CA2671788A1 - Chelating agent - Google Patents
Chelating agent Download PDFInfo
- Publication number
- CA2671788A1 CA2671788A1 CA002671788A CA2671788A CA2671788A1 CA 2671788 A1 CA2671788 A1 CA 2671788A1 CA 002671788 A CA002671788 A CA 002671788A CA 2671788 A CA2671788 A CA 2671788A CA 2671788 A1 CA2671788 A1 CA 2671788A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- compound
- compound according
- methyl
- synthesis
- 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.)
- Abandoned
Links
- 239000002738 chelating agent Substances 0.000 title claims abstract description 28
- 150000001875 compounds Chemical class 0.000 claims abstract description 75
- 230000008685 targeting Effects 0.000 claims abstract description 37
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 25
- 238000006352 cycloaddition reaction Methods 0.000 claims abstract description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 21
- 125000006239 protecting group Chemical group 0.000 claims abstract description 21
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 claims abstract description 19
- 125000000524 functional group Chemical group 0.000 claims abstract description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 15
- 230000001588 bifunctional effect Effects 0.000 claims abstract description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 60
- 238000003786 synthesis reaction Methods 0.000 claims description 55
- 238000000034 method Methods 0.000 claims description 53
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 50
- 238000006243 chemical reaction Methods 0.000 claims description 31
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 28
- 229910001868 water Inorganic materials 0.000 claims description 28
- 206010028980 Neoplasm Diseases 0.000 claims description 27
- 239000002904 solvent Substances 0.000 claims description 27
- QBPPRVHXOZRESW-UHFFFAOYSA-N 1,4,7,10-tetraazacyclododecane Chemical compound C1CNCCNCCNCCN1 QBPPRVHXOZRESW-UHFFFAOYSA-N 0.000 claims description 22
- GYHNNYVSQQEPJS-YPZZEJLDSA-N Gallium-68 Chemical compound [68Ga] GYHNNYVSQQEPJS-YPZZEJLDSA-N 0.000 claims description 20
- 239000013522 chelant Substances 0.000 claims description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 16
- 150000002923 oximes Chemical class 0.000 claims description 15
- 229910052751 metal Inorganic materials 0.000 claims description 13
- 239000002184 metal Substances 0.000 claims description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- 230000021615 conjugation Effects 0.000 claims description 10
- 238000003745 diagnosis Methods 0.000 claims description 8
- 125000000468 ketone group Chemical group 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 8
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052802 copper Inorganic materials 0.000 claims description 6
- 230000003463 hyperproliferative effect Effects 0.000 claims description 6
- 230000001613 neoplastic effect Effects 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000002355 alkine group Chemical group 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 230000000295 complement effect Effects 0.000 claims description 4
- 238000010668 complexation reaction Methods 0.000 claims description 4
- 229910021645 metal ion Inorganic materials 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 235000000346 sugar Nutrition 0.000 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 2
- 229910052692 Dysprosium Inorganic materials 0.000 claims description 2
- GYHNNYVSQQEPJS-OIOBTWANSA-N Gallium-67 Chemical compound [67Ga] GYHNNYVSQQEPJS-OIOBTWANSA-N 0.000 claims description 2
- VWQVUPCCIRVNHF-OIOBTWANSA-N Yttrium-86 Chemical compound [86Y] VWQVUPCCIRVNHF-OIOBTWANSA-N 0.000 claims description 2
- VWQVUPCCIRVNHF-OUBTZVSYSA-N Yttrium-90 Chemical compound [90Y] VWQVUPCCIRVNHF-OUBTZVSYSA-N 0.000 claims description 2
- QQINRWTZWGJFDB-YPZZEJLDSA-N actinium-225 Chemical group [225Ac] QQINRWTZWGJFDB-YPZZEJLDSA-N 0.000 claims description 2
- 229940125666 actinium-225 Drugs 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 2
- JCXGWMGPZLAOME-AKLPVKDBSA-N bismuth-212 Chemical compound [212Bi] JCXGWMGPZLAOME-AKLPVKDBSA-N 0.000 claims description 2
- JCXGWMGPZLAOME-RNFDNDRNSA-N bismuth-213 Chemical compound [213Bi] JCXGWMGPZLAOME-RNFDNDRNSA-N 0.000 claims description 2
- 125000006243 carbonyl protecting group Chemical group 0.000 claims description 2
- RYGMFSIKBFXOCR-IGMARMGPSA-N copper-64 Chemical compound [64Cu] RYGMFSIKBFXOCR-IGMARMGPSA-N 0.000 claims description 2
- RYGMFSIKBFXOCR-AKLPVKDBSA-N copper-67 Chemical compound [67Cu] RYGMFSIKBFXOCR-AKLPVKDBSA-N 0.000 claims description 2
- KBQHZAAAGSGFKK-UHFFFAOYSA-N dysprosium atom Chemical compound [Dy] KBQHZAAAGSGFKK-UHFFFAOYSA-N 0.000 claims description 2
- KBQHZAAAGSGFKK-BJUDXGSMSA-N dysprosium-162 Chemical compound [162Dy] KBQHZAAAGSGFKK-BJUDXGSMSA-N 0.000 claims description 2
- KBQHZAAAGSGFKK-NJFSPNSNSA-N dysprosium-165 Chemical compound [165Dy] KBQHZAAAGSGFKK-NJFSPNSNSA-N 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- GYHNNYVSQQEPJS-AHCXROLUSA-N gallium-66 Chemical compound [66Ga] GYHNNYVSQQEPJS-AHCXROLUSA-N 0.000 claims description 2
- 229940006110 gallium-67 Drugs 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- KJZYNXUDTRRSPN-OUBTZVSYSA-N holmium-166 Chemical compound [166Ho] KJZYNXUDTRRSPN-OUBTZVSYSA-N 0.000 claims description 2
- 229940088597 hormone Drugs 0.000 claims description 2
- 239000005556 hormone Substances 0.000 claims description 2
- APFVFJFRJDLVQX-AHCXROLUSA-N indium-111 Chemical compound [111In] APFVFJFRJDLVQX-AHCXROLUSA-N 0.000 claims description 2
- 229940055742 indium-111 Drugs 0.000 claims description 2
- APFVFJFRJDLVQX-YPZZEJLDSA-N indium-113 Chemical compound [113In] APFVFJFRJDLVQX-YPZZEJLDSA-N 0.000 claims description 2
- WABPQHHGFIMREM-AHCXROLUSA-N lead-203 Chemical compound [203Pb] WABPQHHGFIMREM-AHCXROLUSA-N 0.000 claims description 2
- OHSVLFRHMCKCQY-NJFSPNSNSA-N lutetium-177 Chemical compound [177Lu] OHSVLFRHMCKCQY-NJFSPNSNSA-N 0.000 claims description 2
- PUDIUYLPXJFUGB-OUBTZVSYSA-N praseodymium-142 Chemical compound [142Pr] PUDIUYLPXJFUGB-OUBTZVSYSA-N 0.000 claims description 2
- PUDIUYLPXJFUGB-NJFSPNSNSA-N praseodymium-143 Chemical compound [143Pr] PUDIUYLPXJFUGB-NJFSPNSNSA-N 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- VQMWBBYLQSCNPO-RNFDNDRNSA-N promethium-149 Chemical compound [149Pm] VQMWBBYLQSCNPO-RNFDNDRNSA-N 0.000 claims description 2
- GZCRRIHWUXGPOV-CBESVEIWSA-N terbium-149 Chemical compound [149Tb] GZCRRIHWUXGPOV-CBESVEIWSA-N 0.000 claims description 2
- 229910052723 transition metal Inorganic materials 0.000 claims description 2
- 150000003624 transition metals Chemical class 0.000 claims description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 34
- 239000000243 solution Substances 0.000 description 32
- WDLRUFUQRNWCPK-UHFFFAOYSA-N Tetraxetan Chemical compound OC(=O)CN1CCN(CC(O)=O)CCN(CC(O)=O)CCN(CC(O)=O)CC1 WDLRUFUQRNWCPK-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 29
- 238000004128 high performance liquid chromatography Methods 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000000562 conjugate Substances 0.000 description 23
- 239000007983 Tris buffer Substances 0.000 description 21
- 101150041968 CDC13 gene Proteins 0.000 description 20
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 238000004007 reversed phase HPLC Methods 0.000 description 20
- 239000011347 resin Substances 0.000 description 19
- 229920005989 resin Polymers 0.000 description 19
- 235000019439 ethyl acetate Nutrition 0.000 description 18
- 239000007787 solid Substances 0.000 description 17
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 102000004196 processed proteins & peptides Human genes 0.000 description 16
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 15
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 14
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 239000012043 crude product Substances 0.000 description 12
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 11
- 238000010511 deprotection reaction Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000000746 purification Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 150000001345 alkine derivatives Chemical group 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- -1 poly(amino carboxylate) Polymers 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- STNZNCWQNMGRIM-UHFFFAOYSA-N 2-benzyl-1,4,7,10-tetrakis-(4-methylphenyl)sulfonyl-1,4,7,10-tetrazacyclododecane Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC(CC=2C=CC=CC=2)N(S(=O)(=O)C=2C=CC(C)=CC=2)CCN(S(=O)(=O)C=2C=CC(C)=CC=2)CC1 STNZNCWQNMGRIM-UHFFFAOYSA-N 0.000 description 7
- 241000699660 Mus musculus Species 0.000 description 7
- 238000003776 cleavage reaction Methods 0.000 description 7
- 238000002372 labelling Methods 0.000 description 7
- 238000011580 nude mouse model Methods 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 230000007017 scission Effects 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 238000006736 Huisgen cycloaddition reaction Methods 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000010949 copper Substances 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- IYIVBGQBEMSRLO-UHFFFAOYSA-N methyl 2-(4-iodophenyl)acetate Chemical compound COC(=O)CC1=CC=C(I)C=C1 IYIVBGQBEMSRLO-UHFFFAOYSA-N 0.000 description 6
- 150000004702 methyl esters Chemical class 0.000 description 6
- 210000000056 organ Anatomy 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- OBQRODBYVNIZJU-UHFFFAOYSA-N (4-acetylphenyl)boronic acid Chemical compound CC(=O)C1=CC=C(B(O)O)C=C1 OBQRODBYVNIZJU-UHFFFAOYSA-N 0.000 description 5
- RMMFBFFGGLOIKT-UHFFFAOYSA-N 1,2,5,8-tetrazecane Chemical compound C1CNCCNNCCN1 RMMFBFFGGLOIKT-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 230000035508 accumulation Effects 0.000 description 5
- 238000009825 accumulation Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 238000004108 freeze drying Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000007086 side reaction Methods 0.000 description 5
- FJSHTWVDFAUNCO-UHFFFAOYSA-N 2-(4-iodophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(I)C=C1 FJSHTWVDFAUNCO-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- 229910000366 copper(II) sulfate Inorganic materials 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 4
- OQUXGJRWQDJADK-UHFFFAOYSA-N methyl 2-(4-acetylphenyl)-2-bromoacetate Chemical compound COC(=O)C(Br)C1=CC=C(C(C)=O)C=C1 OQUXGJRWQDJADK-UHFFFAOYSA-N 0.000 description 4
- YMYXBKCGJCTZNT-UHFFFAOYSA-N methyl 2-[4-(2-trimethylsilylethynyl)phenyl]acetate Chemical compound COC(=O)CC1=CC=C(C#C[Si](C)(C)C)C=C1 YMYXBKCGJCTZNT-UHFFFAOYSA-N 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000002287 radioligand Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000007790 solid phase Substances 0.000 description 4
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical class C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 4
- 229940075620 somatostatin analogue Drugs 0.000 description 4
- BFQAFQRXAWEZLD-UHFFFAOYSA-N tert-butyl 2-(4-acetylphenyl)acetate Chemical compound CC(=O)C1=CC=C(CC(=O)OC(C)(C)C)C=C1 BFQAFQRXAWEZLD-UHFFFAOYSA-N 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- DEZPINDTYXXGFX-UHFFFAOYSA-N 4-(3-azidopropylamino)-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)NCCCN=[N+]=[N-] DEZPINDTYXXGFX-UHFFFAOYSA-N 0.000 description 3
- IYMAXBFPHPZYIK-BQBZGAKWSA-N Arg-Gly-Asp Chemical compound NC(N)=NCCC[C@H](N)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(O)=O IYMAXBFPHPZYIK-BQBZGAKWSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 3
- 241001070875 Prochelator Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 238000010462 azide-alkyne Huisgen cycloaddition reaction Methods 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 150000001879 copper Chemical class 0.000 description 3
- 235000018417 cysteine Nutrition 0.000 description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- SPTYPQJTOATFCG-UHFFFAOYSA-N methyl 2-bromo-2-[4-(2-trimethylsilylethynyl)phenyl]acetate Chemical compound COC(=O)C(Br)C1=CC=C(C#C[Si](C)(C)C)C=C1 SPTYPQJTOATFCG-UHFFFAOYSA-N 0.000 description 3
- 238000010647 peptide synthesis reaction Methods 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 239000000700 radioactive tracer Substances 0.000 description 3
- 239000012217 radiopharmaceutical Substances 0.000 description 3
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Classifications
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- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0624587.2A GB0624587D0 (en) | 2006-12-08 | 2006-12-08 | Chelating agent |
| GB0624587.2 | 2006-12-08 | ||
| PCT/GB2007/004733 WO2008068516A1 (en) | 2006-12-08 | 2007-12-10 | Chelating agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2671788A1 true CA2671788A1 (en) | 2008-06-12 |
Family
ID=37711827
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002671788A Abandoned CA2671788A1 (en) | 2006-12-08 | 2007-12-10 | Chelating agent |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20100081799A1 (enExample) |
| EP (1) | EP2099776B1 (enExample) |
| JP (2) | JP5705434B2 (enExample) |
| CN (1) | CN101605768A (enExample) |
| CA (1) | CA2671788A1 (enExample) |
| GB (1) | GB0624587D0 (enExample) |
| IN (1) | IN2009CN02681A (enExample) |
| WO (1) | WO2008068516A1 (enExample) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0624587D0 (en) * | 2006-12-08 | 2007-01-17 | Univ Muenchen Tech | Chelating agent |
| CN102898392B (zh) * | 2012-09-06 | 2015-08-12 | 中国工程物理研究院核物理与化学研究所 | N-乙酰氧苄基-3-[-三叔丁氧甲酰基-四氮杂环十二烷基]中间体及其制备方法 |
| CN104230832B (zh) * | 2014-08-25 | 2018-07-27 | 曲靖师范学院 | 一种4，4’，4”，4”’-(1，4，7，10-四氮杂环十二烷-1，4，7，10-四基)四亚甲基四苯甲醛的合成方法 |
| CN104307495A (zh) * | 2014-10-14 | 2015-01-28 | 常州大学 | 一种含有四氮杂环的新型螯合树脂及其制备方法 |
| WO2018183906A1 (en) | 2017-03-30 | 2018-10-04 | Cornell University | Macrocyclic complexes of alpha-emitting radionuclides and their use in targeted radiotherapy of cancer |
| CN117603148A (zh) | 2017-05-05 | 2024-02-27 | 探针技术开发及商业化中心 | 双官能螯合物的药代动力学增强及其用途 |
| KR20200004861A (ko) * | 2017-05-05 | 2020-01-14 | 퓨전 파마슈티칼즈 인크. | Igf-1r 모노클로날 항체 및 그의 용도 |
| US10093741B1 (en) | 2017-05-05 | 2018-10-09 | Fusion Pharmaceuticals Inc. | IGF-1R monoclonal antibodies and uses thereof |
| KR102152939B1 (ko) * | 2019-04-30 | 2020-09-07 | 한국화학연구원 | 공유결합성 트리아졸로 연결된 가시광선 흡수 광촉매, 이의 제조방법 및 이를 이용한 아자이드-알카인 고리화 첨가반응으로 트리아졸 유도체를 제조하는 방법 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1033030C (zh) * | 1988-06-24 | 1996-10-16 | 唐化学原料公司 | 大环双官能螯合剂及其配合物和抗体共轭物的制备方法 |
| DE353450T1 (de) * | 1988-06-24 | 1990-09-06 | The Dow Chemical Co., Midland, Mich. | Macrocyclische bifunktionelle chelatbildner, komplexe davon und ihre konjugierten antikoerper. |
| US6093382A (en) * | 1998-05-16 | 2000-07-25 | Bracco Research Usa Inc. | Metal complexes derivatized with folate for use in diagnostic and therapeutic applications |
| ES2312983T3 (es) * | 2003-03-19 | 2009-03-01 | Universitatsspital Basel | Conjugados radiomarcados basados en sustancia p y sus usos. |
| WO2005001415A2 (en) * | 2003-05-23 | 2005-01-06 | Epix Pharmaceuticals, Inc. | Optically pure and enriched isomers of chelating ligands and contrast agents |
| WO2006110745A2 (en) * | 2005-04-08 | 2006-10-19 | Cytogen Corporation | Conjugated anti-psma antibodies |
| GB0624587D0 (en) * | 2006-12-08 | 2007-01-17 | Univ Muenchen Tech | Chelating agent |
-
2006
- 2006-12-08 GB GBGB0624587.2A patent/GB0624587D0/en not_active Ceased
-
2007
- 2007-10-10 IN IN2681CHN2009 patent/IN2009CN02681A/en unknown
- 2007-12-10 JP JP2009539809A patent/JP5705434B2/ja not_active Expired - Fee Related
- 2007-12-10 WO PCT/GB2007/004733 patent/WO2008068516A1/en not_active Ceased
- 2007-12-10 EP EP07848478.9A patent/EP2099776B1/en not_active Not-in-force
- 2007-12-10 US US12/517,206 patent/US20100081799A1/en not_active Abandoned
- 2007-12-10 CA CA002671788A patent/CA2671788A1/en not_active Abandoned
- 2007-12-10 CN CNA2007800452581A patent/CN101605768A/zh active Pending
-
2015
- 2015-02-25 JP JP2015034980A patent/JP2015155407A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| GB0624587D0 (en) | 2007-01-17 |
| JP2010511687A (ja) | 2010-04-15 |
| JP2015155407A (ja) | 2015-08-27 |
| JP5705434B2 (ja) | 2015-04-22 |
| US20100081799A1 (en) | 2010-04-01 |
| WO2008068516A1 (en) | 2008-06-12 |
| EP2099776B1 (en) | 2015-10-07 |
| IN2009CN02681A (enExample) | 2015-08-07 |
| EP2099776A1 (en) | 2009-09-16 |
| CN101605768A (zh) | 2009-12-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20161212 |
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| FZDE | Discontinued |
Effective date: 20161212 |