DE69211994T2 - Lignan-analoge, ihre herstellung und hypolipidemische arzneimittel - Google Patents
Lignan-analoge, ihre herstellung und hypolipidemische arzneimittelInfo
- Publication number
- DE69211994T2 DE69211994T2 DE69211994T DE69211994T DE69211994T2 DE 69211994 T2 DE69211994 T2 DE 69211994T2 DE 69211994 T DE69211994 T DE 69211994T DE 69211994 T DE69211994 T DE 69211994T DE 69211994 T2 DE69211994 T2 DE 69211994T2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- preparation
- mmol
- mixture
- dimethoxyphenyl
- 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
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 35
- 230000000055 hyoplipidemic effect Effects 0.000 title claims description 3
- 229940126601 medicinal product Drugs 0.000 title claims 2
- 229930013686 lignan Natural products 0.000 title 1
- 150000005692 lignans Chemical class 0.000 title 1
- 235000009408 lignans Nutrition 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 329
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 125000002243 cyclohexanonyl group Chemical group *C1(*)C(=O)C(*)(*)C(*)(*)C(*)(*)C1(*)* 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 7
- 150000001555 benzenes Chemical class 0.000 claims description 5
- 238000007259 addition reaction Methods 0.000 claims description 4
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 150000002641 lithium Chemical group 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 239000011777 magnesium Substances 0.000 claims description 2
- QEJQEIIPZKQCNP-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 QEJQEIIPZKQCNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 2
- 238000000034 method Methods 0.000 abstract description 119
- -1 lactone compound Chemical class 0.000 abstract description 61
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 5
- 230000018044 dehydration Effects 0.000 abstract description 3
- 238000006297 dehydration reaction Methods 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 description 188
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 178
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 165
- 239000000203 mixture Substances 0.000 description 141
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 129
- 239000000243 solution Substances 0.000 description 101
- 238000006243 chemical reaction Methods 0.000 description 99
- 238000005160 1H NMR spectroscopy Methods 0.000 description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 74
- 239000011541 reaction mixture Substances 0.000 description 71
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- 238000002844 melting Methods 0.000 description 63
- 230000008018 melting Effects 0.000 description 63
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 62
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- 239000012267 brine Substances 0.000 description 50
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 47
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- 238000000746 purification Methods 0.000 description 37
- 239000007858 starting material Substances 0.000 description 37
- 239000013078 crystal Substances 0.000 description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
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- 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 29
- 238000001816 cooling Methods 0.000 description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
- 229920006395 saturated elastomer Polymers 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 26
- 229910002027 silica gel Inorganic materials 0.000 description 26
- 238000003756 stirring Methods 0.000 description 26
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 230000000704 physical effect Effects 0.000 description 24
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 18
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 18
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 108010007622 LDL Lipoproteins Proteins 0.000 description 15
- 102000007330 LDL Lipoproteins Human genes 0.000 description 15
- 235000012000 cholesterol Nutrition 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 150000002596 lactones Chemical class 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- 125000001424 substituent group Chemical group 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 235000019270 ammonium chloride Nutrition 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 11
- 150000001241 acetals Chemical class 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 10
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 150000001299 aldehydes Chemical class 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 108010062497 VLDL Lipoproteins Proteins 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 125000005843 halogen group Chemical group 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 239000012299 nitrogen atmosphere Substances 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 238000008214 LDL Cholesterol Methods 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 150000003254 radicals Chemical group 0.000 description 6
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 6
- 235000019345 sodium thiosulphate Nutrition 0.000 description 6
- 125000003396 thiol group Chemical group [H]S* 0.000 description 6
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 150000002576 ketones Chemical class 0.000 description 5
- FRIJBUGBVQZNTB-UHFFFAOYSA-M magnesium;ethane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C FRIJBUGBVQZNTB-UHFFFAOYSA-M 0.000 description 5
- SFLGSKRGOWRGBR-UHFFFAOYSA-N phthalane Chemical compound C1=CC=C2COCC2=C1 SFLGSKRGOWRGBR-UHFFFAOYSA-N 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
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- 125000002999 4-(trifluoromethyl)benzoyl group Chemical group FC(C1=CC=C(C(=O)*)C=C1)(F)F 0.000 description 4
- 101001053401 Arabidopsis thaliana Acid beta-fructofuranosidase 3, vacuolar Proteins 0.000 description 4
- 101001053395 Arabidopsis thaliana Acid beta-fructofuranosidase 4, vacuolar Proteins 0.000 description 4
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- HULZRAVBXKKDEB-UHFFFAOYSA-N ethyl 3-ethylpent-2-enoate Chemical compound CCOC(=O)C=C(CC)CC HULZRAVBXKKDEB-UHFFFAOYSA-N 0.000 description 1
- RQPGXPUCYFZPGQ-UHFFFAOYSA-N ethyl 3-ethylpentanoate Chemical compound CCOC(=O)CC(CC)CC RQPGXPUCYFZPGQ-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- PFCHFHIRKBAQGU-UHFFFAOYSA-N ethyl n-propyl ketone Natural products CCCC(=O)CC PFCHFHIRKBAQGU-UHFFFAOYSA-N 0.000 description 1
- 210000000497 foam cell Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- YLVLCBHNULZXLQ-UHFFFAOYSA-M magnesium;2h-naphthalen-2-ide;bromide Chemical compound [Mg+2].[Br-].C1=[C-]C=CC2=CC=CC=C21 YLVLCBHNULZXLQ-UHFFFAOYSA-M 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- GFTXWCQFWLOXAT-UHFFFAOYSA-M magnesium;cyclohexane;bromide Chemical compound [Mg+2].[Br-].C1CC[CH-]CC1 GFTXWCQFWLOXAT-UHFFFAOYSA-M 0.000 description 1
- BRKADVNLTRCLOW-UHFFFAOYSA-M magnesium;fluorobenzene;bromide Chemical compound [Mg+2].[Br-].FC1=CC=[C-]C=C1 BRKADVNLTRCLOW-UHFFFAOYSA-M 0.000 description 1
- QGEFGPVWRJCFQP-UHFFFAOYSA-M magnesium;methanidylbenzene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1=CC=CC=C1 QGEFGPVWRJCFQP-UHFFFAOYSA-M 0.000 description 1
- UFQSTBGEWZUCBQ-UHFFFAOYSA-M magnesium;methanidylcyclohexane;bromide Chemical compound [Mg+2].[Br-].[CH2-]C1CCCCC1 UFQSTBGEWZUCBQ-UHFFFAOYSA-M 0.000 description 1
- FCPRDUXJWIUVPZ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=CC=[C-]1 FCPRDUXJWIUVPZ-UHFFFAOYSA-M 0.000 description 1
- FKUUDDGRDRPAQQ-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=C[C-]=C1 FKUUDDGRDRPAQQ-UHFFFAOYSA-M 0.000 description 1
- RBWRWAUAVRMBAC-UHFFFAOYSA-M magnesium;methoxybenzene;bromide Chemical compound [Mg+2].[Br-].COC1=CC=[C-]C=C1 RBWRWAUAVRMBAC-UHFFFAOYSA-M 0.000 description 1
- BVUQKCCKUOSAEV-UHFFFAOYSA-M magnesium;methylbenzene;bromide Chemical compound [Mg+2].[Br-].CC1=CC=[C-]C=C1 BVUQKCCKUOSAEV-UHFFFAOYSA-M 0.000 description 1
- YAMQOOCGNXAQGW-UHFFFAOYSA-M magnesium;methylbenzene;bromide Chemical compound [Mg+2].[Br-].CC1=CC=CC=[C-]1 YAMQOOCGNXAQGW-UHFFFAOYSA-M 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 1
- NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
- VCEWMWORIMNHER-VOTSOKGWSA-N methyl (e)-5-ethyl-4-oxohept-2-enoate Chemical compound CCC(CC)C(=O)\C=C\C(=O)OC VCEWMWORIMNHER-VOTSOKGWSA-N 0.000 description 1
- JFPGPGMQGOOJFG-UHFFFAOYSA-N methyl 1-(2,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-propanoylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C=C1OC JFPGPGMQGOOJFG-UHFFFAOYSA-N 0.000 description 1
- XMUQNWXDCBQIIK-UHFFFAOYSA-N methyl 1-(3,4-dichlorophenyl)-3-(3-ethylpentanoyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(Cl)C(Cl)=C1 XMUQNWXDCBQIIK-UHFFFAOYSA-N 0.000 description 1
- RRVNAOCUWGJRTL-UHFFFAOYSA-N methyl 1-(3,4-difluorophenyl)-3-(3-ethylpentanoyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(F)C(F)=C1 RRVNAOCUWGJRTL-UHFFFAOYSA-N 0.000 description 1
- MFEIUEOHBQSOFY-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(2-ethylbutanoyl)-1,4-dihydroxy-6,7,8-trimethoxy-2h-naphthalene-2-carboxylate Chemical compound COC(=O)C1C(C(=O)C(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C1(O)C1=CC=C(OC)C(OC)=C1 MFEIUEOHBQSOFY-UHFFFAOYSA-N 0.000 description 1
- OPKWYUQDCQFFJZ-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(2-ethylbutanoyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)C(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 OPKWYUQDCQFFJZ-UHFFFAOYSA-N 0.000 description 1
- JNVLVAJREPPNJH-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-1,4-dihydroxy-6,7,8-trimethoxy-2h-naphthalene-2-carboxylate Chemical compound COC(=O)C1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C1(O)C1=CC=C(OC)C(OC)=C1 JNVLVAJREPPNJH-UHFFFAOYSA-N 0.000 description 1
- RYLFAPMVPDFSBO-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-4-hydroxy-5,6,7,8-tetramethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=C(OC)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 RYLFAPMVPDFSBO-UHFFFAOYSA-N 0.000 description 1
- FVYKYVYWOJPISM-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-4-hydroxy-5-(hydroxymethyl)-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=C(CO)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 FVYKYVYWOJPISM-UHFFFAOYSA-N 0.000 description 1
- SODRBBGXKSWACR-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-4-hydroxy-6,7,8-trimethoxy-5-(methoxymethyl)naphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=C(COC)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 SODRBBGXKSWACR-UHFFFAOYSA-N 0.000 description 1
- IVHFYNLMAKGYJF-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-4-hydroxy-6,7,8-trimethoxy-5-methylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=C(C)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 IVHFYNLMAKGYJF-UHFFFAOYSA-N 0.000 description 1
- XOHFAGVUVZAWHM-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(3-ethylpentanoyl)-4-hydroxy-6,7-di(propan-2-yloxy)naphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC(C)C)=C(OC(C)C)C=C2C=1C1=CC=C(OC)C(OC)=C1 XOHFAGVUVZAWHM-UHFFFAOYSA-N 0.000 description 1
- WDOJZCAXPBCKKY-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-3-(4-fluorobenzoyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(F)C=C1 WDOJZCAXPBCKKY-UHFFFAOYSA-N 0.000 description 1
- ASQRKFTXHDFVNO-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-3-propanoyl-6,7-di(propan-2-yloxy)naphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=CC(OC(C)C)=C(OC(C)C)C=C2C=1C1=CC=C(OC)C(OC)=C1 ASQRKFTXHDFVNO-UHFFFAOYSA-N 0.000 description 1
- YFCBQYFJPRZFCC-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-5,6,7,8-tetramethoxy-3-(2-methylpropanoyl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=C(C(=O)C(C)C)C(O)=C2C(OC)=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 YFCBQYFJPRZFCC-UHFFFAOYSA-N 0.000 description 1
- WVPWWTHLDGFIMP-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-5,6,7,8-tetramethoxy-3-propanoylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=C(OC)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 WVPWWTHLDGFIMP-UHFFFAOYSA-N 0.000 description 1
- RWQNYRIKFUDRAN-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-5-(hydroxymethyl)-6,7,8-trimethoxy-3-propanoylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=C(CO)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 RWQNYRIKFUDRAN-UHFFFAOYSA-N 0.000 description 1
- CQIFNXNXNZJETH-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(2,2,3,3,3-pentafluoropropanoyl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=C(C(=O)C(F)(F)C(F)(F)F)C(O)=C2C=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 CQIFNXNXNZJETH-UHFFFAOYSA-N 0.000 description 1
- YQHHBVCALVLEJG-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(2-methoxybenzoyl)naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=CC=C1OC YQHHBVCALVLEJG-UHFFFAOYSA-N 0.000 description 1
- GJYRSVWPANRUNT-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(2-methylbenzoyl)naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=CC=C1C GJYRSVWPANRUNT-UHFFFAOYSA-N 0.000 description 1
- KWSOILCRBSAWIF-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(2-methylpropanoyl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=C(C(=O)C(C)C)C(O)=C2C=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 KWSOILCRBSAWIF-UHFFFAOYSA-N 0.000 description 1
- YINHUVQZSBMUGS-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(2-phenylacetyl)naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)CC1=CC=CC=C1 YINHUVQZSBMUGS-UHFFFAOYSA-N 0.000 description 1
- NZJPLJIRKJSEII-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(3-methoxybenzoyl)naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=CC(OC)=C1 NZJPLJIRKJSEII-UHFFFAOYSA-N 0.000 description 1
- LCHVYRAYDDKNDJ-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(3-methylbenzoyl)naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=CC(C)=C1 LCHVYRAYDDKNDJ-UHFFFAOYSA-N 0.000 description 1
- YGLVYNZDZMLWIB-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(4-methylbenzoyl)naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(C)C=C1 YGLVYNZDZMLWIB-UHFFFAOYSA-N 0.000 description 1
- FLIXAPLKQNHOGO-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(4-propylbenzoyl)naphthalene-2-carboxylate Chemical compound C1=CC(CCC)=CC=C1C(=O)C1=C(O)C2=CC(OC)=C(OC)C(OC)=C2C(C=2C=C(OC)C(OC)=CC=2)=C1C(=O)OC FLIXAPLKQNHOGO-UHFFFAOYSA-N 0.000 description 1
- LNKWKDAGHFFOSQ-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-(naphthalene-2-carbonyl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=C(C(=O)C=2C=C3C=CC=CC3=CC=2)C(O)=C2C=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 LNKWKDAGHFFOSQ-UHFFFAOYSA-N 0.000 description 1
- VQSJTMMRYPHCCA-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-[2-(4-methoxyphenyl)acetyl]naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)CC1=CC=C(OC)C=C1 VQSJTMMRYPHCCA-UHFFFAOYSA-N 0.000 description 1
- LSQPGWAQLSSMTI-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-[4-(trifluoromethyl)benzoyl]naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1 LSQPGWAQLSSMTI-UHFFFAOYSA-N 0.000 description 1
- XXZZJINYRJPAGK-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-3-propanoylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 XXZZJINYRJPAGK-UHFFFAOYSA-N 0.000 description 1
- YMIAHKQBVFXSQH-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-5-(methoxymethyl)-3-propanoylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=C(COC)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 YMIAHKQBVFXSQH-UHFFFAOYSA-N 0.000 description 1
- JWQSSHWBJUHITQ-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-5-methyl-3-(2-methylpropanoyl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=C(C(=O)C(C)C)C(O)=C2C(C)=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 JWQSSHWBJUHITQ-UHFFFAOYSA-N 0.000 description 1
- UGLCIIKMMPYWDW-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-5-methyl-3-propanoylnaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=C(C)C(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(OC)=C1 UGLCIIKMMPYWDW-UHFFFAOYSA-N 0.000 description 1
- OPOKGKXVGYPZLQ-UHFFFAOYSA-N methyl 1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7-di(propan-2-yloxy)-3-[4-(trifluoromethyl)benzoyl]naphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC(C)C)C(OC(C)C)=CC2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1 OPOKGKXVGYPZLQ-UHFFFAOYSA-N 0.000 description 1
- PPGQXIUFJSJUMP-UHFFFAOYSA-N methyl 2-[(4-methoxyphenyl)methyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)NCC(C(=O)OC)CC1=CC=C(OC)C=C1 PPGQXIUFJSJUMP-UHFFFAOYSA-N 0.000 description 1
- FWFGXNSPXJAZCQ-UHFFFAOYSA-N methyl 3-(2,4-difluorobenzoyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(F)C=C1F FWFGXNSPXJAZCQ-UHFFFAOYSA-N 0.000 description 1
- XFOZDDOPDXDCDF-UHFFFAOYSA-N methyl 3-(2-cyclohexylacetyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)CC1CCCCC1 XFOZDDOPDXDCDF-UHFFFAOYSA-N 0.000 description 1
- OQUKCNCUXUCIKE-UHFFFAOYSA-N methyl 3-(3,4-dimethoxybenzoyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(OC)C(OC)=C1 OQUKCNCUXUCIKE-UHFFFAOYSA-N 0.000 description 1
- XOPXSNYHDMZEFI-UHFFFAOYSA-N methyl 3-(3-ethylpentanoyl)-1-(3-fluoro-4-methoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC=C(OC)C(F)=C1 XOPXSNYHDMZEFI-UHFFFAOYSA-N 0.000 description 1
- SDSBHIMIKFEUHM-UHFFFAOYSA-N methyl 3-(3-ethylpentanoyl)-4-hydroxy-6,7,8-trimethoxy-1-(3,4,5-trimethoxyphenyl)naphthalene-2-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC(OC)=C(OC)C(OC)=C2C=1C1=CC(OC)=C(OC)C(OC)=C1 SDSBHIMIKFEUHM-UHFFFAOYSA-N 0.000 description 1
- YOUOLACFGDJYTJ-UHFFFAOYSA-N methyl 3-(4-chlorobenzoyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-5-(hydroxymethyl)-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C(CO)=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(Cl)C=C1 YOUOLACFGDJYTJ-UHFFFAOYSA-N 0.000 description 1
- SMQIBNVITGPRKX-UHFFFAOYSA-N methyl 3-(4-chlorobenzoyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(Cl)C=C1 SMQIBNVITGPRKX-UHFFFAOYSA-N 0.000 description 1
- RLAXRHXJSOOEJK-UHFFFAOYSA-N methyl 3-(4-tert-butylbenzoyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(C(C)(C)C)C=C1 RLAXRHXJSOOEJK-UHFFFAOYSA-N 0.000 description 1
- LLXYQPYWGQBWGM-UHFFFAOYSA-N methyl 3-(cyclohexanecarbonyl)-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1CCCCC1 LLXYQPYWGQBWGM-UHFFFAOYSA-N 0.000 description 1
- FLSVORXBNBMKEA-UHFFFAOYSA-N methyl 3-benzoyl-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxy-5-methylnaphthalene-2-carboxylate Chemical compound OC1=C2C(C)=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=CC=C1 FLSVORXBNBMKEA-UHFFFAOYSA-N 0.000 description 1
- KHBJOBLJLSXZSR-UHFFFAOYSA-N methyl 3-benzoyl-1-(3,4-dimethoxyphenyl)-4-hydroxy-6,7,8-trimethoxynaphthalene-2-carboxylate Chemical compound OC1=C2C=C(OC)C(OC)=C(OC)C2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=CC=C1 KHBJOBLJLSXZSR-UHFFFAOYSA-N 0.000 description 1
- PARWWIKMBHKOLA-UHFFFAOYSA-N methyl 3-pentyl-4,5-dihydro-1,2-oxazole-5-carboxylate Chemical compound CCCCCC1=NOC(C(=O)OC)C1 PARWWIKMBHKOLA-UHFFFAOYSA-N 0.000 description 1
- RPBUCOMQTKQBQG-UHFFFAOYSA-N methyl 4-acetyloxy-5-ethylthiophene-3-carboxylate Chemical compound CCC=1SC=C(C(=O)OC)C=1OC(C)=O RPBUCOMQTKQBQG-UHFFFAOYSA-N 0.000 description 1
- LEAKUJFYXNILRB-UHFFFAOYSA-N methyl 4-oxothiolane-3-carboxylate Chemical compound COC(=O)C1CSCC1=O LEAKUJFYXNILRB-UHFFFAOYSA-N 0.000 description 1
- QRQFZSYEHOMSGD-UHFFFAOYSA-N methyl 5-ethyl-2-hydroxy-4-oxoheptanoate Chemical compound CCC(CC)C(=O)CC(O)C(=O)OC QRQFZSYEHOMSGD-UHFFFAOYSA-N 0.000 description 1
- UMCWVCBIUSLVBZ-UHFFFAOYSA-N methyl 5-ethyl-4-hydroxythiophene-3-carboxylate Chemical compound CCC=1SC=C(C(=O)OC)C=1O UMCWVCBIUSLVBZ-UHFFFAOYSA-N 0.000 description 1
- CBWXHQHXFZOSTO-UHFFFAOYSA-N methyl 5-ethyl-4-methoxythiophene-3-carboxylate Chemical compound CCC=1SC=C(C(=O)OC)C=1OC CBWXHQHXFZOSTO-UHFFFAOYSA-N 0.000 description 1
- BYZIKXIGQANZNV-UHFFFAOYSA-N methyl 6-(3,4-dimethoxyphenyl)-4-oxo-[1,3]benzodioxolo[6,5-h][1,3]benzodioxine-5-carboxylate Chemical compound COC(=O)C1=C2C(=O)OCOC2=C2C=C3OCOC3=CC2=C1C1=CC=C(OC)C(OC)=C1 BYZIKXIGQANZNV-UHFFFAOYSA-N 0.000 description 1
- BGSFURXAWUSYBK-UHFFFAOYSA-N methyl 6-(3,4-dimethoxyphenyl)-7,8,9,10-tetramethoxy-4-oxobenzo[h][1,3]benzodioxine-5-carboxylate Chemical compound COC(=O)C1=C2C(=O)OCOC2=C2C(OC)=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 BGSFURXAWUSYBK-UHFFFAOYSA-N 0.000 description 1
- JSUNKRHYQDUOCT-UHFFFAOYSA-N methyl 6-(3,4-dimethoxyphenyl)-7,8,9-trimethoxy-10-methyl-4-oxobenzo[h][1,3]benzodioxine-5-carboxylate Chemical compound COC(=O)C1=C2C(=O)OCOC2=C2C(C)=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 JSUNKRHYQDUOCT-UHFFFAOYSA-N 0.000 description 1
- VMUOXGLWYRMQAF-UHFFFAOYSA-N methyl 6-(3,4-dimethoxyphenyl)-7,8,9-trimethoxy-4-oxobenzo[h][1,3]benzodioxine-5-carboxylate Chemical compound COC(=O)C1=C2C(=O)OCOC2=C2C=C(OC)C(OC)=C(OC)C2=C1C1=CC=C(OC)C(OC)=C1 VMUOXGLWYRMQAF-UHFFFAOYSA-N 0.000 description 1
- KHIYGFNCSJTJKS-UHFFFAOYSA-N methyl 6-(4-chlorobenzoyl)-8-(3,4-dimethoxyphenyl)-5-hydroxybenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound OC1=C2C=C3OCOC3=CC2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(Cl)C=C1 KHIYGFNCSJTJKS-UHFFFAOYSA-N 0.000 description 1
- HMOUEGNEMCDPPD-UHFFFAOYSA-N methyl 7-(3,4-dimethoxyphenyl)-2-ethyl-5-(3-ethylpentanoyl)-4-hydroxy-3-methoxy-1-benzothiophene-6-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C=2C(OC)=C(CC)SC=2C=1C1=CC=C(OC)C(OC)=C1 HMOUEGNEMCDPPD-UHFFFAOYSA-N 0.000 description 1
- ILCMZDJZTAKPEX-UHFFFAOYSA-N methyl 7-(3,4-dimethoxyphenyl)-4-hydroxy-3-methoxy-5-propanoyl-1-benzothiophene-6-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C=2C(OC)=CSC=2C=1C1=CC=C(OC)C(OC)=C1 ILCMZDJZTAKPEX-UHFFFAOYSA-N 0.000 description 1
- AXUYKAAMNSTRFM-UHFFFAOYSA-N methyl 7-(3,4-dimethoxyphenyl)-5-(3-ethylpentanoyl)-4-hydroxy-1-benzothiophene-6-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C=2C=CSC=2C=1C1=CC=C(OC)C(OC)=C1 AXUYKAAMNSTRFM-UHFFFAOYSA-N 0.000 description 1
- KPHXAZYBAMQXRO-UHFFFAOYSA-N methyl 7-(3,4-dimethoxyphenyl)-5-(3-ethylpentanoyl)-4-hydroxy-3-methoxy-1-benzothiophene-6-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C=2C(OC)=CSC=2C=1C1=CC=C(OC)C(OC)=C1 KPHXAZYBAMQXRO-UHFFFAOYSA-N 0.000 description 1
- BSXGBRYKKSWNEI-UHFFFAOYSA-N methyl 7-(3,4-dimethoxyphenyl)-5-(3-ethylpentanoyl)-4-hydroxy-3-methyl-1-benzothiophene-6-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C=2C(C)=CSC=2C=1C1=CC=C(OC)C(OC)=C1 BSXGBRYKKSWNEI-UHFFFAOYSA-N 0.000 description 1
- PPPACSYKFYUFDB-UHFFFAOYSA-N methyl 7-(4-chlorobenzoyl)-9-(3,4-dimethoxyphenyl)-6-hydroxy-2,3-dihydrobenzo[g][1,4]benzodioxine-8-carboxylate Chemical compound OC1=C2C=C3OCCOC3=CC2=C(C=2C=C(OC)C(OC)=CC=2)C(C(=O)OC)=C1C(=O)C1=CC=C(Cl)C=C1 PPPACSYKFYUFDB-UHFFFAOYSA-N 0.000 description 1
- WICNBEJMABXIFT-UHFFFAOYSA-N methyl 8-(2,3-dimethoxyphenyl)-5-hydroxy-6-[4-(trifluoromethyl)benzoyl]benzo[f][1,3]benzodioxole-7-carboxylate Chemical compound OC1=C2C=C3OCOC3=CC2=C(C=2C(=C(OC)C=CC=2)OC)C(C(=O)OC)=C1C(=O)C1=CC=C(C(F)(F)F)C=C1 WICNBEJMABXIFT-UHFFFAOYSA-N 0.000 description 1
- FIXBQINHXWIUKP-UHFFFAOYSA-N methyl 8-(2,3-dimethoxyphenyl)-6-(3-ethylpentanoyl)-5-hydroxybenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC=3OCOC=3C=C2C=1C1=CC=CC(OC)=C1OC FIXBQINHXWIUKP-UHFFFAOYSA-N 0.000 description 1
- QHUZHDRGCFPCHS-UHFFFAOYSA-N methyl 8-(2,4-dimethoxyphenyl)-5-hydroxy-6-propanoylbenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=CC=3OCOC=3C=C2C=1C1=CC=C(OC)C=C1OC QHUZHDRGCFPCHS-UHFFFAOYSA-N 0.000 description 1
- LEEIWBIWHYHUJM-UHFFFAOYSA-N methyl 8-(2,4-dimethoxyphenyl)-6-(3-ethylpentanoyl)-5-hydroxybenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC=3OCOC=3C=C2C=1C1=CC=C(OC)C=C1OC LEEIWBIWHYHUJM-UHFFFAOYSA-N 0.000 description 1
- SRXHWSGYGGSALW-UHFFFAOYSA-N methyl 8-(3,4-dimethoxyphenyl)-5-hydroxy-6-propanoylbenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=CC=3OCOC=3C=C2C=1C1=CC=C(OC)C(OC)=C1 SRXHWSGYGGSALW-UHFFFAOYSA-N 0.000 description 1
- PAWAGGMAJRYKBB-UHFFFAOYSA-N methyl 8-(3,4-dimethoxyphenyl)-6-(2-ethylbutanoyl)-5-hydroxybenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound COC(=O)C=1C(C(=O)C(CC)CC)=C(O)C2=CC=3OCOC=3C=C2C=1C1=CC=C(OC)C(OC)=C1 PAWAGGMAJRYKBB-UHFFFAOYSA-N 0.000 description 1
- BSZAVXYSCOZANN-UHFFFAOYSA-N methyl 8-(3,4-dimethoxyphenyl)-6-(3-ethylpentanoyl)-5-hydroxybenzo[f][1,3]benzodioxole-7-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC=3OCOC=3C=C2C=1C1=CC=C(OC)C(OC)=C1 BSZAVXYSCOZANN-UHFFFAOYSA-N 0.000 description 1
- PKQPCYLYYPWWTG-UHFFFAOYSA-N methyl 9-(3,4-dimethoxyphenyl)-6-hydroxy-7-propanoyl-2,3-dihydrobenzo[g][1,4]benzodioxine-8-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC)=C(O)C2=CC=3OCCOC=3C=C2C=1C1=CC=C(OC)C(OC)=C1 PKQPCYLYYPWWTG-UHFFFAOYSA-N 0.000 description 1
- XRSMNWJGQCGELS-UHFFFAOYSA-N methyl 9-(3,4-dimethoxyphenyl)-7-(3-ethylpentanoyl)-6-hydroxy-2,3-dihydrobenzo[g][1,4]benzodioxine-8-carboxylate Chemical compound COC(=O)C=1C(C(=O)CC(CC)CC)=C(O)C2=CC=3OCCOC=3C=C2C=1C1=CC=C(OC)C(OC)=C1 XRSMNWJGQCGELS-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- FQRMVGKAQSXDPC-UHFFFAOYSA-N n-(2-ethylbutylidene)hydroxylamine Chemical compound CCC(CC)C=NO FQRMVGKAQSXDPC-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 108010071584 oxidized low density lipoprotein Proteins 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-OUBTZVSYSA-N potassium-40 Chemical compound [40K] ZLMJMSJWJFRBEC-OUBTZVSYSA-N 0.000 description 1
- FLYUMOLYTDQIFN-UHFFFAOYSA-N potassium;bis[dimethyl(phenyl)silyl]azanide Chemical compound [K+].C=1C=CC=CC=1[Si](C)(C)[N-][Si](C)(C)C1=CC=CC=C1 FLYUMOLYTDQIFN-UHFFFAOYSA-N 0.000 description 1
- WCDGRLYFXMYHQB-UHFFFAOYSA-N potassium;diethylazanide Chemical compound [K+].CC[N-]CC WCDGRLYFXMYHQB-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- UKLNMMHNWFDKNT-UHFFFAOYSA-M sodium chlorite Chemical compound [Na+].[O-]Cl=O UKLNMMHNWFDKNT-UHFFFAOYSA-M 0.000 description 1
- 229960002218 sodium chlorite Drugs 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- RRWFKUFMWAQPAL-UHFFFAOYSA-N sodium;dicyclohexylazanide Chemical compound [Na+].C1CCCCC1[N-]C1CCCCC1 RRWFKUFMWAQPAL-UHFFFAOYSA-N 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- MHYGQXWCZAYSLJ-UHFFFAOYSA-N tert-butyl-chloro-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](Cl)(C(C)(C)C)C1=CC=CC=C1 MHYGQXWCZAYSLJ-UHFFFAOYSA-N 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/738—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C69/94—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of polycyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of six-membered aromatic rings
-
- 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
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/18—Radicals substituted by singly bound oxygen or sulfur atoms
- C07D317/22—Radicals substituted by singly bound oxygen or sulfur atoms etherified
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/70—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with ring systems containing two or more relevant rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/22—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one naphthalene or hydrogenated naphthalene ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
- C07D333/64—Oxygen atoms
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Claims (8)
1. Verbindung der Formel (I):
worin R¹ ein Niederalkyl-, Cycloalkyl-, Cycloalkyl-Niederalkylrest, eine Arylgruppe oder ein
Aralkylrest ist, die gegebenenfalls substituiert sind,
R² ein Rest der Formel -COOR' (worin R' ein gegebenenfalls substituierter
Niederalkyl- oder Aralkylrest ist), ein Niederalkyl- oder ein halogenierter Niederalkylrest ist, oder
R¹ und R² zusammen mit einer benachbarten Carbonylgruppe einen Cyclohexanonring der
Formel:
bilden,
R³ eine gegebenenfalls substituierte Phenylgruppe ist, und
der Ring A ein Benzolkern, der gegebenenfalls substituiert ist, oder ein heterocyclischer
Ring ist, der S oder O enthält und gegebenenfalls substituiert ist,
oder deren pharmazeutisch verträgliches Salz.
2. Verbindung nach Anspruch 1, worin R² ein Rest der Formel -COOR' ist, worin R7 wie
vorstehend definiert ist.
3. Verbindung nach Anspruch 1 oder 2, worin der Ring A ein Benzolkern ist, der mit drei
Methoxygruppen substituiert ist, und R³ eine mit zwei Methoxygruppen substituierte
Phenylgruppe ist.
4. 1-(3,4.Dimethoxyphenyl)-3-(3-ethyl-1-oxopentyl)-4-hydroxy-2-methoxycarbonyl-
6,7,8-trimethoxynaphthalin.
5. Verfahren zur Herstellung der Verbindung der Formel (I), umfassend die
Additionsreaktion einer Verbindung der Formel (II):
worin der Ring A und R³ wie vorstehend definiert sind, und einer Verbindung der Formel
(III):
R¹OC-C C-R² (III)
worin R¹ wie vorstehend definiert ist, und R² ein Rest der Formel -COOR' ist (worin R'
ein gegebenenfalls substituierter Niederalkyl- oder Aralkylrest ist).
6. Verfahren zur Herstellung der Verbindung der Formel (I), umfassend die
Substitutionsreaktion einer Verbindung der Formel (IV):
[worin R² ein Rest der Formel -COOR' ist (worin R' ein gegebenenfalls substituierter
Niederalkyloder Aralkylrest ist), und R³ und der Ring A wie vorstehend definiert sind] und einer Verbindung
der Formel (V):
R¹-M (V)
[worin R¹ wie vorstehend definiert ist, und M ein Lithiumatom oder eine Gruppe aus
Magnesiumatom-Halogenatom ist].
7. Arzneimittel, das die Verbindung nach einem der Ansprüche 1 bis 4 als
pharmazeutischen Wirkstoff enthält.
8. Hypolipidemisches Arzneimittel, das die Verbindung nach einem der Ansprüche 1 bis 4
als pharmazeutischen Wirkstoff enthält.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP29811991 | 1991-10-17 | ||
PCT/JP1992/001342 WO1993008155A1 (en) | 1991-10-17 | 1992-10-15 | Lignan analog, production thereof, and hypolipidemic drug |
Publications (2)
Publication Number | Publication Date |
---|---|
DE69211994D1 DE69211994D1 (de) | 1996-08-08 |
DE69211994T2 true DE69211994T2 (de) | 1997-02-20 |
Family
ID=17855421
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69211994T Expired - Fee Related DE69211994T2 (de) | 1991-10-17 | 1992-10-15 | Lignan-analoge, ihre herstellung und hypolipidemische arzneimittel |
DE69228262T Expired - Fee Related DE69228262D1 (de) | 1991-10-17 | 1992-10-15 | Verfahren zum Herstellen von Lignin-Analoga und Ausgangsprodukte dafür |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE69228262T Expired - Fee Related DE69228262D1 (de) | 1991-10-17 | 1992-10-15 | Verfahren zum Herstellen von Lignin-Analoga und Ausgangsprodukte dafür |
Country Status (12)
Country | Link |
---|---|
US (4) | US5420333A (de) |
EP (2) | EP0597107B1 (de) |
JP (1) | JP2839805B2 (de) |
KR (1) | KR100252428B1 (de) |
AT (2) | ATE139990T1 (de) |
DE (2) | DE69211994T2 (de) |
DK (2) | DK0701991T3 (de) |
ES (2) | ES2129733T3 (de) |
GR (1) | GR3020461T3 (de) |
HU (1) | HU211296A9 (de) |
TW (1) | TW209215B (de) |
WO (1) | WO1993008155A1 (de) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2138264C (en) * | 1993-04-16 | 2004-04-06 | Sachio Mori | Preparation of compounds of lignan series |
FR2707980B1 (fr) * | 1993-07-20 | 1995-09-01 | Adir | Nouveaux cyclohept[b]indoles et cyclooct[b]indoles, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
AU2353095A (en) * | 1994-06-22 | 1996-01-15 | Shionogi & Co., Ltd. | Process for producing phthalide compound |
ID18046A (id) * | 1996-08-20 | 1998-02-19 | Takeda Chemical Industries Ltd | Senyawa siklik campuran, pembuatan dan penngunaannya. |
JP2002529409A (ja) * | 1998-11-12 | 2002-09-10 | アルテオン インコーポレーテッド | グルコース及び脂質低下化合物類 |
KR100352269B1 (ko) * | 1999-10-08 | 2002-09-12 | 한국생명공학연구원 | 저밀도 지질 단백질에 대해 항산화 활성을 갖는 리그난계 화합물 |
FR2800738B1 (fr) | 1999-11-04 | 2002-02-08 | Corning Sa | Naphtopyranes ayant un substituant perfluoroalkyle en position 5, preparation et compositions et matrices (co)polymeres les renfermant |
US6770024B1 (en) * | 2000-03-28 | 2004-08-03 | Stony Brook Surgical Innovations, Inc. | Implantable counterpulsation cardiac assist device |
TWI241195B (en) * | 2000-04-10 | 2005-10-11 | Shionogi & Co | Preventive agent for bile acidic diarrhea |
CA2417492A1 (en) * | 2000-08-01 | 2003-01-28 | Shionogi & Co., Ltd. | Preventives or remedies for obesity or fatty liver |
WO2004033411A1 (ja) * | 2002-10-08 | 2004-04-22 | Shionogi & Co., Ltd. | エノンエステルの製造法 |
US7152611B2 (en) * | 2002-12-30 | 2006-12-26 | International Tape Partners, Llc | Coated multifilament dental devices overcoated with imbedded particulate |
GB0307918D0 (en) | 2003-04-05 | 2003-05-14 | Astrazeneca Ab | Therapeutic use |
WO2011150286A2 (en) | 2010-05-26 | 2011-12-01 | Satiogen Pharmaceuticals,Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
CN104023727B (zh) | 2011-10-28 | 2017-04-05 | 鲁美纳医药公司 | 用于治疗小儿胆汁淤积性肝病的胆汁酸再循环抑制剂 |
CN104023718B (zh) | 2011-10-28 | 2017-04-05 | 鲁美纳医药公司 | 用于治疗高胆血症和胆汁淤积性肝病的胆汁酸再循环抑制剂 |
AU2014229050A1 (en) | 2013-03-15 | 2015-10-22 | Lumena Pharmaceuticals Llc | Bile acid recycling inhibitors for treatment of Barrett's esophagus and gastroesophageal reflux disease |
AU2014228850A1 (en) | 2013-03-15 | 2015-10-29 | Lumena Pharmaceuticals Llc | Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease |
JP2022520121A (ja) | 2019-02-12 | 2022-03-28 | ミルム ファーマシューティカルズ インコーポレイテッド | 胆汁うっ滞を治療する方法 |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NO170760C (no) * | 1985-01-10 | 1992-12-02 | Tanabe Seiyaku Co | Analogifremgangsmaate for fremstilling av terapeutisk aktive nafthalenderivater |
JPS6310746A (ja) * | 1986-07-01 | 1988-01-18 | Tanabe Seiyaku Co Ltd | ナフタレン誘導体 |
JPH0372422A (ja) * | 1989-05-16 | 1991-03-27 | Tanabe Seiyaku Co Ltd | 抗脂血剤 |
-
1992
- 1992-10-15 AT AT92921331T patent/ATE139990T1/de not_active IP Right Cessation
- 1992-10-15 EP EP92921331A patent/EP0597107B1/de not_active Expired - Lifetime
- 1992-10-15 US US08/078,205 patent/US5420333A/en not_active Expired - Lifetime
- 1992-10-15 ES ES95117572T patent/ES2129733T3/es not_active Expired - Lifetime
- 1992-10-15 WO PCT/JP1992/001342 patent/WO1993008155A1/ja active IP Right Grant
- 1992-10-15 DE DE69211994T patent/DE69211994T2/de not_active Expired - Fee Related
- 1992-10-15 ES ES92921331T patent/ES2091488T3/es not_active Expired - Lifetime
- 1992-10-15 EP EP95117572A patent/EP0701991B1/de not_active Expired - Lifetime
- 1992-10-15 JP JP4277151A patent/JP2839805B2/ja not_active Expired - Fee Related
- 1992-10-15 DK DK95117572T patent/DK0701991T3/da active
- 1992-10-15 AT AT95117572T patent/ATE175954T1/de not_active IP Right Cessation
- 1992-10-15 DK DK92921331.2T patent/DK0597107T3/da active
- 1992-10-15 DE DE69228262T patent/DE69228262D1/de not_active Expired - Fee Related
- 1992-10-15 KR KR1019930701814A patent/KR100252428B1/ko not_active IP Right Cessation
- 1992-10-17 TW TW081108267A patent/TW209215B/zh active
-
1994
- 1994-09-07 US US08/301,996 patent/US5449814A/en not_active Expired - Lifetime
-
1995
- 1995-04-18 US US08/423,346 patent/US5731455A/en not_active Expired - Fee Related
- 1995-05-22 US US08/445,506 patent/US5502216A/en not_active Expired - Fee Related
- 1995-06-30 HU HU95P/P00635P patent/HU211296A9/hu unknown
-
1996
- 1996-07-04 GR GR960401618T patent/GR3020461T3/el unknown
Also Published As
Publication number | Publication date |
---|---|
US5731455A (en) | 1998-03-24 |
US5502216A (en) | 1996-03-26 |
US5449814A (en) | 1995-09-12 |
EP0597107B1 (de) | 1996-07-03 |
DK0701991T3 (da) | 1999-09-13 |
GR3020461T3 (en) | 1996-10-31 |
ATE175954T1 (de) | 1999-02-15 |
EP0597107A4 (de) | 1994-02-03 |
ES2091488T3 (es) | 1996-11-01 |
EP0701991A1 (de) | 1996-03-20 |
ATE139990T1 (de) | 1996-07-15 |
US5420333A (en) | 1995-05-30 |
WO1993008155A1 (en) | 1993-04-29 |
JPH05310634A (ja) | 1993-11-22 |
JP2839805B2 (ja) | 1998-12-16 |
KR930703236A (ko) | 1993-11-29 |
DE69211994D1 (de) | 1996-08-08 |
HU211296A9 (en) | 1995-11-28 |
TW209215B (de) | 1993-07-11 |
DK0597107T3 (da) | 1996-07-29 |
DE69228262D1 (de) | 1999-03-04 |
EP0701991B1 (de) | 1999-01-20 |
ES2129733T3 (es) | 1999-06-16 |
KR100252428B1 (ko) | 2000-04-15 |
EP0597107A1 (de) | 1994-05-18 |
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