KR101968475B1 - 코엘렌테라진 유도체 및 이를 이용하는 방법 - Google Patents
코엘렌테라진 유도체 및 이를 이용하는 방법 Download PDFInfo
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- KR101968475B1 KR101968475B1 KR1020137014031A KR20137014031A KR101968475B1 KR 101968475 B1 KR101968475 B1 KR 101968475B1 KR 1020137014031 A KR1020137014031 A KR 1020137014031A KR 20137014031 A KR20137014031 A KR 20137014031A KR 101968475 B1 KR101968475 B1 KR 101968475B1
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- alkyl
- coelenterazine
- enzyme
- compound
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- 238000000034 method Methods 0.000 title claims abstract description 21
- YHIPILPTUVMWQT-UHFFFAOYSA-N Oplophorus luciferin Chemical class C1=CC(O)=CC=C1CC(C(N1C=C(N2)C=3C=CC(O)=CC=3)=O)=NC1=C2CC1=CC=CC=C1 YHIPILPTUVMWQT-UHFFFAOYSA-N 0.000 title abstract description 70
- 102000004190 Enzymes Human genes 0.000 claims abstract description 77
- 108090000790 Enzymes Proteins 0.000 claims abstract description 77
- 239000000758 substrate Substances 0.000 claims abstract description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- 150000001875 compounds Chemical class 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000005647 linker group Chemical group 0.000 claims description 19
- 150000001413 amino acids Chemical class 0.000 claims description 18
- 241001465754 Metazoa Species 0.000 claims description 16
- 238000004020 luminiscence type Methods 0.000 claims description 16
- 125000003107 substituted aryl group Chemical group 0.000 claims description 16
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- 230000009261 transgenic effect Effects 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 238000001727 in vivo Methods 0.000 claims description 4
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- 229910052736 halogen Inorganic materials 0.000 claims description 3
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- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 229940088598 enzyme Drugs 0.000 description 69
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 41
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- -1 i.e. Chemical compound 0.000 description 20
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
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- 230000000694 effects Effects 0.000 description 10
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000004432 carbon atom Chemical group C* 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
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- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 6
- 229940126086 compound 21 Drugs 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 235000000346 sugar Nutrition 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- KAEGGIFPLJZUOZ-UHFFFAOYSA-N Renilla luciferin Chemical compound C1=CC(O)=CC=C1C(N1)=CN2C(=O)C(CC=3C=CC=CC=3)=NC2=C1CC1=CC=CC=C1 KAEGGIFPLJZUOZ-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
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- 102000035195 Peptidases Human genes 0.000 description 4
- 108091005804 Peptidases Proteins 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 239000004365 Protease Substances 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
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- 230000014509 gene expression Effects 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 3
- FCKYPQBAHLOOJQ-UHFFFAOYSA-N Cyclohexane-1,2-diaminetetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)C1CCCCC1N(CC(O)=O)CC(O)=O FCKYPQBAHLOOJQ-UHFFFAOYSA-N 0.000 description 3
- 108010047357 Luminescent Proteins Proteins 0.000 description 3
- 102000006830 Luminescent Proteins Human genes 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
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- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 description 3
- 108010052090 Renilla Luciferases Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- AOUOVFRSCMDPFA-QSDJMHMYSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-amino-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]-3-methylbutanoyl]amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O AOUOVFRSCMDPFA-QSDJMHMYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
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- YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 2
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/66—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving luciferase
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| AU2011323418B2 (en) | 2010-11-02 | 2017-07-27 | Promega Corporation | Novel coelenterazine substrates and methods of use |
| WO2013033515A1 (en) * | 2011-09-02 | 2013-03-07 | Promega Corporation | Compounds and methods for assaying redox state of metabolically active cells and methods for measuring nad(p)/nad(p)h |
| WO2014052653A1 (en) | 2012-09-26 | 2014-04-03 | Promega Corporation | Real-time monitoring |
| CN105407723A (zh) | 2013-03-15 | 2016-03-16 | G1治疗公司 | 高效的抗赘生剂和抗增生剂 |
| WO2014144326A1 (en) | 2013-03-15 | 2014-09-18 | G1 Therapeutics, Inc. | Transient protection of normal cells during chemotherapy |
| JP6270127B2 (ja) * | 2014-01-17 | 2018-01-31 | 国立研究開発法人物質・材料研究機構 | ニコチンアデニンジヌクレオチド誘導体を検出する方法 |
| US9927430B2 (en) | 2014-01-29 | 2018-03-27 | Promega Corporation | Pro-substrates for live cell applications |
| JP6703484B2 (ja) * | 2014-01-29 | 2020-06-03 | プロメガ コーポレイションＰｒｏｍｅｇａ Ｃｏｒｐｏｒａｔｉｏｎ | 細胞による取り込み測定のための、標識用試薬としての、キノンでマスクされたプローブ |
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| US9924073B2 (en) * | 2016-02-15 | 2018-03-20 | Promega Corporation | Substituted imidazo[1,2-a]pyrazines as luciferase substrates and preparation method thereof |
| EP3490991B1 (en) | 2016-07-28 | 2021-01-06 | Promega Corporation | Coelenterazine analogues |
| US10316070B2 (en) | 2016-09-09 | 2019-06-11 | Promega Corporation | Dual protected pro-coelenterazine substrates |
| JP7200102B2 (ja) | 2016-11-01 | 2023-01-06 | プロメガ コーポレイション | エネルギー受容体に係留されたセレンテラジン類縁体 |
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| JP7161475B2 (ja) | 2016-12-28 | 2022-10-26 | プロメガ コーポレイション | 官能化ｎａｎｏｌｕｃ阻害剤 |
| EP3395803A1 (en) * | 2017-04-28 | 2018-10-31 | Institut Pasteur | Imidazopyrazine derivatives, process for preparation thereof, and their uses as luciferins |
| WO2019213119A1 (en) | 2018-05-01 | 2019-11-07 | Promega Corporation | Coelenterazine compounds as nanoluc suicide substrates |
| US11390599B2 (en) | 2018-06-01 | 2022-07-19 | Promega Corporation | Inhibitors of oplophorus luciferase-derived bioluminescent complexes |
| KR102114088B1 (ko) * | 2018-09-10 | 2020-06-17 | (주)신우에이엔티 | 웨이퍼 세정용 나노 버블 분사 구조 |
| CN119955899A (zh) | 2018-10-03 | 2025-05-09 | 普洛麦格公司 | 用于稳定腔肠素及其类似物和衍生物的组合物、方法和试剂盒 |
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| PT2635583E (pt) | 2015-09-11 |
| BR112013010484B1 (pt) | 2019-09-03 |
| EP2635583B1 (en) | 2015-06-03 |
| IL225869A (en) | 2017-09-28 |
| US20120107849A1 (en) | 2012-05-03 |
| WO2012061477A1 (en) | 2012-05-10 |
| ES2543913T3 (es) | 2015-08-25 |
| EP2635583A1 (en) | 2013-09-11 |
| PL2635583T3 (pl) | 2015-11-30 |
| US9487520B2 (en) | 2016-11-08 |
| JP2013544242A (ja) | 2013-12-12 |
| JP6040157B2 (ja) | 2016-12-07 |
| AU2011323455B2 (en) | 2017-07-27 |
| BR112013010484A2 (pt) | 2016-07-05 |
| IL225869A0 (en) | 2013-07-31 |
| CA2815381A1 (en) | 2012-05-10 |
| AU2011323455A1 (en) | 2013-05-30 |
| DK2635583T3 (en) | 2015-08-03 |
| KR20140003430A (ko) | 2014-01-09 |
| CA2815381C (en) | 2019-03-19 |
| SG189494A1 (en) | 2013-05-31 |
| CN103180324A (zh) | 2013-06-26 |
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