CN1070852C - 乌头碱型化合物14-o-酰化体的制法 - Google Patents
乌头碱型化合物14-o-酰化体的制法 Download PDFInfo
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- CN1070852C CN1070852C CN92105347A CN92105347A CN1070852C CN 1070852 C CN1070852 C CN 1070852C CN 92105347 A CN92105347 A CN 92105347A CN 92105347 A CN92105347 A CN 92105347A CN 1070852 C CN1070852 C CN 1070852C
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- Prior art keywords
- methyl
- same
- aconine
- methoxyl
- milligrams
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 55
- 238000004519 manufacturing process Methods 0.000 title description 8
- 229930013930 alkaloid Natural products 0.000 title description 5
- 150000003797 alkaloid derivatives Chemical class 0.000 title description 2
- 241000173529 Aconitum napellus Species 0.000 title 1
- 229940023019 aconite Drugs 0.000 title 1
- 239000000126 substance Substances 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- XFSBVAOIAHNAPC-XTHSEXKGSA-N 16-Ethyl-1alpha,6alpha,19beta-trimethoxy-4-(methoxymethyl)-aconitane-3alpha,8,10alpha,11,18alpha-pentol, 8-acetate 10-benzoate Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45C6[C@@H]([C@@]([C@H]31)(OC(C)=O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-XTHSEXKGSA-N 0.000 claims description 14
- XFSBVAOIAHNAPC-UHFFFAOYSA-N Aconitin Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(OC(C)=O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=CC=C1 XFSBVAOIAHNAPC-UHFFFAOYSA-N 0.000 claims description 14
- 229940039750 aconitine Drugs 0.000 claims description 14
- STDXGNLCJACLFY-UHFFFAOYSA-N aconitine Natural products CCN1CC2(COC)C(O)CC(O)C34C5CC6(O)C(OC)C(O)C(OC(=O)C)(C5C6OC(=O)c7ccccc7)C(C(OC)C23)C14 STDXGNLCJACLFY-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 238000005917 acylation reaction Methods 0.000 abstract description 4
- 230000010933 acylation Effects 0.000 abstract 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 440
- -1 Hydroxyl Chemical group 0.000 description 377
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 274
- SQMGCPHFHQGPIF-UUKFDUHUSA-N gns9eex31x Chemical compound O[C@@H]([C@]([C@H]([C@H](O)[C@]12O)OC)(O)C3)[C@H]2[C@@H]3[C@@]2([C@H](C[C@H]3O)OC)[C@H]4[C@@H]1[C@H](OC)[C@@H]2[C@]3(COC)CN4CC SQMGCPHFHQGPIF-UUKFDUHUSA-N 0.000 description 247
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 225
- 238000000862 absorption spectrum Methods 0.000 description 180
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 177
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 175
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 156
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 155
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 120
- 238000004949 mass spectrometry Methods 0.000 description 113
- 238000010521 absorption reaction Methods 0.000 description 112
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 111
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 107
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 101
- 239000000243 solution Substances 0.000 description 79
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 67
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- 238000003756 stirring Methods 0.000 description 58
- 229910021529 ammonia Inorganic materials 0.000 description 56
- 239000002904 solvent Substances 0.000 description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- 238000010898 silica gel chromatography Methods 0.000 description 46
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 45
- 230000002829 reductive effect Effects 0.000 description 44
- 125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 43
- 238000001035 drying Methods 0.000 description 42
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 38
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- 150000002170 ethers Chemical class 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 28
- 238000000605 extraction Methods 0.000 description 27
- 150000008065 acid anhydrides Chemical class 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 238000000926 separation method Methods 0.000 description 24
- AZAZKLKDEOMJBJ-UHFFFAOYSA-N Napellin-N-oxid Natural products C=C1C(O)C23CC1C(O)CC2C12C(O)CCC4(C)CN(CC)C2C3CC41 AZAZKLKDEOMJBJ-UHFFFAOYSA-N 0.000 description 21
- MGTJNQWIXFSPLC-UHFFFAOYSA-N jesaconitine Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(OC(C)=O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=C(OC)C=C1 MGTJNQWIXFSPLC-UHFFFAOYSA-N 0.000 description 21
- IZUTYRYPLISYDD-UHFFFAOYSA-N napelline Natural products CCN1CC2(C)CCC(O)C34C5CC(O)C6CC5(CC(C13)C24)C(O)C6=C IZUTYRYPLISYDD-UHFFFAOYSA-N 0.000 description 21
- 238000007670 refining Methods 0.000 description 19
- XUHJBXVYNBQQBD-UHFFFAOYSA-N mesaconitine Natural products COC1CC(O)C2(COC)CN(C)C3C(C(C45)(OC(C)=O)C(O)C6OC)C(OC)C2C31C4CC6(O)C5OC(=O)C1=CC=CC=C1 XUHJBXVYNBQQBD-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- AZAZKLKDEOMJBJ-AFJRDBIPSA-N 6ppc7ud22e Chemical compound O[C@H]([C@@H]1C[C@@]23[C@@H](C1=C)O)C[C@H]2[C@]12[C@@H](O)CC[C@@]4(C)CN(CC)[C@@H]2[C@@H]3C[C@H]41 AZAZKLKDEOMJBJ-AFJRDBIPSA-N 0.000 description 17
- 238000001816 cooling Methods 0.000 description 17
- 230000006837 decompression Effects 0.000 description 17
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 125000003047 N-acetyl group Chemical group 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000002253 acid Substances 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- AFPHTEQTJZKQAQ-UHFFFAOYSA-N 3-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1 AFPHTEQTJZKQAQ-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 235000011114 ammonium hydroxide Nutrition 0.000 description 12
- 150000004820 halides Chemical class 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 125000002252 acyl group Chemical group 0.000 description 11
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 11
- 238000005406 washing Methods 0.000 description 11
- 239000007864 aqueous solution Substances 0.000 description 10
- QARVLSVVCXYDNA-UHFFFAOYSA-N phenyl bromide Natural products BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 10
- MGTJNQWIXFSPLC-HQARQGIISA-N Jesaconitine Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45C6[C@@H]([C@@]([C@H]31)(OC(C)=O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=C(OC)C=C1 MGTJNQWIXFSPLC-HQARQGIISA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 9
- 229940073608 benzyl chloride Drugs 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 9
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 8
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 8
- 150000003222 pyridines Chemical class 0.000 description 8
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 7
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 7
- 239000012346 acetyl chloride Substances 0.000 description 7
- 125000004423 acyloxy group Chemical group 0.000 description 7
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 7
- 238000004821 distillation Methods 0.000 description 7
- 235000011167 hydrochloric acid Nutrition 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- TUXYZHVUPGXXQG-UHFFFAOYSA-N 4-bromobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1 TUXYZHVUPGXXQG-UHFFFAOYSA-N 0.000 description 6
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 150000004075 acetic anhydrides Chemical class 0.000 description 6
- 125000001931 aliphatic group Chemical group 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethyl monosulfide Natural products CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 6
- 239000011259 mixed solution Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 6
- PBOOZQFGWNZNQE-UHFFFAOYSA-N 3-bromobenzoyl chloride Chemical class ClC(=O)C1=CC=CC(Br)=C1 PBOOZQFGWNZNQE-UHFFFAOYSA-N 0.000 description 5
- 241000227129 Aconitum Species 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- NZCKTGCKFJDGFD-UHFFFAOYSA-N 2-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Br NZCKTGCKFJDGFD-UHFFFAOYSA-N 0.000 description 4
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 4
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 4
- 238000013019 agitation Methods 0.000 description 4
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical class COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 4
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 4
- 239000001110 calcium chloride Substances 0.000 description 4
- 229910001628 calcium chloride Inorganic materials 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000036407 pain Effects 0.000 description 4
- 235000017550 sodium carbonate Nutrition 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 230000001988 toxicity Effects 0.000 description 4
- 231100000419 toxicity Toxicity 0.000 description 4
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 4
- 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 description 3
- RKIDDEGICSMIJA-UHFFFAOYSA-N 4-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Cl)C=C1 RKIDDEGICSMIJA-UHFFFAOYSA-N 0.000 description 3
- 241000212314 Foeniculum Species 0.000 description 3
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
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- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 3
- 125000006011 chloroethoxy group Chemical group 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
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- 230000004054 inflammatory process Effects 0.000 description 3
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- XUHJBXVYNBQQBD-GQPWXMLZSA-N molport-002-525-145 Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@]45[C@@H]6[C@@H](OC)[C@H]([C@@]([C@H]31)(OC(C)=O)[C@@H](O)[C@@H]2OC)[C@H]4N(C)C[C@@]6([C@@H](C[C@@H]5OC)O)COC)C(=O)C1=CC=CC=C1 XUHJBXVYNBQQBD-GQPWXMLZSA-N 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 125000000962 organic group Chemical group 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000012286 potassium permanganate Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
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- YZWKKMVJZFACSU-UHFFFAOYSA-N 1-bromopentane Chemical compound CCCCCBr YZWKKMVJZFACSU-UHFFFAOYSA-N 0.000 description 2
- YVPYMQHYESYLIR-HZKWNRCISA-N 5483by72rt Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45[C@H]6[C@@H]([C@]([C@H]31)(C[C@@H]2OC)OC(C)=O)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=C(OC)C(OC)=C1 YVPYMQHYESYLIR-HZKWNRCISA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- DPMGVDIWDTYPMP-UHFFFAOYSA-N Hypaconitine Natural products COCC12CCC(OC)C3(CN(C)C1)C4CC5(O)C(OC)C(O)C(CC(OC)C23)(OC(=O)C)C4C5OC(=O)c6ccccc6 DPMGVDIWDTYPMP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- YVPYMQHYESYLIR-UHFFFAOYSA-N Pseudoaconitine Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(CC6OC)OC(C)=O)C1C32C4CC6(O)C5OC(=O)C1=CC=C(OC)C(OC)=C1 YVPYMQHYESYLIR-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- YBOFEONRFJMHND-UHFFFAOYSA-N [Br].N#CC#N Chemical compound [Br].N#CC#N YBOFEONRFJMHND-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- MVPPADPHJFYWMZ-IDEBNGHGSA-N chlorobenzene Chemical group Cl[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 MVPPADPHJFYWMZ-IDEBNGHGSA-N 0.000 description 2
- 150000002367 halogens Chemical class 0.000 description 2
- FIDOCHXHMJHKRW-GKVQVCCJSA-N hypaconitine Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@]45[C@@H](OC)CC[C@@]6([C@H]4[C@@H](OC)[C@H]([C@@](OC(C)=O)([C@H]31)[C@@H](O)[C@H]2OC)[C@H]5N(C)C6)COC)C(=O)C1=CC=CC=C1 FIDOCHXHMJHKRW-GKVQVCCJSA-N 0.000 description 2
- 150000002460 imidazoles Chemical class 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([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 2
- 239000003960 organic solvent Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- YRGAYAGBVIXNAQ-UHFFFAOYSA-N 1-chloro-4-methoxybenzene Chemical compound COC1=CC=C(Cl)C=C1 YRGAYAGBVIXNAQ-UHFFFAOYSA-N 0.000 description 1
- SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical class ClCCOC(Cl)=O SVDDJQGVOFZBNX-UHFFFAOYSA-N 0.000 description 1
- AIDLAEPHWROGFI-UHFFFAOYSA-N 2-methylbenzene-1,3-dicarboxylic acid Chemical compound CC1=C(C(O)=O)C=CC=C1C(O)=O AIDLAEPHWROGFI-UHFFFAOYSA-N 0.000 description 1
- DAUAQNGYDSHRET-UHFFFAOYSA-N 3,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1OC DAUAQNGYDSHRET-UHFFFAOYSA-N 0.000 description 1
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical class ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 description 1
- 241000553739 Aconitum carmichaelii var. truppelianum Species 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 229910000497 Amalgam Inorganic materials 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 235000004431 Linum usitatissimum Nutrition 0.000 description 1
- 240000006240 Linum usitatissimum Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 229910003870 O—Li Inorganic materials 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 241000218201 Ranunculaceae Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000002952 aconitine derivatives Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AQIHMSVIAGNIDM-UHFFFAOYSA-N benzoyl bromide Chemical compound BrC(=O)C1=CC=CC=C1 AQIHMSVIAGNIDM-UHFFFAOYSA-N 0.000 description 1
- DHJXZSFKLJCHLH-KYSNEVMMSA-N benzoylaconine Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@@]45C6[C@@H]([C@@]([C@H]31)(O)[C@@H](O)[C@@H]2OC)[C@H](OC)[C@@H]4[C@]([C@@H](C[C@@H]5OC)O)(COC)CN6CC)C(=O)C1=CC=CC=C1 DHJXZSFKLJCHLH-KYSNEVMMSA-N 0.000 description 1
- DHJXZSFKLJCHLH-UHFFFAOYSA-N benzoylaconine Natural products CCN1CC(C(CC2OC)O)(COC)C3C(OC)C(C(C45)(O)C(O)C6OC)C1C32C4CC6(O)C5OC(=O)C1=CC=CC=C1 DHJXZSFKLJCHLH-UHFFFAOYSA-N 0.000 description 1
- ANUZKYYBDVLEEI-UHFFFAOYSA-N butane;hexane;lithium Chemical compound [Li]CCCC.CCCCCC ANUZKYYBDVLEEI-UHFFFAOYSA-N 0.000 description 1
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000496 cardiotonic agent Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229960001076 chlorpromazine Drugs 0.000 description 1
- 230000020335 dealkylation Effects 0.000 description 1
- 238000006900 dealkylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- PHASMOUKYDUAOZ-IXLJIIPOSA-N deoxyaconitine Chemical compound O([C@H]1[C@]2(O)C[C@H]3[C@]45[C@@H](OC)CC[C@@]6(COC)CN(C5[C@H]([C@H](OC)[C@H]64)[C@](OC(C)=O)([C@H]31)[C@@H](O)[C@@H]2OC)CC)C(=O)C1=CC=CC=C1 PHASMOUKYDUAOZ-IXLJIIPOSA-N 0.000 description 1
- PHASMOUKYDUAOZ-UHFFFAOYSA-N deoxyaconitine Natural products C12C(OC(C)=O)(C(O)C3OC)C(C(OC)C45)C6N(CC)CC4(COC)CCC(OC)C56C2CC3(O)C1OC(=O)C1=CC=CC=C1 PHASMOUKYDUAOZ-UHFFFAOYSA-N 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000035619 diuresis Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical class CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- TUHMQDODLHWPCC-UHFFFAOYSA-N formyl cyanide Chemical compound O=CC#N TUHMQDODLHWPCC-UHFFFAOYSA-N 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 229910001502 inorganic halide Inorganic materials 0.000 description 1
- 238000009413 insulation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 235000012204 lemonade/lime carbonate Nutrition 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical class [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XGISHOFUAFNYQF-UHFFFAOYSA-N pentanoyl chloride Chemical compound CCCCC(Cl)=O XGISHOFUAFNYQF-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 235000007715 potassium iodide Nutrition 0.000 description 1
- 229960004839 potassium iodide Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000003696 stearoyl group Chemical group O=C([*])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])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
- RINCXYDBBGOEEQ-UHFFFAOYSA-N succinic anhydride Chemical class O=C1CCC(=O)O1 RINCXYDBBGOEEQ-UHFFFAOYSA-N 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229910052716 thallium Inorganic materials 0.000 description 1
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pain & Pain Management (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP03263354A JP3117251B2 (ja) | 1991-07-08 | 1991-07-08 | １４−Ｏ−ｐ−クロロベンゾイルアコニンおよび鎮痛・抗炎症剤 |
| JP263354/91 | 1991-07-08 | ||
| JP263354/1991 | 1991-07-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1068327A CN1068327A (zh) | 1993-01-27 |
| CN1070852C true CN1070852C (zh) | 2001-09-12 |
Family
ID=17388317
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN92105347A Expired - Lifetime CN1070852C (zh) | 1991-07-08 | 1992-07-04 | 乌头碱型化合物14-o-酰化体的制法 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US5330983A (cg-RX-API-DMAC7.html) |
| EP (1) | EP0547224B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP3117251B2 (cg-RX-API-DMAC7.html) |
| CN (1) | CN1070852C (cg-RX-API-DMAC7.html) |
| DE (1) | DE69117519T2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO1993001175A1 (cg-RX-API-DMAC7.html) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100443083C (zh) * | 2005-03-25 | 2008-12-17 | 成都高新区智爽天然产物科技有限责任公司 | 乌头胺在制药中的用途 |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5770604A (en) * | 1994-02-09 | 1998-06-23 | Sanwa Shoyaku Kabushiki Kaisha | Aconitine compound and an antipyretic/analgesic/anti-inflammatory agent |
| CN103570621B (zh) * | 2013-05-17 | 2015-04-29 | 万邦德制药集团股份有限公司 | 一种（-）-石杉碱甲的制备 |
| CN110092806B (zh) * | 2018-01-30 | 2022-05-17 | 中国医学科学院药物研究所 | 附子中具有镇痛作用的c19二萜生物碱糖苷及其用途 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0248526B2 (ja) * | 1980-02-26 | 1990-10-25 | Murayama Keikichi | Shinkinakoenshozai |
| JPH085862B2 (ja) * | 1987-02-27 | 1996-01-24 | 三和生薬株式会社 | 新規なアコニチン系化合物およびそれらを有効成分とする鎮痛・抗炎症剤 |
| JPH085863B2 (ja) * | 1987-02-27 | 1996-01-24 | 三和生薬株式会社 | １４−アニソイルアコニンおよびそれを有効成分とする新規な鎮痛・抗炎症剤 |
| JPH085865B2 (ja) * | 1987-04-06 | 1996-01-24 | 三和生薬株式会社 | 新規なアコニチン系化合物およびそれらを有効成分とする鎮痛・抗炎症剤 |
| JPH085864B2 (ja) * | 1987-05-08 | 1996-01-24 | 三和生薬株式会社 | 新規なアコニチン系化合物およびそれらを有効成分とする鎮痛・抗炎症剤 |
| JPH01254625A (ja) * | 1988-04-05 | 1989-10-11 | Tsumura & Co | 抗アレルギー剤 |
| JP3037991B2 (ja) * | 1989-12-21 | 2000-05-08 | 三和生薬株式会社 | 新規なアコニチン系化合物および鎮痛・抗炎症剤 |
-
1991
- 1991-07-08 JP JP03263354A patent/JP3117251B2/ja not_active Expired - Lifetime
- 1991-09-27 US US07/989,018 patent/US5330983A/en not_active Expired - Lifetime
- 1991-09-27 EP EP91916949A patent/EP0547224B1/en not_active Expired - Lifetime
- 1991-09-27 DE DE69117519T patent/DE69117519T2/de not_active Expired - Lifetime
- 1991-09-27 WO PCT/JP1991/001298 patent/WO1993001175A1/ja not_active Ceased
-
1992
- 1992-07-04 CN CN92105347A patent/CN1070852C/zh not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100443083C (zh) * | 2005-03-25 | 2008-12-17 | 成都高新区智爽天然产物科技有限责任公司 | 乌头胺在制药中的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1068327A (zh) | 1993-01-27 |
| WO1993001175A1 (fr) | 1993-01-21 |
| EP0547224B1 (en) | 1996-02-28 |
| US5330983A (en) | 1994-07-19 |
| JP3117251B2 (ja) | 2000-12-11 |
| EP0547224A4 (cg-RX-API-DMAC7.html) | 1994-03-23 |
| DE69117519T2 (de) | 1996-07-11 |
| JPH0517448A (ja) | 1993-01-26 |
| DE69117519D1 (de) | 1996-04-04 |
| EP0547224A1 (en) | 1993-06-23 |
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