EP0656884A1 - Polyjodierte verbindungen, verfahren zu ihrer herstellung und diese enthaltendekontrastmittel - Google Patents
Polyjodierte verbindungen, verfahren zu ihrer herstellung und diese enthaltendekontrastmittelInfo
- Publication number
- EP0656884A1 EP0656884A1 EP93919397A EP93919397A EP0656884A1 EP 0656884 A1 EP0656884 A1 EP 0656884A1 EP 93919397 A EP93919397 A EP 93919397A EP 93919397 A EP93919397 A EP 93919397A EP 0656884 A1 EP0656884 A1 EP 0656884A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- group
- represent
- formula
- groups
- compounds
- 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.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 86
- 238000002360 preparation method Methods 0.000 title abstract description 50
- 238000000034 method Methods 0.000 title abstract description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 14
- 239000000460 chlorine Substances 0.000 claims description 38
- 229910052740 iodine Inorganic materials 0.000 claims description 19
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 16
- 239000011630 iodine Substances 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 238000005917 acylation reaction Methods 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000003277 amino group Chemical group 0.000 claims description 11
- 230000010933 acylation Effects 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 9
- 238000005804 alkylation reaction Methods 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 7
- 230000029936 alkylation Effects 0.000 claims description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
- 125000003368 amide group Chemical group 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- 238000005660 chlorination reaction Methods 0.000 claims description 5
- 230000008878 coupling Effects 0.000 claims description 5
- 238000010168 coupling process Methods 0.000 claims description 5
- 238000005859 coupling reaction Methods 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001555 benzenes Chemical class 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000009435 amidation Effects 0.000 claims description 3
- 238000007112 amidation reaction Methods 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 238000002601 radiography Methods 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 239000000243 solution Substances 0.000 description 48
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 238000001704 evaporation Methods 0.000 description 21
- 230000008020 evaporation Effects 0.000 description 21
- 239000000047 product Substances 0.000 description 18
- -1 amine alcohols Chemical class 0.000 description 17
- 239000013078 crystal Substances 0.000 description 17
- 239000002244 precipitate Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 11
- 239000011347 resin Substances 0.000 description 11
- 229920005989 resin Polymers 0.000 description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 8
- MHABMANUFPZXEB-UHFFFAOYSA-N O-demethyl-aloesaponarin I Natural products O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=C(O)C(C(O)=O)=C2C MHABMANUFPZXEB-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- 229910004298 SiO 2 Inorganic materials 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 238000005115 demineralization Methods 0.000 description 5
- 230000002328 demineralizing effect Effects 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- SBMAZEDZVNSPTP-UHFFFAOYSA-N 1,3,5-triiodo-2-(2,4,6-triiodophenyl)benzene Chemical group IC1=CC(I)=CC(I)=C1C1=C(I)C=C(I)C=C1I SBMAZEDZVNSPTP-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000002872 contrast media Substances 0.000 description 3
- 229910052802 copper Inorganic materials 0.000 description 3
- 239000010949 copper Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 2
- ZGCHLAJIRWDGFE-UHFFFAOYSA-N 1-aminopropane-1,1-diol Chemical compound CCC(N)(O)O ZGCHLAJIRWDGFE-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- GFGURBBHVJTXDU-UHFFFAOYSA-N 3-iodo-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC([N+]([O-])=O)=C1 GFGURBBHVJTXDU-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- YTBSYETUWUMLBZ-UHFFFAOYSA-N D-Erythrose Natural products OCC(O)C(O)C=O YTBSYETUWUMLBZ-UHFFFAOYSA-N 0.000 description 2
- 206010056474 Erythrosis Diseases 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- GTTSNKDQDACYLV-UHFFFAOYSA-N Trihydroxybutane Chemical group CCCC(O)(O)O GTTSNKDQDACYLV-UHFFFAOYSA-N 0.000 description 2
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- ALHZEIINTQJLOT-UHFFFAOYSA-N (1-chloro-1-oxopropan-2-yl) acetate Chemical compound ClC(=O)C(C)OC(C)=O ALHZEIINTQJLOT-UHFFFAOYSA-N 0.000 description 1
- OZCRKDNRAAKDAN-HNQUOIGGSA-N (e)-but-1-ene-1,4-diol Chemical compound OCC\C=C\O OZCRKDNRAAKDAN-HNQUOIGGSA-N 0.000 description 1
- KRBIHOANUQUSRV-UHFFFAOYSA-N 1-(oxiran-2-yl)ethane-1,2-diol Chemical compound OCC(O)C1CO1 KRBIHOANUQUSRV-UHFFFAOYSA-N 0.000 description 1
- 239000005631 2,4-Dichlorophenoxyacetic acid Substances 0.000 description 1
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BIRALNDXXLEWHV-UHFFFAOYSA-N 2-propan-2-yl-1,3-dioxane-5-carbonyl chloride Chemical compound CC(C)C1OCC(C(Cl)=O)CO1 BIRALNDXXLEWHV-UHFFFAOYSA-N 0.000 description 1
- YSNYXNGOASZBJN-UHFFFAOYSA-N 3-(2,3-dihydroxypropanoylamino)-5-[3-(2,3-dihydroxypropanoylamino)-5-[2-hydroxyethyl(2,3,4-trihydroxybutyl)carbamoyl]-2,4,6-triiodophenyl]-N-(2-hydroxyethyl)-2,4,6-triiodo-N-(2,3,4-trihydroxybutyl)benzamide Chemical group OC(C(=O)NC=1C(=C(C(=C(C=1I)C(N(CC(C(CO)O)O)CCO)=O)I)C1=C(C(=C(C(=C1I)C(N(CCO)CC(C(CO)O)O)=O)I)NC(C(CO)O)=O)I)I)CO YSNYXNGOASZBJN-UHFFFAOYSA-N 0.000 description 1
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
- XVJSFQJMJQNVGO-UHFFFAOYSA-N 3-(3-carboxy-5-nitrophenyl)-5-nitrobenzoic acid Chemical group [O-][N+](=O)C1=CC(C(=O)O)=CC(C=2C=C(C=C(C=2)C(O)=O)[N+]([O-])=O)=C1 XVJSFQJMJQNVGO-UHFFFAOYSA-N 0.000 description 1
- MKCMCUCPJQAJKH-UHFFFAOYSA-N 3-[3-carbonochloridoyl-5-(diacetylamino)-2,4,6-triiodophenyl]-5-(diacetylamino)-2,4,6-triiodobenzoyl chloride Chemical group CC(=O)N(C(C)=O)C1=C(I)C(C(Cl)=O)=C(I)C(C=2C(=C(C(Cl)=O)C(I)=C(N(C(C)=O)C(C)=O)C=2I)I)=C1I MKCMCUCPJQAJKH-UHFFFAOYSA-N 0.000 description 1
- VUEHQMGMXMKHGT-UHFFFAOYSA-N 3-[3-carboxy-5-(diacetylamino)-2,4,6-triiodophenyl]-5-(diacetylamino)-2,4,6-triiodobenzoic acid Chemical group CC(=O)N(C(C)=O)C1=C(I)C(C(O)=O)=C(I)C(C=2C(=C(C(O)=O)C(I)=C(N(C(C)=O)C(C)=O)C=2I)I)=C1I VUEHQMGMXMKHGT-UHFFFAOYSA-N 0.000 description 1
- VEMYGEPVPLWHRR-UHFFFAOYSA-N 3-[[3-hydroxy-2-(hydroxymethyl)propanoyl]amino]-5-[3-[[3-hydroxy-2-(hydroxymethyl)propanoyl]amino]-2,4,6-triiodo-5-[methyl(2,3,4-trihydroxybutyl)carbamoyl]phenyl]-2,4,6-triiodo-N-methyl-N-(2,3,4-trihydroxybutyl)benzamide Chemical group OCC(C(=O)NC=1C(=C(C(=C(C=1I)C(N(CC(C(CO)O)O)C)=O)I)C1=C(C(=C(C(=C1I)C(N(C)CC(C(CO)O)O)=O)I)NC(C(CO)CO)=O)I)I)CO VEMYGEPVPLWHRR-UHFFFAOYSA-N 0.000 description 1
- LZFOCJBJYWXIQA-UHFFFAOYSA-N 3-acetyloxy-2-oxobutanoic acid Chemical compound CC(=O)OC(C)C(=O)C(O)=O LZFOCJBJYWXIQA-UHFFFAOYSA-N 0.000 description 1
- MFZWEPYJMNTNRS-UHFFFAOYSA-N 3-amino-5-(3-amino-5-carboxy-2,4,6-triiodophenyl)-2,4,6-triiodobenzoic acid Chemical group NC1=C(I)C(C(O)=O)=C(I)C(C=2C(=C(C(O)=O)C(I)=C(N)C=2I)I)=C1I MFZWEPYJMNTNRS-UHFFFAOYSA-N 0.000 description 1
- RNMWRTFLXBCPHP-UHFFFAOYSA-N 3-amino-5-(3-amino-5-carboxyphenyl)benzoic acid Chemical group NC1=CC(C(O)=O)=CC(C=2C=C(C=C(N)C=2)C(O)=O)=C1 RNMWRTFLXBCPHP-UHFFFAOYSA-N 0.000 description 1
- WAZWTTNGHMDUJD-UHFFFAOYSA-N 3-amino-5-[3-amino-5-[2,3-dihydroxypropyl(2,3,4-trihydroxybutyl)carbamoyl]-2,4,6-triiodophenyl]-N-(2,3-dihydroxypropyl)-2,4,6-triiodo-N-(2,3,4-trihydroxybutyl)benzamide Chemical group NC1=C(I)C(C(=O)N(CC(O)CO)CC(O)C(O)CO)=C(I)C(C=2C(=C(C(=O)N(CC(O)CO)CC(O)C(O)CO)C(I)=C(N)C=2I)I)=C1I WAZWTTNGHMDUJD-UHFFFAOYSA-N 0.000 description 1
- SHEBBMVCBRQVQX-UHFFFAOYSA-N 3-amino-5-[3-amino-5-[2-hydroxyethyl(2,3,4-trihydroxybutyl)carbamoyl]-2,4,6-triiodophenyl]-n-(2-hydroxyethyl)-2,4,6-triiodo-n-(2,3,4-trihydroxybutyl)benzamide Chemical group NC1=C(I)C(C(=O)N(CCO)CC(O)C(O)CO)=C(I)C(C=2C(=C(C(=O)N(CCO)CC(O)C(O)CO)C(I)=C(N)C=2I)I)=C1I SHEBBMVCBRQVQX-UHFFFAOYSA-N 0.000 description 1
- AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 description 1
- ABQCBCTXEZLEQC-UHFFFAOYSA-N 4-(2,3-dihydroxypropylamino)butane-1,2,3-triol Chemical compound OCC(O)CNCC(O)C(O)CO ABQCBCTXEZLEQC-UHFFFAOYSA-N 0.000 description 1
- PAHOOYLOBYJWTP-UHFFFAOYSA-N 4-(2-hydroxyethylamino)butane-1,2,3-triol Chemical compound OCCNCC(O)C(O)CO PAHOOYLOBYJWTP-UHFFFAOYSA-N 0.000 description 1
- QGRSTVXBRQIIPF-UHFFFAOYSA-N 4-(methylamino)butane-1,2,3-triol Chemical compound CNCC(O)C(O)CO QGRSTVXBRQIIPF-UHFFFAOYSA-N 0.000 description 1
- NUAPDTFBENBPBC-UHFFFAOYSA-N 4-[benzyl(2,3,4-trihydroxybutyl)amino]butane-1,2,3-triol Chemical compound OCC(O)C(O)CN(CC(O)C(O)CO)CC1=CC=CC=C1 NUAPDTFBENBPBC-UHFFFAOYSA-N 0.000 description 1
- WIFPJDJJFUSIFP-UHFFFAOYSA-N 4-aminobutane-1,2,3-triol Chemical compound NCC(O)C(O)CO WIFPJDJJFUSIFP-UHFFFAOYSA-N 0.000 description 1
- LLKFNPUXQZHIAE-UHFFFAOYSA-N 5-(3-aminopropyl)-8-bromo-3-methyl-2h-pyrazolo[4,3-c]quinolin-4-one Chemical compound O=C1N(CCCN)C2=CC=C(Br)C=C2C2=C1C(C)=NN2 LLKFNPUXQZHIAE-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
- ALDVGIXMUCONHA-UHFFFAOYSA-N C(N)(=O)C=1C(=C(C(=CC=1I)I)C1=C(C=C(C=C1I)I)I)I Chemical group C(N)(=O)C=1C(=C(C(=CC=1I)I)C1=C(C=C(C=C1I)I)I)I ALDVGIXMUCONHA-UHFFFAOYSA-N 0.000 description 1
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 1
- ZTSCVRSXWWAKAD-UHFFFAOYSA-N CC(=O)OCCN(CC(C(COC(=O)C)OC(=O)C)OC(=O)C)C(=O)C1=C(C(=C(C(=C1I)C2=C(C(=C(C(=C2I)N)I)C(=O)N(CCOC(=O)C)CC(C(COC(=O)C)OC(=O)C)OC(=O)C)I)I)N)I Chemical group CC(=O)OCCN(CC(C(COC(=O)C)OC(=O)C)OC(=O)C)C(=O)C1=C(C(=C(C(=C1I)C2=C(C(=C(C(=C2I)N)I)C(=O)N(CCOC(=O)C)CC(C(COC(=O)C)OC(=O)C)OC(=O)C)I)I)N)I ZTSCVRSXWWAKAD-UHFFFAOYSA-N 0.000 description 1
- YTBSYETUWUMLBZ-IUYQGCFVSA-N D-erythrose Chemical compound OC[C@@H](O)[C@@H](O)C=O YTBSYETUWUMLBZ-IUYQGCFVSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- WNQYRJJSKBXWMN-UHFFFAOYSA-N N-(2,3-dihydroxypropyl)-3-[3-[2,3-dihydroxypropyl(2,3,4-trihydroxybutyl)carbamoyl]-5-nitrophenyl]-5-nitro-N-(2,3,4-trihydroxybutyl)benzamide Chemical group [N+](=O)([O-])C=1C=C(C=C(C=1)C(N(CC(C(CO)O)O)CC(CO)O)=O)C1=CC(=CC(=C1)C(N(CC(CO)O)CC(C(CO)O)O)=O)[N+](=O)[O-] WNQYRJJSKBXWMN-UHFFFAOYSA-N 0.000 description 1
- SNRRFRFNBFLFFZ-UHFFFAOYSA-N N-(2-hydroxyethyl)-3-[3-[2-hydroxyethyl(2,3,4-trihydroxybutyl)carbamoyl]-2,4,6-triiodophenyl]-2,4,6-triiodo-N-(2,3,4-trihydroxybutyl)benzamide Chemical group OCCN(C(=O)C=1C(=CC(=C(C=1I)C1=C(C=C(C(=C1I)C(N(CCO)CC(C(CO)O)O)=O)I)I)I)I)CC(C(CO)O)O SNRRFRFNBFLFFZ-UHFFFAOYSA-N 0.000 description 1
- MHHVXFHRRCSEGT-UHFFFAOYSA-N N-methyl-3-[3-[methyl(2,3,4-trihydroxybutyl)carbamoyl]-5-nitrophenyl]-5-nitro-N-(2,3,4-trihydroxybutyl)benzamide Chemical group [N+](=O)([O-])C=1C=C(C=C(C=1)C(N(CC(C(CO)O)O)C)=O)C1=CC(=CC(=C1)C(N(C)CC(C(CO)O)O)=O)[N+](=O)[O-] MHHVXFHRRCSEGT-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- LFZYTHQYPVCNAQ-UHFFFAOYSA-N [2,3-diacetyloxy-4-[[3-amino-5-[3-amino-2,4,6-triiodo-5-[methyl(2,3,4-triacetyloxybutyl)carbamoyl]phenyl]-2,4,6-triiodobenzoyl]-methylamino]butyl] acetate Chemical group CC(=O)OCC(OC(C)=O)C(OC(C)=O)CN(C)C(=O)C1=C(I)C(N)=C(I)C(C=2C(=C(C(=O)N(C)CC(OC(C)=O)C(COC(C)=O)OC(C)=O)C(I)=C(N)C=2I)I)=C1I LFZYTHQYPVCNAQ-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 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
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229940039231 contrast media Drugs 0.000 description 1
- 238000006264 debenzylation reaction Methods 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- CGNYRXBURZLBKG-UHFFFAOYSA-N methyl 3-(3-methoxycarbonyl-5-nitrophenyl)-5-nitrobenzoate Chemical group [O-][N+](=O)C1=CC(C(=O)OC)=CC(C=2C=C(C=C(C=2)C(=O)OC)[N+]([O-])=O)=C1 CGNYRXBURZLBKG-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- DJQIYGIGFCBHDK-UHFFFAOYSA-N n-(2,3-dihydroxypropyl)-3-[3-[2,3-dihydroxypropyl(2,3,4-trihydroxybutyl)carbamoyl]-5-(2-hydroxypropanoylamino)-2,4,6-triiodophenyl]-5-(2-hydroxypropanoylamino)-2,4,6-triiodo-n-(2,3,4-trihydroxybutyl)benzamide Chemical group CC(O)C(=O)NC1=C(I)C(C(=O)N(CC(O)CO)CC(O)C(O)CO)=C(I)C(C=2C(=C(C(=O)N(CC(O)CO)CC(O)C(O)CO)C(I)=C(NC(=O)C(C)O)C=2I)I)=C1I DJQIYGIGFCBHDK-UHFFFAOYSA-N 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- VLZLOWPYUQHHCG-UHFFFAOYSA-N nitromethylbenzene Chemical compound [O-][N+](=O)CC1=CC=CC=C1 VLZLOWPYUQHHCG-UHFFFAOYSA-N 0.000 description 1
- 239000003690 nonionic contrast media Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 210000002330 subarachnoid space Anatomy 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- 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
-
- 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
Definitions
- the present invention relates to new polyiodinated compounds which can be used in contrast products for radiography.
- the invention also relates to a process for the preparation of these compounds and to the contrast products containing them.
- the subject of the invention is therefore poly-iodinated compounds of formula:
- R 1 and R 2 which are identical or different from each other, represent a group of formula
- R 3 , R 4 identical or different from each other, represent a group of formula
- R 5 and R 6 , R 7 and R 8 which are identical or different from each other represent a hydrogen atom, a linear or branched C 1 -C 6 alkyl group, a hydroxy- or polyhydroxy-C 1 alkyl group - Linear or branched C 6 , optionally also comprising one or more C 1 -C 6 alkoxy groups, in particular methoxy or ethoxy, a C 1 -C 6 alkoxy group, linear or branched C 1 -C 6 alkyl or a hydroxy- or polyhydroxy-alkoxy- (C 1 -C 6 ) linear or branched C 1 -C 6 alkyl, said substituents R 1 , R 2 , R 3 , R 4 comprising in total at least ten hydroxy groups.
- R 5 , R 6 and R 8 are chosen from -CH 3 , -CH 2 OH, -CH 2 -CH 2 OH,
- R 5 represents the group
- R 6 is chosen from -CH 3 , -CH 2 -CH 2 OH, and .
- R 7 is as defined above
- R 8 is chosen from -CH 3 , -CH 2 OH,, -CHOH-CH 2 OH and
- the preferred compounds of the present invention are those in which:
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group -NH-CO-CHOH-CH 2 OH (compound No. 1); - R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group -NH-CO-CH 3 (compound No. 3);
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group and R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- R 1 and R 2 represent the group
- R 3 and R 4 represent the group
- the compounds of general formula (I) of the present invention can be prepared by alkylation and / or acylation reactions.
- the compounds of general formula (I) of the present invention can in particular be prepared by a process comprising the following stages:
- X being chosen from chlorine, bromine and iodine and
- R ' 1 , R' 2 represent the group -CO 2 R with R representing a C 1 -C 6 alkyl group, and R ' 3 , R' 4 represent the group -NO 2 so as to obtain a compound of formula IV:
- R ' 1 , R' 2 , R ' 3 and R' 4 are as defined above.
- R 5 and R 6 being defined as above;
- step a) deprotection of the protected hydroxy groups and optionally alkylation of the amido groups by a reagent of formula ZR 7 , Z being a labile group such as Cl, Br or I and R 7 being as defined above.
- the reaction of step a) preferably takes place in an appropriate solvent such as xylene, nitrobenzene, nitrotoluene, DMF or pyridine, in the presence of a metal catalyst such as copper according to the method of Ullman (E. FANTA, Chem. Rev. 64, 613, 1964).
- step c) is a catalytic reduction by hydrogen on palladium carbon or on Ranney nickel or a chemical reduction.
- step d) takes place under usual conditions, such as by aqueous ICI or I 2 , in the presence of K1 / ethylamine at temperatures between 0 ° C and 100 ° C.
- acylation and alkylation reactions of steps f) and g) are carried out under conventional conditions, in the presence of a strong base.
- the compounds of formula (I) of the present invention can also be prepared by a process comprising the following steps:
- R 5 and R 6 being as defined above;
- the compounds of formula I of the present invention can also be prepared by a process comprising the following stages:
- X being chosen from chlorine, bromine and iodine and R ' 1 , R' 2 representing the group -CO 2 R with R representing H or a C 1 -C 6 alkyl group, and R ' 3 , R' 4 representing the group -NO 2 so as to obtain a compound of formula IV:
- R ' 1 , R' 2 , R ' 3 and R' 4 are as defined above;
- amine alcohols used to obtain the preferred compounds of the present invention can be prepared in the following manner: Preparation of the amine alcohol n ° 1 a) Preparation of the compound of formula
- the compound is prepared according to the method described above.
- butene 1,4-diol (commercially available from the company Aldrich-Strasbourg), butene 3,4-diol is prepared according to the method of rearrangement described in US Patent 4,661,646.
- the invention encompasses not only the compounds of formula (I) in the form of a racemic mixture but also the stereoisomers such as enantiomers, diastereoisomers, atropoisomers, SYN-ANTI, ENDO-EXO, EZ isomers, linked to the presence asymmetric carbon atoms and / or rotation impediments due to steric hindrance provided by iodine atoms and / or by the substituents R 1 to R 4 of the compounds of formula (I).
- the present invention also relates to contrast products which comprise at least one compound of formula (I).
- contrast media are used in humans and animals for radiological purposes.
- the preferred pharmaceutical form of the contrast agents according to the invention consists of aqueous solutions of the compounds.
- the compounds are encapsulated inside liposomes.
- the aqueous solutions generally contain a total of 5 to 100 g of compounds per 100 ml and the injectable amount of such solutions can generally vary from 1 to 1000 ml.
- the solutions can also contain additives such as a sodium salt including sodium citrate, heparin and sodium EDTA calcium.
- compositions can be administered by any of the routes conventionally used for iodinated nonionic contrast media.
- routes conventionally used for iodinated nonionic contrast media can be administered by enteral or parenteral route (intravenous, intraarterial, opacification of the cavities) and in particular in the subarachnoid space.
- the residual paste is washed with 2 ⁇ 500 ml of petroleum ether, then taken up in ether.
- the brown precipitate formed is drained and then purified by chromatography on silica. After evaporation, 20 g of brown crystals are obtained.
- step a) To the solution obtained in step a) are added dropwise 4.35 ml (0.024 mole) of a 70% IC1 solution. When the addition is complete, the reaction mixture is brought to 80 ° C. for 18 h and then left for 12 h at room temperature. The brown solution obtained is evaporated and then returned to iodization with 1.45 ml of 70% IC1 in 20 ml of MeOH. After 10 h at 80 ° the solvent is evaporated and the paste washed with acetone. The product is taken up in ether, then dried. 2.1 g of white crystals are obtained.
- the slightly concentrated reaction medium is poured onto 200 cm 3 of ice-cold H 2 O. After filtration of the precipitate, 10 g of a cream solid are obtained.
- Example 1 12.5 g (0.0376 mol) of the compound obtained in 4) of Example 1 are added to a solution of 100 ml of SOCl 2 and 0.1 ml of DMF. The solution is brought to reflux for 5 hours. After distillation of SOCl 2 , the paste obtained is dissolved in CH 2 Cl 2 and poured dropwise at 20 ° C in a solution containing 20.5 g (0.105 mole) of N-2,3 propanediol-N, 2,3 , 4-trihydroxybutylamine and 14.6 ml (0.105 mole) of triethylamine dissolved in 80 ml of DMAC. After addition, the mixture is stirred for 4 hours at room temperature. After filtration of the triethylamine hydrochloride, the solvent is evaporated. The paste obtained is purified by passage over H + resin. After evaporation of the solvent, 33 g of brown oil are obtained.
- step a) To the solution obtained in step a) are added dropwise 54 ml (0.3 mole) of a 70% ICl solution. When the addition is complete, the reaction mixture is left at room temperature for 12 hours. The solution is poured into 2000 ml of ether, the precipitate obtained is filtered and then washed with ether. After drying, the product obtained is returned to iodization with 54 ml (0.3 mole) of 70% IC1 in 500 ml of MeOH. After 12 hours at 50 ° C the same treatment as above is applied to the solution. The precipitate obtained is returned a third time to iodization with 27 ml of IC1 (0.15 mole) in 300 ml of MeOH.
- the paste obtained is purified by passage over H + resin. After evaporation of the solvent, 150 g of brown oil are obtained.
- step a) To the solution obtained in step a) are added dropwise 62 ml (0.353 mole) of a 10% ICl solution. When the addition is complete, the reaction mixture is left at room temperature for 12 hours. The solution is poured into 2000 ml of ether, the precipitate obtained is filtered, then washed with ether. After drying, the product obtained is returned to iodization with 31 ml of 70% IC1 (0.17 mole) in 300 ml of MeOH. After 12 hours at 50 ° C, the same treatment as above is applied to the solution. Cream crystals are obtained.
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)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9210270 | 1992-08-25 | ||
FR9210270A FR2695125B1 (fr) | 1992-08-25 | 1992-08-25 | Nouveaux composés poly-iodés, procédé de préparation, produit de contraste les contenant. |
PCT/FR1993/000824 WO1994004488A1 (fr) | 1992-08-25 | 1993-08-24 | Nouveaux composes poly-iodes, procede de preparation, produit de contraste les contenant |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0656884A1 true EP0656884A1 (de) | 1995-06-14 |
Family
ID=9433015
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP93919397A Withdrawn EP0656884A1 (de) | 1992-08-25 | 1993-08-24 | Polyjodierte verbindungen, verfahren zu ihrer herstellung und diese enthaltendekontrastmittel |
Country Status (15)
Country | Link |
---|---|
US (1) | US5618977A (de) |
EP (1) | EP0656884A1 (de) |
JP (1) | JPH08500355A (de) |
CN (1) | CN1090572A (de) |
AU (1) | AU4964493A (de) |
CA (1) | CA2142986A1 (de) |
FI (1) | FI950874A (de) |
FR (1) | FR2695125B1 (de) |
HU (1) | HUT70943A (de) |
IL (1) | IL106768A0 (de) |
NO (1) | NO950665L (de) |
PL (1) | PL307587A1 (de) |
TR (1) | TR26907A (de) |
WO (1) | WO1994004488A1 (de) |
ZA (1) | ZA936188B (de) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6310243B1 (en) | 1994-09-23 | 2001-10-30 | Nycomed Imaging As | Iodinated x-ray contrast media |
GB9419206D0 (en) * | 1994-09-23 | 1994-11-09 | Nycomed Innovation Ab | Contrast media |
GB9419203D0 (en) * | 1994-09-23 | 1994-11-09 | Nycomed Innovation Ab | Contrast media |
IT1271134B (it) * | 1994-12-01 | 1997-05-26 | Bracco Spa | Derivati iodurati del bifenile e loro impiego diagnostico |
US6265610B1 (en) | 1999-01-12 | 2001-07-24 | The University Of North Carolina At Chapel Hill | Contrast media for angiography |
EP1940841B9 (de) | 2005-10-07 | 2017-04-19 | Guerbet | Verbindungen mit einem eine biologische zielstruktur erkennenden teil, das mit einem zum komplexieren von gallium fähigen signalteil gekoppelt ist |
US10918742B2 (en) | 2016-03-25 | 2021-02-16 | Nanoprobes, Inc. | Iodine-based particles |
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 |
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 |
IL90326A (en) * | 1988-06-02 | 1993-05-13 | Guerbet Sa | Non-ionic triiodobenzene compounds and contrast media containing them |
-
1992
- 1992-08-25 FR FR9210270A patent/FR2695125B1/fr not_active Expired - Fee Related
-
1993
- 1993-08-23 IL IL106768A patent/IL106768A0/xx unknown
- 1993-08-24 WO PCT/FR1993/000824 patent/WO1994004488A1/fr not_active Application Discontinuation
- 1993-08-24 JP JP6505969A patent/JPH08500355A/ja active Pending
- 1993-08-24 AU AU49644/93A patent/AU4964493A/en not_active Abandoned
- 1993-08-24 PL PL93307587A patent/PL307587A1/xx unknown
- 1993-08-24 US US08/387,721 patent/US5618977A/en not_active Expired - Lifetime
- 1993-08-24 EP EP93919397A patent/EP0656884A1/de not_active Withdrawn
- 1993-08-24 CA CA002142986A patent/CA2142986A1/en not_active Abandoned
- 1993-08-24 HU HU9500578A patent/HUT70943A/hu unknown
- 1993-08-24 ZA ZA936188A patent/ZA936188B/xx unknown
- 1993-08-25 CN CN93118233A patent/CN1090572A/zh active Pending
- 1993-08-25 TR TR00731/93A patent/TR26907A/xx unknown
-
1995
- 1995-02-22 NO NO950665A patent/NO950665L/no unknown
- 1995-02-24 FI FI950874A patent/FI950874A/fi unknown
Non-Patent Citations (1)
Title |
---|
See references of WO9404488A1 * |
Also Published As
Publication number | Publication date |
---|---|
AU4964493A (en) | 1994-03-15 |
FI950874A0 (fi) | 1995-02-24 |
NO950665D0 (no) | 1995-02-22 |
CN1090572A (zh) | 1994-08-10 |
NO950665L (no) | 1995-04-24 |
HU9500578D0 (en) | 1995-04-28 |
FR2695125B1 (fr) | 1994-12-23 |
TR26907A (tr) | 1994-08-22 |
ZA936188B (en) | 1994-06-24 |
CA2142986A1 (en) | 1994-03-03 |
IL106768A0 (en) | 1993-12-08 |
JPH08500355A (ja) | 1996-01-16 |
FR2695125A1 (fr) | 1994-03-04 |
FI950874A (fi) | 1995-02-24 |
PL307587A1 (en) | 1995-05-29 |
WO1994004488A1 (fr) | 1994-03-03 |
HUT70943A (en) | 1995-11-28 |
US5618977A (en) | 1997-04-08 |
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