CN109678848B - 香豆素/吡啶酮杂合衍生物及其制备方法与应用 - Google Patents
香豆素/吡啶酮杂合衍生物及其制备方法与应用 Download PDFInfo
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- CN109678848B CN109678848B CN201811635128.XA CN201811635128A CN109678848B CN 109678848 B CN109678848 B CN 109678848B CN 201811635128 A CN201811635128 A CN 201811635128A CN 109678848 B CN109678848 B CN 109678848B
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- coumarin
- methyl
- dropwise adding
- methanol
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- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 238000002360 preparation method Methods 0.000 title claims abstract description 29
- 229960000956 coumarin Drugs 0.000 title claims abstract description 22
- 235000001671 coumarin Nutrition 0.000 title claims abstract description 22
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 title claims abstract description 16
- -1 iron ions Chemical class 0.000 claims abstract description 64
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 13
- 102000010909 Monoamine Oxidase Human genes 0.000 claims abstract description 12
- 108010062431 Monoamine oxidase Proteins 0.000 claims abstract description 12
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003814 drug Substances 0.000 claims abstract description 10
- 229910052742 iron Inorganic materials 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 26
- 230000000694 effects Effects 0.000 claims description 8
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 7
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 6
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 3
- 239000013522 chelant Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 7
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 309
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 240
- 238000006243 chemical reaction Methods 0.000 description 208
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 92
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 92
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
- 239000007787 solid Substances 0.000 description 51
- 239000000243 solution Substances 0.000 description 33
- 229910001868 water Inorganic materials 0.000 description 29
- 239000003480 eluent Substances 0.000 description 27
- 239000002994 raw material Substances 0.000 description 26
- 238000012544 monitoring process Methods 0.000 description 25
- 238000010438 heat treatment Methods 0.000 description 24
- 238000010791 quenching Methods 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 23
- 229910052927 chalcanthite Inorganic materials 0.000 description 23
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 23
- 229960005055 sodium ascorbate Drugs 0.000 description 23
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 239000003960 organic solvent Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- IEHFVZKMAOKFTR-UHFFFAOYSA-N 7-prop-2-ynoxychromen-2-one Chemical compound C1=C(OCC#C)C=C2OC(=O)C=CC2=C1 IEHFVZKMAOKFTR-UHFFFAOYSA-N 0.000 description 7
- 150000004775 coumarins Chemical class 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- JDUCPLRZJGIPSZ-UHFFFAOYSA-N 1-(2-azidoethyl)-5-methoxy-2-methylpyridin-4-one Chemical compound N(=[N+]=[N-])CCN1C=C(C(C=C1C)=O)OC JDUCPLRZJGIPSZ-UHFFFAOYSA-N 0.000 description 5
- LIPRKYKMVQPYPG-UHFFFAOYSA-N 3-Hydroxy-2H-pyran-2-one Chemical compound OC1=CC=COC1=O LIPRKYKMVQPYPG-UHFFFAOYSA-N 0.000 description 5
- VHHLBUXCUIGPQG-UHFFFAOYSA-N 4-prop-2-ynoxychromen-2-one Chemical compound C1=CC=C2OC(=O)C=C(OCC#C)C2=C1 VHHLBUXCUIGPQG-UHFFFAOYSA-N 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 238000004448 titration Methods 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- PFEWKPRBKLEHCX-UHFFFAOYSA-N 3,4-dimethyl-7-prop-2-ynoxychromen-2-one Chemical compound CC=1C(OC2=CC(=CC=C2C=1C)OCC#C)=O PFEWKPRBKLEHCX-UHFFFAOYSA-N 0.000 description 4
- NGUGNENOVOKDEF-UHFFFAOYSA-N 3-azido-1H-pyridin-2-one Chemical compound [N-]=[N+]=Nc1ccc[nH]c1=O NGUGNENOVOKDEF-UHFFFAOYSA-N 0.000 description 4
- JMRVCASGJDEETF-UHFFFAOYSA-N 3-hydroxy-2-(hydroxymethyl)-6-methyl-1-[2-[4-[(2-oxochromen-7-yl)oxymethyl]triazol-1-yl]ethyl]pyridin-4-one Chemical compound OC1=C(N(C(=CC1=O)C)CCN1N=NC(=C1)COC1=CC=C2C=CC(OC2=C1)=O)CO JMRVCASGJDEETF-UHFFFAOYSA-N 0.000 description 4
- ABWCZVWLCRRWNY-UHFFFAOYSA-N 3-hydroxy-2-(hydroxymethyl)-6-methyl-1-[3-[4-[(2-oxochromen-7-yl)oxymethyl]triazol-1-yl]propyl]pyridin-4-one Chemical compound OC1=C(N(C(=CC1=O)C)CCCN1N=NC(=C1)COC1=CC=C2C=CC(OC2=C1)=O)CO ABWCZVWLCRRWNY-UHFFFAOYSA-N 0.000 description 4
- NTNZDKLXIBVSQQ-UHFFFAOYSA-N 4-methyl-7-prop-2-ynoxychromen-2-one Chemical compound C1=C(OCC#C)C=CC2=C1OC(=O)C=C2C NTNZDKLXIBVSQQ-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 150000001414 amino alcohols Chemical class 0.000 description 4
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- YGZIIBMNUUXCLU-UHFFFAOYSA-N 3-prop-2-ynoxychromen-2-one Chemical compound C1=CC=CC2=C1OC(=O)C(OCC#C)=C2 YGZIIBMNUUXCLU-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- OMOVVBIIQSXZSZ-UHFFFAOYSA-N [6-(4-acetyloxy-5,9a-dimethyl-2,7-dioxo-4,5a,6,9-tetrahydro-3h-pyrano[3,4-b]oxepin-5-yl)-5-formyloxy-3-(furan-3-yl)-3a-methyl-7-methylidene-1a,2,3,4,5,6-hexahydroindeno[1,7a-b]oxiren-4-yl] 2-hydroxy-3-methylpentanoate Chemical compound CC12C(OC(=O)C(O)C(C)CC)C(OC=O)C(C3(C)C(CC(=O)OC4(C)COC(=O)CC43)OC(C)=O)C(=C)C32OC3CC1C=1C=COC=1 OMOVVBIIQSXZSZ-UHFFFAOYSA-N 0.000 description 3
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 3
- 239000011755 sodium-L-ascorbate Substances 0.000 description 3
- 235000019187 sodium-L-ascorbate Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- HSHMKKYFBYAEEK-UHFFFAOYSA-N 1-(2-azidoethyl)-2-ethyl-3-methoxypyridin-4-one Chemical compound N(=[N+]=[N-])CCN1C(=C(C(C=C1)=O)OC)CC HSHMKKYFBYAEEK-UHFFFAOYSA-N 0.000 description 2
- MWEAVIQUZWAWOO-UHFFFAOYSA-N 1-(2-azidoethyl)-3-methoxy-2-methylpyridin-4-one Chemical compound N(=[N+]=[N-])CCN1C(=C(C(C=C1)=O)OC)C MWEAVIQUZWAWOO-UHFFFAOYSA-N 0.000 description 2
- BOFMHKVEOAYCCJ-UHFFFAOYSA-N 1-(3-azidopropyl)-3-methoxy-2-methylpyridin-4-one Chemical compound N(=[N+]=[N-])CCCN1C(=C(C(C=C1)=O)OC)C BOFMHKVEOAYCCJ-UHFFFAOYSA-N 0.000 description 2
- XXFUZSHTIOFGNV-UHFFFAOYSA-N 1-bromoprop-1-yne Chemical compound CC#CBr XXFUZSHTIOFGNV-UHFFFAOYSA-N 0.000 description 2
- KTWNGAHCPMRRBF-UHFFFAOYSA-N 2-ethyl-3-hydroxy-1-[3-[4-[(2-oxochromen-4-yl)oxymethyl]triazol-1-yl]propyl]pyridin-4-one Chemical compound C(C)C=1N(C=CC(C=1O)=O)CCCN1N=NC(=C1)COC1=CC(OC2=CC=CC=C12)=O KTWNGAHCPMRRBF-UHFFFAOYSA-N 0.000 description 2
- NUCFFOLCSNAZGG-UHFFFAOYSA-N 2-ethyl-3-hydroxy-1-[3-[4-[(2-oxochromen-7-yl)oxymethyl]triazol-1-yl]propyl]pyridin-4-one Chemical compound C(C)C=1N(C=CC(C=1O)=O)CCCN1N=NC(=C1)COC1=CC=C2C=CC(OC2=C1)=O NUCFFOLCSNAZGG-UHFFFAOYSA-N 0.000 description 2
- IHRIZPXINIZBGM-UHFFFAOYSA-N 3-hydroxy-2,6-dimethyl-1-[2-[4-[(2-oxochromen-7-yl)oxymethyl]triazol-1-yl]ethyl]pyridin-4-one Chemical compound OC1=C(N(C(=CC1=O)C)CCN1N=NC(=C1)COC1=CC=C2C=CC(OC2=C1)=O)C IHRIZPXINIZBGM-UHFFFAOYSA-N 0.000 description 2
- AEWCCVLDTNAPID-UHFFFAOYSA-N 3-hydroxy-2,6-dimethyl-1-[3-[4-[(2-oxochromen-7-yl)oxymethyl]triazol-1-yl]propyl]pyridin-4-one Chemical compound OC1=C(N(C(=CC1=O)C)CCCN1N=NC(=C1)COC1=CC=C2C=CC(OC2=C1)=O)C AEWCCVLDTNAPID-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 2
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 2
- 230000007131 anti Alzheimer effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 230000009920 chelation Effects 0.000 description 2
- 238000001311 chemical methods and process Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 229960003530 donepezil Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
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- 229960003980 galantamine Drugs 0.000 description 2
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
- 229960004640 memantine Drugs 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
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- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000002798 spectrophotometry method Methods 0.000 description 2
- 229960001685 tacrine Drugs 0.000 description 2
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 150000003852 triazoles Chemical class 0.000 description 2
- AVNCQZBYLBPZOV-UHFFFAOYSA-N 1-(3-azidopropyl)-2-ethyl-3-methoxypyridin-4-one Chemical compound N(=[N+]=[N-])CCCN1C(=C(C(C=C1)=O)OC)CC AVNCQZBYLBPZOV-UHFFFAOYSA-N 0.000 description 1
- LDBLUIPRCAYEJS-UHFFFAOYSA-N 1-(3-azidopropyl)-3-methoxy-2,6-dimethylpyridin-4-one Chemical compound N(=[N+]=[N-])CCCN1C(=C(C(C=C1C)=O)OC)C LDBLUIPRCAYEJS-UHFFFAOYSA-N 0.000 description 1
- HOUDGIMFZMMLBF-UHFFFAOYSA-N 1-(3-azidopropyl)-5-methoxy-2-methylpyridin-4-one Chemical compound N(=[N+]=[N-])CCCN1C=C(C(C=C1C)=O)OC HOUDGIMFZMMLBF-UHFFFAOYSA-N 0.000 description 1
- YKSDQXQXSGUDRE-UHFFFAOYSA-N 2-ethyl-3-hydroxy-1-[3-[4-[(2-oxochromen-3-yl)oxymethyl]triazol-1-yl]propyl]pyridin-4-one Chemical compound C(C)C=1N(C=CC(C=1O)=O)CCCN1N=NC(=C1)COC=1C(OC2=CC=CC=C2C=1)=O YKSDQXQXSGUDRE-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- LQUSVSANJKHVTM-UHFFFAOYSA-N 3-hydroxy-3h-pyridin-4-one Chemical class OC1C=NC=CC1=O LQUSVSANJKHVTM-UHFFFAOYSA-N 0.000 description 1
- BLFRQYKZFKYQLO-UHFFFAOYSA-N 4-aminobutan-1-ol Chemical compound NCCCCO BLFRQYKZFKYQLO-UHFFFAOYSA-N 0.000 description 1
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- SUTWPJHCRAITLU-UHFFFAOYSA-N 6-aminohexan-1-ol Chemical compound NCCCCCCO SUTWPJHCRAITLU-UHFFFAOYSA-N 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102000004338 Transferrin Human genes 0.000 description 1
- 108090000901 Transferrin Proteins 0.000 description 1
- GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 230000006741 behavioral dysfunction Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
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- 238000001704 evaporation Methods 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
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- 239000010452 phosphate Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- GGOZGYRTNQBSSA-UHFFFAOYSA-N pyridine-2,3-diol Chemical class OC1=CC=CN=C1O GGOZGYRTNQBSSA-UHFFFAOYSA-N 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
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Classifications
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- 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
- C07D405/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hospice & Palliative Care (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
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CN110804045B (zh) * | 2019-11-08 | 2021-07-27 | 浙江工业大学 | 具潜在抗ad活性的香豆素杂合吡啶酮酰胺衍生物及其制备方法与应用 |
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