IL127467A - Metal bridles made of polyamycarboxylic macrocycles and their use and diagnostic imaging - Google Patents
Metal bridles made of polyamycarboxylic macrocycles and their use and diagnostic imagingInfo
- Publication number
- IL127467A IL127467A IL12746798A IL12746798A IL127467A IL 127467 A IL127467 A IL 127467A IL 12746798 A IL12746798 A IL 12746798A IL 12746798 A IL12746798 A IL 12746798A IL 127467 A IL127467 A IL 127467A
- Authority
- IL
- Israel
- Prior art keywords
- conh
- groups
- group
- chelate
- compound
- Prior art date
Links
- 229910052751 metal Inorganic materials 0.000 title claims abstract description 22
- 239000002184 metal Substances 0.000 title claims abstract description 22
- 150000002678 macrocyclic compounds Chemical class 0.000 title description 4
- 238000002059 diagnostic imaging Methods 0.000 title description 3
- 239000013522 chelant Substances 0.000 claims abstract description 71
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 23
- 150000001768 cations Chemical class 0.000 claims abstract description 22
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 20
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 16
- 230000005298 paramagnetic effect Effects 0.000 claims abstract description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 10
- 229910002091 carbon monoxide Inorganic materials 0.000 claims abstract description 9
- 125000003368 amide group Chemical group 0.000 claims abstract description 6
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims abstract description 4
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 4
- 150000007530 organic bases Chemical class 0.000 claims abstract description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims abstract description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 4
- 229910052688 Gadolinium Inorganic materials 0.000 claims description 31
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims description 31
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 230000005291 magnetic effect Effects 0.000 claims description 7
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 6
- 239000002872 contrast media Substances 0.000 claims description 4
- 238000003384 imaging method Methods 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 102100027451 4-hydroxybenzoate polyprenyltransferase, mitochondrial Human genes 0.000 claims description 2
- 101000725614 Homo sapiens 4-hydroxybenzoate polyprenyltransferase, mitochondrial Proteins 0.000 claims description 2
- SQQWBSBBCSFQGC-JLHYYAGUSA-N ubiquinone-2 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CCC=C(C)C)=C(C)C1=O SQQWBSBBCSFQGC-JLHYYAGUSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 103
- 229910001868 water Inorganic materials 0.000 description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 87
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 85
- 239000002244 precipitate Substances 0.000 description 69
- 238000003756 stirring Methods 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- 239000003480 eluent Substances 0.000 description 49
- 238000004128 high performance liquid chromatography Methods 0.000 description 48
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 239000000203 mixture Substances 0.000 description 45
- 239000002609 medium Substances 0.000 description 41
- 239000000047 product Substances 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 37
- -1 aminoethanol Chemical class 0.000 description 36
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 36
- 229920005989 resin Polymers 0.000 description 35
- 239000011347 resin Substances 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 32
- 235000019441 ethanol Nutrition 0.000 description 31
- 239000002253 acid Substances 0.000 description 28
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- 150000001412 amines Chemical class 0.000 description 20
- 239000012429 reaction media Substances 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 17
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
- 150000001414 amino alcohols Chemical class 0.000 description 14
- 159000000000 sodium salts Chemical class 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 13
- 229920001429 chelating resin Polymers 0.000 description 13
- 238000000034 method Methods 0.000 description 13
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 12
- QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000000129 anionic group Chemical group 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 125000002091 cationic group Chemical group 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 12
- 239000012528 membrane Substances 0.000 description 12
- 238000000108 ultra-filtration Methods 0.000 description 12
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 230000008878 coupling Effects 0.000 description 11
- 238000010168 coupling process Methods 0.000 description 11
- 238000005859 coupling reaction Methods 0.000 description 11
- 239000012467 final product Substances 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 239000001257 hydrogen Substances 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- GVJXGCIPWAVXJP-UHFFFAOYSA-N 2,5-dioxo-1-oxoniopyrrolidine-3-sulfonate Chemical compound ON1C(=O)CC(S(O)(=O)=O)C1=O GVJXGCIPWAVXJP-UHFFFAOYSA-N 0.000 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 description 8
- 239000005711 Benzoic acid Substances 0.000 description 8
- 102100021935 C-C motif chemokine 26 Human genes 0.000 description 8
- 101000897493 Homo sapiens C-C motif chemokine 26 Proteins 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 235000010233 benzoic acid Nutrition 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- WQINSVOOIJDOLJ-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)acetic acid Chemical compound C1=CC=C2C(=O)N(CC(=O)O)C(=O)C2=C1 WQINSVOOIJDOLJ-UHFFFAOYSA-N 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
- 239000006229 carbon black Substances 0.000 description 7
- 238000006698 hydrazinolysis reaction Methods 0.000 description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 description 7
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 6
- 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 6
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 229960004050 aminobenzoic acid Drugs 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- IZOOGPBRAOKZFK-UHFFFAOYSA-K gadopentetate Chemical compound [Gd+3].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O IZOOGPBRAOKZFK-UHFFFAOYSA-K 0.000 description 6
- 229940005649 gadopentetate Drugs 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 238000010668 complexation reaction Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 239000003456 ion exchange resin Substances 0.000 description 5
- 229920003303 ion-exchange polymer Polymers 0.000 description 5
- 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 5
- 125000005544 phthalimido group Chemical group 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 230000002792 vascular Effects 0.000 description 5
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 4
- 238000002595 magnetic resonance imaging Methods 0.000 description 4
- 150000002828 nitro derivatives Chemical class 0.000 description 4
- QRBHFBLGTROTMF-UHFFFAOYSA-N octa acid cavitand Chemical compound O1C(C=2C=C3C=C(C=2)OC=2C=C(C=C(C=2)C(O)=O)OC=2C=C4C=C(C=2)OC=2C=C(C=C(C=2)C(O)=O)OC=2C=C(C=C5C=2)OC=2C=C(C=C(C=2)C(O)=O)OC=2C=C(C=C6C=2)OC=2C=C(C=C(C=2)C(O)=O)O3)OC(C(C2CCC(=O)O)=CC=3C(CCC(O)=O)C7=CC=8C(CCC(O)=O)C9=C%10)=CC=3OC6OC7=CC=8OC5OC9=CC3=C%10C(CCC(O)=O)C5=CC2=C1C=C5OC4O3 QRBHFBLGTROTMF-UHFFFAOYSA-N 0.000 description 4
- 230000020477 pH reduction Effects 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
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- 241001465754 Metazoa Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
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- 229960003375 aminomethylbenzoic acid Drugs 0.000 description 3
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- 125000004185 ester group Chemical group 0.000 description 3
- VRHAQNTWKSVEEC-UHFFFAOYSA-N ethyl 1,3-dioxoisoindole-2-carboxylate Chemical compound C1=CC=C2C(=O)N(C(=O)OCC)C(=O)C2=C1 VRHAQNTWKSVEEC-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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- CMIHHWBVHJVIGI-UHFFFAOYSA-N gadolinium(iii) oxide Chemical compound [O-2].[O-2].[O-2].[Gd+3].[Gd+3] CMIHHWBVHJVIGI-UHFFFAOYSA-N 0.000 description 3
- GFSTXYOTEVLASN-UHFFFAOYSA-K gadoteric acid Chemical compound [Gd+3].OC(=O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 GFSTXYOTEVLASN-UHFFFAOYSA-K 0.000 description 3
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- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
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- 239000011780 sodium chloride Substances 0.000 description 3
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
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- 238000003786 synthesis reaction Methods 0.000 description 3
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- CYQMHINCNSQMFB-YOBQRZKDSA-N (2r,3s,4r,5s)-6-(2,3-dihydroxypropylamino)hexane-1,2,3,4,5-pentol Chemical compound OCC(O)CNC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO CYQMHINCNSQMFB-YOBQRZKDSA-N 0.000 description 2
- FURLCQRFFWBENR-UHFFFAOYSA-N 1-benzyl-1,4,7,10-tetrazacyclododecane Chemical compound C=1C=CC=CC=1CN1CCNCCNCCNCC1 FURLCQRFFWBENR-UHFFFAOYSA-N 0.000 description 2
- GIAFURWZWWWBQT-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanol Chemical compound NCCOCCO GIAFURWZWWWBQT-UHFFFAOYSA-N 0.000 description 2
- JNPIEYPDEUFUNV-UHFFFAOYSA-N 2-[(2-aminoacetyl)amino]-3-n-iodobenzene-1,3-dicarboxamide Chemical compound NCC(=O)NC1=C(C(N)=O)C=CC=C1C(=O)NI JNPIEYPDEUFUNV-UHFFFAOYSA-N 0.000 description 2
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- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 230000004856 capillary permeability Effects 0.000 description 1
- ONANWDUDFJIIGP-UHFFFAOYSA-N carbamoyl carbamoperoxoate Chemical compound NC(=O)OOC(N)=O ONANWDUDFJIIGP-UHFFFAOYSA-N 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000005341 cation exchange Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- ONCCWDRMOZMNSM-FBCQKBJTSA-N compound Z Chemical compound N1=C2C(=O)NC(N)=NC2=NC=C1C(=O)[C@H]1OP(O)(=O)OC[C@H]1O ONCCWDRMOZMNSM-FBCQKBJTSA-N 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 239000000412 dendrimer Substances 0.000 description 1
- 229920000736 dendritic polymer Polymers 0.000 description 1
- 238000011026 diafiltration Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical class [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- MEANOSLIBWSCIT-UHFFFAOYSA-K gadolinium trichloride Chemical compound Cl[Gd](Cl)Cl MEANOSLIBWSCIT-UHFFFAOYSA-K 0.000 description 1
- DPNNNPAKRZOSMO-UHFFFAOYSA-K gadoteridol Chemical compound [Gd+3].CC(O)CN1CCN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC1 DPNNNPAKRZOSMO-UHFFFAOYSA-K 0.000 description 1
- 229960005451 gadoteridol Drugs 0.000 description 1
- 229960002059 gadoversetamide Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229910044991 metal oxide Inorganic materials 0.000 description 1
- 150000004706 metal oxides Chemical class 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- BLVRMPAIJHFKRN-UHFFFAOYSA-N methyl 4-[(4-nitrophenyl)carbamoyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1 BLVRMPAIJHFKRN-UHFFFAOYSA-N 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- ADAMEOZKZQRNKP-UHFFFAOYSA-N n'-propylmethanediimine Chemical compound CCCN=C=N ADAMEOZKZQRNKP-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 238000009206 nuclear medicine Methods 0.000 description 1
- 150000002892 organic cations Chemical class 0.000 description 1
- 239000012430 organic reaction media Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- DRKHJSDSSUXYTE-UHFFFAOYSA-L oxidanium;2-[bis[2-[carboxylatomethyl-[2-(2-methoxyethylamino)-2-oxoethyl]amino]ethyl]amino]acetate;gadolinium(3+) Chemical compound [OH3+].[Gd+3].COCCNC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CCN(CC([O-])=O)CC(=O)NCCOC DRKHJSDSSUXYTE-UHFFFAOYSA-L 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 150000003017 phosphorus Chemical class 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 239000012465 retentate Substances 0.000 description 1
- 150000003290 ribose derivatives Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical group OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
- 125000003142 tertiary amide group Chemical group 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000001173 tumoral effect Effects 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000004034 viscosity adjusting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/085—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier conjugated systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/08—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by the carrier
- A61K49/10—Organic compounds
- A61K49/101—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals
- A61K49/106—Organic compounds the carrier being a complex-forming compound able to form MRI-active complexes with paramagnetic metals the complex-forming compound being cyclic, e.g. DOTA
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Radiology & Medical Imaging (AREA)
- Medicinal Chemistry (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Polyamides (AREA)
- Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)
- Polyesters Or Polycarbonates (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9715642A FR2772025B1 (fr) | 1997-12-10 | 1997-12-10 | Chelates metalliques de macrocycles polyaminocarboxyliques et leur application a l'imagerie par resonance magnetique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL127467A0 IL127467A0 (en) | 1999-10-28 |
| IL127467A true IL127467A (en) | 2001-04-30 |
Family
ID=9514428
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12746798A IL127467A (en) | 1997-12-10 | 1998-12-09 | Metal bridles made of polyamycarboxylic macrocycles and their use and diagnostic imaging |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US6187285B1 (ko) |
| EP (1) | EP0922700B1 (ko) |
| JP (1) | JP3020938B2 (ko) |
| KR (1) | KR100473240B1 (ko) |
| CN (1) | CN1132822C (ko) |
| AT (1) | ATE223906T1 (ko) |
| AU (1) | AU743361B2 (ko) |
| BR (1) | BR9805801A (ko) |
| CA (1) | CA2254261A1 (ko) |
| CZ (1) | CZ293218B6 (ko) |
| DE (1) | DE69807830T2 (ko) |
| DK (1) | DK0922700T3 (ko) |
| EA (1) | EA001387B1 (ko) |
| ES (1) | ES2183303T3 (ko) |
| FR (1) | FR2772025B1 (ko) |
| HK (1) | HK1021976A1 (ko) |
| HU (1) | HU221604B (ko) |
| IL (1) | IL127467A (ko) |
| NO (1) | NO318037B1 (ko) |
| NZ (1) | NZ333264A (ko) |
| PL (1) | PL330214A1 (ko) |
| PT (1) | PT922700E (ko) |
| TR (1) | TR199802559A2 (ko) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2793795B1 (fr) * | 1999-05-21 | 2001-08-03 | Guerbet Sa | Isomeres de tetramides du complexe de gadolinium de l'acide (1,4,7,10-tetrazacyclododecane)1,4,7,10-tetra(2-glutarique) leur procede de preparation et leur application en imagerie medicale |
| FR2829492B1 (fr) * | 2001-09-11 | 2005-01-28 | Guerbet Sa | Procede de preparation de la disorbitylamine |
| FR2836916B1 (fr) * | 2002-03-05 | 2004-06-11 | Guerbet Sa | Oligomeres de chelates de gadolinium, leur application comme produits de contraste en imagerie par resonance magnetique et leurs intermediaires de synthese |
| AU2003250658B2 (en) | 2002-07-18 | 2009-07-16 | Helix Biopharma Corp. | Use of urease for inhibiting cancer cell growth |
| EP1608319A4 (en) * | 2003-04-03 | 2007-02-28 | Univ California | IMPROVED HEMMER FOR SOLUBLE EPOXY HYDROLASE |
| FR2856689A1 (fr) * | 2003-06-25 | 2004-12-31 | Guerbet Sa | Composes specifiques a forte relaxivite |
| FR2857967B1 (fr) * | 2003-07-25 | 2015-04-24 | Centre Nat Rech Scient | Complexes de lanthanide, leur preparation et leurs utilisations |
| FR2867473B1 (fr) | 2004-03-12 | 2006-06-23 | Guerbet Sa | Compose de porphyrines et utilisation a haut champ en irm |
| EP1771205B1 (en) | 2004-06-18 | 2016-10-26 | Ambrx, Inc. | Novel antigen-binding polypeptides and their uses |
| FR2886294B1 (fr) | 2005-05-26 | 2007-07-20 | Rhodia Chimie Sa | Procede de preparation de composes organosiliciques |
| FR2914303A1 (fr) * | 2007-03-28 | 2008-10-03 | Guerbet Sa | Composes pour le diagnostic de l'apoptose. |
| CA2699394C (en) | 2007-09-17 | 2020-03-24 | The Regents Of The University Of California | Internalizing human monoclonal antibodies targeting prostate cancer cells in situ |
| WO2011048004A1 (en) * | 2009-10-23 | 2011-04-28 | Boehringer Ingelheim International Gmbh | Inhibitors of the microsomal prostaglandin e2 synthase-1 |
| US20140170068A1 (en) | 2011-03-11 | 2014-06-19 | Board Of Regents Of The University Of Nebraska | Biomarker for coronary artery disease |
| EP3019615B1 (en) | 2013-07-12 | 2021-04-07 | Helmholtz-Zentrum für Infektionsforschung GmbH | Cystobactamides |
| CA2968270C (en) | 2014-11-26 | 2022-11-01 | Helmholtz-Zentrum Fur Infektionsforschung Gmbh | Further natural cystobactamides, synthetic derivatives thereof, and use thereof in treating bacterial infections |
| GB201421162D0 (en) * | 2014-11-28 | 2015-01-14 | Ge Healthcare As | Lanthanide complex formulations |
| CA3006759A1 (en) | 2015-11-30 | 2017-06-08 | The Regents Of The University Of California | Tumor-specific payload delivery and immune activation using a human antibody targeting a highly specific tumor cell surface antigen |
| US12049511B2 (en) | 2016-11-10 | 2024-07-30 | Fortis Therapeutics, Inc. | Engineered CD46-specific effector cells and uses thereof in the treatment of cancer |
| FR3069245B1 (fr) * | 2017-07-21 | 2019-07-26 | Guerbet | Ligands macrocycliques lipophiles, leurs complexes ainsi que leurs utilisations medicales |
| CN108610274B (zh) * | 2018-02-12 | 2021-09-28 | 中国人民解放军第二军医大学 | 一组环γ-聚谷氨酸系列分子及其制备方法和应用 |
| US20200298194A1 (en) * | 2019-03-21 | 2020-09-24 | Massachusetts Institute Of Technology | Aramid amphiphile self-assembled nanostructures |
| CA3188728A1 (en) | 2020-08-07 | 2022-02-10 | Marc Nasoff | Immunoconjugates targeting cd46 and methods of use thereof |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5648063A (en) * | 1981-07-24 | 1997-07-15 | Schering Aktiengesellschaft | Sterile composition comprising a chelate complex for magnetic resonance imaging |
| US5422096A (en) * | 1985-05-08 | 1995-06-06 | The General Hospital Corporation | Hydroxy-aryl metal chelates for diagnostic NMR imaging |
| MX174467B (es) * | 1986-01-23 | 1994-05-17 | Squibb & Sons Inc | 1,4,7-triscarboximetil-1,4,7,10-tetraazaciclodo decano substituido en 1 y compuestos analogos |
| GB8916781D0 (en) * | 1989-07-21 | 1989-09-06 | Nycomed As | Compositions |
| US5679810A (en) * | 1990-01-19 | 1997-10-21 | Salutar, Inc. | Linear oligomeric polychelant compounds |
| DE4035760A1 (de) * | 1990-11-08 | 1992-05-14 | Schering Ag | Mono-n-substituierte 1,4,7,10-tetraazacyclododecan-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel |
| DE4115789A1 (de) * | 1991-05-10 | 1992-11-12 | Schering Ag | Makrocyclische polymer-komplexbildner, deren komplexe, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische mittel |
| AU654201B2 (en) * | 1991-06-21 | 1994-10-27 | Mobil Oil Corporation | Olefin oligomerization process |
| ATE199550T1 (de) * | 1993-12-30 | 2001-03-15 | Guerbet Sa | Polyaminierte liganden, metallkomplexe, verfahren zur herstellung und diagnostische und therapeutische verwendungen |
| GB9407435D0 (en) * | 1994-04-14 | 1994-06-08 | Nycomed Salutar Inc | Compounds |
| IT1274038B (it) * | 1994-07-29 | 1997-07-14 | Bracco Spa | Chelanti macrociclici loro chelati e relativi usi in campo diagnostico |
| IT1272870B (it) * | 1995-01-10 | 1997-07-01 | Ing Ruggeri Guido Dr | Apparecchiatura per il prelievo multiplo di campioni liquidi e procedimento per il suo impiego |
| EP0833668A4 (en) * | 1995-06-20 | 2001-12-12 | Gen Hospital Corp | INHIBITATION OF THE HEPATITIS B VIRUS REPLICATION |
| FR2736051B3 (fr) * | 1995-06-29 | 1997-09-26 | Guerbet Sa | Complexes metalliques de polyaminoacides, leur procede de preparation et leur utilisation en imagerie diagnostique |
| US5900228A (en) * | 1996-07-31 | 1999-05-04 | California Institute Of Technology | Bifunctional detection agents having a polymer covalently linked to an MRI agent and an optical dye |
-
1997
- 1997-12-10 FR FR9715642A patent/FR2772025B1/fr not_active Expired - Fee Related
-
1998
- 1998-12-09 CA CA002254261A patent/CA2254261A1/fr not_active Abandoned
- 1998-12-09 DE DE69807830T patent/DE69807830T2/de not_active Expired - Fee Related
- 1998-12-09 CZ CZ19984054A patent/CZ293218B6/cs not_active IP Right Cessation
- 1998-12-09 HU HU9802849A patent/HU221604B/hu not_active IP Right Cessation
- 1998-12-09 NO NO19985762A patent/NO318037B1/no unknown
- 1998-12-09 PT PT98403108T patent/PT922700E/pt unknown
- 1998-12-09 NZ NZ333264A patent/NZ333264A/xx unknown
- 1998-12-09 DK DK98403108T patent/DK0922700T3/da active
- 1998-12-09 ES ES98403108T patent/ES2183303T3/es not_active Expired - Lifetime
- 1998-12-09 AU AU96133/98A patent/AU743361B2/en not_active Ceased
- 1998-12-09 US US09/207,513 patent/US6187285B1/en not_active Expired - Fee Related
- 1998-12-09 EP EP98403108A patent/EP0922700B1/fr not_active Expired - Lifetime
- 1998-12-09 TR TR1998/02559A patent/TR199802559A2/xx unknown
- 1998-12-09 EA EA199800998A patent/EA001387B1/ru not_active IP Right Cessation
- 1998-12-09 AT AT98403108T patent/ATE223906T1/de not_active IP Right Cessation
- 1998-12-09 IL IL12746798A patent/IL127467A/en not_active IP Right Cessation
- 1998-12-10 JP JP10377822A patent/JP3020938B2/ja not_active Expired - Fee Related
- 1998-12-10 KR KR10-1998-0054764A patent/KR100473240B1/ko not_active IP Right Cessation
- 1998-12-10 CN CN98126925A patent/CN1132822C/zh not_active Expired - Fee Related
- 1998-12-10 BR BR9805801-0A patent/BR9805801A/pt not_active Application Discontinuation
- 1998-12-10 PL PL98330214A patent/PL330214A1/xx not_active Application Discontinuation
-
2000
- 2000-02-12 HK HK00100860A patent/HK1021976A1/xx not_active IP Right Cessation
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