JPH10503169A - 新しい官能化親水性アクリジニウムエステル - Google Patents
新しい官能化親水性アクリジニウムエステルInfo
- Publication number
- JPH10503169A JPH10503169A JP7526216A JP52621695A JPH10503169A JP H10503169 A JPH10503169 A JP H10503169A JP 7526216 A JP7526216 A JP 7526216A JP 52621695 A JP52621695 A JP 52621695A JP H10503169 A JPH10503169 A JP H10503169A
- Authority
- JP
- Japan
- Prior art keywords
- acridinium ester
- analyte
- sample
- dmae
- group
- 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.)
- Granted
Links
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical class C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 title claims abstract description 26
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 claims abstract description 87
- 229960003604 testosterone Drugs 0.000 claims abstract description 44
- 239000012491 analyte Substances 0.000 claims abstract description 43
- 239000000523 sample Substances 0.000 claims abstract description 43
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 37
- 150000002148 esters Chemical class 0.000 claims abstract description 13
- 241000710799 Rubella virus Species 0.000 claims abstract description 12
- 238000000034 method Methods 0.000 claims description 63
- 239000000700 radioactive tracer Substances 0.000 claims description 63
- 150000001875 compounds Chemical group 0.000 claims description 42
- RXNXLAHQOVLMIE-UHFFFAOYSA-N phenyl 10-methylacridin-10-ium-9-carboxylate Chemical compound C12=CC=CC=C2[N+](C)=C2C=CC=CC2=C1C(=O)OC1=CC=CC=C1 RXNXLAHQOVLMIE-UHFFFAOYSA-N 0.000 claims description 39
- 102000004169 proteins and genes Human genes 0.000 claims description 33
- -1 amino, hydroxyl Chemical group 0.000 claims description 27
- 239000000126 substance Substances 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 108091034117 Oligonucleotide Proteins 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 11
- 241000700605 Viruses Species 0.000 claims description 11
- 239000000427 antigen Substances 0.000 claims description 11
- 108091007433 antigens Proteins 0.000 claims description 11
- 102000036639 antigens Human genes 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 230000002860 competitive effect Effects 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 230000021615 conjugation Effects 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 150000004820 halides Chemical class 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 229940088597 hormone Drugs 0.000 claims description 7
- 239000005556 hormone Substances 0.000 claims description 7
- 239000003270 steroid hormone Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 claims description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052698 phosphorus Inorganic materials 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 5
- 150000007942 carboxylates Chemical class 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 239000011574 phosphorus Substances 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 238000006467 substitution reaction Methods 0.000 claims description 4
- 150000003515 testosterones Chemical class 0.000 claims description 4
- 230000003612 virological effect Effects 0.000 claims description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000013566 allergen Substances 0.000 claims description 3
- 229960002684 aminocaproic acid Drugs 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000012039 electrophile Substances 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000002858 neurotransmitter agent Substances 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 239000003053 toxin Substances 0.000 claims description 3
- 231100000765 toxin Toxicity 0.000 claims description 3
- 108700012359 toxins Proteins 0.000 claims description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims description 2
- 108090001008 Avidin Proteins 0.000 claims description 2
- 241000894006 Bacteria Species 0.000 claims description 2
- 102000004127 Cytokines Human genes 0.000 claims description 2
- 108090000695 Cytokines Proteins 0.000 claims description 2
- 108020004414 DNA Proteins 0.000 claims description 2
- 102000052510 DNA-Binding Proteins Human genes 0.000 claims description 2
- 108700020911 DNA-Binding Proteins Proteins 0.000 claims description 2
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 2
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 2
- 108010090804 Streptavidin Proteins 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 229920001477 hydrophilic polymer Polymers 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108020003175 receptors Proteins 0.000 claims description 2
- 102000005962 receptors Human genes 0.000 claims description 2
- 229920002521 macromolecule Polymers 0.000 claims 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
- 229920000642 polymer Chemical group 0.000 claims 2
- 238000004132 cross linking Methods 0.000 claims 1
- 230000000415 inactivating effect Effects 0.000 claims 1
- 230000002194 synthesizing effect Effects 0.000 claims 1
- 238000003556 assay Methods 0.000 abstract description 80
- 238000003018 immunoassay Methods 0.000 abstract description 21
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 238000003786 synthesis reaction Methods 0.000 abstract description 13
- 230000035945 sensitivity Effects 0.000 abstract description 11
- 239000002502 liposome Substances 0.000 abstract description 9
- 238000000159 protein binding assay Methods 0.000 abstract description 4
- 239000005081 chemiluminescent agent Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
- 201000005404 rubella Diseases 0.000 description 50
- 239000000243 solution Substances 0.000 description 43
- 238000006243 chemical reaction Methods 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 238000002372 labelling Methods 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 239000012299 nitrogen atmosphere Substances 0.000 description 19
- 238000003756 stirring Methods 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000001514 detection method Methods 0.000 description 14
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 13
- 230000027455 binding Effects 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 11
- 229940098773 bovine serum albumin Drugs 0.000 description 11
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 9
- 229910019142 PO4 Chemical group 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 235000021317 phosphate Nutrition 0.000 description 8
- 239000010452 phosphate Substances 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
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- 108020004707 nucleic acids Proteins 0.000 description 6
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- 150000007523 nucleic acids Chemical class 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- DZBUGLKDJFMEHC-UHFFFAOYSA-O acridine;hydron Chemical compound C1=CC=CC2=CC3=CC=CC=C3[NH+]=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-O 0.000 description 5
- 230000008901 benefit Effects 0.000 description 5
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- 150000003839 salts Chemical group 0.000 description 4
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
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- OZFAFGSSMRRTDW-UHFFFAOYSA-N (2,4-dichlorophenyl) benzenesulfonate Chemical compound ClC1=CC(Cl)=CC=C1OS(=O)(=O)C1=CC=CC=C1 OZFAFGSSMRRTDW-UHFFFAOYSA-N 0.000 description 2
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- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.以下の化学式を有するアクリジニウムエステルであって、 ここで、 R1は、24までの炭素と、窒素、酸素、リンおよび硫黄からなる群より選択 される20までの異種原子とを有する、アルキル、アルケニル、アルキニル、アリ ールまたはアラルキルであり; R2、R3、R5、およびR7は、水素、アミノ、ヒドロキシル、ハロゲン化物 、ニトロ、−CN、−SO3H、−SCN、−R、−OR、−NHCOR、−C OR、−COOR、または−CONHRであり、ここで、Rは、24までの炭素と 、窒素、酸素、リンおよび硫黄からなる群より選択される20までの異種原子とを 有する、アルキル、アルケニル、アルキニル、アリールまたはアラルキルであり ; R4およびR8は、分枝のない、8までの炭素を有する、アルキル、アルケニ ル、アルキニル、アラルキルまたはアルコキシルであり、側鎖基が2より多い炭 素を有し; R6が以下の置換基:R6=R9−R10を示し、 ここで、R9は、要求されないが必要に応じて、P、S、N、またはOであっ て差支えない5までの異種原子を有する、アルキル基またはアラルキル基であっ て差支えなく、R10は、求電子体、リービング基、これら2種類の性質が組み合 わされた基、または以下の化学構造式から選択される基であり; ここで、Yはハロゲン化物であり、Rはアルキル、アリール、アラルキル基で あり、ここで、フェノキシ環上のR5、R6、およびR7置換位置は相互に交換可 能であることを特徴とするアクリジニウムエステル。 2.R1がスルホプロピル基またはスルホエチル基であり;R2が水素、メトキシ 、エトキシ、ニトロまたはハロゲンであり;R3、R5、およびR7が水素であり ;R4およびR8がメチル、エチルまたはイソプロピル基であり;R6がN−スク シンイミジルオキシカルボニル、N−スクシンイミジルオキシカルボニルアルキ ル、またはカルボキシレートであることを特徴とする請求の範囲第1項記載のア クリジニウムエステル。 3.前記アクリジニウムエステルが、化合物または高分子に直接的または間接的 に接合されていることを特徴とする請求の範囲第1項記載のアクリジニウムエ ステル接合体。 4.前記接合が二官能化架橋体により生じることを特徴とする請求の範囲第3項 記載のアクリジニウムエステル。 5.前記接合が、ヘキシル−1,6−ジアミン、エチレンジアミン、またはアミ ノカプロン酸により生じることを特徴とする請求の範囲第3項記載のアクリジニ ウムエステル。 6.前記高分子が、タンパク質、ペプチド、不活化タンパク質、DNA、RNA 、オリゴヌクレオチド、神経伝達物質、ホルモン、ステロイドホルモン、ウイル ス、細菌、トキシンおよびサイトカインからなる群より選択されることを特徴と する請求の範囲第3項記載のアクリジニウムエステル。 7.前記タンパク質が、抗体、抗体断片、アビジン、ストレプトアビジン、アレ ルゲン、受容体タンパク質、DNA結合タンパク質、不活化タンパク質、神経伝 達物質、ホルモン、ウイルス抗原、細菌抗原、トキシンおよびサイトカニンから なる群より選択されることを特徴とする請求の範囲第6項記載のアクリジニウム エステル。 8.前記化合物がハプテンまたは小生物学的活性分子であることを特徴とする請 求の範囲第3項記載のアクリジニウムエステル。 9.前記ハプテンがステロイドホルモンであることを特徴とする請求の範囲第8 項記載のアクリジニウムエステル。 10.前記ステロイドホルモンがテストステロンであり、前記架橋およびリンカー アームが、C−19−C結合、オレフィンC−19結合またはC19−O結合に より接続されていることを特徴とする請求の範囲第9項記載のアクリジニウムエ ステル。 11.前記ステロイドホルモンがテストステロンであり、前記接合が、ヘキシル− 1,6−ジアミン、エチレンジアミン、またはアミノカプロン酸により生じるこ とを特徴とする請求の範囲第9項記載のアクリジニウムエステル。 12.前記ステロイドホルモンが、下記の化学構造式: からなる群より選択されるテストステロン誘導体であることを特徴とする請求の 範囲第9項記載のアクリジニウムエステル。 13.前記高分子が風疹ウイルスであることを特徴とする請求の範囲第3項記載の アクリジニウムエステル。 14.化学構造式: の化合物を、化学構造式: の化合物の組み合わせる工程からなるアクリジンエステルの合成方法であって、 ここで、R2、R3、R5、R7が、水素、ハロゲン化物、ニトロ、−R、−O R、−CN、−NHCOR、−COR、−COOR、または−CONHRであり 、Rがアルキル、アルケニル、アルキニル、またはアラルキルであり、ここで、 R4およびR8がRであり、Rが上述のように定義したものであることを特徴とす る方法。 15.化学構造式: の化合物を、化学構造式: の化合物と組み合わせる工程からなるDMAeE−NHSの合成方法。 16.試料中の分析物の量を測定する方法であって、 a.分析物を特異的に、試料中の濃度に比例して検出し、 b.該試料中の分析物の濃度に直接的または間接的に比例している請求の範囲 第1項記載の化学発光親水性アクリジニウムエステルにより発せられる信号を測 定する、 各工程からなることを特徴とする方法。 17.a.試料を、親水性アクリジニウムエステル標識付け検出体分子と接触させ 、該検出体分子が必要に応じて2種類以上の分子単位の複合体であり、 b.結合した検出体および分析物を隔離し、 c.過剰の検出体を洗い流し、 d.分析物結合検出体からの信号を測定する、 各工程からなることを特徴とする試料中の分析物を検出する請求の範囲第16項 記載の方法。 18.a.試料を、親水性アクリジニウムエステル標識付け競合トレーサ、および 前記分析物の特異的結合体と接触させ、 b.該特異的結合体を回収し、 c.結合したトレーサにより発せられる信号を測定する、 各工程からなることを特徴とする試料中の分析物を検出する請求の範囲第16項 記載の方法。 19.a.試料を、親水性アクリジニウムエステル標識付け競合トレーサ、および 分析物の特異的結合体と接触させ、 b.該特異的結合体を回収し、 c.未結合トレーサにより発せられた信号を測定する、 各工程からなることを特徴とする試料中の分析物を検出する請求の範囲第16項 記載の方法。 20.a.試料を、第1の特異的結合体、および第2の親水性アクリジニウムエス テル標識付け特異的結合体と接触させ、 b.信号を検出する、 各工程からなることを特徴とする試料中の分析物を検出する請求の範囲第16項 記載の方法。 21.a.試料を、親水性アクリジニウムエステル標識付け検出体および該検出体 に対する競合結合体と接触させ、 b.該競合結合体に結合した検出体を隔離し、 c.過剰の検出体および検出体に結合した分析物を洗い流し、 d.前記競合結合体に結合した検出体からの信号を測定する、 各工程からなることを特徴とする試料中の分析物を検出する請求の範囲第16項 記載の方法。 22.放出剤が用いられることを特徴とする請求の範囲第21項記載の方法。 23.放出剤が用いられないことを特徴とする請求の範囲第21項記載の方法。 24.オリゴヌクレオチドが高分子に接合され、該高分子がさらに多数のアクリジ ニウムエステルおよび必要に応じて多数の親水性ポリマーに接合されていること を特徴とする請求の範囲第3項記載のアクリジニウムエステル接合体。 25.前記オリゴヌクレオチドが遺伝子プローブであることを特徴とする請求の範 囲第24項記載のアクリジニウムエステル接合体。
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US08/225,165 | 1994-04-08 | ||
US08/225,165 US5656426A (en) | 1988-08-01 | 1994-04-08 | Functionaized hydrophilic acridinium esters |
PCT/IB1995/000244 WO1995027702A1 (en) | 1994-04-08 | 1995-04-06 | Novel functionalized hydrophilic acridinium esters |
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EP (2) | EP0982298A1 (ja) |
JP (1) | JP3844358B2 (ja) |
AT (1) | ATE231130T1 (ja) |
AU (1) | AU703436B2 (ja) |
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CA (1) | CA2186463A1 (ja) |
DE (1) | DE69529409T2 (ja) |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005507942A (ja) * | 2001-10-31 | 2005-03-24 | クエスト ダイアグノスティクス インヴェストメンツ インコーポレイテッド | 化学発光化合物およびその使用 |
JP2005536748A (ja) * | 2002-08-20 | 2005-12-02 | クエスト ダイアグノスティックス インヴェストメンツ インコーポレイテッド | 親水性化学発光アクリジニウムラベル化剤 |
US7824928B2 (en) | 2002-08-20 | 2010-11-02 | Quest Diagnostics Investments Incorporated | Hydrophilic chemiluminescent acridinium labeling reagents |
JP2011503235A (ja) * | 2007-11-20 | 2011-01-27 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | イオン液体中でのアクリジン化合物の容易なn−アルキル化 |
JP2011257410A (ja) * | 2002-06-17 | 2011-12-22 | Abbott Laboratories | アッセイコンジュゲート及びその使用 |
JP2020511431A (ja) * | 2017-02-23 | 2020-04-16 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレイテッド | 化学発光アンドロステンジオンコンジュゲート |
Families Citing this family (28)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6514987B1 (en) * | 1997-01-06 | 2003-02-04 | Cerus Corporation | Frangible compounds for pathogen inactivation |
US6391540B1 (en) | 1997-09-22 | 2002-05-21 | Chiron Corporation | Method for detecting antibodies in a sample |
ES2316171T3 (es) | 1997-09-22 | 2009-04-01 | Novartis Vaccines And Diagnostics, Inc. | Tampones para estabilizar antigenos hcv. |
ES2320055T3 (es) | 1998-08-11 | 2009-05-18 | Siemens Healthcare Diagnostics Inc. | Compuestos de uso acridino quiminolumicentes en el infrarrojo cercano y sus usos. |
US6673560B1 (en) | 1998-11-25 | 2004-01-06 | Bayer Corporation | Measurement of hydride using chemiluminescent acridinium compounds and applications thereof |
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US6783948B1 (en) * | 1999-07-30 | 2004-08-31 | Bayer Corporation | Chemiluminescent acridinium compounds and analogues thereof as substrates of hydrolytic enzymes |
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US6348317B1 (en) * | 1999-11-18 | 2002-02-19 | The Arizona Board Of Regents | Fluorescent and DNA cleavage properties of peptide/dye conjugates |
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US6664043B2 (en) * | 2001-07-03 | 2003-12-16 | Bayer Corporation | Acridinium ester labels having hydrophilic modifiers |
US7319041B2 (en) * | 2002-09-27 | 2008-01-15 | Siemens Medical Solutions Diagnostic | Applications of acridinium compounds and derivatives in homogeneous assays |
US7309615B2 (en) * | 2002-09-27 | 2007-12-18 | Siemens Medical Solutions Diagnostic | High quantum yield acridinium compounds and their uses in improving assay sensitivity |
US20090068635A1 (en) * | 2007-09-06 | 2009-03-12 | Muerhoff Anthony S | Indirectly labelled assay conjugates and methods of preparing and using same |
BRPI1009804A2 (pt) | 2009-03-27 | 2015-08-25 | Protea Biopharma N V | Métodos para detecção e tratamento de doença de príon aberrante |
EP2501681B1 (en) | 2009-11-16 | 2016-05-25 | Siemens Healthcare Diagnostics Inc. | Zwitterion-containing acridinium compounds |
JP2013534909A (ja) | 2010-05-21 | 2013-09-09 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | 両性イオン性試薬 |
US9512080B2 (en) | 2012-07-10 | 2016-12-06 | Siemens Healthcare Diagnostics Inc. | Synthesis of acridinium compounds by N-alkylation of acridans |
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WO2019116234A1 (en) | 2017-12-12 | 2019-06-20 | Nestec S.A. | Methods for determining microbiome ribosomal rna composition changes |
JP7085654B2 (ja) | 2018-06-25 | 2022-06-16 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレイテッド | アクリダン類のn-アルキル化 |
US11237170B2 (en) | 2018-12-04 | 2022-02-01 | Aat Bioquest, Inc. | Styryl phenols, derivatives and their use in methods of analyte detection |
CN115136006A (zh) * | 2020-03-04 | 2022-09-30 | 美国西门子医学诊断股份有限公司 | 放大免疫测定信号的方法 |
US20230112563A1 (en) * | 2020-03-04 | 2023-04-13 | Siemens Healthcare Diagnostics Inc. | Compositions and methods of using modified liposomes |
CN112684163B (zh) * | 2021-01-29 | 2022-08-09 | 安邦(厦门)生物科技有限公司 | 一种吖啶类化合物标记原料工作液及制备方法 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4031117A (en) * | 1975-09-22 | 1977-06-21 | Becton, Dickinson And Company | Testosterone derivatives |
US4197286A (en) * | 1977-09-27 | 1980-04-08 | Southwest Research Institute | Testosterone derivatives and assay method |
GB2112779B (en) * | 1981-12-11 | 1986-10-15 | Welsh Nat School Med | Aryl acridinium esters as luminescent labelling materials |
US4745181A (en) * | 1986-10-06 | 1988-05-17 | Ciba Corning Diagnostics Corp. | Polysubstituted aryl acridinium esters |
DE3750503T2 (de) * | 1986-10-22 | 1995-02-09 | Abbott Lab | Chemilumineszierende Acridinium- und Phenantridiniumsalze. |
US5281712A (en) * | 1987-12-31 | 1994-01-25 | London Diagnostics, Inc. | Ammonium substituted chemiluminescent labels and their conjugates, and assays therefrom |
US5321136A (en) * | 1987-12-31 | 1994-06-14 | London Diagnostics, Inc. | Peri substituted fused ring chemiluminescent labels and their conjugates, and assays therefrom |
NZ227506A (en) * | 1987-12-31 | 1992-06-25 | London Diagnostics Inc | Specific binding assays using chemiluminescent compounds |
AU634716B2 (en) * | 1988-08-01 | 1993-03-04 | Ciba Corning Diagnostics Corp. | Method for detection of an analyte using acridinium esters and liposomes |
CA1339491C (en) * | 1988-09-26 | 1997-10-07 | Say-Jong Law | Nucleophilic polysubstituted aryl acridinium ester and uses thereof |
US5241070A (en) * | 1988-09-26 | 1993-08-31 | Ciba Corning Diagnostics Corp. | Nucleophilic polysubstituted aryl acridinium esters and uses thereof |
JP3584379B2 (ja) * | 1993-02-04 | 2004-11-04 | 持田製薬株式会社 | アクリジニウム化合物およびアクリジニウム化合物複合体 |
-
1994
- 1994-04-08 US US08/225,165 patent/US5656426A/en not_active Expired - Lifetime
-
1995
- 1995-04-06 AU AU20816/95A patent/AU703436B2/en not_active Expired
- 1995-04-06 ES ES95913298T patent/ES2188654T3/es not_active Expired - Lifetime
- 1995-04-06 BR BR9507307A patent/BR9507307A/pt not_active Application Discontinuation
- 1995-04-06 EP EP99203889A patent/EP0982298A1/en not_active Withdrawn
- 1995-04-06 EP EP95913298A patent/EP0754178B1/en not_active Expired - Lifetime
- 1995-04-06 DE DE69529409T patent/DE69529409T2/de not_active Expired - Lifetime
- 1995-04-06 CA CA002186463A patent/CA2186463A1/en not_active Abandoned
- 1995-04-06 WO PCT/IB1995/000244 patent/WO1995027702A1/en active IP Right Grant
- 1995-04-06 PL PL95316794A patent/PL316794A1/xx unknown
- 1995-04-06 AT AT95913298T patent/ATE231130T1/de not_active IP Right Cessation
- 1995-04-06 JP JP52621695A patent/JP3844358B2/ja not_active Expired - Lifetime
Cited By (9)
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JP2005507942A (ja) * | 2001-10-31 | 2005-03-24 | クエスト ダイアグノスティクス インヴェストメンツ インコーポレイテッド | 化学発光化合物およびその使用 |
JP2011257410A (ja) * | 2002-06-17 | 2011-12-22 | Abbott Laboratories | アッセイコンジュゲート及びその使用 |
JP2005536748A (ja) * | 2002-08-20 | 2005-12-02 | クエスト ダイアグノスティックス インヴェストメンツ インコーポレイテッド | 親水性化学発光アクリジニウムラベル化剤 |
US7824928B2 (en) | 2002-08-20 | 2010-11-02 | Quest Diagnostics Investments Incorporated | Hydrophilic chemiluminescent acridinium labeling reagents |
JP4699756B2 (ja) * | 2002-08-20 | 2011-06-15 | クエスト ダイアグノスティックス インヴェストメンツ インコーポレイテッド | 親水性化学発光アクリジニウムラベル化剤 |
US8034636B2 (en) | 2002-08-20 | 2011-10-11 | Quest Diagnostics Investments Incorporated | Hydrophilic chemiluminescent acridinium labeling reagents |
JP2011503235A (ja) * | 2007-11-20 | 2011-01-27 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレーテッド | イオン液体中でのアクリジン化合物の容易なn−アルキル化 |
JP2020511431A (ja) * | 2017-02-23 | 2020-04-16 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレイテッド | 化学発光アンドロステンジオンコンジュゲート |
JP2022008971A (ja) * | 2017-02-23 | 2022-01-14 | シーメンス・ヘルスケア・ダイアグノスティックス・インコーポレイテッド | 化学発光アンドロステンジオンコンジュゲート |
Also Published As
Publication number | Publication date |
---|---|
BR9507307A (pt) | 1997-09-02 |
DE69529409D1 (de) | 2003-02-20 |
EP0982298A1 (en) | 2000-03-01 |
US5656426A (en) | 1997-08-12 |
WO1995027702A1 (en) | 1995-10-19 |
AU703436B2 (en) | 1999-03-25 |
CA2186463A1 (en) | 1995-10-19 |
ES2188654T3 (es) | 2003-07-01 |
JP3844358B2 (ja) | 2006-11-08 |
ATE231130T1 (de) | 2003-02-15 |
EP0754178A1 (en) | 1997-01-22 |
AU2081695A (en) | 1995-10-30 |
PL316794A1 (en) | 1997-02-17 |
DE69529409T2 (de) | 2003-08-14 |
EP0754178B1 (en) | 2003-01-15 |
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