- Optimisation of the preparation and isolation of 5-amino-2,4,6-triiodoisophthalic acid dichloride
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A scaleable process for the chlorination of 5-amino-2,4,6-triiodoisophthalic acid to the corresponding acid chloride, a building block for the synthesis of iodinated X-ray contrast agents, has been developed. Two dimeric byproducts have been isolated and assigned structures consistent with an amide and an anhydride. Hydrolysis of the N-sulfinyl intermediate and simultaneous crystallisation of the phthalic acid chloride have been optimised by applying fractional factorial design.
- Gijsen, Harrie J.M.,Van Bakel, Herman C.C.K.,Zwaan, Wim,Hulshof, Lumbertus A.
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Read Online
- Iopamidol synthesis and preparation of iopamidol synthesis intermediate
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The invention relates to the technical field of chemical synthesis processes, particularly to iopamidol synthesis and preparation of an iopamidol synthesis intermediate. According to the present invention, by adjusting the feeding weight ratio, optimizing the reaction conditions and improving the iopamidol synthesis route, the requirements on the compound reaction conditions are low, the control of the reaction is simple, and the yield is increased while the quality of the intermediate product is greatly improved so as to reduce the process control difficulty in the iopamidol production process and improve the quality and the qualification rate of iopamidol; and various steps of the preparation process are simple, the solvents and the process conditions are safe and easy to perform, the environmental protection production is achieved, and the method has broad application prospects.
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- 9 - Azabicyclo [3.3.1] nonane coupling [...] compound and its preparation method and use thereof (by machine translation)
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The invention discloses a 9 - azabicyclo [3.3.1] nonane coupling [...] compound, its preparation method comprises the following steps: in the organic solvent, the 9 - nitrogen (6' - amino) oneself amidogen - 9 - 9 - azabicyclo [3.3.1] nonane - 3 α - alkyl amino formic acid benzene and chloro acetyl three iodo aniline derivatives in accordance with the 1: 1.0 - 1.5 molar ratio, for the catalysis of cesium hydroxide at room temperature reaction in the 20 - 30 the H, obtained as the product of the 9 - azabicyclo [3.3.1] nonane coupling [...] compound. The invention also discloses the use thereof: a contrast agent for early diagnosis of breast cancer. (by machine translation)
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Paragraph 0058; 0059; 0063
(2018/11/22)
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- Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage
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Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.
- Stewart, Rachel C.,Patwa, Amit N.,Lusic, Hrvoje,Freedman, Jonathan D.,Wathier, Michel,Snyder, Brian D.,Guermazi, Ali,Grinstaff, Mark W.
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p. 5543 - 5555
(2017/07/22)
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- BIODEGRADABLE COMPUTED TOMOGRAPHY CONTRAST AGENTS
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Biodegradable computed tomography (CT) contrast agents comprising a polyiodinated aryl contrast agent that is crosslinked by an organic disulfide are described herein. The contrast agents can be used to image a tissue region by administering an effective amount of the biodegradable CT contrast agent to a subject, allowing a sufficient amount of time for the biodegradable CT contrast agent to enter the tissue region, and performing x-ray computed tomography imaging of the tissue region of the subject.
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Paragraph 0067
(2015/05/05)
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- The synthesis and evaluation of trimeric X-ray contrast agents
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Novel trimeric iodinated contrast agents with low osmolality have been prepared and evaluated with the aim of improving the already good safety profile of such agents. While the aim of low osmolality was achieved, the viscosity of the trimeric agents was found to be generally higher than current dimeric agents in clinical use.
- Newington, Ian M.,Humphries, Gareth,Lasbistes, Nicolas,Morisson-Iveson, Véronique,Nairne, James,Passmore, Joanna,Thanning, Mikkel,Wistrand, Lars-G?ran,Wynn, Duncan
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scheme or table
p. 3065 - 3067
(2011/06/23)
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- CONTRAST AGENTS
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The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a triamine alkyl central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.
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Page/Page column 14-15
(2009/03/07)
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- CONTRAST AGENTS
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The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a tris(aminoalkyl)amine group allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.
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Page/Page column 11-12
(2009/03/07)
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- Effect of contrast agent charge on visualization of articular cartilage using computed tomography: Exploiting electrostatic interactions for improved sensitivity
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(Chemical Equation Presented) The synthesis and evaluation of a new class of cationic iodinated contrast agents for the imaging of cartilage using computed tomography (CT) are described. In direct comparisons with anionic contrast agents, the cationic contrast agents afforded higher equilibrium concentrations in the articular cartilage of ex vivo rabbit femurs and thus greater imaging sensitivity. Variations in CT intensity across the sample reflected the inhomogeneous distribution of glycosaminoglycans in the tissue as confirmed by histological analysis. We anticipate that this work represents the first step in the development of sensitive, nondestructive CT-based methods to characterize the biochemical properties of cartilage using cationic contrast agents.
- Joshi, Neel S.,Bansal, Prashant N.,Stewart, Rachel C.,Snyder, Brian D.,Grinstaff, Mark W.
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supporting information; experimental part
p. 13234 - 13235
(2010/01/29)
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- TRISUBSTITUTED TRIAZAMACROCYCLI C COMPOUNDS AND THEIR USE AS CONTRAST AGENTS
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The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing a saturated triaza cyclic central moiety containing carbonyl functions allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.
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Page/Page column 12; 14; 15
(2008/12/04)
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- CONTRAST AGENTS
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The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic N-heterocyclic central moiety such as pyrrolidine or piperidine heterocycles allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging, in particular in X-ray imaging, and to contrast media containing such compounds.
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Page/Page column 8
(2008/12/04)
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- CONTRAST AGENTS
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The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety containing amide functions allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.
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Page/Page column 17; 48-49
(2008/06/13)
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- CONTRAST AGENTS
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The present invention relates to iodine containing compounds containing a central optionally substituted cyclohexane central moiety allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to the use of such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.
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Page/Page column 13
(2008/06/13)
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- Contrast Agents
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The present invention relates to a class of compounds and to diagnostic compositions containing such compounds where the compounds are iodine containing compounds. More specifically the iodine containing compounds are chemical compounds containing an aliphatic central moiety containing hydroxyl groups allowing for the arrangement of three iodinated phenyl groups bound thereto. The invention also relates to methods employing such diagnostic compositions as contrast agents in diagnostic imaging and in particular in X-ray imaging and to contrast media containing such compounds.
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Page/Page column 6
(2010/11/28)
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- DETERMINATION OF KIDNEY FUNCTION
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The present invention provides an isotopically labelled marker of formula (I): where R1 -R5 are as defined herein; characterised in that one or more of the H, N, C or O atoms in the compound of formula (I) is replaced with one or more of2H, 13C, 15N, 17O or 18O respectively, methods for using the inventive marker in detecting the presence or absence of a filtration marker in a sample, measuring the rate of glomerular filtration in a subject and/or diagnosing kidney disease and/or damage in a subject.
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Page/Page column 21
(2010/11/26)
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- Synthesis and evaluation of potential CT (computer tomography) contrast agents for bone structure and microdamage analysis
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The design and synthesis of several novel X-ray contrast agents 1-3, developed for targeting bone structures, and in particularly microcracks in bones, using CT (Computer Tomography) detection is described. These contrast agents are based on the use of the well known triiodobenzene platform, which was conjugated into one or more phenyliminodiacetate moieties, which can be used to 'lock' onto bone matrices. Compounds 1-3 were all tested for their ability to visualise cracks in bone structures (bovine bones) using μ-CT imaging. The Royal Society of Chemistry 2006.
- Parkesh, Raman,Gowin, Wolfgang,Lee, T. Clive,Gunnlaugsson, Thorfinnur
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p. 3611 - 3617
(2008/09/19)
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- Highly-iodinated fullerene as a contrast agent for X-ray imaging
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The first fullerene-based X-ray contrast agent (CA) has been designed, synthesized, and characterized. The new CA is an externally functionalized derivative of C60 that is conceptually based on contemporary X-ray CA, all of which use iodine as the X-ray attenuating vehicle and are based on the 2,4,6-triiodinated-benzene-ring substructure. Using a modified Bingel-type reaction, a single addend containing 6 iodine atoms and 8 protected hydroxyl groups was appended to C60 followed by the addition of 4 more addends each containing 4 protected hydroxyl groups. Final deprotection afforded the highly water-soluble (>460 mg/mL), non-ionic, highly-iodinated (24% I) fullerene for application as an X-ray contrast agent.
- Wharton, Tim,Wilson, Lon J.
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p. 3545 - 3554
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF A DICARBOXYLIC ACID DICHLORIDE
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The present invention refers to a Process for the preparation of S-(-)-5-[[2-(acetyloxy)-1-oxopropyl]amino]-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride of formula (I) comprising the reaction between S-(-)-[2-(acetyloxy)]propionic acid chloride and 5-amino-2,4,6-triiodo-, 1,3-benzenedicarboxylic acid dichloride, in an aprotic dipolar solvent and in presence of a halogenhydric acid.
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- Radio-contrast agents
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An imaging or contrast agent comprising a stereoisomer of a compound with at least one chiral centre, wherein said stereoisomer is in stereoisomeric excess and causes fewer adverse side effects on administration, or is less chemotoxic, than at least one other stereoisomer of said chiral compound.
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- A PROCESS FOR THE PREPARATION OF 5- ACETYL (2,3-DIHYDROXYPROPYL)AMINO]-N,N'-BIS (2,3-DIHYDROXYPROPYL)-2,4,6- TRIIODO-1,3-BENZENEDICARBOXAMIDE
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A process for the preparation of 5-[acetyl(2,3-dihydroxypropyl)amino]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide of formula (I), starting from 5-amino-1,3-benzenedicarboxylic acid of formula (II), comprising the following steps: step a) is the reaction in heterogeneous phase between 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid and thionyl chloride in a solvent selected from the group consisting of: straight or branched (C7-C16) hydrocarbons, (C7-C8) aromatic hydrocarbons, 1,1,1-trichloroethane, n-butyl acetate, diglyme (diethylene glycol dimethyl ether), in the presence of catalytic amounts of a tertiary amine, to give compound (III); step b) is the acetylation reaction of compound (III) with glacial acetic acid both as the solvent and the reagent and thionyl chloride; step c) is the formation of compound (V) by reaction of the compound (IV) with 1-amino-2,3-propanediol, by reaction of compound (IV) in a dipolar aprotic solvent, selected from the group of dimethylformamide (DMF), dimethylacetamide (DMA), dimethylsulfoxide (DMSO) or N-methyl-pyrrolidinone; step d) is the alkylation of the compound (V) in aqueous solution at basic pH, by addition of a sodium hydroxide-calcium hydroxide mixture, with 3-chloro-1,2-propanediol or epichlorohydrin, at a temperature of 40-90 DEG C.
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- Process for preparing 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination of the corresponding acid in the presence of a tertiary amine salt or quaternary ammonium salt
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A process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorinating 5-amino-2,4,6-triiodoisophthalic acid with thionyl chloride in the presence of a suitable solvent and of a tertiary amine salt or quaternary ammonium salt in a molar ratio from 1;1 to 1;2 with respect to 5-amino-2,4,6-triiodoisophathalic acid is described. 5-amino-2,4,6-triiodoisophthalic acid dichloride is an intermediate useful for the preparation of iodinated contrast agents.
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- Process for the preparation of 5-(acetyl(2,3-dihydroxypropyl)amino-N,N-bis(2,3-dihydroxypropyl)-2,4,6-t riiodo
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A process for the preparation of 5-[acetyl(2,3-dihydroxypropyl)amino]-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide of formula (I), starting from 5-amino-1,3-benzenedicarboxylic acid of formula (II), comprising the following steps: step a) is the reaction in heterogeneous phase between 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid and thionyl chloride in a solvent selected from the group consisting of: straight or branched (C7 -C16) hydrocarbons, (C7 -C8) aromatic hydrocarbons, 1,1,1-trichloroethane, n-butyl acetate, diglyme (diethylene glycol dimethyl ether), in the presence of catalytic amounts of a tertiary amine, to give compound (III); step b) is the acetylation reaction of compound (III) with glacial acetic acid both as the solvent and the reagent and thionyl chloride; step c) is the formation of compound (V) by reaction of the compound (IV) with 1-amino-2,3-propanediol, by reaction of compound (IV) in a dipolar aprotic solvent, selected from the group of dimethylformamide (DMF), dimethylacetamide (DMA), dimethylsulfoxide (DMSO) or N-methyl-pyrrolidinone; step d) is the alkylation of the compound (V) in aqueous solution at basic pH, by addition of a sodium hydroxide-calcium hydroxide mixture, with 3-chloro-1,2-propanediol or epichlorohydrin, at a temperature of 40-90° C.
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- Preparation process of acyl halide or sulfonyl halide
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A preparation process of acyl halide or sulfonyl halide which comprises reacting corresponding carboxylic acid or sulfonic acid with a haloiminium salt represented by the general formula (1): STR1 wherein R1 and R2 are same or different lower alkyl groups, X is a halogen atom, and n is an integer of 2 or 3.
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- Process for the preparation of a dicarboxylic acid dichloride
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The present invention refers to a process for the preparation of 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride, comprising the reaction in heterogeneous phase between 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid and thionyl chloride, in a solvent selected from the group consisting of: (C7 -C16) linear or branched hydrocarbons, (C7 -C8) aromatic hydrocarbons, 1,1,1-trichloroethane, n-butylacetate, diglyme (diethylenglycoledimethylether), and in the presence of a catalytic amount of a tertiary amine.
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- Process for the preparation of 5-amino-2,4,6-Triiodoisophthalic acid dichloride by chlorination with thionyl chloride in the presence of a catalyst
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A process for the preparation of 5-amino-2,4,6-triiodoisophthalic acid dichloride by chlorination of 5-amino-2,4,6-triiodoisophthalic acid with thionyl chloride in the presence of a suitable solvent characterized in that the reaction is carried out in the presence of catalytic amounts of a tetraalkylammonium salt of formula wherein X is halogen, mesylate or tosylate; R1, R2, R3 and R4, the same or different, are C1 -C20 alkyl groups so that the total number of carbon atoms of the groups R1, R2, R3 and R4 is higher than 16. The 5-amino-2,4,6-triiodoisophthalic acid dichloride obtained according to the process of the present invention is useful as intermediate in the synthesis of iodinated contrast media.
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- Carboxamide non-ionic contrast media
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Novel triiodo 5-aminoisophthaldiamides are provided, where the amino and one of the amide nitrogens are substituted. The compounds have at least two hydroxyl groups and are found to provide low viscosity and osmolality. Procedures for preparing the compounds are provided.
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- Process for the preparation of a dicarboxylic acid di-chloride
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The present invention refers to a Process for the preparation of S-(-)-5-??2-(acetyloxy)-1-oxopropyl!amino!-2,4,6-triiodo-1,3-benzenedicarboxylic acid dichloride of formula (I) comprising the reaction between S-(-)-?2-(acetyloxy)!propionic acid chloride and 5-amino-2,4,6-triiodo-, 1,3-benzenedicarboxylic acid dichloride, in an aprotic dipolar solvent and in presence of a halogenhydric acid.
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- Compounds which can be used in contrast products for radiography
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Polyiodinated nonionic compound that have the formula: STR1
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- Heterocyclic Nonionic X-ray Contrast Agents. 3. The Synthesis of 5--2,4,6-triiodo-1,3-benzenedicarboxamide Derivatives
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The syntheses of 2,4,6-triiodo-1,3-benzenedicarboxamide analogs, 12c, 12e, and 17c, of interest as X-ray diagnostic agents and in which the 5 position is linked to the N atom of a 4-(hydroxymethyl)-oxazolidin-2-one moiety, are described.The heterocycle was built from suitably protected 5-amino-2,4,6-triiodo-1,3-benzenedicarboxylic acid derivatives by a three-step procedure consisting of (1) phosgene treatment to obtain the corresponding isocyanates, (2) phenylmercuric chloride-catalyzed addition of glycidol (10) resulting in glycidil carbamates, and (3) pyridine-catalyzed intramolecular N-alkylation, followed by deprotection, to obtain the oxazolidin-2-ones.The intramolecular N-alkylation reaction was highly regioselective and was not appreciably accompanied by O-alkylation products under the experimental conditions employed.The two carboxamide nitrogen atoms in the intermediates and end products carry either 2,3-dihydroxypropyl or 1,3-dihydroxypropyl residues.These highly congested benzenoid compounds exhibited interesting NMR spectral features due to atropisomerism arising from hindrance to free rotation about the three single bonds that link the aromatic moiety to the N-containing functionalities.
- Pillai, K. M. R.,Diamantidis, G.,Duncan, L.,Ranganathan, R. S.
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p. 1344 - 1350
(2007/10/02)
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- Nonionic X-ray contrast agents, compositions and methods
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Triiodinated isophthalamide derivatives, useful as X-ray contrast agents, having at least one amide group derived from the amino-alcohol, 3-(N-2-hydroxyethyl)amino-1,2-propanediol, which provides high water solubility and low mammalian toxicity, and methods of preparing them. Methods of preparing 3-(N-2-hydroxyethyl)amino-1,2-propanediol are provided.
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- Triiodoisophthalamide X-ray contrast agent
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Novel X-ray contrast agents, i.e., N,N'-bis(2,3-dihydroxypropyl)-5-N-(2-hydroxyethyl)glycolamido-2,4,6-triiodoisophthalamide.
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- N-Triiodobenzoylaminoacyl polyhydroxic amines
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Nonionic triiodobenzoyl amino acyl derivatives of polyhydroxy amines. Such amines are useful as nonionic X-ray contrast agents. For Example 2-(3-acetamido-2,4,6-triiodo-5-N-methylacetamidobenzoyl glycylamino)-2-deoxy-D-glucitol is especially useful in angiography.
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