DE4311021A1 - Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Mittel - Google Patents
Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische MittelInfo
- Publication number
- DE4311021A1 DE4311021A1 DE4311021A DE4311021A DE4311021A1 DE 4311021 A1 DE4311021 A1 DE 4311021A1 DE 4311021 A DE4311021 A DE 4311021A DE 4311021 A DE4311021 A DE 4311021A DE 4311021 A1 DE4311021 A1 DE 4311021A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- carbon atoms
- amino
- hydrogen atom
- carboxy
- 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- Withdrawn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 description 74
- 238000000034 method Methods 0.000 title claims description 23
- 239000012217 radiopharmaceutical Substances 0.000 title claims description 19
- 229940121896 radiopharmaceutical Drugs 0.000 title claims description 13
- 230000002799 radiopharmaceutical effect Effects 0.000 title claims description 13
- 239000000203 mixture Substances 0.000 title claims description 11
- 238000002360 preparation method Methods 0.000 title claims description 8
- 230000008569 process Effects 0.000 title claims description 6
- 239000002738 chelating agent Substances 0.000 title description 5
- 229910052713 technetium Inorganic materials 0.000 title description 5
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 title description 5
- 230000001588 bifunctional effect Effects 0.000 title description 2
- 150000003281 rhenium Chemical class 0.000 title 1
- -1 acyl radicals Chemical class 0.000 claims description 90
- 125000004432 carbon atom Chemical group C* 0.000 claims description 67
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 48
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 37
- 125000003277 amino group Chemical group 0.000 claims description 31
- GKLVYJBZJHMRIY-OUBTZVSYSA-N Technetium-99 Chemical compound [99Tc] GKLVYJBZJHMRIY-OUBTZVSYSA-N 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 229940056501 technetium 99m Drugs 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 150000003431 steroids Chemical class 0.000 claims description 20
- 229920002521 macromolecule Polymers 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 16
- 108090000623 proteins and genes Proteins 0.000 claims description 14
- 230000008878 coupling Effects 0.000 claims description 12
- 238000010168 coupling process Methods 0.000 claims description 12
- 238000005859 coupling reaction Methods 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical group CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 7
- HSFWRNGVRCDJHI-UHFFFAOYSA-N Acetylene Chemical compound C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical group OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 7
- 239000003446 ligand Substances 0.000 claims description 7
- 229910052702 rhenium Inorganic materials 0.000 claims description 7
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 108050009340 Endothelin Proteins 0.000 claims description 5
- 102000002045 Endothelin Human genes 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 5
- 150000005840 aryl radicals Chemical class 0.000 claims description 5
- 239000000654 additive Substances 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 239000012634 fragment Substances 0.000 claims description 4
- 238000011503 in vivo imaging Methods 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 239000002502 liposome Substances 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- NTSBFTNRWQVBCA-IVGDYKFASA-N His-leu-asp-ile-ile-trp Chemical compound C([C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)[C@@H](C)CC)C1=CN=CN1 NTSBFTNRWQVBCA-IVGDYKFASA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical group OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 2
- 108010002990 endothelin (16-21) Proteins 0.000 claims description 2
- 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims 1
- 210000003608 fece Anatomy 0.000 claims 1
- 239000000243 solution Substances 0.000 description 119
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 66
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 49
- 239000008363 phosphate buffer Substances 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 36
- 229910000397 disodium phosphate Inorganic materials 0.000 description 36
- 235000019800 disodium phosphate Nutrition 0.000 description 36
- 239000003480 eluent Substances 0.000 description 36
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 23
- 230000002829 reductive effect Effects 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
- 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 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 238000004458 analytical method Methods 0.000 description 18
- 238000004128 high performance liquid chromatography Methods 0.000 description 18
- 150000003254 radicals Chemical class 0.000 description 18
- GZNAASVAJNXPPW-UHFFFAOYSA-M tin(4+) chloride dihydrate Chemical compound O.O.[Cl-].[Sn+4] GZNAASVAJNXPPW-UHFFFAOYSA-M 0.000 description 18
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 230000003637 steroidlike Effects 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 13
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 9
- BXSAYSZDNNICIF-UHFFFAOYSA-N 5-amino-4-oxopent-2-ynamide Chemical compound NCC(=O)C#CC(N)=O BXSAYSZDNNICIF-UHFFFAOYSA-N 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- 238000003745 diagnosis Methods 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- UGIQXQULMZDGKA-UHFFFAOYSA-N 3-[[2-[(5-amino-2,5-dioxopent-3-ynyl)amino]-2-oxoethyl]carbamothioyl]-4-oxopentanoic acid Chemical compound C(C)(=O)C(C(=S)NCC(=O)NCC(=O)C#CC(=O)N)CC(=O)O UGIQXQULMZDGKA-UHFFFAOYSA-N 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- BGHTWOYKKAWKTR-UHFFFAOYSA-N 3-[[5-[(2-aminoacetyl)amino]-4-oxopent-2-ynoyl]carbamothioyl]-n-hexadecyl-4-oxopentanamide Chemical compound CCCCCCCCCCCCCCCCNC(=O)CC(C(C)=O)C(=S)NC(=O)C#CC(=O)CNC(=O)CN BGHTWOYKKAWKTR-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 4
- 150000001718 carbodiimides Chemical class 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000008139 complexing agent Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- XHJCROKRCYDMLQ-UHFFFAOYSA-N 5-[(2-aminoacetyl)amino]-4-oxopent-2-ynamide Chemical compound NCC(=O)NCC(=O)C#CC(N)=O XHJCROKRCYDMLQ-UHFFFAOYSA-N 0.000 description 3
- CAYYGMMKIQUTDW-ZDUSSCGKSA-N C(CCCCC)(=O)N[C@@H](CCS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N Chemical compound C(CCCCC)(=O)N[C@@H](CCS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N CAYYGMMKIQUTDW-ZDUSSCGKSA-N 0.000 description 3
- SVZMKJHZVHSSDI-KRWDZBQOSA-N C(CCCCCCCCC)(=O)N[C@@H](CCS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N Chemical compound C(CCCCCCCCC)(=O)N[C@@H](CCS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N SVZMKJHZVHSSDI-KRWDZBQOSA-N 0.000 description 3
- XRKFPCLUNXCIOX-IBGZPJMESA-N C(CCCCCCCCCCC)(=O)N[C@@H](CCS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N Chemical compound C(CCCCCCCCCCC)(=O)N[C@@H](CCS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N XRKFPCLUNXCIOX-IBGZPJMESA-N 0.000 description 3
- AEYICAGTFKTDQA-UHFFFAOYSA-O CC(N(C)CC(NCC(C#CC(N)=O)=O)=O)=[S+]C(C)=O Chemical compound CC(N(C)CC(NCC(C#CC(N)=O)=O)=O)=[S+]C(C)=O AEYICAGTFKTDQA-UHFFFAOYSA-O 0.000 description 3
- KRAZNRMWPNBQLM-JTQLQIEISA-O CC(NCC(N[C@@H](CCC(N)=O)C(C#CC(N)=O)=O)=O)=[S+]C(C)=O Chemical compound CC(NCC(N[C@@H](CCC(N)=O)C(C#CC(N)=O)=O)=O)=[S+]C(C)=O KRAZNRMWPNBQLM-JTQLQIEISA-O 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000002372 labelling Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 238000009206 nuclear medicine Methods 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000003270 steroid hormone Substances 0.000 description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- GTBKDWNKTUJRJH-UHFFFAOYSA-N 2-acetylsulfanylacetic acid;1-hydroxypyrrolidine-2,5-dione Chemical compound CC(=O)SCC(O)=O.ON1C(=O)CCC1=O GTBKDWNKTUJRJH-UHFFFAOYSA-N 0.000 description 2
- YBERYMGJSHOLEV-NSHDSACASA-O CC(N[C@@H](CCC(N)=O)C(NCC(C#CC(N)=O)=O)=O)=[S+]C(C)=O Chemical compound CC(N[C@@H](CCC(N)=O)C(NCC(C#CC(N)=O)=O)=O)=[S+]C(C)=O YBERYMGJSHOLEV-NSHDSACASA-O 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 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
- 101100208721 Mus musculus Usp5 gene Proteins 0.000 description 2
- 101001068640 Nicotiana tabacum Basic form of pathogenesis-related protein 1 Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- FHNINJWBTRXEBC-UHFFFAOYSA-N Sudan III Chemical compound OC1=CC=C2C=CC=CC2=C1N=NC(C=C1)=CC=C1N=NC1=CC=CC=C1 FHNINJWBTRXEBC-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 239000012736 aqueous medium Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 150000001576 beta-amino acids Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000006894 reductive elimination reaction Methods 0.000 description 2
- AHTFMWCHTGEJHA-UHFFFAOYSA-N s-(2,5-dioxooxolan-3-yl) ethanethioate Chemical compound CC(=O)SC1CC(=O)OC1=O AHTFMWCHTGEJHA-UHFFFAOYSA-N 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 229940099373 sudan iii Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000012876 topography Methods 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- SIFCHNIAAPMMKG-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) acetate Chemical compound CC(=O)ON1C(=O)CCC1=O SIFCHNIAAPMMKG-UHFFFAOYSA-N 0.000 description 1
- ADFXKUOMJKEIND-UHFFFAOYSA-N 1,3-dicyclohexylurea Chemical compound C1CCCCC1NC(=O)NC1CCCCC1 ADFXKUOMJKEIND-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- FJLUATLTXUNBOT-UHFFFAOYSA-N 1-Hexadecylamine Chemical compound CCCCCCCCCCCCCCCCN FJLUATLTXUNBOT-UHFFFAOYSA-N 0.000 description 1
- WUAPFZMCVAUBPE-NJFSPNSNSA-N 188Re Chemical compound [188Re] WUAPFZMCVAUBPE-NJFSPNSNSA-N 0.000 description 1
- 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 1
- BQHFYSWNHZMMDO-UHFFFAOYSA-N 2-[2-[(1-carboxy-2-sulfanylethyl)amino]ethylamino]-3-sulfanylpropanoic acid Chemical compound OC(=O)C(CS)NCCNC(CS)C(O)=O BQHFYSWNHZMMDO-UHFFFAOYSA-N 0.000 description 1
- RXACEEPNTRHYBQ-UHFFFAOYSA-N 2-[[2-[[2-[(2-sulfanylacetyl)amino]acetyl]amino]acetyl]amino]acetic acid Chemical compound OC(=O)CNC(=O)CNC(=O)CNC(=O)CS RXACEEPNTRHYBQ-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- LRZSAGKIMYFLHY-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;dihydrate Chemical compound O.O.OC(=O)CC(O)(C(O)=O)CC(O)=O LRZSAGKIMYFLHY-UHFFFAOYSA-N 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- OROGUZVNAFJPHA-UHFFFAOYSA-N 3-hydroxy-2,4-dimethyl-2H-thiophen-5-one Chemical compound CC1SC(=O)C(C)=C1O OROGUZVNAFJPHA-UHFFFAOYSA-N 0.000 description 1
- BLDNPOAZAHHNSV-UHFFFAOYSA-N 5-[[2-[(2-chloroacetyl)amino]acetyl]amino]-4-oxopent-2-ynamide Chemical compound NC(=O)C#CC(=O)CNC(=O)CNC(=O)CCl BLDNPOAZAHHNSV-UHFFFAOYSA-N 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- BSAQBJDGMULJQS-SFHVURJKSA-N C(CCCCCCCCCCC)(=O)N[C@@H](CS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N Chemical compound C(CCCCCCCCCCC)(=O)N[C@@H](CS)C(=O)NCC(=O)NCC(=O)C#CC(=O)N BSAQBJDGMULJQS-SFHVURJKSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 102100033902 Endothelin-1 Human genes 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102000004856 Lectins Human genes 0.000 description 1
- 108090001090 Lectins Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002873 Polyethylenimine Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 241000710779 Trina Species 0.000 description 1
- VEJXYBLYLRPHPK-UHFFFAOYSA-N [Mo].[Tc] Chemical compound [Mo].[Tc] VEJXYBLYLRPHPK-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000007259 addition reaction Methods 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 210000000709 aorta Anatomy 0.000 description 1
- 238000000376 autoradiography Methods 0.000 description 1
- 238000003339 best practice Methods 0.000 description 1
- OYVAGSVQBOHSSS-WXFSZRTFSA-O bleomycin Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](OC1C(C(O)C(O)C(CO)O1)OC1C(C(OC(N)=O)C(O)C(CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-WXFSZRTFSA-O 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000536 complexating effect Effects 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- NQGIJDNPUZEBRU-UHFFFAOYSA-N dodecanoyl chloride Chemical compound CCCCCCCCCCCC(Cl)=O NQGIJDNPUZEBRU-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000004676 glycans Polymers 0.000 description 1
- 150000002332 glycine derivatives Chemical class 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- VCMGMSHEPQENPE-UHFFFAOYSA-N ketamine hydrochloride Chemical compound [Cl-].C=1C=CC=C(Cl)C=1C1([NH2+]C)CCCCC1=O VCMGMSHEPQENPE-UHFFFAOYSA-N 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000002523 lectin Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229940057952 methanol Drugs 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- LKFCPWBGBPJDRC-UHFFFAOYSA-M potassium;thiobenzate Chemical compound [K+].[O-]C(=S)C1=CC=CC=C1 LKFCPWBGBPJDRC-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- HCJTYESURSHXNB-UHFFFAOYSA-N propynamide Chemical compound NC(=O)C#C HCJTYESURSHXNB-UHFFFAOYSA-N 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000011363 radioimmunotherapy Methods 0.000 description 1
- WUAPFZMCVAUBPE-IGMARMGPSA-N rhenium-186 Chemical compound [186Re] WUAPFZMCVAUBPE-IGMARMGPSA-N 0.000 description 1
- 229940069575 rompun Drugs 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 108020003113 steroid hormone receptors Proteins 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
- A61K51/088—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins conjugates with carriers being peptides, polyamino acids or proteins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F13/00—Compounds containing elements of Groups 7 or 17 of the Periodic Table
- C07F13/005—Compounds without a metal-carbon linkage
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/57536—Endothelin, vasoactive intestinal contractor [VIC]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Optics & Photonics (AREA)
- Physics & Mathematics (AREA)
- Toxicology (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4311021A DE4311021A1 (de) | 1993-03-31 | 1993-03-31 | Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Mittel |
JP6521540A JPH08508261A (ja) | 1993-03-31 | 1994-03-29 | 二官能価キレート剤及びそれらの放射性医薬への使用 |
KR1019950704236A KR960701667A (ko) | 1993-03-31 | 1994-03-29 | 2작용기성 킬레이트제, 그 테크네튬 및 레늄 착물과 이들의 제조방법 및 이들 화합물을 함유하는 방사성 약물 |
AU65015/94A AU6501594A (en) | 1993-03-31 | 1994-03-29 | Bifunctional chelators and their use in radiopharmaceuticals |
PCT/DE1994/000369 WO1994022491A1 (de) | 1993-03-31 | 1994-03-29 | Bifunktionelle chelatbildner und ihre anwendung in der radiopharmazeutik |
HU9502858A HUT72733A (en) | 1993-03-31 | 1994-03-29 | Process for producing bifunctional chelators, their technecium- and rhenium-complexes and radiopharmaceuticals containing them |
EP94912439A EP0692979A1 (de) | 1993-03-31 | 1994-03-29 | Bifunktionelle chelatbildner und ihre anwendung in der radiopharmazeutik |
NZ263792A NZ263792A (en) | 1993-03-31 | 1994-03-29 | Tc and re chelate compounds and use in radiopharmaceutical compounds |
CA002156618A CA2156618A1 (en) | 1993-03-31 | 1994-03-29 | Bifunctional chelators and their use in radiopharmaceuticals |
NO953865A NO953865L (no) | 1993-03-31 | 1995-09-29 | Bifunksjonelle chelatorer og deres anvendelse i radiofarmasöytiske midler |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4311021A DE4311021A1 (de) | 1993-03-31 | 1993-03-31 | Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Mittel |
Publications (1)
Publication Number | Publication Date |
---|---|
DE4311021A1 true DE4311021A1 (de) | 1994-10-27 |
Family
ID=6484685
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE4311021A Withdrawn DE4311021A1 (de) | 1993-03-31 | 1993-03-31 | Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Mittel |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP0692979A1 (no) |
JP (1) | JPH08508261A (no) |
KR (1) | KR960701667A (no) |
AU (1) | AU6501594A (no) |
CA (1) | CA2156618A1 (no) |
DE (1) | DE4311021A1 (no) |
HU (1) | HUT72733A (no) |
NO (1) | NO953865L (no) |
NZ (1) | NZ263792A (no) |
WO (1) | WO1994022491A1 (no) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997012902A1 (en) * | 1995-10-05 | 1997-04-10 | Darwin Discovery Limited | Thio-substituted peptides as inhibitors for metalloproteinases and tnf liberation |
Families Citing this family (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4310999C2 (de) * | 1993-03-31 | 1996-07-18 | Diagnostikforschung Inst | Bifunktionelle chalkogenatom-unterbrochene Chelatbildner vom Typ XN¶1¶S¶1¶X' für radioaktive Isotope und deren Metallkomplexe, Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Mittel |
DE4311022C2 (de) * | 1993-03-31 | 1996-07-11 | Diagnostikforschung Inst | Bifunktionelle chalkogenatom-unterbrochene Chelatbildner vom Typ S¶3¶N¶2¶ für radioaktive Isotope und deren Metallkomplexe, Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Mittel |
DE4337600A1 (de) * | 1993-11-01 | 1995-05-04 | Diagnostikforschung Inst | N-Alkyl-Peptidchelatbildner, deren Metallkomplexe mit Radionukliden, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Zusammesetzungen |
US5632969A (en) * | 1994-10-13 | 1997-05-27 | Merck & Co., Inc. | N3 S2 chelating ligands optionally radiolabelled with Tc or Re, useful for diagnostic or therapeutic applications |
AU701279B2 (en) * | 1995-05-10 | 1999-01-21 | Darwin Discovery Limited | Peptide compounds which inhibit metalloproteinase and TNF liberation and their therapeutic uses |
DE19652374A1 (de) * | 1996-12-04 | 1998-06-10 | Schering Ag | Verwendung von Endothelin-Konjugaten in der Therapie, neue Endothelin-Konjugate, diese enthaltende Mittel, sowie Verfahren zu deren Herstellung |
NZ511705A (en) * | 2001-05-14 | 2004-03-26 | Horticulture & Food Res Inst | Methods and rapid immunoassay device for detecting progesterone and other steroids |
MXPA04007252A (es) | 2002-01-29 | 2005-03-31 | Wyeth Corp | Composiciones y metodos para modular los hemicanales de conexina. |
CN100528241C (zh) * | 2002-05-06 | 2009-08-19 | 恩多塞特公司 | 维生素-定向的显象剂 |
WO2014007632A1 (en) * | 2012-07-06 | 2014-01-09 | Stichting Het Nederlands Kanker Instituut | Cysteine protease capturing agents |
CA3026074A1 (en) | 2016-06-01 | 2017-12-07 | M3 Biotechnology, Inc. | N-hexanoic-l-tyrosine-l-isoleucine-(6)-aminohexanoic amide compounds and their use to treat neurodegenerative diseases |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1989000557A1 (en) * | 1987-07-16 | 1989-01-26 | Cockbain, Julian, Roderick, Michaelson | Aminopolycarboxylic acids and derivatives thereof |
AU1995392A (en) * | 1991-05-08 | 1992-12-21 | Mallinckrodt Medical, Inc. | Technetium chelates to be used for determining the renal function |
JPH0570484A (ja) * | 1991-09-12 | 1993-03-23 | Hitachi Chem Co Ltd | ペプチドおよびその塩 |
DE69332470D1 (de) * | 1992-02-06 | 2002-12-12 | Biosynthema Inc | Liganden zur verbesserung der metallchelatbildungskinetik |
-
1993
- 1993-03-31 DE DE4311021A patent/DE4311021A1/de not_active Withdrawn
-
1994
- 1994-03-29 EP EP94912439A patent/EP0692979A1/de not_active Withdrawn
- 1994-03-29 JP JP6521540A patent/JPH08508261A/ja active Pending
- 1994-03-29 WO PCT/DE1994/000369 patent/WO1994022491A1/de not_active Application Discontinuation
- 1994-03-29 HU HU9502858A patent/HUT72733A/hu unknown
- 1994-03-29 AU AU65015/94A patent/AU6501594A/en not_active Abandoned
- 1994-03-29 NZ NZ263792A patent/NZ263792A/en unknown
- 1994-03-29 CA CA002156618A patent/CA2156618A1/en not_active Abandoned
- 1994-03-29 KR KR1019950704236A patent/KR960701667A/ko not_active Application Discontinuation
-
1995
- 1995-09-29 NO NO953865A patent/NO953865L/no unknown
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997012902A1 (en) * | 1995-10-05 | 1997-04-10 | Darwin Discovery Limited | Thio-substituted peptides as inhibitors for metalloproteinases and tnf liberation |
Also Published As
Publication number | Publication date |
---|---|
NO953865D0 (no) | 1995-09-29 |
AU6501594A (en) | 1994-10-24 |
KR960701667A (ko) | 1996-03-28 |
NZ263792A (en) | 1997-02-24 |
JPH08508261A (ja) | 1996-09-03 |
NO953865L (no) | 1995-11-23 |
HUT72733A (en) | 1996-05-28 |
WO1994022491A1 (de) | 1994-10-13 |
EP0692979A1 (de) | 1996-01-24 |
HU9502858D0 (en) | 1995-11-28 |
CA2156618A1 (en) | 1994-10-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE69126124T2 (de) | Polymere träger zur freisetzung kovalent gebundener wirkstoffe | |
EP0417870B1 (de) | Chelatbildner zur Komplexierung von radioaktiven Isotopen, deren Metallkomplexe sowie ihre Verwendung in Diagnostik und Therapie | |
EP0692976B1 (de) | Chelatbildner vom typ xn 1?s 1?o 1? für radioaktive isotope, deren metallkomplexe und ihre verwendung in diagnostik und therapie | |
DE4311021A1 (de) | Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Mittel | |
WO1997010852A2 (de) | Bifunktionelle sulfidhaltige sulfonamid-chelatbildner vom typ xsns für radioaktive isotope | |
EP0851771A2 (de) | Bifunktionelle nicotinamid-chelatbildner vom typ n2s2 für radioaktive isotope | |
DE19536785A1 (de) | Bifunktionelle sulfidhaltige Sulfonamid-Chelatbildner vom Typ S¶2¶NY für radioaktive Isotope | |
DE19860289C2 (de) | Neue Chelatoren sowie deren Tricarbonyl-Komplexe mit Technetium und Rhenium | |
EP0502595A2 (de) | Amid-Chelate, deren Metallkomplexe sowie ihre Verwendung in Diagnostik und Therapie | |
EP0692981B1 (de) | Chelatbildner vom typ xn 1?s 1?x' für radioaktive isotope, deren metallkomplexe und ihre verwendung in diagnostik und therapie | |
DE69501981T2 (de) | Liganden und deren metallkomplexe | |
EP0692980B1 (de) | Chelatbildner vom typ s3n2 für radioaktive isotope, deren metallkomplexe und ihre verwendung in diagnostik und therapie | |
DE69023616T2 (de) | Radionukleid-chelatverbindungen zur radiomarkierung von proteinen. | |
EP0726909A1 (de) | N-alkyl-peptidchelatbildner, deren metallkomplexe mit radionukliden, verfahren zu ihrer herstellung und diese verbindungen enthaltende radiopharmazeutische zusammensetzungen | |
DE4425781A1 (de) | Technetium-Sulfonamid-Komplexe, deren Verwendung, diese enthaltende pharmazeutische Mittel, sowie Verfahren zur Herstellung der Komplexe und Mittel | |
EP0474323A1 (de) | Reduzierende Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung sowie deren Verwendung in Diagnostik und Therapie | |
EP0588229A2 (de) | Makrozyklische Chelatbildner zur Herstellung von Technetium- oder Rheniumkomplexen | |
DE19536780A1 (de) | Bifunktionelle sulfidhaltige Sulfonamid-Chelatbildner vom Typ XSNY für radioaktive Isotope |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
OP8 | Request for examination as to paragraph 44 patent law | ||
8130 | Withdrawal |