ZA200405175B - Coumarines useful as biomarkers. - Google Patents
Coumarines useful as biomarkers. Download PDFInfo
- Publication number
- ZA200405175B ZA200405175B ZA200405175A ZA200405175A ZA200405175B ZA 200405175 B ZA200405175 B ZA 200405175B ZA 200405175 A ZA200405175 A ZA 200405175A ZA 200405175 A ZA200405175 A ZA 200405175A ZA 200405175 B ZA200405175 B ZA 200405175B
- Authority
- ZA
- South Africa
- Prior art keywords
- formula
- compound
- cha
- defined above
- chromen
- Prior art date
Links
- 239000000090 biomarker Substances 0.000 title description 3
- 235000001671 coumarin Nutrition 0.000 title description 2
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 55
- 229910052731 fluorine Inorganic materials 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 24
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 12
- 150000003839 salts Chemical group 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 9
- 238000002372 labelling Methods 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 238000001727 in vivo Methods 0.000 claims description 6
- 238000000338 in vitro Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 230000002285 radioactive effect Effects 0.000 claims description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- 210000005013 brain tissue Anatomy 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 208000037259 Amyloid Plaque Diseases 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 238000012544 monitoring process Methods 0.000 claims description 3
- 210000002682 neurofibrillary tangle Anatomy 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- MAVYKZTVGAVXRQ-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)-7-[4-(2-fluoroethyl)piperazin-1-yl]chromen-2-one Chemical compound C1CN(CCF)CCN1C1=CC=C(C=C(C=2SC3=CC=CC=C3N=2)C(=O)O2)C2=C1 MAVYKZTVGAVXRQ-UHFFFAOYSA-N 0.000 claims description 2
- LTEUAXFPVLRRKX-UHFFFAOYSA-N ClC1=CC2=C(N=C(S2)C=2C(OC3=CC(=CC=C3C2)N(C)C)=O)C=C1.N1C(=NC2=C1C=CC=C2)C=2C(OC1=CC(=CC=C1C2)N(C)C)=O.CN(C2=CC=C1C=C(C(OC1=C2)=O)C2=NC1=C(N2C)C=CC=C1)C Chemical compound ClC1=CC2=C(N=C(S2)C=2C(OC3=CC(=CC=C3C2)N(C)C)=O)C=C1.N1C(=NC2=C1C=CC=C2)C=2C(OC1=CC(=CC=C1C2)N(C)C)=O.CN(C2=CC=C1C=C(C(OC1=C2)=O)C2=NC1=C(N2C)C=CC=C1)C LTEUAXFPVLRRKX-UHFFFAOYSA-N 0.000 claims description 2
- REJFTEQLGQHTIK-UHFFFAOYSA-N O1C(=NC2=C1C=CC=C2)C=2C(OC1=CC(=CC=C1C2)NC)=O.O2C(=NC1=C2C=CC=C1)C=1C(OC2=CC(=CC=C2C1)N(C)C)=O.S1C(=NC2=C1C=CC=C2)C=2C(OC1=CC(=CC=C1C2)N(C)C)=O Chemical compound O1C(=NC2=C1C=CC=C2)C=2C(OC1=CC(=CC=C1C2)NC)=O.O2C(=NC1=C2C=CC=C1)C=1C(OC2=CC(=CC=C2C1)N(C)C)=O.S1C(=NC2=C1C=CC=C2)C=2C(OC1=CC(=CC=C1C2)N(C)C)=O REJFTEQLGQHTIK-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 238000000799 fluorescence microscopy Methods 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 239000003550 marker Substances 0.000 claims description 2
- 238000002600 positron emission tomography Methods 0.000 claims description 2
- 238000002603 single-photon emission computed tomography Methods 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000012267 brine Substances 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 229960004132 diethyl ether Drugs 0.000 description 4
- AIOVHQHTHZJMPA-UHFFFAOYSA-N methyl 2-(1,3-benzothiazol-2-yl)acetate Chemical compound C1=CC=C2SC(CC(=O)OC)=NC2=C1 AIOVHQHTHZJMPA-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- FJYMSXRUUXFMST-UHFFFAOYSA-N 1-(2-fluoroethyl)-7-hydroxy-3,4-dihydro-2h-quinoline-6-carbaldehyde Chemical compound FCCN1CCCC2=C1C=C(O)C(C=O)=C2 FJYMSXRUUXFMST-UHFFFAOYSA-N 0.000 description 2
- JTLAIKFGRHDNQM-UHFFFAOYSA-N 1-bromo-2-fluoroethane Chemical compound FCCBr JTLAIKFGRHDNQM-UHFFFAOYSA-N 0.000 description 2
- XUYBQHIQYKVMTE-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)-7-[4-(2-hydroxyethyl)piperazin-1-yl]chromen-2-one Chemical compound C1CN(CCO)CCN1C1=CC=C(C=C(C=2SC3=CC=CC=C3N=2)C(=O)O2)C2=C1 XUYBQHIQYKVMTE-UHFFFAOYSA-N 0.000 description 2
- LRAGEJPCNKMCHP-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)-7-piperazin-1-ylchromen-2-one Chemical compound C1=CC=2C=C(C=3SC4=CC=CC=C4N=3)C(=O)OC=2C=C1N1CCNCC1 LRAGEJPCNKMCHP-UHFFFAOYSA-N 0.000 description 2
- UZPHWIWUSZOTQC-UHFFFAOYSA-N 3-[4-(2-fluoroethyl)piperazin-1-yl]phenol Chemical compound OC1=CC=CC(N2CCN(CCF)CC2)=C1 UZPHWIWUSZOTQC-UHFFFAOYSA-N 0.000 description 2
- AYGYICRITMSJOC-UHFFFAOYSA-N 3-piperazin-1-ylphenol Chemical compound OC1=CC=CC(N2CCNCC2)=C1 AYGYICRITMSJOC-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- GXHDQOJKMCTCPL-UHFFFAOYSA-N 4-[2-fluoroethyl(methyl)amino]-2-hydroxybenzaldehyde Chemical compound FCCN(C)C1=CC=C(C=O)C(O)=C1 GXHDQOJKMCTCPL-UHFFFAOYSA-N 0.000 description 2
- KADBGBPYCGQDFK-UHFFFAOYSA-N 4-[4-(2-fluoroethyl)piperazin-1-yl]-2-hydroxybenzaldehyde Chemical compound C1=C(C=O)C(O)=CC(N2CCN(CCF)CC2)=C1 KADBGBPYCGQDFK-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical class C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HJJRGZMJZDSMDB-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinolin-7-ol Chemical compound C1CCNC2=CC(O)=CC=C21 HJJRGZMJZDSMDB-UHFFFAOYSA-N 0.000 description 1
- GTHPDGCEHJADIW-UHFFFAOYSA-N 1-(2-fluoroethyl)-2,3,4,6-tetrahydroquinoline-7,7-diol Chemical compound C1CCN(CCF)C2=CC(O)(O)CC=C21 GTHPDGCEHJADIW-UHFFFAOYSA-N 0.000 description 1
- IHZMECVRSCZAHU-UHFFFAOYSA-N 2-(6-chloroimidazo[1,2-a]pyridin-2-yl)acetic acid Chemical compound C1=C(Cl)C=CC2=NC(CC(=O)O)=CN21 IHZMECVRSCZAHU-UHFFFAOYSA-N 0.000 description 1
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- PILLGAYDFOMSTJ-UHFFFAOYSA-N 2-hydroxy-4-piperazin-1-ylbenzaldehyde Chemical compound C1=C(C=O)C(O)=CC(N2CCNCC2)=C1 PILLGAYDFOMSTJ-UHFFFAOYSA-N 0.000 description 1
- QSECPQCFCWVBKM-UHFFFAOYSA-N 2-iodoethanol Chemical compound OCCI QSECPQCFCWVBKM-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- CKQYPOSBCXTFDJ-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)-7-(4-methylpiperazin-1-yl)chromen-2-one Chemical compound C1CN(C)CCN1C1=CC=C(C=C(C=2SC3=CC=CC=C3N=2)C(=O)O2)C2=C1 CKQYPOSBCXTFDJ-UHFFFAOYSA-N 0.000 description 1
- QCBSZFPJLKZCEG-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-yl)-7-[2-fluoroethyl(methyl)amino]chromen-2-one Chemical compound C1=CC=C2SC(C3=CC4=CC=C(C=C4OC3=O)N(CCF)C)=NC2=C1 QCBSZFPJLKZCEG-UHFFFAOYSA-N 0.000 description 1
- DZEHEYGEFMLFED-UHFFFAOYSA-N 3-(5-chloro-1,3-benzoxazol-2-yl)-7-(dimethylamino)chromen-2-one Chemical compound ClC1=CC=C2OC(C3=CC4=CC=C(C=C4OC3=O)N(C)C)=NC2=C1 DZEHEYGEFMLFED-UHFFFAOYSA-N 0.000 description 1
- MAXBVGJEFDMHNV-UHFFFAOYSA-N 5-chloropyridin-2-amine Chemical compound NC1=CC=C(Cl)C=N1 MAXBVGJEFDMHNV-UHFFFAOYSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 229910019210 POCl4 Inorganic materials 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012216 imaging agent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- UTBCRHAMJFMIIR-UHFFFAOYSA-N methyl 3-chloro-3-oxopropanoate Chemical compound COC(=O)CC(Cl)=O UTBCRHAMJFMIIR-UHFFFAOYSA-N 0.000 description 1
- HFLMYYLFSNEOOT-UHFFFAOYSA-N methyl 4-chloro-3-oxobutanoate Chemical compound COC(=O)CC(=O)CCl HFLMYYLFSNEOOT-UHFFFAOYSA-N 0.000 description 1
- 210000001682 neurofibril Anatomy 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Sampling And Sample Adjustment (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0205281.9A GB0205281D0 (en) | 2002-03-06 | 2002-03-06 | Organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200405175B true ZA200405175B (en) | 2005-06-21 |
Family
ID=9932424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200405175A ZA200405175B (en) | 2002-03-06 | 2004-06-29 | Coumarines useful as biomarkers. |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US7569337B2 (es) |
| EP (1) | EP1483262B1 (es) |
| JP (2) | JP4247123B2 (es) |
| KR (1) | KR20040095257A (es) |
| CN (1) | CN1628114A (es) |
| AR (1) | AR038723A1 (es) |
| AT (1) | ATE378333T1 (es) |
| AU (1) | AU2003210418A1 (es) |
| BR (1) | BR0308211A (es) |
| CA (1) | CA2472298A1 (es) |
| CO (1) | CO5611123A2 (es) |
| DE (1) | DE60317476T2 (es) |
| EC (1) | ECSP045255A (es) |
| ES (1) | ES2294304T3 (es) |
| GB (1) | GB0205281D0 (es) |
| MX (1) | MXPA04008570A (es) |
| NO (1) | NO20044174L (es) |
| PE (1) | PE20030890A1 (es) |
| PL (1) | PL370916A1 (es) |
| PT (1) | PT1483262E (es) |
| RU (1) | RU2004129733A (es) |
| TW (1) | TW200400049A (es) |
| WO (1) | WO2003074519A1 (es) |
| ZA (1) | ZA200405175B (es) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0205281D0 (en) * | 2002-03-06 | 2002-04-17 | Novartis Ag | Organic compounds |
| WO2005040337A2 (en) * | 2003-05-20 | 2005-05-06 | The Regents Of The University Of California | METHODS FOR BINDING AGENTS TO β-AMYLOID PLAQUES |
| JP4000353B2 (ja) | 2004-11-26 | 2007-10-31 | 国立大学法人 長崎大学 | アミロイド関連疾患診断用組成物 |
| JP2007084526A (ja) * | 2004-11-26 | 2007-04-05 | Nagasaki Univ | アミロイド関連疾患診断用組成物 |
| TW200803903A (en) * | 2006-04-28 | 2008-01-16 | Nihon Mediphysics Co Ltd | Novel compound having affinity to amyloid |
| TW200808795A (en) * | 2006-05-19 | 2008-02-16 | Nihon Mediphysics Co Ltd | Novel compound having affinity for amyloid |
| TW200811175A (en) * | 2006-06-21 | 2008-03-01 | Nihon Mediphysics Co Ltd | Novel compound with affinity with amyloid |
| CA2655826A1 (en) * | 2006-06-21 | 2007-12-27 | Nihon Medi-Physics Co., Ltd. | Novel compound having affinity for amyloid |
| KR101485445B1 (ko) | 2007-02-13 | 2015-01-22 | 니혼 메디피직스 가부시키가이샤 | 방사성 화상진단제의 제조 방법 |
| KR20100091965A (ko) * | 2007-10-24 | 2010-08-19 | 니혼 메디피직스 가부시키가이샤 | 신규 아밀로이드 친화성 화합물 |
| EP2218463A1 (en) * | 2007-10-30 | 2010-08-18 | Nihon Medi-Physics Co., Ltd. | Use of novel compound having affinity for amyloid, and process for production of the same |
| EP2216050A4 (en) * | 2007-10-30 | 2012-11-21 | Nihon Mediphysics Co Ltd | USE OF NEW COMPOUNDS WITH AMYLOID AFFINITY AND METHOD OF MANUFACTURING THEREOF |
| CA2861609C (en) | 2011-12-30 | 2021-02-16 | Ptc Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| EP2804852A2 (en) | 2012-01-20 | 2014-11-26 | Regents Of The University Of Minnesota | Therapeutic compounds |
| US9399649B2 (en) | 2012-01-26 | 2016-07-26 | Ptc Therapeutics, Inc. | Compounds for treating spinal muscular atrophy |
| PE20142364A1 (es) | 2012-02-10 | 2015-01-10 | Hoffmann La Roche | Compuestos para tratar atrofia muscular espinal |
| KR102099997B1 (ko) * | 2012-03-01 | 2020-04-13 | 피티씨 테라퓨틱스, 인크. | 척수성 근위축증을 치료하기 위한 화합물 |
| EA028382B1 (ru) | 2012-03-23 | 2017-11-30 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | Соединения для лечения спинальной мышечной атрофии |
| CN104987328A (zh) * | 2012-05-23 | 2015-10-21 | 复旦大学 | 7-氧、硫或氮杂取代香豆素及其衍生物和用途 |
| EP3082820B1 (en) | 2013-12-19 | 2022-07-20 | PTC Therapeutics, Inc. | Methods for modulating the amount of rna transcripts |
| EP4249472A3 (en) | 2015-05-30 | 2023-12-13 | PTC Therapeutics, Inc. | Methods for modulating rna splicing |
| IL281633B (en) | 2015-12-10 | 2022-07-01 | Ptc Therapeutics Inc | Methods for treating Huntington's disease |
| EP3544435A4 (en) | 2016-11-28 | 2020-11-04 | PTC Therapeutics, Inc. | RNA SPLICE MODULATION PROCESSES |
| EP4257596A3 (en) * | 2016-12-22 | 2023-12-06 | Illumina Cambridge Limited | Coumarin compounds and their uses as fluorescent labels |
| CN108061725B (zh) * | 2017-02-16 | 2020-04-21 | 昆明医科大学 | 1,8-萘啶基荧光分子探针在氯胺酮娱乐性滥用神经机制研究及成瘾程度诊断中的应用 |
| EP3634953B1 (en) | 2017-06-05 | 2024-01-03 | PTC Therapeutics, Inc. | Compounds for treating huntington's disease |
| CN111372611A (zh) | 2017-06-14 | 2020-07-03 | Ptc医疗公司 | 修饰rna剪接的方法 |
| CA3067591A1 (en) | 2017-06-28 | 2019-01-03 | Ptc Therapeutics, Inc. | Methods for treating huntington's disease |
| US11395822B2 (en) | 2017-06-28 | 2022-07-26 | Ptc Therapeutics, Inc. | Methods for treating Huntington's disease |
| CA3094703A1 (en) | 2018-03-27 | 2019-10-03 | Ptc Therapeutics, Inc. | Compounds for treating huntington's disease |
| US11685746B2 (en) | 2018-06-27 | 2023-06-27 | Ptc Therapeutics, Inc. | Heteroaryl compounds for treating Huntington's disease |
| WO2020005873A1 (en) | 2018-06-27 | 2020-01-02 | Ptc Therapeutics, Inc. | Heterocyclic and heteroaryl compounds for treating huntington's disease |
| MX2020013384A (es) * | 2019-03-01 | 2021-04-28 | Illumina Cambridge Ltd | Compuestos de comarina sustituidos con amina exocíclica y sus usos como etiquetas fluorescentes. |
| CN112300201B (zh) * | 2020-12-07 | 2021-11-23 | 南京林业大学 | 一种三聚茚基香豆素-咔咯-卟啉四元体系星型化合物的合成及其制备方法 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH390250A (de) * | 1958-06-19 | 1965-07-30 | Geigy Ag J R | Verfahren zur Herstellung von fluoreszierenden Farbstoffen |
| DE2065552A1 (de) * | 1970-06-20 | 1974-03-07 | Bayer Ag | Oxazolyl-essigsaeurederivate |
| JPS5529110B2 (es) * | 1972-12-25 | 1980-08-01 | ||
| DE2410634A1 (de) * | 1974-03-06 | 1975-09-18 | Basf Ag | 3-benzofurylcumarine |
| DE2411969A1 (de) * | 1974-03-13 | 1975-09-25 | Bayer Ag | Farbstofflaser |
| DE2525986A1 (de) * | 1975-06-11 | 1977-05-05 | Bayer Ag | Cumarinverbindungen |
| LU78311A1 (de) * | 1977-10-13 | 1979-06-01 | Ciba Geigy Ag | Neue cumarinfarbstoffe,deren herstellung und verwendung |
| US4892922A (en) * | 1987-11-30 | 1990-01-09 | Eastman Kodak Company | Polyester polymer containing the residue of a benzopyran colorant compound and shaped articles produced therefrom |
| JPH01169327A (ja) * | 1987-12-25 | 1989-07-04 | Mitsui Toatsu Chem Inc | 紫外線検知用樹脂組成物 |
| JP2999841B2 (ja) * | 1991-04-03 | 2000-01-17 | 三井化学株式会社 | 発光スクリーン用樹脂組成物 |
| DE69216498T2 (de) * | 1991-08-13 | 1997-04-30 | Bayer Ag | Fluoreszierendes Etikett |
| JPH073179A (ja) * | 1993-06-15 | 1995-01-06 | Nippon Kayaku Co Ltd | インクジェットプリント用インク組成物及びこれを用いる染色法 |
| JP4028155B2 (ja) * | 2000-04-11 | 2007-12-26 | 日本カーバイド工業株式会社 | 蛍光性再帰反射シート |
| GB0205281D0 (en) * | 2002-03-06 | 2002-04-17 | Novartis Ag | Organic compounds |
-
2002
- 2002-03-06 GB GBGB0205281.9A patent/GB0205281D0/en not_active Ceased
-
2003
- 2003-03-04 AR ARP030100711A patent/AR038723A1/es unknown
- 2003-03-04 PE PE2003000207A patent/PE20030890A1/es not_active Application Discontinuation
- 2003-03-04 TW TW092104534A patent/TW200400049A/zh unknown
- 2003-03-05 ES ES03743381T patent/ES2294304T3/es not_active Expired - Lifetime
- 2003-03-05 PT PT03743381T patent/PT1483262E/pt unknown
- 2003-03-05 DE DE60317476T patent/DE60317476T2/de not_active Expired - Fee Related
- 2003-03-05 JP JP2003572987A patent/JP4247123B2/ja not_active Expired - Fee Related
- 2003-03-05 BR BR0308211-3A patent/BR0308211A/pt not_active IP Right Cessation
- 2003-03-05 RU RU2004129733/04A patent/RU2004129733A/ru not_active Application Discontinuation
- 2003-03-05 AU AU2003210418A patent/AU2003210418A1/en not_active Abandoned
- 2003-03-05 PL PL03370916A patent/PL370916A1/xx not_active Application Discontinuation
- 2003-03-05 AT AT03743381T patent/ATE378333T1/de not_active IP Right Cessation
- 2003-03-05 WO PCT/EP2003/002251 patent/WO2003074519A1/en active IP Right Grant
- 2003-03-05 KR KR10-2004-7013763A patent/KR20040095257A/ko not_active Application Discontinuation
- 2003-03-05 EP EP03743381A patent/EP1483262B1/en not_active Expired - Lifetime
- 2003-03-05 US US10/506,381 patent/US7569337B2/en not_active Expired - Fee Related
- 2003-03-05 CA CA002472298A patent/CA2472298A1/en not_active Abandoned
- 2003-03-05 MX MXPA04008570A patent/MXPA04008570A/es active IP Right Grant
- 2003-03-05 CN CNA038032163A patent/CN1628114A/zh active Pending
-
2004
- 2004-06-29 ZA ZA200405175A patent/ZA200405175B/en unknown
- 2004-08-27 EC EC2004005255A patent/ECSP045255A/es unknown
- 2004-09-15 CO CO04091787A patent/CO5611123A2/es not_active Application Discontinuation
- 2004-09-30 NO NO20044174A patent/NO20044174L/no not_active Application Discontinuation
-
2008
- 2008-11-27 JP JP2008302570A patent/JP2009102322A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003074519A1 (en) | 2003-09-12 |
| DE60317476D1 (de) | 2007-12-27 |
| EP1483262B1 (en) | 2007-11-14 |
| CA2472298A1 (en) | 2003-09-12 |
| TW200400049A (en) | 2004-01-01 |
| US20050169837A1 (en) | 2005-08-04 |
| EP1483262A1 (en) | 2004-12-08 |
| PE20030890A1 (es) | 2003-12-05 |
| BR0308211A (pt) | 2004-12-21 |
| CO5611123A2 (es) | 2006-02-28 |
| AR038723A1 (es) | 2005-01-26 |
| CN1628114A (zh) | 2005-06-15 |
| GB0205281D0 (en) | 2002-04-17 |
| KR20040095257A (ko) | 2004-11-12 |
| NO20044174L (no) | 2004-09-30 |
| ATE378333T1 (de) | 2007-11-15 |
| JP2009102322A (ja) | 2009-05-14 |
| US7569337B2 (en) | 2009-08-04 |
| ES2294304T3 (es) | 2008-04-01 |
| PL370916A1 (en) | 2005-06-13 |
| PT1483262E (pt) | 2008-02-11 |
| JP2005526749A (ja) | 2005-09-08 |
| DE60317476T2 (de) | 2008-05-21 |
| AU2003210418A1 (en) | 2003-09-16 |
| RU2004129733A (ru) | 2005-06-27 |
| JP4247123B2 (ja) | 2009-04-02 |
| ECSP045255A (es) | 2004-09-28 |
| MXPA04008570A (es) | 2004-12-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ZA200405175B (en) | Coumarines useful as biomarkers. | |
| JP6951767B2 (ja) | 抗癌薬として使用される複素環式化合物 | |
| DK2152258T3 (en) | Derivatives of fluorene, anthracene, xanthene, acridine dibenzosuberone AND DERIVATIVES AND USES | |
| CN102264707B (zh) | 双环型杂环化合物 | |
| CA2797708C (en) | Process for synthesizing oxidized lactam compounds | |
| KR102305710B1 (ko) | Gpr84 수용체 길항제 및 이의 용도 | |
| CN114072411B (zh) | 作为Wee1抑制剂的嘧啶衍生物 | |
| JP2012501346A5 (es) | ||
| BG107460A (bg) | Производни на бензимидазола, тяхното получаване иприложението им в терапията | |
| KR20160006207A (ko) | 사이클로알킬산 유도체, 그의 제조 방법, 및 그의 약학적 용도 | |
| TWI485147B (zh) | 製備苯并咪唑-２-基嘧啶衍生物之方法 | |
| CA3182595A1 (en) | Immunosuppressant, and preparation method therefor and use thereof | |
| KR20240099134A (ko) | 세포내 kras g12c 단백질을 표적화하기 위한 공유 결합제를 포함하는 접합체 | |
| HUE024989T2 (en) | Azaindole derivatives as ABI and SRC protein kinase inhibitors | |
| WO1996030348A1 (en) | Synthesis of bis-indolylmaleimides | |
| JP2005530691A (ja) | 新規なチロインジシンとその関連プロセス、薬学的組成物および方法 | |
| AU2020410900A1 (en) | Compound used as RET kinase inhibitor and application thereof | |
| CA2227985A1 (en) | Quinone compound, its production and use | |
| TWI823255B (zh) | 作為Wee-1抑制劑的稠環化合物 | |
| NZ202981A (en) | A process for the preparation of pyrazino(2,1-a)isoquinoline derivatives | |
| JP2023505239A (ja) | 新規オーロラキナーゼ阻害剤およびその使用 | |
| DK157021B (da) | Analogifremgangsmaade til fremstilling af 2,3-polymethylen-4-oxo-4h-pyrido- eller -azepinooe1,2-aaapyrimidiner eller farmaceutisk acceptable syreadditionssalte eller kvaternaere salte deraf | |
| EP0977757B1 (en) | 9,10-diazatricyclo 4.2.1.1?2,5 ]decane and 9,10-diazatricyclo 3.3.1.1?2,6 ]decane derivatives having analgesic activity | |
| US6252082B1 (en) | Pyridone derivatives, their preparation and their use as synthesis intermediates | |
| AU2007203498A1 (en) | Coumarines useful as biomarkers |