useful in preparing multimeric SLe X compositions. In particular, the disclosed SLe X compounds can be used to prepare selectin binding ligand conjugates by linking them to a reporter moiety, such as a contrast agent, a radiodiagnostic agent, or a cytotoxic or chemotherapeutic agent. The SLe X compounds and conjugates of the invention exhibit binding to selectin that is similar to native Sialyl Le X , and are, therefore, useful for diagnosing and treating selectin-mediated disorders and related conditions.
摘要翻译：本文公开了一类可连接的四糖化合物，其包括唾液酸路易斯X（SLe X）的氨基苯基糖苷和相关类似物。这些化合物具有可共轭的亲核基团，使得它们可用于制备多聚体SLe X组合物。特别地，所公开的SLe x化合物可用于通过将选择素结合配体缀合物与报告基因部分如造影剂，放射性诊断剂或细胞毒性或化学治疗剂连接而制备。本发明的SLe X化合物和缀合物显示出与天然唾液酸基Le X类似的选择蛋白结合，因此可用于诊断和治疗选择素介导的病症和相关病症。

9. 发明申请

WO1998034908A1 PROCESS FOR THE CRYSTALLIZATION FROM A LINEAR OR BRANCHED (C5-C6) ALCOHOL OR THEIR MIXTURES OF (S)-N,N'-bis[2-HYDROXY-1- (HYDROXYMETHYL)ETHYL]-5-[ (2-HYDROXY-1-OXOPROPYl)AMINO]-2,4,6- TRIIODO-1,3-BENZENDICARBOXAMIDE 审中-公开
标题翻译：由（S）-N，N'-双[2-羟基-1-（羟基甲基）乙基] -5 - [（2-羟基-2-甲氧基乙基）乙基）乙基]酯的（C5-C6）醇或其混合物的结晶的方法， 1-氧代壬基）氨基] -2,4,6-三硫代-1,3-苯二甲酰胺
公开(公告)号：WO1998034908A1
公开(公告)日：1998-08-13
申请号：PCT/IB1997000106
申请日：1997-02-11
申请人： BRACCO INTERNATIONAL B.V. , DESANTIS, Nicola
发明人： BRACCO INTERNATIONAL B.V.
IPC分类号： C07C231/22
CPC分类号： C07C231/22 , C07C237/46
摘要： Disclosed is a new process for the crystallisation of (S)-N,N'-bis[2-hydroxy-1- (hydroxymethyl)ethyl]-5-[ (2-hydroxy-1-oxopropyl)amino] -2,4,6-triiodo-1,3-benzendicarboxamide (I), using a linear or branched (C5-C6) alcohol or their mixtures.
摘要翻译：公开了（S）-N，N'-双[2-羟基-1-（羟甲基）乙基] -5 - [（2-羟基-1-氧代丙基）氨基] -2,4 ，6-三碘-1,3-苯二甲酰胺（I），使用直链或支链（C5-C6）醇或它们的混合物。

10. 发明申请

WO1997014443A1 MAGNETICALLY LABELED CHEMOATTRACTANTS AS TARGETED CONTRAST AGENTS IN THE NMR IMAGING OF LIVING TISSUES 审中-公开
标题翻译：作为生物组织核磁共振成像中靶向对比剂的磁性标记化学试剂
公开(公告)号：WO1997014443A1
公开(公告)日：1997-04-24
申请号：PCT/IB1996001103
申请日：1996-10-18
申请人： BRACCO INTERNATIONAL B.V.
发明人： BRACCO INTERNATIONAL B.V. , TWEEDLE, Michael, F. , KUMAR, Krishan , EATON, Stephen
IPC分类号： A61K49/00
CPC分类号： A61K49/14 , A61K49/085 , A61K49/1839 , A61K49/1866 , A61K49/1896 , A61K51/088
摘要： The present invention addresses magnetically labeled chemoattractants, e.g. chemotactic peptides, for the detection and investigation of diseased or disordered tissue sites or organs in the body of human and animal patients. The chemotactic peptides have the general formula: N(X)-Y-Leu-Phe-Z-A-W wherein (X) is H or a protective group such as formyl, acetyl, t-Boc, or the like; Y is Nle or Met; Z is a chemical bond, an aminoacid or an oligopeptide, e.g. (N( gamma ))Lys, Ile, Asp, Nle-Tyr-Lys, or (Gly)n, n being 1 to 4; A is a linker; and W is a suitably derivatized paramagnetic macrocyclic chelate or magnetic particle. The invention also concerns physiologically acceptable administrable compositions or formulations comprising the labeled chemoattractants, methods for preparing the chemoattractants and the formulations, and methods of using the formulations for detecting, localizing and diagnosing infected or inflammatory sites, or other trauma in the organism.
摘要翻译：本发明涉及磁性标记的化学引诱物，例如趋化肽，用于检测和调查人和动物患者体内的病变或无序组织部位或器官。趋化肽具有以下通式：N（X）-Y-Leu-Phe-Z-A-W其中（X）为H或保护基如甲酰基，乙酰基，t-Boc等; Y是Nle或Met; Z是化学键，氨基酸或寡肽，例如。（N（γ））Lys，Ile，Asp，Nle-Tyr-Lys或（Gly）n，n为1至4; A是一个连接符; W是适当衍生的顺磁性大环螯合物或磁性颗粒。本发明还涉及生理上可接受的可施用的组合物或包含标记的化学引诱物的制剂，用于制备化学引诱物和制剂的方法，以及使用该制剂用于检测，定位和诊断感染或炎症部位或生物体中的其他创伤的方法。

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