DE2726196C2 - 2,4,6-Trijod-N,N'-bis(2,3-dihydroxypropyl)-isophthalamide, Verfahren zu deren Herstellung und diese enthaltende radiologische Mittel - Google Patents
2,4,6-Trijod-N,N'-bis(2,3-dihydroxypropyl)-isophthalamide, Verfahren zu deren Herstellung und diese enthaltende radiologische MittelInfo
- Publication number
- DE2726196C2 DE2726196C2 DE2726196A DE2726196A DE2726196C2 DE 2726196 C2 DE2726196 C2 DE 2726196C2 DE 2726196 A DE2726196 A DE 2726196A DE 2726196 A DE2726196 A DE 2726196A DE 2726196 C2 DE2726196 C2 DE 2726196C2
- Authority
- DE
- Germany
- Prior art keywords
- ray contrast
- dihydroxypropyl
- bis
- triiodo
- 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 description 11
- 238000002360 preparation method Methods 0.000 title claims description 4
- YIPGLACOACNFML-UHFFFAOYSA-N 1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical class OCC(O)CNC(=O)C1=C(I)C=C(I)C(C(=O)NCC(O)CO)=C1I YIPGLACOACNFML-UHFFFAOYSA-N 0.000 title claims 3
- 150000001875 compounds Chemical class 0.000 claims description 64
- 239000000243 solution Substances 0.000 claims description 26
- 239000002872 contrast media Substances 0.000 claims description 20
- -1 N-substituted triiodobenzamides Chemical class 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229940039231 contrast media Drugs 0.000 claims description 8
- 238000002347 injection Methods 0.000 claims description 6
- 239000007924 injection Substances 0.000 claims description 6
- 231100000419 toxicity Toxicity 0.000 claims description 6
- 230000001988 toxicity Effects 0.000 claims description 6
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- 206010029155 Nephropathy toxic Diseases 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 231100000053 low toxicity Toxicity 0.000 claims description 4
- 230000007694 nephrotoxicity Effects 0.000 claims description 4
- 231100000417 nephrotoxicity Toxicity 0.000 claims description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 239000011630 iodine Substances 0.000 claims description 3
- 230000000694 effects Effects 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- 238000002583 angiography Methods 0.000 claims 3
- 238000009608 myelography Methods 0.000 claims 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 claims 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 claims 2
- 238000007487 urography Methods 0.000 claims 2
- 238000012800 visualization Methods 0.000 claims 2
- WGTJGVDPCKNNFQ-UHFFFAOYSA-N 3-n-(2,3-dihydroxypropyl)benzene-1,3-dicarboxamide Chemical class NC(=O)C1=CC=CC(C(=O)NCC(O)CO)=C1 WGTJGVDPCKNNFQ-UHFFFAOYSA-N 0.000 claims 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000004202 carbamide Substances 0.000 claims 1
- 230000002490 cerebral effect Effects 0.000 claims 1
- 229940109239 creatinine Drugs 0.000 claims 1
- 238000003384 imaging method Methods 0.000 claims 1
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 claims 1
- 230000003204 osmotic effect Effects 0.000 claims 1
- 230000002093 peripheral effect Effects 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 21
- 239000000203 mixture Substances 0.000 description 18
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- QZUPTXGVPYNUIT-UHFFFAOYSA-N isophthalamide Chemical compound NC(=O)C1=CC=CC(C(N)=O)=C1 QZUPTXGVPYNUIT-UHFFFAOYSA-N 0.000 description 9
- 239000008215 water for injection Substances 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 5
- 230000021736 acetylation Effects 0.000 description 5
- 238000006640 acetylation reaction Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 230000026045 iodination Effects 0.000 description 5
- 238000006192 iodination reaction Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 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 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- GGTSJKFPGKFLCZ-UHFFFAOYSA-N dimethyl 5-nitrobenzene-1,3-dicarboxylate Chemical compound COC(=O)C1=CC(C(=O)OC)=CC([N+]([O-])=O)=C1 GGTSJKFPGKFLCZ-UHFFFAOYSA-N 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 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 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 3
- KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 3
- SHWNNYZBHZIQQV-UHFFFAOYSA-J EDTA monocalcium diisodium salt Chemical compound [Na+].[Na+].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O SHWNNYZBHZIQQV-UHFFFAOYSA-J 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000003957 anion exchange resin Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 239000003729 cation exchange resin Substances 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229960001866 silicon dioxide Drugs 0.000 description 3
- 229950004777 sodium calcium edetate Drugs 0.000 description 3
- KSPPWGQIGVSIRK-UHFFFAOYSA-N 1-nitrocyclohexa-3,5-diene-1,3-dicarboxylic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)(C(O)=O)C1 KSPPWGQIGVSIRK-UHFFFAOYSA-N 0.000 description 2
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 description 2
- SSZWWUDQMAHNAQ-UHFFFAOYSA-N 3-chloropropane-1,2-diol Chemical compound OCC(O)CCl SSZWWUDQMAHNAQ-UHFFFAOYSA-N 0.000 description 2
- XOZGAPXHJKSZCU-UHFFFAOYSA-N 5-amino-1-n,3-n-bis(2,3-dihydroxypropyl)benzene-1,3-dicarboxamide Chemical compound NC1=CC(C(=O)NCC(O)CO)=CC(C(=O)NCC(O)CO)=C1 XOZGAPXHJKSZCU-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 229910002674 PdO Inorganic materials 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940009662 edetate Drugs 0.000 description 2
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N isophthalic acid Chemical compound OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 description 2
- 238000007069 methylation reaction Methods 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LJEBHEAPZMNBSI-UHFFFAOYSA-N 1-n,3-n-bis(2,3-dihydroxypropyl)-5-nitrobenzene-1,3-dicarboxamide Chemical compound OCC(O)CNC(=O)C1=CC(C(=O)NCC(O)CO)=CC([N+]([O-])=O)=C1 LJEBHEAPZMNBSI-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
- JUJWROOIHBZHMG-QYKNYGDISA-N 2-deuteriopyridine Chemical compound [2H]C1=CC=CC=N1 JUJWROOIHBZHMG-QYKNYGDISA-N 0.000 description 1
- VYWYYJYRVSBHJQ-UHFFFAOYSA-N 3,5-dinitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 VYWYYJYRVSBHJQ-UHFFFAOYSA-N 0.000 description 1
- SCJSIJNHSLUYAR-UHFFFAOYSA-N 5-(diacetylamino)-2,4,6-triiodobenzene-1,3-dicarbonyl chloride Chemical compound CC(=O)N(C(C)=O)C1=C(I)C(C(Cl)=O)=C(I)C(C(Cl)=O)=C1I SCJSIJNHSLUYAR-UHFFFAOYSA-N 0.000 description 1
- HYGGDKPPAGGKNN-UHFFFAOYSA-N 5-acetamido-2,4,6-triiodobenzene-1,3-dicarbonyl chloride Chemical compound CC(=O)NC1=C(I)C(C(Cl)=O)=C(I)C(C(Cl)=O)=C1I HYGGDKPPAGGKNN-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
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 239000004593 Epoxy Substances 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
- 229910004373 HOAc Inorganic materials 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 230000000397 acetylating effect Effects 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 230000009435 amidation Effects 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000011651 chromium Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- 150000005690 diesters Chemical class 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000012336 iodinating agent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical class N* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000012070 reactive reagent Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 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
- C07C237/32—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 the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by oxygen atoms
-
- 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
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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB24338/76A GB1548594A (en) | 1976-06-11 | 1976-06-11 | Triiodoisophthalic acid amides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2726196A1 DE2726196A1 (de) | 1977-12-22 |
| DE2726196C2 true DE2726196C2 (de) | 1983-12-29 |
Family
ID=10210154
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2726196A Expired DE2726196C2 (de) | 1976-06-11 | 1977-06-10 | 2,4,6-Trijod-N,N'-bis(2,3-dihydroxypropyl)-isophthalamide, Verfahren zu deren Herstellung und diese enthaltende radiologische Mittel |
Country Status (11)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19510864A1 (de) * | 1995-03-16 | 1996-09-19 | Schering Ag | Röntgenkontrastmittel für die Computertomographie und Urographie |
Families Citing this family (101)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1132901A (en) * | 1978-07-04 | 1982-10-05 | Fridtjov B. Rakli | Aniline x-ray agent and buffer whose ph decreases with temperature |
| DE2909439A1 (de) | 1979-03-08 | 1980-09-18 | Schering Ag | Neue nichtionische roentgenkontrastmittel |
| US4256729A (en) * | 1979-03-23 | 1981-03-17 | Mallinckrodt, Inc. | N,N'-Bis-(2,3-dihydroxypropyl)-2,4,6-triiodo-5-(2-keto-L-gulonamido)isophthalamide and radiological compositions containing same |
| 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 |
| IT1207226B (it) * | 1979-08-09 | 1989-05-17 | Bracco Ind Chimica Spa | Derivati dell'acido 2,4,6-triiodo-isoftalico, metodo per la loro preparazione e mezzi di contrasto che li contengono. |
| DE3001292A1 (de) * | 1980-01-11 | 1981-07-16 | Schering Ag Berlin Und Bergkamen, 1000 Berlin | Nichtionische 5-c-substituierte 2,4,6-trijod-isophthalsaeure-derivate |
| DE3038853A1 (de) | 1980-10-10 | 1982-05-27 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Neue n-hydroxy-alkylierte dicarbonsaeure-bis-(3,5-dicarbamoyl-2,4,6-trijodanilide), deren herstellung und diese enthaltende roentgenkonstrastmittel (ii) |
| JPS58102200A (ja) * | 1981-12-14 | 1983-06-17 | 日本原子力事業株式会社 | 沈降分離槽 |
| DE3150916A1 (de) * | 1981-12-18 | 1983-06-30 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | N-hydroxyaethylierte 2,4,6-trijodaminoisiophthalsaeure-bis- trihydroxybutylamide, deren herstellung und diese enthaltende roentgenkontrastmittel" |
| US4396598A (en) * | 1982-01-11 | 1983-08-02 | Mallinckrodt, Inc. | Triiodoisophthalamide X-ray contrast agent |
| DK162045C (da) * | 1982-10-01 | 1992-02-10 | Nyegaard & Co As | Trijodbenzenderivater, fremgangsmaade til fremstilling deraf og radiologiske praeparater indeholdende saadanne forbindelser |
| US5204086A (en) * | 1982-10-01 | 1993-04-20 | Nycomed Imaging As | X-ray contrast agent |
| EP0108638B1 (en) * | 1982-11-08 | 1986-07-16 | NYEGAARD & CO. A/S | X-ray contrast agents |
| US5191119A (en) * | 1983-10-20 | 1993-03-02 | Cook Imaging Corp. | Process for producing non-ionic radiographic contrast media utilizing N-allylation |
| US4584401A (en) * | 1983-10-20 | 1986-04-22 | Biophysica Foundation | Methods and compositions involving polyhydroxylated polyiodo non-ionic contrast media |
| JPS6091807U (ja) * | 1983-11-30 | 1985-06-22 | 松下電器産業株式会社 | テ−ブル |
| JPS634809Y2 (US20100292554A1-20101118-C00004.png) * | 1984-10-04 | 1988-02-08 | ||
| US4954348A (en) * | 1985-08-09 | 1990-09-04 | Cook Imaging Corporation | Non-ionic polyol contrast media from ionic contrast media |
| DE3689330T2 (de) * | 1985-08-09 | 1994-05-19 | Cook Imaging Corp | Nichtionische polyolkontrastmittel aus ionischen kontrastmitteln. |
| US5035877A (en) * | 1985-08-09 | 1991-07-30 | Cook Imaging Corporation | Non-ionic contrast media from ionic contrast media |
| JPH0637447B2 (ja) * | 1987-10-31 | 1994-05-18 | 東洋紡績株式会社 | 新規アミド化合物 |
| US5698739A (en) * | 1989-07-05 | 1997-12-16 | Schering Aktiengesellschaft | Carboxamide non-ionic contrast media |
| GB8919929D0 (en) * | 1989-09-04 | 1989-10-18 | Nycomed As | Compositions |
| US5232685A (en) * | 1989-11-03 | 1993-08-03 | Schering Aktiengesellschaft | Nonionic x-ray contrast medium with high iodine content |
| DE3937118A1 (de) * | 1989-11-03 | 1991-05-08 | Schering Ag | Nichtionische roentgenkontrastmittel mit hohem jodgehalt |
| US5614638A (en) * | 1989-11-29 | 1997-03-25 | Bracco International B.V. | Nonionic radiographic contrast agents |
| CA2029830A1 (en) * | 1989-11-29 | 1991-05-30 | Ramachandran S. Ranganathan | Nonionic radiographic contrast agents |
| 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 |
| US5191120A (en) * | 1989-12-13 | 1993-03-02 | Mallinckrodt Medical, Inc. | Process for preparing nonionic X-ray contrast agents |
| US4997983A (en) * | 1990-01-31 | 1991-03-05 | Mallinckrodt, Inc. | Process for production of ioversol |
| US5527926A (en) * | 1990-11-26 | 1996-06-18 | Bracco International B.V. | Methods and compositions for using non-ionic contrast agents to reduce the risk of clot formation in diagnostic procedures |
| US5356613A (en) * | 1991-03-18 | 1994-10-18 | Mallinckrodt Medical, Inc. | X-ray contrast agents, compositions and methods |
| DE4109169A1 (de) * | 1991-03-20 | 1992-09-24 | Koehler Chemie Dr Franz | Wasserloesliche nicht ionische roentgenkontrastmittel sowie mittel und verfahren zu ihrer herstellung |
| US5169864A (en) * | 1991-11-15 | 1992-12-08 | Baxter International Inc. | Unbuffered premixed ranitidine formulation |
| JPH07501809A (ja) * | 1991-12-03 | 1995-02-23 | マリンクロッド・メディカル・インコーポレイテッド | 非イオン性ｘ線造影剤組成物およびその製造方法 |
| US5278311A (en) * | 1992-06-05 | 1994-01-11 | E. R. Squibb & Sons, Inc. | Nonionic radiographic contrast agents |
| WO1994005337A1 (en) * | 1992-09-02 | 1994-03-17 | Mallinckrodt Medical, Inc. | Nonionic x-ray contrast agents, compositions and methods |
| IL110391A (en) * | 1993-07-30 | 1998-12-06 | Zambon Spa | Process for the formation of infamidol |
| US5665331A (en) * | 1995-01-10 | 1997-09-09 | Nanosystems L.L.C. | Co-microprecipitation of nanoparticulate pharmaceutical agents with crystal growth modifiers |
| US5662883A (en) * | 1995-01-10 | 1997-09-02 | Nanosystems L.L.C. | Microprecipitation of micro-nanoparticulate pharmaceutical agents |
| US5716642A (en) * | 1995-01-10 | 1998-02-10 | Nano Systems L.L.C. | Microprecipitation of nanoparticulate pharmaceutical agents using surface active material derived from similar pharmaceutical agents |
| US5560932A (en) * | 1995-01-10 | 1996-10-01 | Nano Systems L.L.C. | Microprecipitation of nanoparticulate pharmaceutical agents |
| US5543133A (en) * | 1995-02-14 | 1996-08-06 | Nanosystems L.L.C. | Process of preparing x-ray contrast compositions containing nanoparticles |
| IT1275429B (it) * | 1995-05-18 | 1997-08-07 | Zambon Spa | Processo per la preparazione di un intermedio utile nella sintesi di composti organici |
| CN1078201C (zh) * | 1995-11-20 | 2002-01-23 | 江苏省原子医学研究所 | 一种碘海醇的制备方法 |
| GB9618055D0 (en) * | 1996-08-29 | 1996-10-09 | Nycomed Imaging As | Process |
| US5840967A (en) | 1996-08-29 | 1998-11-24 | Nycomed Imaging As | Process for the preparation of contrast agents |
| GB9618056D0 (en) * | 1996-08-29 | 1996-10-09 | Nycomed Imaging As | Process |
| US5705692A (en) * | 1996-09-27 | 1998-01-06 | Abbott Laboratories | Process for the preparation of iohexol |
| PT101919B (pt) * | 1996-09-30 | 2000-01-31 | Hovione Sociedade Quimica Sa | Um processo para a purificacao de tohexol |
| US5861140A (en) * | 1996-11-20 | 1999-01-19 | Hoechst Celanese Corp. | Tripodal paramagnetic contrast agents for MR imaging |
| US5861138A (en) * | 1996-11-20 | 1999-01-19 | Hoechst Celanese Corp. | Ligands for MRI contrast agent |
| US5824821A (en) * | 1997-02-07 | 1998-10-20 | Nycomed Imaging As | Process for the preparation of iodinated contrast agents and intermediates therefor |
| US5847212A (en) * | 1997-04-21 | 1998-12-08 | Abbott Laboratories | Process for the preparation of iohexol |
| GB9710726D0 (en) * | 1997-05-23 | 1997-07-16 | Nycomed Imaging As | Compound |
| GB9710725D0 (en) | 1997-05-23 | 1997-07-16 | Nycomed Imaging As | Process |
| US6137006A (en) * | 1997-05-23 | 2000-10-24 | Nycomed Imaging As | Preparation of tri-iodo benzene compounds |
| GB9710728D0 (en) * | 1997-05-23 | 1997-07-16 | Nycomed Imaging As | Method |
| IT1292037B1 (it) * | 1997-05-30 | 1999-01-25 | Bracco Spa | Processo per la preparazione di 5-(acetil 62,3-diidrossipropil)- ammino)-n,n'-bis(2,3-diidrossipropil)-2,4,6-triiodo-1,3-benzen- |
| US5820851A (en) * | 1997-08-21 | 1998-10-13 | Hoechst Celanese Corporation | Tripodal pyridine ligands as MRI contrast agents |
| US5869025A (en) * | 1997-08-21 | 1999-02-09 | Hoechst Celanese Corporation | Tripodal aromatic heterocycle carboxamide MRI contrast agents |
| US5824288A (en) * | 1997-08-21 | 1998-10-20 | Hoechst Celanese Corporation | Thio-substituted pyridines as MRI ligand precursors |
| US5869026A (en) * | 1997-08-21 | 1999-02-09 | Hoechst Celanese Corp. | Tripodal carboxamide ligands for MRI contrast agents |
| US5858329A (en) * | 1997-08-21 | 1999-01-12 | Hoechst Celanese Corporation | MRI diagnostic procedures using tripodal pyridinyl metal complexes |
| GB9720969D0 (en) * | 1997-10-02 | 1997-12-03 | Nycomed Imaging As | Process |
| GB9725010D0 (en) * | 1997-11-26 | 1998-01-28 | Nycomed Imaging As | Process |
| US20040170561A1 (en) * | 1998-09-08 | 2004-09-02 | Jesse Salb | Functional radiographic imaging methods and agents |
| US6751290B2 (en) | 1998-09-08 | 2004-06-15 | Veritas Pharmaceuticals, Inc. | Radiographic assessment of tissue after exposure to a compound |
| US6226352B1 (en) | 1998-09-08 | 2001-05-01 | Veritas Pharmaceuticals, Inc. | System and method for radiographic imaging of tissue |
| US6723746B2 (en) * | 1998-09-08 | 2004-04-20 | Veritas Pharmaceuticals, Inc. | Functional radiographic imaging methods and agents |
| GB9825095D0 (en) * | 1998-11-16 | 1999-01-13 | Nycomed Imaging As | Chemical process |
| EP1263324B1 (en) | 2000-03-16 | 2009-12-02 | Veritas Pharmaceuticals | Radiographic assessment of tissue response to compounds |
| AU2002245169A1 (en) | 2000-11-10 | 2002-07-08 | Wm. Marsh Rice University | Fullerene (c60)-based x-ray contrast agent for diagnostic imaging |
| IT1319670B1 (it) | 2000-12-01 | 2003-10-23 | Bracco Spa | Processo per la preparazione di 5-ammino-n,n'-bis(2-idrossi-1-(idrossimetil)etil))-1,3-benzendicarbossammide (i) e 5-ammino-n,n'- |
| ITMI20010773A1 (it) * | 2001-04-11 | 2002-10-11 | Chemi Spa | Processo per la produzione di ioexolo ad elevata purezza |
| KR20030032185A (ko) * | 2001-10-16 | 2003-04-26 | 동국제약 주식회사 | Ｎ,ｎ'-비스[2,3-디히드록시프로필]-2,4,6-트리요오드-5-아세틸아미도 이소 프탈아미드의 결정화방법 |
| EA011516B1 (ru) | 2005-01-13 | 2009-04-28 | Синвеншен Аг | Композиционный материал и способ его изготовления |
| JP4801661B2 (ja) * | 2005-03-18 | 2011-10-26 | マナック株式会社 | ５−アミノ−２，４，６−トリヨードイソフタル酸誘導体のアセチル化方法 |
| PT103391B (pt) | 2005-11-24 | 2008-10-30 | Hovione Farmaciencia S A | Processo para fabrico de lohexol |
| CN100344606C (zh) * | 2005-12-28 | 2007-10-24 | 江苏省原子医学研究所 | 一种碘昔兰的制备方法 |
| EP2093206A1 (en) | 2008-02-20 | 2009-08-26 | BRACCO IMAGING S.p.A. | Process for the iodination of aromatic compounds |
| US20110256068A1 (en) | 2009-01-09 | 2011-10-20 | Wistand Lars-Goeran | Contrast media compositions |
| DK2451994T3 (da) | 2009-07-07 | 2014-01-20 | Bracco Imaging Spa | Fremgangsmåde til fremstilling af et ioderende middel |
| EP2277859A1 (en) * | 2009-07-21 | 2011-01-26 | GE Healthcare AS | Acetylation using reduced concentration of acetic acid anhydride for synthesizing non-ionic X-ray contrast agents |
| EP2277851A1 (en) * | 2009-07-21 | 2011-01-26 | GE Healthcare AS | Acetylation using reduced volume of acetic acid anhydride for synthesizing non-ionic X-ray contrast agents |
| US20110021821A1 (en) * | 2009-07-21 | 2011-01-27 | Ge Healthcare As | Continuous acetylation process in synthesis of non-ionic x-ray contrast agents |
| KR101585751B1 (ko) * | 2010-07-12 | 2016-01-14 | 지이 헬스케어 에이에스 | 저농도의 조영제 및/또는 저방사선량의 x-선 영상화 |
| CN102249948B (zh) * | 2011-05-23 | 2014-01-29 | 苏州昊帆生物科技有限公司 | 5-乙酰氨基-n,n’-双-(2,3-二羟基丙基)-2,4,6-三碘间苯二甲酰胺的合成方法 |
| EP2606912A1 (en) * | 2011-12-23 | 2013-06-26 | Central Medical Service Co., Ltd. | Contrast medium composition with contrast enhancement effect by comprising highly concentrated agent |
| WO2015082720A1 (en) | 2013-12-06 | 2015-06-11 | Ge Healthcare As | Alternative process for the purification of an intermediate in the synthesis of non-ionic x-ray contrast agents |
| EP3077366B1 (en) * | 2013-12-06 | 2017-08-09 | GE Healthcare AS | Alternative acetylation process in the synthesis of non-ionic xray contrast agents |
| WO2015082718A1 (en) * | 2013-12-06 | 2015-06-11 | Ge Healthcare As | Alternative process for the purification of an intermediate in the synthesis of non-ionic x-ray contrast agents |
| RU2711501C2 (ru) | 2014-03-04 | 2020-01-17 | Оцука Фармасьютикал Ко., Лтд. | Порошок йогексола и способ его применения |
| PT108524B (pt) * | 2015-06-02 | 2017-12-15 | Hovione Farmaciência S A | Processo para a preparação de intermediários úteis na preparação de agentes de contraste não-iónicos |
| CN107778191A (zh) * | 2016-08-26 | 2018-03-09 | 正大天晴药业集团股份有限公司 | 一种碘普罗胺及其中间体的制备方法 |
| RU2655619C1 (ru) * | 2017-06-13 | 2018-05-29 | Алексей Георгиевич Александров | Способ получения фармацевтической субстанции на основе йогексола |
| CN107857714B (zh) * | 2017-11-29 | 2020-11-13 | 上海司太立制药有限公司 | 一种碘海醇中间体杂质的制备方法和用途 |
| CN108191690A (zh) * | 2017-12-11 | 2018-06-22 | 天津河清化学工业有限公司 | 碘海醇节能环保的连续化制备方法 |
| CN108191689A (zh) * | 2017-12-11 | 2018-06-22 | 天津河清化学工业有限公司 | 一种新型碘海醇节能环保的连续化制备方法 |
| EP4001261A1 (en) | 2020-11-23 | 2022-05-25 | Justesa Imagen S.A.U | Procedure for obtaining high purity iohexol |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL34803A (en) * | 1969-06-27 | 1975-03-13 | Nyegaard & Co As | N-hydroxyalkyl substituted benzamides and iodo methanesulfonamide and radiological compositions containing them |
| GB1321591A (en) | 1969-06-27 | 1973-06-27 | Nyegaard & Co As | Non-ionic iodinated x-ray contrast agents |
| 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 |
| BE788054A (fr) * | 1971-08-26 | 1973-02-26 | Bracco Ind Chimica Spa | Nouvel agent de contraste radiographique et procede pour le preparer |
| CH608189A5 (US20100292554A1-20101118-C00004.png) * | 1974-12-13 | 1978-12-29 | Savac Ag |
-
1976
- 1976-06-11 GB GB24338/76A patent/GB1548594A/en not_active Expired
-
1977
- 1977-06-10 JP JP6936377A patent/JPS5321137A/ja active Granted
- 1977-06-10 NL NLAANVRAGE7706385,A patent/NL175814C/xx not_active IP Right Cessation
- 1977-06-10 SE SE7706792A patent/SE441181B/xx not_active IP Right Cessation
- 1977-06-10 BE BE178353A patent/BE855580A/xx not_active IP Right Cessation
- 1977-06-10 FR FR7717904A patent/FR2354316A1/fr active Granted
- 1977-06-10 DK DK258477A patent/DK150504C/da not_active IP Right Cessation
- 1977-06-10 CH CH718677A patent/CH630064A5/de not_active IP Right Cessation
- 1977-06-10 DE DE2726196A patent/DE2726196C2/de not_active Expired
-
1979
- 1979-08-24 US US06/069,589 patent/US4250113A/en not_active Expired - Lifetime
-
1983
- 1983-11-17 HK HK566/83A patent/HK56683A/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19510864A1 (de) * | 1995-03-16 | 1996-09-19 | Schering Ag | Röntgenkontrastmittel für die Computertomographie und Urographie |
Also Published As
| Publication number | Publication date |
|---|---|
| US4250113A (en) | 1981-02-10 |
| JPS5654310B2 (US20100292554A1-20101118-C00004.png) | 1981-12-24 |
| DK150504C (da) | 1988-01-11 |
| FR2354316B1 (US20100292554A1-20101118-C00004.png) | 1982-11-12 |
| SE7706792L (sv) | 1977-12-12 |
| GB1548594A (en) | 1979-07-18 |
| DE2726196A1 (de) | 1977-12-22 |
| SE441181B (sv) | 1985-09-16 |
| BE855580A (fr) | 1977-12-12 |
| CH630064A5 (de) | 1982-05-28 |
| NL175814C (nl) | 1985-01-02 |
| FR2354316A1 (fr) | 1978-01-06 |
| DK150504B (da) | 1987-03-16 |
| JPS5321137A (en) | 1978-02-27 |
| HK56683A (en) | 1983-11-25 |
| NL7706385A (nl) | 1977-12-13 |
| DK258477A (da) | 1977-12-12 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE2726196C2 (de) | 2,4,6-Trijod-N,N'-bis(2,3-dihydroxypropyl)-isophthalamide, Verfahren zu deren Herstellung und diese enthaltende radiologische Mittel | |
| DE2031724C3 (de) | N-substituierte Trijodbenz- bzw. Jodmethansulfon-am'ide, Verfahren zu deren Herstellung und radiologische Zusammensetzungen | |
| EP0612322B1 (de) | Verfahren zur trennung von 5-methyl-tetrahydrofolsäure | |
| EP0308364B1 (de) | Neue Dicarbonsäure-bis(3,5-dicarbamoyl-2,4,6-Triiodanilide), Verfahren zu deren Herstellung sowie diese enthaltende Röntgenkontrastmittel | |
| EP0049745B1 (de) | Neue N-Hydroxy-alkylierte Dicarbonsäure-bis-(3,5-dicarbamoyl-2,4,6-trijodanilide), deren Herstellung und diese enthaltende Röntgenkontrastmittel | |
| DE2805928A1 (de) | Wasserloesliche, nicht ionische roentgenkontrastmittel und verfahren zu ihrer herstellung | |
| DE3709230A1 (de) | Neues calciumsalz der valproinsaeure | |
| DE3429949A1 (de) | Neue nicht -ionische 2,4,6-trijod-isophthalsaeure-bis-amide, verfahren zu ihrer herstellung und ihre verwendung als roentgenkontrastmittel | |
| DE2928417A1 (de) | Trijodierte basen | |
| EP0406992B1 (de) | Neue, nicht-ionische Carboxamid-Kontrastmittel | |
| DE2366349C2 (de) | Verfahren zur Herstellung von 5-Methyl-1-phenyl-2-(1H)-pyridon | |
| DE3536093C2 (US20100292554A1-20101118-C00004.png) | ||
| DE19900172A1 (de) | Verfahren zur Herstellung von L-p-Boronophenylalanin und Zwischenprodukt zur Herstellung desselben | |
| DE69014581T2 (de) | Nichtionische Jodverbindungen, Verfahren zu ihrer Herstellung und sie enthaltende Kontrastmittel. | |
| DE69214934T2 (de) | Nichtionische jodhaltige röntgenstrahlenkontrastmittel, verfahren zu ihrer herstellung und diese enthaltende zusammensetzungen | |
| DE2715382A1 (de) | Kontrastmittel fuer roentgenaufnahmen | |
| CH616403A5 (en) | Process for the preparation of 2,4,6-triodoisophthalamides which are readily soluble in water. | |
| DE69401327T2 (de) | Nicht-ionische iod-dimere als röntgenkontrastmittel, verfahren zu ihrer herstellung und galenische zusammensetzungen die diese enthalten | |
| DE1493979C3 (de) | Bis-(5-amino-2,4,6-trijod-N-alkylisophthalsäureamid) -Derivate von Dicarbonsäuren, deren Salze mit pharmazeutisch verwendbaren Kationen, Verfahren zur Herstellung dieser Verbindungen und diese enthaltende Röntgenkontrastmittel | |
| AT282594B (de) | Verfahren zur herstellung von neuem racemischem oder optisch aktivem (1-2'-nitrilophenoxy)-2-hydroxy-3-isopropylaminopropan und dessen salzen | |
| DE767161C (de) | Verfahren zur Herstellung von ª‰-(p-Oxyphenyl)-isopropylmethylaminen | |
| DE2913173A1 (de) | Szintillographisches mittel und verfahren zu seiner herstellung | |
| DE1926557A1 (de) | Cholecystographische Roentgenkontrastmittel | |
| DE943947C (de) | Verfahren zur Herstellung der erythro-1-p-Nitrophenyl-2-amino-1, 3-propandiole | |
| DE2547789C3 (de) | 5-Hydroxypropionylamino-2,4,6-trijodisophthalsäure-bis-(dihydroxypropylamide), Verfahren zu ihrer Herstellung und diese enthaltende Röntgenkontrastmittel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OD | Request for examination | ||
| 8126 | Change of the secondary classification |
Free format text: C07C102/00 A61K 49/04 |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: NYCOMED A/S, OSLO, NO |
|
| 8328 | Change in the person/name/address of the agent |
Free format text: ZUMSTEIN, F., DIPL.-CHEM. DR.RER.NAT. ASSMANN, E., DIPL.-CHEM. DR.RER.NAT. KLINGSEISEN, F., DIPL.-ING., PAT.-ANWAELTE, 8000 MUENCHEN |