DE69323090T2 - 4-ALKOXY-2,6-DI-t-BUTYLPHENOLDERIVATE - Google Patents
4-ALKOXY-2,6-DI-t-BUTYLPHENOLDERIVATEInfo
- Publication number
- DE69323090T2 DE69323090T2 DE69323090T DE69323090T DE69323090T2 DE 69323090 T2 DE69323090 T2 DE 69323090T2 DE 69323090 T DE69323090 T DE 69323090T DE 69323090 T DE69323090 T DE 69323090T DE 69323090 T2 DE69323090 T2 DE 69323090T2
- Authority
- DE
- Germany
- Prior art keywords
- tert
- butyl
- acetoxy
- mixture
- solution
- 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.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 169
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 6
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 4
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 4
- 125000002252 acyl group Chemical group 0.000 claims abstract description 3
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 49
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- 125000004433 nitrogen atom Chemical class N* 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 72
- 238000003786 synthesis reaction Methods 0.000 abstract description 69
- 229910052760 oxygen Inorganic materials 0.000 abstract description 9
- 239000001301 oxygen Substances 0.000 abstract description 9
- 230000003078 antioxidant effect Effects 0.000 abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 8
- 239000001257 hydrogen Substances 0.000 abstract description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
- 208000010125 myocardial infarction Diseases 0.000 abstract description 6
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 3
- 150000002829 nitrogen Chemical group 0.000 abstract description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
- 150000002431 hydrogen Chemical class 0.000 abstract 1
- 239000011593 sulfur Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 237
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 160
- 239000000243 solution Substances 0.000 description 126
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 113
- 239000000203 mixture Substances 0.000 description 112
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- 238000005160 1H NMR spectroscopy Methods 0.000 description 80
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
- 239000012141 concentrate Substances 0.000 description 60
- 238000010898 silica gel chromatography Methods 0.000 description 58
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 51
- 238000000605 extraction Methods 0.000 description 48
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 41
- 238000001816 cooling Methods 0.000 description 39
- 239000012044 organic layer Substances 0.000 description 37
- 229920006395 saturated elastomer Polymers 0.000 description 37
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 32
- -1 alkyl radical Chemical class 0.000 description 32
- 238000003756 stirring Methods 0.000 description 32
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- 239000012299 nitrogen atmosphere Substances 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 26
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
- 238000002844 melting Methods 0.000 description 25
- 230000008018 melting Effects 0.000 description 25
- 238000000034 method Methods 0.000 description 24
- 239000012230 colorless oil Substances 0.000 description 23
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 21
- 235000017557 sodium bicarbonate Nutrition 0.000 description 21
- 108010007622 LDL Lipoproteins Proteins 0.000 description 20
- 102000007330 LDL Lipoproteins Human genes 0.000 description 20
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 238000010438 heat treatment Methods 0.000 description 16
- 230000003859 lipid peroxidation Effects 0.000 description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 14
- 235000019270 ammonium chloride Nutrition 0.000 description 14
- 239000012280 lithium aluminium hydride Substances 0.000 description 12
- 230000008569 process Effects 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 10
- AKXFJUUGOGZHQF-UHFFFAOYSA-N 4,6-ditert-butyl-1-benzofuran-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1C=CO2 AKXFJUUGOGZHQF-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- 239000012312 sodium hydride Substances 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 8
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 8
- 239000003963 antioxidant agent Substances 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 229960004488 linolenic acid Drugs 0.000 description 8
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 8
- 230000004048 modification Effects 0.000 description 8
- 238000012986 modification Methods 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 description 8
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 239000000524 Thiobarbituric Acid Reactive Substance Substances 0.000 description 7
- 108010093894 Xanthine oxidase Proteins 0.000 description 7
- 102100033220 Xanthine oxidase Human genes 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229940098779 methanesulfonic acid Drugs 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- OKLPSIJWGLWCOR-UHFFFAOYSA-N (2,6-ditert-butyl-4-hydroxy-3-methylphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C(C)=C1C(C)(C)C OKLPSIJWGLWCOR-UHFFFAOYSA-N 0.000 description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 6
- 108010023244 Lactoperoxidase Proteins 0.000 description 6
- 102000045576 Lactoperoxidases Human genes 0.000 description 6
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 239000012298 atmosphere Substances 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 208000023589 ischemic disease Diseases 0.000 description 6
- 229940057428 lactoperoxidase Drugs 0.000 description 6
- HWYHZTIRURJOHG-UHFFFAOYSA-N luminol Chemical compound O=C1NNC(=O)C2=C1C(N)=CC=C2 HWYHZTIRURJOHG-UHFFFAOYSA-N 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 230000001590 oxidative effect Effects 0.000 description 6
- SKKZEOWXZNQGGG-UHFFFAOYSA-N (2,6-ditert-butyl-4-hydroxyphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C=C1C(C)(C)C SKKZEOWXZNQGGG-UHFFFAOYSA-N 0.000 description 5
- LHXBIWSIWVQZCO-UHFFFAOYSA-N 2,4,6-tritert-butyl-1-benzofuran-5-ol Chemical compound OC1=C(C(C)(C)C)C=C2OC(C(C)(C)C)=CC2=C1C(C)(C)C LHXBIWSIWVQZCO-UHFFFAOYSA-N 0.000 description 5
- GIUGSQPFGPYKAZ-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dimethyl-7-propyl-3h-1-benzofuran-5-ol Chemical compound OC1=C(C(C)(C)C)C(CCC)=C2OC(C)(C)CC2=C1C(C)(C)C GIUGSQPFGPYKAZ-UHFFFAOYSA-N 0.000 description 5
- DLUCSASGCZZESI-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dipropyl-3h-1-benzofuran-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1OC(CCC)(CCC)C2 DLUCSASGCZZESI-UHFFFAOYSA-N 0.000 description 5
- ZJQROHZHGAYXEJ-UHFFFAOYSA-N 4,6-ditert-butyl-2,3-dihydro-1-benzofuran-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1CCO2 ZJQROHZHGAYXEJ-UHFFFAOYSA-N 0.000 description 5
- BFHOUCVIUPGOEW-UHFFFAOYSA-N 4,6-ditert-butyl-2-octyl-2,3-dihydro-1-benzofuran-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1OC(CCCCCCCC)C2 BFHOUCVIUPGOEW-UHFFFAOYSA-N 0.000 description 5
- UTAJKNCSKCIDLQ-UHFFFAOYSA-N 4-tert-butyl-5-phenylmethoxy-1-benzofuran-2-carbaldehyde Chemical compound C1=CC=2OC(C=O)=CC=2C(C(C)(C)C)=C1OCC1=CC=CC=C1 UTAJKNCSKCIDLQ-UHFFFAOYSA-N 0.000 description 5
- LXEKPEMOWBOYRF-QDBORUFSSA-N AAPH Chemical compound Cl.Cl.NC(=N)C(C)(C)\N=N\C(C)(C)C(N)=N LXEKPEMOWBOYRF-QDBORUFSSA-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
- 238000001914 filtration Methods 0.000 description 5
- 239000011259 mixed solution Substances 0.000 description 5
- 230000009257 reactivity Effects 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- ZXLSPBINTBCOEN-UHFFFAOYSA-N (2,6-ditert-butyl-3-formyl-4-hydroxyphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C(C=O)=C1C(C)(C)C ZXLSPBINTBCOEN-UHFFFAOYSA-N 0.000 description 4
- XCRRGMKOURUQBY-UHFFFAOYSA-N (2,6-ditert-butyl-4-hydroxy-3-prop-2-enylphenyl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C(O)C(CC=C)=C1C(C)(C)C XCRRGMKOURUQBY-UHFFFAOYSA-N 0.000 description 4
- ATFPLQAPABRYMU-UHFFFAOYSA-N (4,6-ditert-butyl-1-benzofuran-5-yl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2OC=CC2=C1C(C)(C)C ATFPLQAPABRYMU-UHFFFAOYSA-N 0.000 description 4
- OPAGKTCPAHGILI-UHFFFAOYSA-N (4,6-ditert-butyl-2,2-dimethyl-3h-1-benzofuran-5-yl) acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2OC(C)(C)CC2=C1C(C)(C)C OPAGKTCPAHGILI-UHFFFAOYSA-N 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- YLOHHUKVCVOPID-UHFFFAOYSA-N 4,6-ditert-butyl-2-methyl-1-benzofuran-5-ol Chemical compound OC1=C(C(C)(C)C)C=C2OC(C)=CC2=C1C(C)(C)C YLOHHUKVCVOPID-UHFFFAOYSA-N 0.000 description 4
- 229910015900 BF3 Inorganic materials 0.000 description 4
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000007818 Grignard reagent Substances 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical class [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 4
- NETVTKTYVRJDLE-LFIBNONCSA-N [4,6-ditert-butyl-2-[(e)-5-hydroxy-4-methylpent-3-enyl]-2-methyl-3h-1-benzofuran-5-yl] acetate Chemical compound CC(=O)OC1=C(C(C)(C)C)C=C2OC(C)(CC\C=C(/C)CO)CC2=C1C(C)(C)C NETVTKTYVRJDLE-LFIBNONCSA-N 0.000 description 4
- AOAOSQXWCCKTQY-UHFFFAOYSA-N [4-[3-(4-acetyloxy-3,5-ditert-butyl-2-methylphenoxy)propoxy]-2,6-ditert-butyl-3-methylphenyl] acetate Chemical compound CC1=C(C(C)(C)C)C(OC(=O)C)=C(C(C)(C)C)C=C1OCCCOC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1C AOAOSQXWCCKTQY-UHFFFAOYSA-N 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- MXZACTZQSGYANA-UHFFFAOYSA-N chembl545463 Chemical compound Cl.C1=CC(OC)=CC=C1C(N=C1)=CN2C1=NC(C)=C2O MXZACTZQSGYANA-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- CYAJEMFRSQGFIG-ISWIILBPSA-N microcystin-LA Natural products CO[C@@H](Cc1ccccc1)[C@@H](C)C=C(C)C=C[C@H](NC(=O)CNC(=O)[C@@H](C)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](C)NC(=O)C(=C)N(C)C(=O)CC[C@@H](C)C(=O)O)C(=O)O)[C@H](C)C(=O)N CYAJEMFRSQGFIG-ISWIILBPSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- HJYCVQWBZKFFSM-UHFFFAOYSA-N (2,6-ditert-butyl-3-methyl-4-propoxyphenyl) acetate Chemical compound CCCOC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1C HJYCVQWBZKFFSM-UHFFFAOYSA-N 0.000 description 3
- BPEMFEJKXADBPJ-UHFFFAOYSA-N (2,6-ditert-butyl-4-methoxy-3-prop-2-enylphenyl) acetate Chemical compound COC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1CC=C BPEMFEJKXADBPJ-UHFFFAOYSA-N 0.000 description 3
- GTKGUPGJCXOVIH-UHFFFAOYSA-N (2,6-ditert-butyl-4-methoxyphenyl) acetate Chemical compound COC1=CC(C(C)(C)C)=C(OC(C)=O)C(C(C)(C)C)=C1 GTKGUPGJCXOVIH-UHFFFAOYSA-N 0.000 description 3
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- PWHHPOIUNAHINY-UHFFFAOYSA-N 3,5-ditert-butyl-2-methylcyclohexa-2,5-diene-1,4-dione Chemical compound CC1=C(C(C)(C)C)C(=O)C(C(C)(C)C)=CC1=O PWHHPOIUNAHINY-UHFFFAOYSA-N 0.000 description 1
- VTOQFOCYBTVOJZ-UHFFFAOYSA-N 3-bromopentane Chemical compound CCC(Br)CC VTOQFOCYBTVOJZ-UHFFFAOYSA-N 0.000 description 1
- NAJNFAJWECFFBQ-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-diheptyl-3h-1-benzofuran-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1OC(CCCCCCC)(CCCCCCC)C2 NAJNFAJWECFFBQ-UHFFFAOYSA-N 0.000 description 1
- RRWLJZSMVYCTBL-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dihexyl-3h-1-benzofuran-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1OC(CCCCCC)(CCCCCC)C2 RRWLJZSMVYCTBL-UHFFFAOYSA-N 0.000 description 1
- XZZFNPFTUFXNRE-UHFFFAOYSA-N 4,6-ditert-butyl-2,2-dimethyl-3h-1-benzofuran-5-ol Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC2=C1CC(C)(C)O2 XZZFNPFTUFXNRE-UHFFFAOYSA-N 0.000 description 1
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- AGTISLWNTUXUPE-UHFFFAOYSA-N 4,6-ditert-butyl-2-methyl-2-(4,8,12-trimethyltridecyl)-3h-1-benzofuran-5-ol Chemical compound C1=C(C(C)(C)C)C(O)=C(C(C)(C)C)C2=C1OC(CCCC(C)CCCC(C)CCCC(C)C)(C)C2 AGTISLWNTUXUPE-UHFFFAOYSA-N 0.000 description 1
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- 229940125898 compound 5 Drugs 0.000 description 1
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- KZENFXVDPUMQOE-UHFFFAOYSA-N ethyl 2-(triphenyl-$l^{5}-phosphanylidene)propanoate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=C(C)C(=O)OCC)C1=CC=CC=C1 KZENFXVDPUMQOE-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 238000005227 gel permeation chromatography Methods 0.000 description 1
- 125000002350 geranyl group Chemical group [H]C([*])([H])/C([H])=C(C([H])([H])[H])/C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-N hydroperoxyl Chemical compound O[O] OUUQCZGPVNCOIJ-UHFFFAOYSA-N 0.000 description 1
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- 230000000977 initiatory effect Effects 0.000 description 1
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 230000007654 ischemic lesion Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- 239000011654 magnesium acetate Substances 0.000 description 1
- 235000011285 magnesium acetate Nutrition 0.000 description 1
- 229940069446 magnesium acetate Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- QYZFTMMPKCOTAN-UHFFFAOYSA-N n-[2-(2-hydroxyethylamino)ethyl]-2-[[1-[2-(2-hydroxyethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]diazenyl]-2-methylpropanamide Chemical compound OCCNCCNC(=O)C(C)(C)N=NC(C)(C)C(=O)NCCNCCO QYZFTMMPKCOTAN-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000002900 organolithium compounds Chemical class 0.000 description 1
- 239000012285 osmium tetroxide Substances 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- 230000001151 other effect Effects 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 238000005502 peroxidation Methods 0.000 description 1
- 229940097156 peroxyl Drugs 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000010410 reperfusion Effects 0.000 description 1
- 102000014452 scavenger receptors Human genes 0.000 description 1
- 108010078070 scavenger receptors Proteins 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/79—Benzo [b] furans; Hydrogenated benzo [b] furans with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/20—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms
- C07C47/277—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/017—Esters of hydroxy compounds having the esterified hydroxy group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP32110192 | 1992-10-16 | ||
| PCT/JP1993/001489 WO1994008930A1 (fr) | 1992-10-16 | 1993-10-18 | DERIVE DE 4-ALCOXY-2,6-DI-t-BUTHYLPHENOL |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69323090D1 DE69323090D1 (de) | 1999-02-25 |
| DE69323090T2 true DE69323090T2 (de) | 2000-01-27 |
Family
ID=18128834
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69323090T Expired - Fee Related DE69323090T2 (de) | 1992-10-16 | 1993-10-18 | 4-ALKOXY-2,6-DI-t-BUTYLPHENOLDERIVATE |
Country Status (14)
| Country | Link |
|---|---|
| US (3) | US5574178A (enExample) |
| EP (1) | EP0665208B1 (enExample) |
| KR (1) | KR100247213B1 (enExample) |
| CN (1) | CN1054128C (enExample) |
| AT (1) | ATE175658T1 (enExample) |
| AU (1) | AU6241894A (enExample) |
| CA (1) | CA2147263C (enExample) |
| DE (1) | DE69323090T2 (enExample) |
| DK (1) | DK0665208T3 (enExample) |
| ES (1) | ES2128440T3 (enExample) |
| GR (1) | GR3029810T3 (enExample) |
| SG (1) | SG49937A1 (enExample) |
| TW (1) | TW393475B (enExample) |
| WO (1) | WO1994008930A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995029906A1 (en) * | 1994-04-28 | 1995-11-09 | Meiji Milk Products Co., Ltd. | Benzofuran derivative and use thereof |
| US5674876A (en) * | 1995-01-20 | 1997-10-07 | Research Development Foundation | ρ-heteroatom-substituted phenols and uses thereof |
| EP0749972A1 (en) * | 1995-06-21 | 1996-12-27 | Merrell Pharmaceuticals Inc. | A process for preparing 1-(3-trialkylsilylphenyl)-2,2,2-trifluoromethyl ethanone derivatives |
| TW565558B (en) * | 1995-11-09 | 2003-12-11 | Chugai Pharmaceutical Co Ltd | Intimal thickening inhibitory agent |
| KR100383835B1 (ko) * | 1996-06-26 | 2003-08-27 | 쥬가이 세이야쿠 가부시키가이샤 | 신장질환치료제및장기보존제 |
| US6114572A (en) * | 1996-11-20 | 2000-09-05 | Hoechst Marion Roussel, Inc. | Substituted phenols and thiophenols useful as antioxidant agents |
| NZ335440A (en) * | 1996-11-20 | 2001-07-27 | Aventis Pharma Inc | Control of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediated effects to treat chronic inflammatory disorders like atheriosclerosis |
| US5679820A (en) * | 1996-12-16 | 1997-10-21 | General Electric Company | Silylated ultraviolet light absorbers having resistance to humidity |
| WO1998050025A1 (en) * | 1997-05-08 | 1998-11-12 | Chugai Seiyaku Kabushiki Kaisha | Preventives/remedies for arteriosclerosis |
| TW472051B (en) * | 1997-05-23 | 2002-01-11 | Chugai Pharmaceutical Co Ltd | 2,3-dihydrobenzofuran derivatives |
| EP1172104A4 (en) * | 1999-02-23 | 2002-11-27 | Chugai Pharmaceutical Co Ltd | PREPARATIONS FROM SOFT POCKET CAPSULES CONTAINING DIHYDROBENZOFURANE DERIVATIVES |
| DE19941595A1 (de) * | 1999-09-01 | 2001-03-08 | Basf Ag | Verwendung von anellierten Benzolderivaten als Antioxidans oder Radikalfänger in kosmetischen Zubereitungen |
| EP1304328A4 (en) * | 2000-07-19 | 2004-06-16 | Chugai Pharmaceutical Co Ltd | METHOD FOR PRODUCING A BENZOFURANE DERIVATIVE |
| US20040242678A1 (en) * | 2001-08-31 | 2004-12-02 | Shinji Yokoyama | Apolipo protein e secretion promoters |
| US20050159476A1 (en) * | 2002-03-29 | 2005-07-21 | Chugai Seiyaku Kabushiki Kaisha | Pharmaceutical composition for preventing or treating respiratory disease |
| US6882245B2 (en) * | 2002-06-05 | 2005-04-19 | Rf Stream Corporation | Frequency discrete LC filter bank |
| US20070066681A1 (en) * | 2003-09-26 | 2007-03-22 | Chugai Seiyaku Kaushiki Kaisha | Pharmaceutical composition for treating fatty liver or hepatic disease |
| CN110940747B (zh) * | 2019-12-03 | 2022-06-28 | 酒泉市食品检验检测中心 | 一种马铃薯及其制品中α-茄碱和α-卡茄碱的测定方法 |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH085871B2 (ja) * | 1986-12-27 | 1996-01-24 | 武田薬品工業株式会社 | クマラン誘導体およびその製造法 |
| DE3777366D1 (de) * | 1986-12-27 | 1992-04-16 | Takeda Chemical Industries Ltd | 2,3-dihydro-cumaron-derivate, ihre herstellung und verwendung. |
| JP2855341B2 (ja) * | 1988-06-10 | 1999-02-10 | 武田薬品工業株式会社 | 新規２―置換クマラン誘導体 |
| JP2855340B2 (ja) * | 1988-06-10 | 1999-02-10 | 武田薬品工業株式会社 | ２―置換クマラン誘導体 |
| IT1229482B (it) * | 1988-08-01 | 1991-09-03 | Foscama Biomed Chim Farma | Acidi (rs) 2 (2,3 diidro 5 idrossi 4,6,7 trimetilbenzofuranil) acetico e 2 (2,3 diidro 5 acilossi 4,6,7 trimetilbenzofuranil) acetici e loro esteri, utili come farmaci mucoregolatori ed antiischemici. |
| US4966907A (en) * | 1988-08-12 | 1990-10-30 | Merck & Co., Inc. | 6-substituted 5-hydroxy-2,3-dihydrobenzofurans as inhibitors of leukotriene biosynthesis |
| JPH02121975A (ja) * | 1988-10-28 | 1990-05-09 | Eisai Co Ltd | ２，３−ジヒドロベンゾフラン誘導体 |
| US5091533A (en) * | 1990-03-12 | 1992-02-25 | Merck Frosst Canada, Inc. | 5-hydroxy-2,3-dihydrobenzofuran analogs as leukotriene biosynthesis inhibitors |
| DE4109627A1 (de) * | 1991-03-23 | 1992-09-24 | Boehringer Mannheim Gmbh | Neue phenolether, verfahren zu ihrer herstellung und arzneimittel, die diese verbindungen enthalten |
| JPH04300878A (ja) * | 1991-03-28 | 1992-10-23 | Fujirebio Inc | ベンゼンジオール誘導体 |
| CA2124086A1 (en) * | 1991-11-22 | 1993-05-27 | Ronald H. Lane | Tocotrienols and tocotrienol-like compounds and methods for their use |
| JP3150740B2 (ja) * | 1991-12-26 | 2001-03-26 | エーザイ株式会社 | ジヒドロベンゾフラン誘導体 |
| DE69314022T2 (de) * | 1992-04-06 | 1998-02-12 | Merrell Pharma Inc | Derivate von 2,3-dihydro-2,2,4,6,7-pentaalkyl-5-benzofuranen |
-
1993
- 1993-10-15 TW TW082108556A patent/TW393475B/zh not_active IP Right Cessation
- 1993-10-16 CN CN93120400A patent/CN1054128C/zh not_active Expired - Fee Related
- 1993-10-16 SG SG1996009546A patent/SG49937A1/en unknown
- 1993-10-18 DK DK93922643T patent/DK0665208T3/da active
- 1993-10-18 KR KR1019950701454A patent/KR100247213B1/ko not_active Expired - Fee Related
- 1993-10-18 DE DE69323090T patent/DE69323090T2/de not_active Expired - Fee Related
- 1993-10-18 AT AT93922643T patent/ATE175658T1/de not_active IP Right Cessation
- 1993-10-18 ES ES93922643T patent/ES2128440T3/es not_active Expired - Lifetime
- 1993-10-18 WO PCT/JP1993/001489 patent/WO1994008930A1/ja not_active Ceased
- 1993-10-18 EP EP93922643A patent/EP0665208B1/en not_active Expired - Lifetime
- 1993-10-18 AU AU62418/94A patent/AU6241894A/en not_active Abandoned
- 1993-10-18 US US08/416,862 patent/US5574178A/en not_active Expired - Fee Related
- 1993-10-18 CA CA002147263A patent/CA2147263C/en not_active Expired - Fee Related
-
1995
- 1995-05-18 US US08/444,055 patent/US5606089A/en not_active Expired - Fee Related
-
1996
- 1996-08-21 US US08/700,834 patent/US5663373A/en not_active Expired - Fee Related
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1999
- 1999-03-29 GR GR990400900T patent/GR3029810T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1054128C (zh) | 2000-07-05 |
| ATE175658T1 (de) | 1999-01-15 |
| KR950703503A (ko) | 1995-09-20 |
| KR100247213B1 (ko) | 2000-03-15 |
| WO1994008930A1 (fr) | 1994-04-28 |
| CA2147263C (en) | 2004-12-21 |
| GR3029810T3 (en) | 1999-06-30 |
| SG49937A1 (en) | 1998-06-15 |
| EP0665208A1 (en) | 1995-08-02 |
| US5606089A (en) | 1997-02-25 |
| US5574178A (en) | 1996-11-12 |
| ES2128440T3 (es) | 1999-05-16 |
| AU6241894A (en) | 1994-05-09 |
| DE69323090D1 (de) | 1999-02-25 |
| DK0665208T3 (da) | 1999-08-30 |
| CN1112115A (zh) | 1995-11-22 |
| EP0665208B1 (en) | 1999-01-13 |
| TW393475B (en) | 2000-06-11 |
| EP0665208A4 (enExample) | 1995-08-23 |
| US5663373A (en) | 1997-09-02 |
| CA2147263A1 (en) | 1994-04-28 |
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| 8339 | Ceased/non-payment of the annual fee |