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1. 发明申请

US20140024717A1 Process For The Preparation Of A Sulfated Derivative Of 3,5-Diiodo-O-[3-Iodophenyl]-L-Tyrosine 有权
标题翻译： 3,5-二碘-O- [3-碘苯基] -L-酪氨酸的硫酸化衍生物的制备方法
公开(公告)号：US20140024717A1
公开(公告)日：2014-01-23
申请号：US14110237
申请日：2012-04-05
申请人： Pier Lucio Anelli , Maria Argese , Luciano Lattuada , Federico Maisano , Sonia Gazzetto , Laura Galimberti , Valeria Boi , Giovanni Rivolta , Livio Cavalieri , Fulvia Vella
发明人： Pier Lucio Anelli , Maria Argese , Luciano Lattuada , Federico Maisano , Sonia Gazzetto , Laura Galimberti , Valeria Boi , Giovanni Rivolta , Livio Cavalieri , Fulvia Vella
IPC分类号： A61K31/198 , C07D495/04 , C07F1/04
CPC分类号： C07C303/24 , A61K9/2054 , A61K31/198 , C07C227/16 , C07D495/04 , C07F1/04 , C07C305/24 , C07C229/36
摘要： The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L-tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chloro-sulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.
摘要翻译：本发明涉及通过从相应的方法开始制备3,5-二碘-O- [3-碘-4-（磺酰氧基）苯基] -L-酪氨酸衍生物（T3S）的单钠盐的方法酚类化合物，在氯磺酸和二甲基乙酰胺作为溶剂的存在下。如此获得的T3S化合物可以方便地以纯的形式以良好的产率分离为固体。本发明还涉及T3S制备方法，其中起始试剂是T2，并且还包含片剂中这种化合物的制剂。此外，本发明公开了基于T3S衍生物的非放射性免疫测定法。

2. 发明授权

US09890116B2 Process for the preparation of a sulfated derivative of 3,5-diiodo-O-[3-iodophenyl]-L-tyrosine 有权
公开(公告)号：US09890116B2
公开(公告)日：2018-02-13
申请号：US14110237
申请日：2012-04-05
申请人： Pier Lucio Anelli , Maria Argese , Luciano Lattuada , Sonia Gazzetto , Laura Galimberti , Valeria Boi , Livio Cavalieri , Fulvia Vella
发明人： Pier Lucio Anelli , Maria Argese , Luciano Lattuada , Sonia Gazzetto , Laura Galimberti , Valeria Boi , Livio Cavalieri , Fulvia Vella
IPC分类号： C07C303/24 , A61K9/20 , A61K31/198 , C07D495/04 , C07C227/16 , C07F1/04
CPC分类号： C07C303/24 , A61K9/2054 , A61K31/198 , C07C227/16 , C07D495/04 , C07F1/04 , C07C305/24 , C07C229/36
摘要： The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L-tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chloro-sulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.

3. 发明授权

US06652834B2 Amphipatic polycarboxylic chelates and complexes with paramagnetic metals as MRI contrast agents 失效
公开(公告)号：US06652834B2
公开(公告)日：2003-11-25
申请号：US10014358
申请日：2001-12-14
申请人： Pier Lucio Anelli , Luciano Lattuada , Fulvio Uggeri , Giovanna Lux , Michele Serleti , Milena Gabellini , Hervé Tournier
发明人： Pier Lucio Anelli , Luciano Lattuada , Fulvio Uggeri , Giovanna Lux , Michele Serleti , Milena Gabellini , Hervé Tournier
IPC分类号： C07C23307
CPC分类号： C07J41/0055 , A61K49/06 , A61K49/1812 , C07C229/16 , C07C229/76 , C07C233/47 , C07C237/08 , C07C237/10 , C07C237/12 , C07F9/091 , Y10S977/896 , Y10S977/927 , Y10S977/93
摘要： Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI) The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.

4. 发明申请

US20110275850A1 Process For The Preparation Of Triiodinated Carboxylic Aromatic Derivatives 有权
标题翻译：三碘化羧基芳族衍生物的制备方法
公开(公告)号：US20110275850A1
公开(公告)日：2011-11-10
申请号：US13143225
申请日：2010-03-12
申请人： Pier Lucio Anelli , Marino Brocchetta , Roberta Fretta , Luciano Lattuada , Armando Mortillaro
发明人： Pier Lucio Anelli , Marino Brocchetta , Roberta Fretta , Luciano Lattuada , Armando Mortillaro
IPC分类号： C07C231/10 , C07C231/02
CPC分类号： C07C237/46 , C07C231/02 , C07C231/10 , C07C235/16
摘要： The present invention relates to a process for the preparation of given carboxamido compounds, in particular of 2,4,6-triiodoisophthalic acid derivatives, as useful intermediates for the preparation of X-ray contrast media among which is iopamidol. The said process comprises reacting suitable N-sulfinyl intermediate compounds with a commercially available α-hydroxyacid or a salt thereof.
摘要翻译：本发明涉及制备给定的甲酰氨基化合物，特别是2,4,6-三碘代邻苯二甲酸衍生物的方法，作为制备X射线造影剂的有用中间体，其中碘帕醇。所述方法包括使合适的N-亚磺酰基中间体化合物与市售的α-羟基酸或其盐反应。

5. 发明授权

US06342598B1 Amphipatic polycarboxylic chelates and complexes with paramagnetic metals as MRI contrast agents 有权
标题翻译：两性多羧酸螯合物和与顺磁金属的复合物作为MRI造影剂
公开(公告)号：US06342598B1
公开(公告)日：2002-01-29
申请号：US09448289
申请日：1999-11-24
申请人： Pier Lucio Anelli , Luciano Lattuada , Fulvio Uggeri , Giovanna Lux , Michele Serleti , Milena Gabellini , Hervé Tournier
发明人： Pier Lucio Anelli , Luciano Lattuada , Fulvio Uggeri , Giovanna Lux , Michele Serleti , Milena Gabellini , Hervé Tournier
IPC分类号： C07D25702
CPC分类号： C07J41/0055 , A61K49/06 , A61K49/1812 , C07C229/16 , C07C229/76 , C07C233/47 , C07C237/08 , C07C237/10 , C07C237/12 , C07F9/091 , Y10S977/896 , Y10S977/927 , Y10S977/93
摘要： Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI). The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.
摘要翻译：取代的多羧酸配体分子和所述配体的相应金属配合物，优选顺磁性金属配合物，用于在磁共振成像（MRI）领域中产生应答。多羧酸配体的顺磁配合物具有有利的张力活性，并且可用作用于调查血液池的制剂中的MRI造影剂。

6. 发明授权

US09096495B2 Process for the preparation of triiodinated carboxylic aromatic derivatives 有权
标题翻译：三碘化羧酸衍生物的制备方法
公开(公告)号：US09096495B2
公开(公告)日：2015-08-04
申请号：US13143225
申请日：2010-03-12
申请人： Pier Lucio Anelli , Marino Brocchetta , Roberta Fretta , Luciano Lattuada , Armando Mortillaro
发明人： Pier Lucio Anelli , Marino Brocchetta , Roberta Fretta , Luciano Lattuada , Armando Mortillaro
IPC分类号： C07C233/06 , C07C237/46 , C07C231/02 , C07C231/10
CPC分类号： C07C237/46 , C07C231/02 , C07C231/10 , C07C235/16
摘要： The present invention relates to a process for the preparation of given carboxamido compounds, in particular of 2,4,6-triiodoisophthalic acid derivatives, as useful intermediates for the preparation of X-ray contrast media among which is iopamidol. The said process comprises reacting suitable N-sulfinyl intermediate compounds with a commercially available α-hydroxyacid or a salt thereof.
摘要翻译：本发明涉及制备给定的甲酰氨基化合物，特别是2,4,6-三碘代邻苯二甲酸衍生物的方法，作为制备X射线造影剂的有用中间体，其中碘帕醇。所述方法包括使合适的N-亚磺酰基中间体化合物与市售的α-羟基酸或其盐反应。

7. 发明授权

US06461588B1 Use of bile acid conjugates, derivatives thereof with metal complexes as blood pool agents for nuclear magnetic resonance diagnostics 有权
标题翻译：使用胆汁酸共轭物，其衍生物与金属络合物作为核磁共振诊断的血液池剂
公开(公告)号：US06461588B1
公开(公告)日：2002-10-08
申请号：US09318618
申请日：1999-05-26
申请人： Pier Lucio Anelli , Marino Brocchetta , Christoph De Haen , Ornella Gazzotti , Luciano Lattuada , Giovanna Lux , Giuseppe Manfredi , Pierfrancesco Morosini , Daniela Palano , Michele Serleti , Fulvio Uggeri , Massimo Visigalli
发明人： Pier Lucio Anelli , Marino Brocchetta , Christoph De Haen , Ornella Gazzotti , Luciano Lattuada , Giovanna Lux , Giuseppe Manfredi , Pierfrancesco Morosini , Daniela Palano , Michele Serleti , Fulvio Uggeri , Massimo Visigalli
IPC分类号： A61B5055
CPC分类号： A61K49/10 , A61K49/085 , Y10S977/928 , Y10S977/929 , Y10S977/93
摘要： Blood pool imaging contrast agents containing paramagnetic bi- and tri-valent metal ion chelates of bile acid conjugates with molecules having chelating activity are used in magnetic resonance imaging of the vascular system and particularly the coronaries.
摘要翻译：血液成像造影剂含有胆酸偶联物与具有螯合活性的分子的顺磁性二价和三价金属离子螯合物用于血管系统特别是冠状动脉的磁共振成像。

8. 发明授权

US5649537A Paramagnetic metal icon chelates and use thereof as contrast agents in magnetic resonance imaging 失效
标题翻译：顺磁性金属图标螯合物及其在磁共振成像中作为造影剂的用途
公开(公告)号：US5649537A
公开(公告)日：1997-07-22
申请号：US443342
申请日：1995-05-17
申请人： Pier Lucio Anelli , Christoph De Haen , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri
发明人： Pier Lucio Anelli , Christoph De Haen , Luciano Lattuada , Pierfrancesco Morosini , Fulvio Uggeri
IPC分类号： A61K47/48 , A61K49/00 , A61K49/08 , A61K51/04 , A61B5/055
CPC分类号： A61K49/10 , A61K49/085 , A61K51/0493 , A61K51/0497 , A61K2123/00
摘要： Novel paramagnetic metal ion chelates and their use as contrast agents in the diagnostic technique known as "magnetic resonance imaging" (M.R.I.) of the gastrointestinal tract and particularly of the liver, are described. The novel compounds result from the conjugation of a bile acid with a chelating agent and are capable of chelating the ions of bivalent and trivalent metals. The compounds have formula A-L-B in which A is the residue of a bile acid and derivatives of a bile acid, B is the residue of a chelating agent of a bivalent or trivalent metal ion having an atomic number of 20 to 31, 39, 42, 43, 44, 49, 57 to 83, L is a ligand between A and B.
摘要翻译：描述了新型顺磁性金属离子螯合物及其在称为“磁共振成像”（M.R.I.）的胃肠道特别是肝脏的诊断技术中作为造影剂的用途。新型化合物由胆汁酸与螯合剂结合而产生，并能螯合二价和三价金属的离子。所述化合物具有式ALB，其中A是胆汁酸的残基和胆汁酸的衍生物，B是二价或三价金属离子的螯合剂的残基，其原子序数为20至31,39,42， 43，44，49，57至83，L是A和B之间的配体。

9. 发明申请

US20120232151A1 Process for the Preparation of Gadobenate Dimeglumine Complex in a Solid Form 审中-公开
标题翻译：以固体形式制备钆酸二甲酚复合物的方法
公开(公告)号：US20120232151A1
公开(公告)日：2012-09-13
申请号：US13510409
申请日：2010-11-23
申请人： Pier Lucio Anelli , Pierfrancesco Morisini , Silvia Ceragioli , Fulvio Uggeri , Luciano Lattuada , Roberta Fretta , Aurelia Ferrigato
发明人： Pier Lucio Anelli , Pierfrancesco Morisini , Silvia Ceragioli , Fulvio Uggeri , Luciano Lattuada , Roberta Fretta , Aurelia Ferrigato
IPC分类号： C07C227/00 , A61K31/197 , C07C229/36
CPC分类号： A61K49/1887 , A61K9/0019 , B29C67/24 , C07C213/10 , C07C227/38 , C07C227/40 , Y10T428/2982 , C07C229/22
摘要： The present invention discloses a process for the preparation of gadobenate dimeglumine complex in a solid form. In particular, said solid form is conveniently obtained by spray-drying a corresponding liquid suspension at a given temperature and concentration. The present invention is particularly advantageous for the industrial scale as the solid form may be obtained by employing water as a solvent, which is a non-toxic solvent, easy to handle and basically not requiring troublesome health or safety precautions.
摘要翻译：本发明公开了一种以固体形式制备钆酸二甲酚络合物的方法。特别地，所述固体形式通过在给定温度和浓度下喷雾干燥相应的液体悬浮液而方便地得到。本发明对于工业规模是特别有利的，因为固体形式可以通过使用水作为溶剂，其是无毒溶剂，易于处理并且基本上不需要麻烦的健康或安全预防措施来获得。

10. 发明授权

US07034183B2 Process for the preparation of iopamidol and the new intermediated therein 有权
标题翻译：制备碘帕醇及其中间体的方法
公开(公告)号：US07034183B2
公开(公告)日：2006-04-25
申请号：US10433389
申请日：2001-11-29
申请人： Pier Lucio Anelli , Marino Brocchetta , Giovanna Lux , Enrico Cappelletti
发明人： Pier Lucio Anelli , Marino Brocchetta , Giovanna Lux , Enrico Cappelletti
IPC分类号： C07C233/65
CPC分类号： C07C231/02 , C07C237/46
摘要： A process for the preparation of (S)-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5-[(2-hydroxy-1-oxo-propyl)amino]-2,4,6-triiodo-1,3-benzendicarboxamide (iopamidol) starting from 5-amino-N,N′-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-2,4,6-triiodo-1,3-benzenedicarboxamide (II) which process comprises a) reacting the compound of formula (II) with a suitable protecting agent, to give a compound of formula (III) wherein R is a group of formula A or B wherein R1 is a hydrogen atom, a C1÷C4 straight or branched alkoxy group, R2 is hydrogen, a C1÷C4 straight or branched alkoxy group and R3 ?is a C1÷C4 straight or branched alkyl group, a trifuoromethyl or a trichloromethyl group; b) acylating the amino group in position 5 of the intermediate compound of formula (III), by reaction with a (S)-2-(acetyloxy)propanoyl chloride to give a compound of formula (IV) wherein R is as defined above; and c) removing all the acyl groups present in the compound of formula (IV) under basic conditions, with prior cleavage of the cyclic protections of the hydroxy groups in the carboxamido substituents under acidic conditions, when R is a group of formula A carboxamido hydroxy groups under acidic conditions. The invention also refers to the new intermediates of formula (III) and (IV) wherein —R is a group A.
摘要翻译：制备（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， 5-氨基-N，N'-双[2-羟基-1-（羟甲基）乙基] -2,4,6-三碘-1,3-苯二甲酰胺的6-三碘-1,3-苯二甲酰胺（碘帕醇）（II）所述方法包括a）使式（II）化合物与合适的保护剂反应，得到其中R为式A或B的基团的式（III）化合物，其中R 1 >是氢原子，C 1或C 4直链或支链烷氧基，R 2是氢，C 1 直链或支链烷氧基，R 3？是C / C 直链或支链烷基，三氟甲基或三氯甲基; b）通过与（S）-2-（乙酰氧基）丙酰氯反应，酰化式（III）中间体化合物的第5位的氨基，得到其中R如上定义的式（Ⅳ）化合物; 和c）在碱性条件下除去存在于式（Ⅳ）化合物中的所有酰基，在R是式A的基团时，先前在酸性条件下，在甲酰氨基取代基中羟基的环保保护被切割。在酸性条件下。本发明还涉及式（III）和（IV）的新中间体，其中-R是基团A.

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