JPWO2011125331A1 - 金属サレン錯体誘導体及びその製造方法 - Google Patents
金属サレン錯体誘導体及びその製造方法 Download PDFInfo
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- JPWO2011125331A1 JPWO2011125331A1 JP2012509317A JP2012509317A JPWO2011125331A1 JP WO2011125331 A1 JPWO2011125331 A1 JP WO2011125331A1 JP 2012509317 A JP2012509317 A JP 2012509317A JP 2012509317 A JP2012509317 A JP 2012509317A JP WO2011125331 A1 JPWO2011125331 A1 JP WO2011125331A1
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- 229910052751 metal Inorganic materials 0.000 title claims abstract description 33
- 239000002184 metal Substances 0.000 title claims abstract description 33
- VEUMANXWQDHAJV-UHFFFAOYSA-N 2-[2-[(2-hydroxyphenyl)methylideneamino]ethyliminomethyl]phenol Chemical compound OC1=CC=CC=C1C=NCCN=CC1=CC=CC=C1O VEUMANXWQDHAJV-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 11
- 239000000427 antigen Substances 0.000 claims abstract description 10
- 102000036639 antigens Human genes 0.000 claims abstract description 10
- 108091007433 antigens Proteins 0.000 claims abstract description 10
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 9
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 9
- 108090000790 Enzymes Proteins 0.000 claims abstract description 6
- 102000004190 Enzymes Human genes 0.000 claims abstract description 6
- 108091034117 Oligonucleotide Proteins 0.000 claims abstract description 5
- 150000001413 amino acids Chemical class 0.000 claims abstract description 5
- 102000039446 nucleic acids Human genes 0.000 claims abstract description 5
- 108020004707 nucleic acids Proteins 0.000 claims abstract description 5
- 150000007523 nucleic acids Chemical class 0.000 claims abstract description 5
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 239000003431 cross linking reagent Substances 0.000 claims description 18
- 238000009833 condensation Methods 0.000 claims description 14
- 230000005494 condensation Effects 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000003368 amide group Chemical group 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 7
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical group ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 5
- -1 antibody Proteins 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 150000002170 ethers Chemical class 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- 239000004971 Cross linker Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 3
- 125000002228 disulfide group Chemical group 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-UHFFFAOYSA-N 0.000 description 2
- IJFXRHURBJZNAO-UHFFFAOYSA-N 3-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC(O)=C1 IJFXRHURBJZNAO-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 229940125797 compound 12 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 2
- 239000004312 hexamethylene tetramine Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 229960004011 methenamine Drugs 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- ZUSSTQCWRDLYJA-UHFFFAOYSA-N n-hydroxy-5-norbornene-2,3-dicarboximide Chemical compound C1=CC2CC1C1C2C(=O)N(O)C1=O ZUSSTQCWRDLYJA-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- FQKFPGMGQXQHLP-UHFFFAOYSA-N 1-hydroxytriazole Chemical class ON1C=CN=N1 FQKFPGMGQXQHLP-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
- HJBLUNHMOKFZQX-UHFFFAOYSA-N 3-hydroxy-1,2,3-benzotriazin-4-one Chemical compound C1=CC=C2C(=O)N(O)N=NC2=C1 HJBLUNHMOKFZQX-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 229910052693 Europium Inorganic materials 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 239000004201 L-cysteine Substances 0.000 description 1
- 235000013878 L-cysteine Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229910052779 Neodymium Inorganic materials 0.000 description 1
- 108090000526 Papain Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229910052772 Samarium Inorganic materials 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- NIZAXAZMLBIWGR-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(C=C1)O.C(C)OC(C(C#N)=NO)=O Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)O.C(C)OC(C(C#N)=NO)=O NIZAXAZMLBIWGR-UHFFFAOYSA-N 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- DXZMZUCQXBXNBS-UHFFFAOYSA-N benzotriazol-1-yl-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N([P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 DXZMZUCQXBXNBS-UHFFFAOYSA-N 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229910052804 chromium Inorganic materials 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- DWYMPOCYEZONEA-UHFFFAOYSA-L fluoridophosphate Chemical compound [O-]P([O-])(F)=O DWYMPOCYEZONEA-UHFFFAOYSA-L 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052741 iridium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 229910052750 molybdenum Inorganic materials 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910052762 osmium Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 229940055729 papain Drugs 0.000 description 1
- 235000019834 papain Nutrition 0.000 description 1
- IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910052702 rhenium Inorganic materials 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/547—Chelates, e.g. Gd-DOTA or Zinc-amino acid chelates; Chelate-forming compounds, e.g. DOTA or ethylenediamine being covalently linked or complexed to the pharmacologically- or therapeutically-active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
- A61K9/0009—Galenical forms characterised by the drug release technique; Application systems commanded by energy involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
(II)
(II)の「・O−」に金属サレン錯体(A)が結合し、iとjの少なくとも一つに前記機能性分子(C)に結合するジスルフィド基(−S−S−)が結合している。
(III)
(III)の「・C(O)−」に金属サレン錯体(A)が結合し、iとjの少なくとも一つに前記機能性分子(C)に結合するジスルフィド基が結合している。
(IV)
前記(IV)の「・CH2−」に金属サレン錯体(A)が結合し、iとjの少なくとも一つに前記機能性分子(C)に結合するジスルフィド基が結合している。
カルボジイミド系縮合剤
ジイソプロピルカルボジイミド(DIPC)
1−エチル−3−(3−ジメチルアミノプロピル)−カルボジイミド(EDC=WSCI)、
1−エチル−3−(3−ジメチルアミノプロピル)−カルボジイミド塩酸塩(WSCI・HCl)、
ジシクロヘキシルカルボジイミド(DCC)
[O−(7−アザベンゾトリアゾール−1−イル)−1,1,3,3−テトラメチルウロニウムヘキサフルオロホスフェート
O−ベンゾトリアゾール−1−イル−N,N,N′,N′−テトラメチルウロニウムヘキサフルオロホスフェート
ベンゾトリアゾール−1−イル−オキシ−トリス−ピロリジノホスホニウムヘキサフルオロホスフェート、ベンゾトリアゾール−1−イル−トリス(ジメチルアミノ)ホスホニウムヘキサフルオロリン化物塩(BOP)
ジフェニルホスホリルアジド(DPPA)
N−ヒドロキシ多価カルボン酸イミド類
N−ヒドロキシコハク酸イミド(HONS u)、
N−ヒドロキシ−5−ノルボルネン−2,3−ジカルボン酸イミド(HONB)
1−ヒドロキシベンゾトリアゾール(HOBt)、
3−ヒドロキシ−4−オキソ−3,4−ジヒドロ−1,2,3−ベンゾトリアジン(HO Obt)、
2−ヒドロキシイミノ−2−シアノ酢酸エチルエステル
p-ニトロフェノール(HONp)、
ペンタフルオロフェノール(HOPfp)
金属サレン錯体:縮合助剤:縮合剤=1:1〜2:1〜2
化合物7A(134mg,0.338mmol)、化合物8(122mg,0.721mmol):架橋剤分子、diisopropylcarbodiimide (ジイソプロピルカーボジイミド)(170μmol):脱水縮合剤、NaHCO3 (75mg; 0.89mmol)をTHF(テトラヒドロフラン)(20mL)にN, N-4-(ジメチルアミノピリジン)dimethylaminopyridinを 0.1Mを溶かした溶液に入れ、室温で2時間攪拌した。溶液は、エチルアセテートとヘキサンを1:1で混ぜた溶液に混ぜてシリカゲル(20g)を用いたクロマトグラフィーで化合物9(黄色、115g、収率62%)を得た。
化合物9(17mg,31μmol)、FeCl3(11mg,)をメタノール(4mL)にいれ、室温、大気中で16時間攪拌した。茶色の化合物が得られた。その後、真空中で乾燥させた。得られた化合物はジクロロメタン400mlで希釈し、塩性溶液で2回洗浄し、Na2SO4で乾燥させ、真空中で乾燥させたところ化合物10(18mg、収率90%)が得られた。
化合物10とシグマアルドリッチから購入したたんぱく質(papain-lyophilisate, 10mg)とL-cysteine (10mg)を水(H2O、1mL)に30分入れて攪拌した。その後、リン酸緩衝液(300μL、1M)、pH=7.01で攪拌した。そして、攪拌から6時間後化合物11及び化合物12(両方のSH基にPapainが結合)が合成された。
Claims (11)
- A−B−C(A:金属サレン錯体、B:ジスルフィド結合、エーテル結合、エステル結合、アミド結合の少なくとも一つを備える結合領域、C:酵素、抗体、抗原、ペプチド、アミノ酸、オリゴヌクレオチド、タンパク質、核酸、及び、医薬分子の少なくとも一つからなる機能性分子)で表わされる、金属サレン錯体誘導体。
- 前記結合領域(B)は前記金属サレン錯体(A)と前記機能性分子(C)とを架橋する架橋剤分子を備え、前記金属サレン錯体(A)と前記架橋剤分子とがジスルフィド結合、エーテル結合、エステル結合、又は、アミド結合によって結合し、前記架橋剤分子と前記機能性分子(C)とがジスルフィド結合、エーテル結合、エステル結合、又は、アミド結合によって結合されている、請求項1記載の金属サレン錯体誘導体。
- 前記ジスルフィド結合領域(B)は、前記金属サレン錯体(A)に置換基として導入されたSH基と前記機能性分子(C)のSH基とが結合して得られたものであるか、又は、前記金属サレン錯体(A)又は前記機能性分子(C)のSH基と前記架橋剤分子のSH基とが結合して得られたものである、請求項2記載の金属サレン錯体誘導体。
- 前記エーテル結合領域(B)は、前記金属サレン錯体(A)に置換基として導入された水酸基と前記機能性分子(C)の水酸基とが結合して得られたものであるか、又は、前記金属サレン錯体(A)又は前記機能性分子(C)の水酸基と前記架橋剤分子の水酸基とが結合して得られたものである、請求項2記載の金属サレン錯体誘導体。
- 前記エステル結合領域(B)は、
前記金属サレン錯体(A)に置換基として導入された水酸基又はカルボキシル基と、前記機能性分子(C)のカルボキシル基と水酸基とが結合して得られたものであるか、
又は、
前記金属サレン錯体(A)又は前記機能性分子(C)の水酸基又はカルボキシル基と、前記機能性分子(C)のカルボキシル基又は水酸基とが結合して得られたものである、
請求項2記載の金属サレン錯体誘導体。 - 前記アミド結合領域(B)は、
前記金属サレン錯体(A)に置換基として導入されたアミド基又はカルボキシル基と、前記機能性分子(C)のカルボキシル基又はアミド基とが結合して得られたものであるか、
又は、
前記金属サレン錯体(A)又は前記機能性分子(C)のカルボキシル基又はアミド基と、前記機能性分子(C)のアミド基とカルボキシル基とが結合して得られたものである、請求項2記載の金属サレン錯体誘導体。 - 金属サレン錯体に、酵素、抗体、抗原、ペプチド、アミノ酸、オリゴヌクレオチド、タンパク質、核酸、及び、医薬分子の少なくとも一つからなる機能性分子を、ジスルフィド結合、エーテル結合、エステル結合、アミド結合の少なくとも一つを介して結合させる、金属サレン錯体誘導体の製造方法。
- 前記金属サレン錯体と前記機能性分子とを架橋剤分子を介して結合させる、請求項8記載の金属サレン錯体誘導体の製造方法。
- 前記金属サレン錯体と縮合助剤分子とを脱水縮合して両者の活性エステルを生成し、当該活性エステルに前記機能性分子を反応させることにより、前記活性エステルの前記縮合助剤分子を置換して、前記金属サレン錯体と前記目的成分とを結合する、請求項8記載の金属サレン錯体誘導体の製造方法。
- 前記縮合助剤分子がN−ヒドロキシコハク酸イミドである、請求項10記載の金属サレン錯体誘導体の製造方法。
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Family Cites Families (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5403834A (en) * | 1992-12-07 | 1995-04-04 | Eukarion, Inc. | Synthetic catalytic free radical scavengers useful as antioxidants for prevention and therapy of disease |
CA2232821A1 (en) * | 1995-09-28 | 1997-04-03 | California Institute Of Technology | Metal complexes as cysteine protease inhibitors |
GB9613068D0 (en) * | 1996-06-21 | 1996-08-28 | Secr Defence | Metal-containing side chain liquid crystal polymers |
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US20090169484A1 (en) * | 2007-12-28 | 2009-07-02 | Ihi Corporation | Iron-salen complex |
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US20090286968A1 (en) * | 2008-04-25 | 2009-11-19 | Auburn University | 2-Quinoxalinol Salen Compounds and Uses Thereof |
JP2009274962A (ja) * | 2008-05-12 | 2009-11-26 | Yoshihiro Ishikawa | 鉄サレン錯体、磁性を有する薬剤、薬剤の誘導システム、並びに磁気検出装置 |
JP5408905B2 (ja) | 2008-05-27 | 2014-02-05 | 義弘 石川 | 抗体又は抗原の定量方法 |
US8198322B2 (en) | 2008-06-25 | 2012-06-12 | Board Of Regents, The University Of Texas System | Apoptotic and anti-tumor activities of metallo-salens |
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