WO1989008101A1 - Agents de contraste de rayons x non-ioniques, compositions et procedes - Google Patents
Agents de contraste de rayons x non-ioniques, compositions et procedes Download PDFInfo
- Publication number
- WO1989008101A1 WO1989008101A1 PCT/US1989/000519 US8900519W WO8908101A1 WO 1989008101 A1 WO1989008101 A1 WO 1989008101A1 US 8900519 W US8900519 W US 8900519W WO 8908101 A1 WO8908101 A1 WO 8908101A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- compound
- bis
- dihydroxypropyl
- triiodoisophthalamide
- radiological
- Prior art date
Links
- 239000002872 contrast media Substances 0.000 title claims abstract description 16
- 239000000203 mixture Substances 0.000 title claims description 24
- 238000000034 method Methods 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 29
- HIOAHDYCFCTHHE-UHFFFAOYSA-N 1-n,3-n-bis(2,3-dihydroxypropyl)-5-[2-hydroxyethyl-(2-methoxyacetyl)amino]-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound COCC(=O)N(CCO)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I HIOAHDYCFCTHHE-UHFFFAOYSA-N 0.000 claims abstract description 8
- KMROSAYUJCTELW-UHFFFAOYSA-N 1-n,3-n-bis(2,3-dihydroxypropyl)-5-[(2-hydroxyacetyl)-(2-methoxyethyl)amino]-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound COCCN(C(=O)CO)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I KMROSAYUJCTELW-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000012800 visualization Methods 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000000243 solution Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- 239000007832 Na2SO4 Substances 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000002002 slurry Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- MUJGKJDSVJWBLH-UHFFFAOYSA-N [2-acetyloxy-3-[[3-[(2-acetyloxyacetyl)amino]-5-(2,3-diacetyloxypropylcarbamoyl)-2,4,6-triiodobenzoyl]amino]propyl] acetate Chemical compound CC(=O)OCC(OC(C)=O)CNC(=O)C1=C(I)C(NC(=O)COC(C)=O)=C(I)C(C(=O)NCC(COC(C)=O)OC(C)=O)=C1I MUJGKJDSVJWBLH-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 238000002583 angiography Methods 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 229940125782 compound 2 Drugs 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- SHUOZUDQONPJGS-UHFFFAOYSA-N [2-acetyloxy-3-[[3-amino-5-(2,3-diacetyloxypropylcarbamoyl)-2,4,6-triiodobenzoyl]amino]propyl] acetate Chemical compound CC(=O)OCC(OC(C)=O)CNC(=O)C1=C(I)C(N)=C(I)C(C(=O)NCC(COC(C)=O)OC(C)=O)=C1I SHUOZUDQONPJGS-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000004262 preparative liquid chromatography Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000012258 stirred mixture Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- RGHQKFQZGLKBCF-UHFFFAOYSA-N 2-bromoethyl acetate Chemical compound CC(=O)OCCBr RGHQKFQZGLKBCF-UHFFFAOYSA-N 0.000 description 1
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical compound COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
- KAEGSAWWVYMWIQ-UHFFFAOYSA-N 5-amino-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I KAEGSAWWVYMWIQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 0 CC(O*(*C(c(c(I)c(c(C)c1C)N)c1I)=O)=*)=O Chemical compound CC(O*(*C(c(c(I)c(c(C)c1C)N)c1I)=O)=*)=O 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- CDVPCFSKIJFHQP-UHFFFAOYSA-N [2-acetyloxy-3-[[3-(2,3-diacetyloxypropylcarbamoyl)-2,4,6-triiodo-5-[(2-methoxyacetyl)amino]benzoyl]amino]propyl] acetate Chemical compound COCC(=O)NC1=C(I)C(C(=O)NCC(COC(C)=O)OC(C)=O)=C(I)C(C(=O)NCC(COC(C)=O)OC(C)=O)=C1I CDVPCFSKIJFHQP-UHFFFAOYSA-N 0.000 description 1
- RXDLGFMMQFNVLI-UHFFFAOYSA-N [Na].[Na].[Ca] Chemical compound [Na].[Na].[Ca] RXDLGFMMQFNVLI-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000002584 aortography Methods 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000013155 cardiography Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- -1 etc. Chemical compound 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000007487 urography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and at least three atoms of bromine or iodine, bound to carbon atoms of the same non-condensed six-membered aromatic ring
Definitions
- This invention relates to X-ray contrast agents and, more particularly, to novel nonionic X-ray contrast agents, radiological compositions containing such agents and methods for X-ray visualization utilizing such compositions .
- Nonionic contrast agents for intravascular and central nervous system visualization are complex molecules.
- the iodine in the molecule provides opacification to the x-rays.
- the remainder of the molecule provides the framework for transport of the iodine atoms.
- the structural arrangement of the molecule is important in providing stability, solubility and biological safety in various organs.
- a stable carbon-iodine bond is achieved in most compounds by attaching it to an aromatic nucleus.
- An enhanced degree of solubiity as well as safety is conferred on the molecule by the addition of suitable solubilizing and detoxifying groups.
- intravascular and central nervous system nonionic contrast agents are often incompatible so that all such agents represent compromises.
- the controlling factors are pharmacological inertness; i.e., in vivo safety and high water solubility.
- the ideal intravascular or central nervous system nonionic agent represents a compromise in an attempt to obtain the following criteria: (1) maximum opacif ication to x-rays; (2) pharmacological inertness; (3) high water solubility; (4) stability; (5) selective excretion; (6) low viscosity; and (7) minimal osmotic effects.
- non-ionic contrast agents which meet all or substantially all the foregoing criteria.
- X is selected from the group consisting of hydroxymethyl and methoxymethyl and Y is selected from the group consisting of hydroxy and methoxy.
- the invention is specifically directed to the compounds N,N'-bis(2,3-dihydroxypropyl)-5-(N-(2-methoxyethyl)glycolamido]-2,4,6-triiodoisophthalamide and N,N'-bis-(2,3-dihydroxypropyl)-5-[N-(2-hydroxyethyl)-methoxyacetamido]-2,4,6-triiodoisophthalamide.
- the invention is also directed to radiological compositions containing such compounds and methods for utilizing such compounds in x-ray visualization.
- compounds of the formula set out above are suitable for use as nonionic x-ray contrast agents. More specifically in the practice of the invention, the compounds N,N'-bis(2,3-dihydroxypropyl)-5-[N-(2-methoxyethyl)glycolamid ⁇ ]-2,4,6-triiodoisophthalamide and N,N'-bis- (2,3-dihydroxypropyl)-5- ⁇ N-(2-hydroxyethyl)-methoxyacetamido]-2,4,6-triiodoisophthalamide may be used as nonionic x-ray contrast agents. These agents may be used in various radiographic procedures including those involving cardiography, coronary ar teriography, aortography, cerebral and peripheral angiography, orthography, intravenous pyelography and urography.
- radiological compositions may be prepared containing one of the aforementioned compounds as an x-ray contrast agent together with a pharmaceutically acceptable radiological vehicle.
- Radiological vehicles include those that are suitable for injection such as aqueous buffer solutions; e.g., tris(hydroxymethyl) amino methane (and its salts), phosphate, citrate, bicarbonate, etc., sterile water for injection, physiological saline, and balanced ionic solutions containing chloride and/or bicarbonate salts of normal blood plasma cations such as Ca, Na, K and Mg.
- aqueous buffer solutions e.g., tris(hydroxymethyl) amino methane (and its salts), phosphate, citrate, bicarbonate, etc.
- sterile water for injection physiological saline
- physiological saline e.g., sterile water for injection
- physiological saline e.g., sterile water for injection
- physiological saline e.g., sterile water for injection
- physiological saline e.g., sterile water for injection
- physiological saline e.g., sterile water for
- the concentration of the x-ray contrast agents of the invention in the pharmaceutically acceptable vehicle varies with the particular field of use. A sufficient amount is present to provide satisfactory x-ray visualization. For example, when using aqueous solutions for angiography, the concentration of iodine is generally 140-400 mg/ml and the dose is 25-300 ml.
- the radiological composition is administered so that the contrast agent remains in the living animal body for about 2 to 3 hours, although both shorter and longer residence periods are normally acceptable.
- N,N'-bis-(2,3-dihydroxypropyl)-5-[N-(2-methoxyethyl)glycolamido]-2,4,6triiodoisophthalamide and N,N'-bis(2,3-dihydroxypropyl) 5-[N-(2-hydroxyethyl)-methoxyacetamido]-2,4,6-triiodoisophthalamide may be formulated for vascular visualization conveniently in vials or ampoules containing 10 to 500 ml. of an aqueous solution.
- the radiological compositions of the invention may be used in the usual way in x-ray procedures. For example, in the case of selective coronary arteriography, a sufficient amount of the radiological composition to provide adequate visualization is injected into the coronary system and then the system is scanned with a suitable device such as a fluoroscope.
- N,N'-bis(2,3-dihydroxypropyl)-5-[N-( 2-methoxyethyl)glycolamido]-2,4,6-triiodoisophthalamide and N,N'-bis(2,3-dihydroxypro ⁇ yl)-5-[N-(2-hydroxyethyl)- methoxyacetamido]-2,4,6-triiodoisophthalamide and the intermediates therefor may be prepared in accordance with the procedures set out below. All temperature designations are in degrees centigrade. The following examples illustrate the practice of the invention.
- the acute intravenous toxicities of the compounds of Examples 1 and 2 were determined as follows.
- a solution of the compounds of Example 1 and 2 was injected into the lateral tail vein of young adult male and female mice (Sasco mice in the case of the compound of Example 1 and Charles River mice in the case of the compound of Example 2) at the rate of 1 ml/min. Following injections, the animals were observed for immediate reactions and then daily throughout a seven day observation period.
- the LD 50 values were calculated by the method of Litchfield and Wilcoxon (J. Pharmacol. Exp. Therap. 96:99-113, 1949) with the following results.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Des composés tels que N, N'-bis(2,3-dihydroxypropyle)-5-[N-(2-méthoxyéthyle)glycolamido]-2,4,6-triiodoisophthalamide, et N, N'-bis (2,3-dihydroxypropyle)-5-[N-(2-hydroxyéthyle)méthoxyacétamido]-2,4,6-triiodoisophthalamide, sont utiles pour une utilisation comme agents de contraste de rayons X.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP1503065A JPH0625094B2 (ja) | 1988-03-01 | 1989-02-09 | 非イオン性x線コントラスト剤、組成物及び方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16263288A | 1988-03-01 | 1988-03-01 | |
US162,632 | 1988-03-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1989008101A1 true WO1989008101A1 (fr) | 1989-09-08 |
Family
ID=22586472
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1989/000519 WO1989008101A1 (fr) | 1988-03-01 | 1989-02-09 | Agents de contraste de rayons x non-ioniques, compositions et procedes |
Country Status (4)
Country | Link |
---|---|
EP (1) | EP0410974A4 (fr) |
JP (1) | JPH0625094B2 (fr) |
AU (1) | AU612510B2 (fr) |
WO (1) | WO1989008101A1 (fr) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1991011431A1 (fr) * | 1990-01-31 | 1991-08-08 | Mallinckrodt, Inc. | Procede de production d'ioversol |
WO1991013636A1 (fr) * | 1990-03-09 | 1991-09-19 | Cockbain, Julian, Roderick, Michaelson | Milieux contrastants |
WO1992009562A1 (fr) * | 1990-11-21 | 1992-06-11 | Mallinckrodt Medical, Inc. | Nouveaux agents de contraste aux rayons x, composition et procede de preparation |
EP0516050A3 (en) * | 1991-05-31 | 1993-03-03 | E.R. Squibb & Sons, Inc. | Methods and compositions for using non-ionic contrast agents to reduce the risk of clot formation in diagnostic procedures |
US5869024A (en) * | 1989-11-29 | 1999-02-09 | Bracco International B.V. | Methods and compositions for using non-ionic contrast agents to reduce the risk of clot formation in diagnostic procedures |
KR101833334B1 (ko) * | 2016-04-29 | 2018-02-28 | (주)유케이케미팜 | 신규 중간체 화합물 및 이를 이용한 이오메프롤의 제조방법 |
CN115160174A (zh) * | 2022-07-09 | 2022-10-11 | 浙江海洲制药有限公司 | 一种碘佛醇的合成方法 |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5013865A (en) * | 1988-04-06 | 1991-05-07 | Mallinckrodt, Inc. | Process for the preparation of 2,4,6-triiodo-5-amino-N-alkylisophthalamic acid and 2,4,6-triiodo-5-amino-isophthalamide compounds |
DE4109169A1 (de) * | 1991-03-20 | 1992-09-24 | Koehler Chemie Dr Franz | Wasserloesliche nicht ionische roentgenkontrastmittel sowie mittel und verfahren zu ihrer herstellung |
GB9710726D0 (en) * | 1997-05-23 | 1997-07-16 | Nycomed Imaging As | Compound |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4364921A (en) * | 1979-03-08 | 1982-12-21 | Schering, Aktiengesellschaft | Novel triiodinated isophthalic acid diamides as nonionic X-ray contrast media |
US4396598A (en) * | 1982-01-11 | 1983-08-02 | Mallinckrodt, Inc. | Triiodoisophthalamide X-ray contrast agent |
US4474747A (en) * | 1981-08-28 | 1984-10-02 | Guerbet S.A. | Process for increasing the tolerance of X-ray contrast media, and contrast media obtained thereby |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3429949A1 (de) * | 1984-08-10 | 1986-02-20 | Schering AG, 1000 Berlin und 4709 Bergkamen | Neue nicht -ionische 2,4,6-trijod-isophthalsaeure-bis-amide, verfahren zu ihrer herstellung und ihre verwendung als roentgenkontrastmittel |
US5066823A (en) * | 1987-05-22 | 1991-11-19 | Bracco Industria Chemica S.P.A. | Preparation of 5-acylamino-2,4,6-triiodo- or tribromo-benzoic acid derivatives |
DE3731542A1 (de) * | 1987-09-17 | 1989-03-30 | Schering Ag | Neue dicarbonsaeure-bis(3,5-dicarbamoyl-2,4,6-triiod-anilide), verfahren zu deren herstellung sowie diese enthaltende roentgenkontrastmittel |
-
1989
- 1989-02-09 WO PCT/US1989/000519 patent/WO1989008101A1/fr not_active Application Discontinuation
- 1989-02-09 EP EP19890903414 patent/EP0410974A4/en not_active Withdrawn
- 1989-02-09 JP JP1503065A patent/JPH0625094B2/ja not_active Expired - Lifetime
- 1989-02-09 AU AU40727/89A patent/AU612510B2/en not_active Ceased
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4364921A (en) * | 1979-03-08 | 1982-12-21 | Schering, Aktiengesellschaft | Novel triiodinated isophthalic acid diamides as nonionic X-ray contrast media |
US4474747A (en) * | 1981-08-28 | 1984-10-02 | Guerbet S.A. | Process for increasing the tolerance of X-ray contrast media, and contrast media obtained thereby |
US4396598A (en) * | 1982-01-11 | 1983-08-02 | Mallinckrodt, Inc. | Triiodoisophthalamide X-ray contrast agent |
Non-Patent Citations (1)
Title |
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See also references of EP0410974A4 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5869024A (en) * | 1989-11-29 | 1999-02-09 | Bracco International B.V. | Methods and compositions for using non-ionic contrast agents to reduce the risk of clot formation in diagnostic procedures |
WO1991011431A1 (fr) * | 1990-01-31 | 1991-08-08 | Mallinckrodt, Inc. | Procede de production d'ioversol |
WO1991013636A1 (fr) * | 1990-03-09 | 1991-09-19 | Cockbain, Julian, Roderick, Michaelson | Milieux contrastants |
TR25738A (tr) * | 1990-03-09 | 1993-09-01 | Nycomed As | Katiyonlar iceren kontrast ortami. |
US5328680A (en) * | 1990-03-09 | 1994-07-12 | Nycomed Imaging As | Contrast media comprising a non-ionic contrast agent with low levels of sodium & calcium ions |
USRE36418E (en) * | 1990-03-09 | 1999-11-30 | Nycomed Imaging As | Contrast media comprising a non-ionic contrast agent with low levels of sodium and calcium ions |
WO1992009562A1 (fr) * | 1990-11-21 | 1992-06-11 | Mallinckrodt Medical, Inc. | Nouveaux agents de contraste aux rayons x, composition et procede de preparation |
EP0516050A3 (en) * | 1991-05-31 | 1993-03-03 | E.R. Squibb & Sons, Inc. | Methods and compositions for using non-ionic contrast agents to reduce the risk of clot formation in diagnostic procedures |
KR101833334B1 (ko) * | 2016-04-29 | 2018-02-28 | (주)유케이케미팜 | 신규 중간체 화합물 및 이를 이용한 이오메프롤의 제조방법 |
CN115160174A (zh) * | 2022-07-09 | 2022-10-11 | 浙江海洲制药有限公司 | 一种碘佛醇的合成方法 |
Also Published As
Publication number | Publication date |
---|---|
EP0410974A1 (fr) | 1991-02-06 |
AU4072789A (en) | 1989-09-22 |
JPH03504124A (ja) | 1991-09-12 |
EP0410974A4 (en) | 1991-09-11 |
JPH0625094B2 (ja) | 1994-04-06 |
AU612510B2 (en) | 1991-07-11 |
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