CA1186333A - N-hydroxyalkylated dicarboxylic acid bis-(3,5- dicarbamoyl-2,4,6-triiodoanilides), process for their preparation, and x-ray contrast preparations containing them - Google Patents
N-hydroxyalkylated dicarboxylic acid bis-(3,5- dicarbamoyl-2,4,6-triiodoanilides), process for their preparation, and x-ray contrast preparations containing themInfo
- Publication number
- CA1186333A CA1186333A CA000383725A CA383725A CA1186333A CA 1186333 A CA1186333 A CA 1186333A CA 000383725 A CA000383725 A CA 000383725A CA 383725 A CA383725 A CA 383725A CA 1186333 A CA1186333 A CA 1186333A
- Authority
- CA
- Canada
- Prior art keywords
- bis
- straight
- hydroxyethyl
- produced
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000000034 method Methods 0.000 title claims abstract description 61
- 230000008569 process Effects 0.000 title claims abstract description 56
- 238000002360 preparation method Methods 0.000 title claims abstract description 9
- 150000001990 dicarboxylic acid derivatives Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 239000000126 substance Substances 0.000 claims abstract description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 13
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 7
- 239000011630 iodine Substances 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 96
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 67
- -1 alkyl radical Chemical class 0.000 claims description 55
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 43
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 37
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 229960004063 propylene glycol Drugs 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 20
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 claims description 18
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 13
- 235000006408 oxalic acid Nutrition 0.000 claims description 12
- 150000003254 radicals Chemical class 0.000 claims description 12
- 150000003931 anilides Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- CQWXKASOCUAEOW-UHFFFAOYSA-N 2-[2-(carboxymethoxy)ethoxy]acetic acid Chemical compound OC(=O)COCCOCC(O)=O CQWXKASOCUAEOW-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- SSZWWUDQMAHNAQ-UHFFFAOYSA-N 3-chloropropane-1,2-diol Chemical compound OCC(O)CCl SSZWWUDQMAHNAQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004593 Epoxy Chemical group 0.000 claims description 2
- 229910052783 alkali metal Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims 9
- 229910052739 hydrogen Inorganic materials 0.000 claims 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 6
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical group CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 claims 1
- DQSWHEHCNFKNSQ-UHFFFAOYSA-N 5-[2-hydroxyethyl-[3-[N-(2-hydroxyethyl)-2,4,6-triiodo-3,5-bis(1,3,4-trihydroxybutan-2-ylcarbamoyl)anilino]-3-oxopropanoyl]amino]-2,4,6-triiodo-1-N,3-N-bis(1,3,4-trihydroxybutan-2-yl)benzene-1,3-dicarboxamide Chemical compound OC(C(CO)NC(=O)C=1C(=C(N(C(CC(=O)N(C2=C(C(=C(C(=C2I)C(NC(C(CO)O)CO)=O)I)C(NC(C(CO)O)CO)=O)I)CCO)=O)CCO)C(=C(C=1I)C(NC(C(CO)O)CO)=O)I)I)CO DQSWHEHCNFKNSQ-UHFFFAOYSA-N 0.000 claims 1
- ZHQKLVLVYBUSGP-UHFFFAOYSA-N 5-[[2-[3,5-bis(2,3-dihydroxypropylcarbamoyl)-N-(2-hydroxyethyl)-2,4,6-triiodoanilino]-2-oxoacetyl]-(2-hydroxyethyl)amino]-1-N,3-N-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound OC(CNC(=O)C=1C(=C(N(C(C(=O)N(C2=C(C(=C(C(=C2I)C(NCC(CO)O)=O)I)C(NCC(CO)O)=O)I)CCO)=O)CCO)C(=C(C=1I)C(NCC(CO)O)=O)I)I)CO ZHQKLVLVYBUSGP-UHFFFAOYSA-N 0.000 claims 1
- CVCDAQZCKFZEAH-UHFFFAOYSA-N 5-[[2-[3,5-bis[2,3-dihydroxypropyl(methyl)carbamoyl]-2,4,6-triiodoanilino]-2-oxoacetyl]amino]-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1-n,3-n-dimethylbenzene-1,3-dicarboxamide Chemical compound OCC(O)CN(C)C(=O)C1=C(I)C(C(=O)N(CC(O)CO)C)=C(I)C(NC(=O)C(=O)NC=2C(=C(C(=O)N(C)CC(O)CO)C(I)=C(C(=O)N(C)CC(O)CO)C=2I)I)=C1I CVCDAQZCKFZEAH-UHFFFAOYSA-N 0.000 claims 1
- FDDCFSDCRDUMAF-UHFFFAOYSA-N 5-[[2-[3,5-bis[2,3-dihydroxypropyl(methyl)carbamoyl]-N-(2-hydroxyethyl)-2,4,6-triiodoanilino]-2-oxoacetyl]-(2-hydroxyethyl)amino]-1-N,3-N-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1-N,3-N-dimethylbenzene-1,3-dicarboxamide Chemical compound OC(CN(C(=O)C=1C(=C(N(C(C(=O)N(C2=C(C(=C(C(=C2I)C(N(C)CC(CO)O)=O)I)C(N(C)CC(CO)O)=O)I)CCO)=O)CCO)C(=C(C=1I)C(N(C)CC(CO)O)=O)I)I)C)CO FDDCFSDCRDUMAF-UHFFFAOYSA-N 0.000 claims 1
- HBXRNTJBJBWPBD-UHFFFAOYSA-N 5-[[3-[3,5-bis(2,3-dihydroxypropylcarbamoyl)-2,4,6-triiodoanilino]-3-oxopropanoyl]amino]-1-N,3-N-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound OC(CNC(=O)C=1C(=C(NC(CC(=O)NC2=C(C(=C(C(=C2I)C(NCC(CO)O)=O)I)C(NCC(CO)O)=O)I)=O)C(=C(C=1I)C(NCC(CO)O)=O)I)I)CO HBXRNTJBJBWPBD-UHFFFAOYSA-N 0.000 claims 1
- DPBNBXDPSDROGF-UHFFFAOYSA-N C(CO)N(CCO)C(=O)C1=C(C(=C(C(=C1I)NC(=O)CC(=O)NC2=C(C(=C(C(=C2I)C(=O)N(CCO)CCO)I)C(=O)N(CCO)CCO)I)I)C(=O)N(CCO)CCO)I Chemical compound C(CO)N(CCO)C(=O)C1=C(C(=C(C(=C1I)NC(=O)CC(=O)NC2=C(C(=C(C(=C2I)C(=O)N(CCO)CCO)I)C(=O)N(CCO)CCO)I)I)C(=O)N(CCO)CCO)I DPBNBXDPSDROGF-UHFFFAOYSA-N 0.000 claims 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims 1
- SHZFUNVIUYYTES-UHFFFAOYSA-N N,N'-bis[2,4,6-triiodo-3,5-bis(1,3,4-trihydroxybutan-2-yl)phenyl]propanediamide Chemical compound OC(C(CO)C=1C(=C(NC(CC(=O)NC2=C(C(=C(C(=C2I)C(C(CO)O)CO)I)C(C(CO)O)CO)I)=O)C(=C(C=1I)C(C(CO)O)CO)I)I)CO SHZFUNVIUYYTES-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical group O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 239000000376 reactant Substances 0.000 claims 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 239000002872 contrast media Substances 0.000 abstract description 11
- 229940039231 contrast media Drugs 0.000 abstract description 8
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 abstract description 6
- 230000000144 pharmacologic effect Effects 0.000 abstract description 2
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000000354 decomposition reaction Methods 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 150000002500 ions Chemical class 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- NBTOZLQBSIZIKS-UHFFFAOYSA-N methoxide Chemical compound [O-]C NBTOZLQBSIZIKS-UHFFFAOYSA-N 0.000 description 5
- 235000013772 propylene glycol Nutrition 0.000 description 5
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 229940113088 dimethylacetamide Drugs 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000002583 angiography Methods 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000009608 myelography Methods 0.000 description 3
- 230000003204 osmotic effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 150000000000 tetracarboxylic acids Chemical class 0.000 description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
- KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- NVTRPRFAWJGJAJ-UHFFFAOYSA-L EDTA monocalcium salt Chemical compound [Ca+2].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O NVTRPRFAWJGJAJ-UHFFFAOYSA-L 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
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- BAQCROVBDNBEEB-UBYUBLNFSA-N Metrizamide Chemical compound CC(=O)N(C)C1=C(I)C(NC(C)=O)=C(I)C(C(=O)N[C@@H]2[C@H]([C@H](O)[C@@H](CO)OC2O)O)=C1I BAQCROVBDNBEEB-UBYUBLNFSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000019634 flavors Nutrition 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000008040 ionic compounds Chemical class 0.000 description 2
- XQZXYNRDCRIARQ-LURJTMIESA-N iopamidol Chemical compound C[C@H](O)C(=O)NC1=C(I)C(C(=O)NC(CO)CO)=C(I)C(C(=O)NC(CO)CO)=C1I XQZXYNRDCRIARQ-LURJTMIESA-N 0.000 description 2
- 229960004647 iopamidol Drugs 0.000 description 2
- 229960000554 metrizamide Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 2
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 1
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 1
- CRVYPNHLIAWRNV-UHFFFAOYSA-N 2,4,6-triiodobenzoic acid Chemical class OC(=O)C1=C(I)C=C(I)C=C1I CRVYPNHLIAWRNV-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- WOMTYMDHLQTCHY-UHFFFAOYSA-N 3-methylamino-1,2-propanediol Chemical compound CNCC(O)CO WOMTYMDHLQTCHY-UHFFFAOYSA-N 0.000 description 1
- JEZJSNULLBSYHV-UHFFFAOYSA-N 5-amino-2,4,6-triiodobenzene-1,3-dicarboxylic acid Chemical compound NC1=C(I)C(C(O)=O)=C(I)C(C(O)=O)=C1I JEZJSNULLBSYHV-UHFFFAOYSA-N 0.000 description 1
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 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
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- CTKINSOISVBQLD-UHFFFAOYSA-N Glycidol Chemical compound OCC1CO1 CTKINSOISVBQLD-UHFFFAOYSA-N 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 235000014676 Phragmites communis Nutrition 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 238000006359 acetalization reaction Methods 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003074 arachnoiditis Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940009662 edetate Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 125000001145 hydrido group Chemical group *[H] 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- SXYFKXOFMCIXQW-UHFFFAOYSA-N propanedioyl dichloride Chemical compound ClC(=O)CC(Cl)=O SXYFKXOFMCIXQW-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000007487 urography Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000003966 vascular damage Effects 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Photoreceptors In Electrophotography (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEP3038853.5 | 1980-10-10 | ||
| DE19803038853 DE3038853A1 (de) | 1980-10-10 | 1980-10-10 | Neue n-hydroxy-alkylierte dicarbonsaeure-bis-(3,5-dicarbamoyl-2,4,6-trijodanilide), deren herstellung und diese enthaltende roentgenkonstrastmittel (ii) |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1186333A true CA1186333A (en) | 1985-04-30 |
Family
ID=6114382
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000383725A Expired CA1186333A (en) | 1980-10-10 | 1981-08-12 | N-hydroxyalkylated dicarboxylic acid bis-(3,5- dicarbamoyl-2,4,6-triiodoanilides), process for their preparation, and x-ray contrast preparations containing them |
Country Status (14)
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3364536D1 (en) * | 1982-11-08 | 1986-08-21 | Nyegaard & Co As | X-ray contrast agents |
| NL194579C (nl) * | 1983-01-21 | 2002-08-05 | Schering Ag | Diagnostisch middel. |
| FR2541272A1 (fr) * | 1983-02-23 | 1984-08-24 | Guerbet Sa | Composes bromes et produits opacifiants en contenant |
| 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 |
| DE3739098A1 (de) * | 1987-11-16 | 1989-05-24 | Schering Ag | Neue substituierte dicarbonsaeure-bis(3,5-dicarbamoyl-2,4,6- trijod-anilide), verfahren zu deren herstellung sowie diese enthaltende roentgenkontrastmittel |
| GB8906130D0 (en) * | 1989-03-17 | 1989-05-04 | Nycomed As | Compositions |
| US5698739A (en) * | 1989-07-05 | 1997-12-16 | Schering Aktiengesellschaft | Carboxamide non-ionic contrast media |
| US5075502A (en) * | 1989-12-13 | 1991-12-24 | Mallinckrodt, Inc. | Nonionic x-ray contrast agents, compositions and methods |
| US5191120A (en) * | 1989-12-13 | 1993-03-02 | Mallinckrodt Medical, Inc. | Process for preparing nonionic X-ray contrast agents |
| GB9020091D0 (en) * | 1990-09-14 | 1990-10-24 | Nycomed As | Contrast media |
| WO1993010078A1 (es) * | 1991-11-18 | 1993-05-27 | Centro Investigacion Justesa Imagen S.A. | Nuevos agentes yodados no ionicos de contraste a los rayos x, metodo para su preparacion y composiciones galenicas que los contienen |
| WO1993010825A1 (en) * | 1991-12-03 | 1993-06-10 | Mallinckrodt Medical, Inc. | Nonionic x-ray contrast agents, compositions and methods |
| FR2687669B1 (fr) * | 1992-02-24 | 1997-12-19 | Guerbet Sa | Composes utilisables dans des produits de contraste pour la radiographie. |
| AU5093993A (en) * | 1992-09-02 | 1994-03-29 | Mallinckrodt Medical, Inc. | Nonionic X-ray contrast agents compositions and methods |
| WO1995026331A1 (es) * | 1994-03-25 | 1995-10-05 | Centro Investigacion Justesa Imagen, S.A. | Nuevos dimeros iodados no ionicos como agentes de contraste a los rayos x, metodo para su preparacion y composiciones farmaceuticas que los contienen |
| AU2002245169A1 (en) | 2000-11-10 | 2002-07-08 | Wm. Marsh Rice University | Fullerene (c60)-based x-ray contrast agent for diagnostic imaging |
| PL1836239T3 (pl) | 2005-01-13 | 2009-04-30 | Cinvention Ag | Materiał kompozytowy zawierający nanocząstki węgla |
| CN101687051A (zh) | 2007-07-12 | 2010-03-31 | 通用电气医疗集团股份有限公司 | 造影剂 |
| US20100221192A1 (en) | 2007-10-12 | 2010-09-02 | Duncan George Wynn | Contrast agents |
| JP2011500530A (ja) | 2007-10-12 | 2011-01-06 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | 造影剤 |
| WO2009047319A1 (en) | 2007-10-12 | 2009-04-16 | Ge Healthcare As | Contrast agents |
| WO2009047316A1 (en) | 2007-10-12 | 2009-04-16 | Ge Healthcare As | Contrast agents |
| US8445725B2 (en) * | 2008-01-14 | 2013-05-21 | Mallinckrodt Llc | Process for the preparation of iosimenol |
| WO2012136813A2 (en) | 2011-04-07 | 2012-10-11 | Universitetet I Oslo | Agents for medical radar diagnosis |
| CN107249570B (zh) | 2014-11-21 | 2022-08-09 | 丹麦技术大学 | 用于局部药物释放的凝胶制剂 |
| SG11201809729XA (en) | 2016-05-20 | 2018-12-28 | Univ Denmark Tech Dtu | Palpable marker composition |
| WO2020249801A1 (en) | 2019-06-12 | 2020-12-17 | Technical University Of Denmark | Dissacharide formulations for controlled drug release |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4021481A (en) | 1969-06-27 | 1977-05-03 | Nyegaard & Co. A/S | Amido derivatives of 2,4,6-triiodobenzoic acids containing at least one N-hydroxyalkyl and at least two hydroxyl groups |
| DE2031724C3 (de) | 1969-06-27 | 1979-06-28 | Nyegaard & Co. A/S., Oslo | N-substituierte Trijodbenz- bzw. Jodmethansulfon-am'ide, Verfahren zu deren Herstellung und radiologische Zusammensetzungen |
| DD104193A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1972-12-22 | 1974-03-05 | ||
| CH608189A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1974-12-13 | 1978-12-29 | Savac Ag | |
| GB1491129A (en) | 1975-06-04 | 1977-11-09 | Guerbet Sa | Iodo-benzene derivatives and an x-ray contrast medium containing them |
| GB1548594A (en) | 1976-06-11 | 1979-07-18 | Nyegaard & Co As | Triiodoisophthalic acid amides |
| DE2628517C2 (de) * | 1976-06-23 | 1985-02-21 | Schering AG, 1000 Berlin und 4709 Bergkamen | Dicarbonsäure-bis(3,5-dicarbamoyl-2,4,6-trijodanilid)-Verbindungen, Verfahren zu ihrer Herstellung und Röntgenkontrastmittel |
| CH626873A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1977-03-28 | 1981-12-15 | Bracco Ind Chimica Spa | |
| US4230845A (en) | 1978-08-31 | 1980-10-28 | Mallinckrodt, Inc. | Polyhydroxy-alkyl-3,5-disubstituted-2,4,6-triiodocarbanilates |
| DE2852094A1 (de) * | 1978-11-30 | 1980-06-12 | Schering Ag | Neue roentgenkontrastmittel |
| DE2909439A1 (de) * | 1979-03-08 | 1980-09-18 | Schering Ag | Neue nichtionische roentgenkontrastmittel |
| DE2928417A1 (de) | 1979-07-12 | 1981-01-29 | Schering Ag | Trijodierte basen |
| IT1193211B (it) * | 1979-08-09 | 1988-06-15 | Bracco Ind Chimica Spa | Derivati dell'acido 2,4,6-triiodo-isoftalico,metodo per la loro preparazione e mezzi di contrasto che li contengono |
-
1980
- 1980-10-10 DE DE19803038853 patent/DE3038853A1/de not_active Withdrawn
-
1981
- 1981-07-07 DK DK300281A patent/DK158468C/da not_active IP Right Cessation
- 1981-07-31 IL IL63480A patent/IL63480A/xx not_active IP Right Cessation
- 1981-08-07 AT AT81106183T patent/ATE10488T1/de not_active IP Right Cessation
- 1981-08-07 EP EP81106183A patent/EP0049745B1/de not_active Expired
- 1981-08-07 DE DE8181106183T patent/DE3167463D1/de not_active Expired
- 1981-08-11 GR GR65764A patent/GR75308B/el unknown
- 1981-08-11 AU AU73978/81A patent/AU545934B2/en not_active Ceased
- 1981-08-12 IE IE1841/81A patent/IE51495B1/en not_active IP Right Cessation
- 1981-08-12 ES ES504701A patent/ES504701A0/es active Granted
- 1981-08-12 CA CA000383725A patent/CA1186333A/en not_active Expired
- 1981-08-12 US US06/292,115 patent/US4426371A/en not_active Expired - Lifetime
- 1981-08-13 JP JP56126061A patent/JPS57145849A/ja active Granted
- 1981-08-13 NO NO812753A patent/NO154550C/no unknown
- 1981-08-13 PH PH26047A patent/PH18855A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP0049745A1 (de) | 1982-04-21 |
| GR75308B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1984-07-13 |
| EP0049745B1 (de) | 1984-11-28 |
| US4426371A (en) | 1984-01-17 |
| NO154550C (no) | 1986-10-15 |
| IL63480A0 (en) | 1981-10-30 |
| JPS57145849A (en) | 1982-09-09 |
| DE3038853A1 (de) | 1982-05-27 |
| IE51495B1 (en) | 1987-01-07 |
| NO812753L (no) | 1982-04-13 |
| IL63480A (en) | 1984-03-30 |
| AU545934B2 (en) | 1985-08-08 |
| IE811841L (en) | 1982-05-10 |
| DE3167463D1 (en) | 1985-01-10 |
| ES8205757A1 (es) | 1982-08-16 |
| NO154550B (no) | 1986-07-07 |
| DK158468C (da) | 1990-10-08 |
| ATE10488T1 (de) | 1984-12-15 |
| AU7397881A (en) | 1982-04-22 |
| JPH0222066B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1990-05-17 |
| DK158468B (da) | 1990-05-21 |
| PH18855A (en) | 1985-10-21 |
| ES504701A0 (es) | 1982-08-16 |
| DK300281A (da) | 1982-04-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1186333A (en) | N-hydroxyalkylated dicarboxylic acid bis-(3,5- dicarbamoyl-2,4,6-triiodoanilides), process for their preparation, and x-ray contrast preparations containing them | |
| EP0108638B1 (en) | X-ray contrast agents | |
| EP0299795B1 (en) | Aminopolycarboxylic acids and derivatives thereof | |
| US5885548A (en) | Multiply substituted DTPA derivatives and their metal complexes, and their metal complexes, pharmaceutical agents that contain these complexes, their use in diagnosis and therapy, as well as process for the production of pharmaceutical agents | |
| HK1003572B (en) | Aminocarboxylic acids and derivatives thereof | |
| IE62460B1 (en) | New dicarboxylic acid-bis-(3,5-dicarbamoyl-2,4,6-triiodoanilides), process for their production as well as x-ray contrast media containing them | |
| DE3150916C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| KR19980701674A (ko) | 비스무트 화합물 | |
| CA1303505C (en) | Anti-tumor compositions containing 5, 5-dimethyl-2- phenyl-4-thiazolidine carboxylic acid or 5, 5- dimethyl-2-(2-hydroxyphenyl)-4-thiazolidine carboxylic acid | |
| US3692824A (en) | Novel 3,5-substituted 2,4,6-triiodobenzoic acids and salts thereof | |
| US6040432A (en) | Metal complexes, of DTPA derivatives suitable for use in diagnosis and therapy | |
| US3804892A (en) | Novel 3,5-substituted 2,4,6-triiodobenzoic acids and salts thereof | |
| US5733522A (en) | Derivatized DTPA complexes, pharmaceutical agents containing these compounds, their use and process for their production | |
| CA1099707A (en) | Aglycones and processes for their preparation | |
| IE64759B1 (en) | New substituted dicarboxylic acid-bis (3,5-dicarbamoyl-2,4,6-triiodoanilides) process for their production as well as x-ray contrast media containing them | |
| EP0642492B1 (en) | 5,5'-/(1,3-propanediyl) bis-/imino(2-oxo-2,1-ethanediyl)acetylimino/bis(2,4,6-triiodo-1,3-benzenedicarboxyamides), and contrast media containing them | |
| DE3215676A1 (de) | Amidinderivate, verfahren zu deren herstellung und pharmazeutische mittel, die diese verbindungen enthalten | |
| US3632738A (en) | Method for the x-ray visualization of body cavities and a preparation for carrying out the method | |
| CA2100338A1 (en) | Non ionic iodized agents for x-ray contrasting, method for preparing them and galenical compositions containing them | |
| HK1006019B (en) | Non-ionic iodinated compounds, procedure for their preparation and contrast agents containing them | |
| HK1006019A1 (en) | Non-ionic iodinated compounds, procedure for their preparation and contrast agents containing them | |
| AU617338B2 (en) | Aminopolycarboxylic acids and derivatives thereof | |
| US5871755A (en) | Dehydroalanine derivatives for protecting the skin, the mucous membranes and/or the hair from oxidative stress, cosmetic or dermatological compositions containing them | |
| HUT73493A (en) | Salts and complexes of n,n`-bis(dicarboxy-methyl)-1,4,10,13-tetraoxa-7,16-diaza-cyclooctadekane derivatives, ad pharmaceutical compositions containing them | |
| JPH0546346B2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |