FI66857C - Foerfarande foer framstaellning av nya farmaceutiskt anvaendbara 3-substituerade dibensofuranderivat - Google Patents
Foerfarande foer framstaellning av nya farmaceutiskt anvaendbara 3-substituerade dibensofuranderivat Download PDFInfo
- Publication number
- FI66857C FI66857C FI750646A FI750646A FI66857C FI 66857 C FI66857 C FI 66857C FI 750646 A FI750646 A FI 750646A FI 750646 A FI750646 A FI 750646A FI 66857 C FI66857 C FI 66857C
- Authority
- FI
- Finland
- Prior art keywords
- formula
- chloro
- acid
- dibenzofuran
- acetic acid
- Prior art date
Links
- 239000003814 drug Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 58
- 238000002360 preparation method Methods 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 38
- -1 3-substituted dibenzofuran Chemical class 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 238000009835 boiling Methods 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 239000007858 starting material Substances 0.000 claims description 7
- 239000011593 sulfur Substances 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- QSPFQSQSKYWHRZ-UHFFFAOYSA-N 1-(8-chlorodibenzofuran-3-yl)ethanone Chemical compound CC(=O)C1=CC2=C(C=C1)C1=C(O2)C=CC(Cl)=C1 QSPFQSQSKYWHRZ-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 150000002825 nitriles Chemical class 0.000 claims description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 150000001412 amines Chemical class 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910000464 lead oxide Inorganic materials 0.000 claims description 3
- YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 claims description 3
- KWGCXQZMMAVJTB-UHFFFAOYSA-N 2-(8-chlorodibenzofuran-3-yl)propanoic acid Chemical compound C1=C(Cl)C=C2C3=CC=C(C(C(O)=O)C)C=C3OC2=C1 KWGCXQZMMAVJTB-UHFFFAOYSA-N 0.000 claims description 2
- AKCRQHGQIJBRMN-UHFFFAOYSA-N 2-chloroaniline Chemical compound NC1=CC=CC=C1Cl AKCRQHGQIJBRMN-UHFFFAOYSA-N 0.000 claims description 2
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- OKSYBDRWKMOWKY-UHFFFAOYSA-N 2-dibenzofuran-3-yl-2-oxoacetic acid Chemical compound OC(=O)C(=O)c1ccc2c(c1)oc1ccccc21 OKSYBDRWKMOWKY-UHFFFAOYSA-N 0.000 claims 1
- DNXUGBMARDFRGG-UHFFFAOYSA-N 3,6-dioxocyclohexa-1,4-diene-1,2-dicarbonitrile Chemical compound O=C1C=CC(=O)C(C#N)=C1C#N DNXUGBMARDFRGG-UHFFFAOYSA-N 0.000 claims 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 81
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
- 239000000243 solution Substances 0.000 description 72
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 65
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 60
- 239000000203 mixture Substances 0.000 description 53
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 229960000583 acetic acid Drugs 0.000 description 44
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
- 238000010992 reflux Methods 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- MVJQACPZNRHBAZ-UHFFFAOYSA-N 2-(8-chlorodibenzofuran-3-yl)acetic acid Chemical compound C1=C(Cl)C=C2C3=CC=C(CC(=O)O)C=C3OC2=C1 MVJQACPZNRHBAZ-UHFFFAOYSA-N 0.000 description 13
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 230000008961 swelling Effects 0.000 description 8
- 230000000202 analgesic effect Effects 0.000 description 7
- DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 238000001035 drying Methods 0.000 description 6
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 5
- 238000010533 azeotropic distillation Methods 0.000 description 5
- 125000004494 ethyl ester group Chemical group 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 235000019341 magnesium sulphate Nutrition 0.000 description 5
- GEEGRIYRQCBJLM-UHFFFAOYSA-N methyl 2-(8-chlorodibenzofuran-3-yl)acetate Chemical compound C1=C(Cl)C=C2C3=CC=C(CC(=O)OC)C=C3OC2=C1 GEEGRIYRQCBJLM-UHFFFAOYSA-N 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- QUSQGKXXRMYAAY-UHFFFAOYSA-N ethyl 2-(8-chloro-1,2,3,4-tetrahydrodibenzofuran-3-yl)acetate Chemical compound O1C2=CC=C(Cl)C=C2C2=C1CC(CC(=O)OCC)CC2 QUSQGKXXRMYAAY-UHFFFAOYSA-N 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- YHPWWRUAUKXKCB-UHFFFAOYSA-N methyl 2-(8-chlorodibenzofuran-3-yl)-2-oxoacetate Chemical compound ClC=1C=CC2=C(C3=C(O2)C=C(C=C3)C(C(=O)OC)=O)C1 YHPWWRUAUKXKCB-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 229920000137 polyphosphoric acid Polymers 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- ZIYOAMMZCMIUDK-UHFFFAOYSA-N ethyl 2-(3-bromo-4-oxocyclohexyl)acetate Chemical compound CCOC(=O)CC1CCC(=O)C(Br)C1 ZIYOAMMZCMIUDK-UHFFFAOYSA-N 0.000 description 3
- MRNYTIZAHZSCBD-UHFFFAOYSA-N ethyl 2-(3-bromo-4-oxocyclohexyl)propanoate Chemical compound CCOC(=O)C(C)C1CCC(=O)C(Br)C1 MRNYTIZAHZSCBD-UHFFFAOYSA-N 0.000 description 3
- BSLZJWORHMXDMN-UHFFFAOYSA-N ethyl 2-(8-chlorodibenzofuran-3-yl)acetate Chemical compound C1=C(Cl)C=C2C3=CC=C(CC(=O)OCC)C=C3OC2=C1 BSLZJWORHMXDMN-UHFFFAOYSA-N 0.000 description 3
- NECDXIMDUJJBDS-UHFFFAOYSA-N ethyl 2-[3-(4-chlorophenoxy)-4-oxocyclohexyl]acetate Chemical compound C1C(CC(=O)OCC)CCC(=O)C1OC1=CC=C(Cl)C=C1 NECDXIMDUJJBDS-UHFFFAOYSA-N 0.000 description 3
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- MKWRHVCICXQBJA-UHFFFAOYSA-N methyl 2-dibenzofuran-3-yl-2-oxoacetate Chemical compound C1=CC(=CC=2OC3=C(C21)C=CC=C3)C(C(=O)OC)=O MKWRHVCICXQBJA-UHFFFAOYSA-N 0.000 description 3
- FJYVIDBKISZAGH-UHFFFAOYSA-N methyl 2-oxo-2-(6,7,8,9-tetrahydrodibenzofuran-3-yl)acetate Chemical compound C1=CC(=CC=2OC3=C(C21)CCCC3)C(C(=O)OC)=O FJYVIDBKISZAGH-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000859 sublimation Methods 0.000 description 3
- 230000008022 sublimation Effects 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 2
- PWXYWLZWPWNUAY-UHFFFAOYSA-N 2-(8-chlorodibenzofuran-3-yl)acetamide Chemical compound C1=C(Cl)C=C2C3=CC=C(CC(=O)N)C=C3OC2=C1 PWXYWLZWPWNUAY-UHFFFAOYSA-N 0.000 description 2
- KGUAOPOMGRAOAB-UHFFFAOYSA-N 2-(dimethylamino)ethyl 2-(8-chlorodibenzofuran-3-yl)acetate;hydrochloride Chemical compound Cl.C1=C(Cl)C=C2C3=CC=C(CC(=O)OCCN(C)C)C=C3OC2=C1 KGUAOPOMGRAOAB-UHFFFAOYSA-N 0.000 description 2
- WQMAANNAZKNUDL-UHFFFAOYSA-N 2-dimethylaminoethyl chloride Chemical compound CN(C)CCCl WQMAANNAZKNUDL-UHFFFAOYSA-N 0.000 description 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- LJMSAUILRDVXCA-UHFFFAOYSA-N 2-methoxy-2-oxoacetic acid;hydrochloride Chemical compound Cl.COC(=O)C(O)=O LJMSAUILRDVXCA-UHFFFAOYSA-N 0.000 description 2
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- WCZIARVYDOMVCX-UHFFFAOYSA-N 8-chlorodibenzofuran-3-carbonyl chloride Chemical compound ClC=1C=CC2=C(C3=C(O2)C=C(C=C3)C(=O)Cl)C=1 WCZIARVYDOMVCX-UHFFFAOYSA-N 0.000 description 2
- WWNQLIFPLRYBNP-UHFFFAOYSA-N 8-chlorodibenzofuran-3-carboxylic acid Chemical group ClC=1C=CC2=C(C3=C(O2)C=C(C=C3)C(=O)O)C1 WWNQLIFPLRYBNP-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WJLCXQOEESZRPK-UHFFFAOYSA-N CC1=C(C=CC2=C1OC3=C2C=C(C=C3)Cl)CC(=O)O Chemical compound CC1=C(C=CC2=C1OC3=C2C=C(C=C3)Cl)CC(=O)O WJLCXQOEESZRPK-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000003356 anti-rheumatic effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- DNAPLNCLIFMNQY-UHFFFAOYSA-N diethyl 2-(8-chlorodibenzofuran-3-carbonyl)propanedioate Chemical compound C(C)OC(C(C(=O)OCC)C(=O)C=1C=CC2=C(OC3=C2C=C(C=C3)Cl)C1)=O DNAPLNCLIFMNQY-UHFFFAOYSA-N 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 2
- DMXCNZAFVCEWKL-UHFFFAOYSA-N ethyl 2-[3-(4-chlorophenoxy)-4-oxocyclohexyl]propanoate Chemical compound C1C(C(C)C(=O)OCC)CCC(=O)C1OC1=CC=C(Cl)C=C1 DMXCNZAFVCEWKL-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 230000002140 halogenating effect Effects 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- LREHXNMBUBVFHA-UHFFFAOYSA-N 1,2,3,4-tetrahydrodibenzofuran Chemical compound O1C2=CC=CC=C2C2=C1CCCC2 LREHXNMBUBVFHA-UHFFFAOYSA-N 0.000 description 1
- QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- HOWYULDSABKYGR-UHFFFAOYSA-N 2-(1-methyldibenzofuran-3-yl)acetic acid Chemical compound O1C2=CC=CC=C2C2=C1C=C(CC(O)=O)C=C2C HOWYULDSABKYGR-UHFFFAOYSA-N 0.000 description 1
- KJNBXCPVUPRFSZ-UHFFFAOYSA-N 2-(8-chlorodibenzofuran-3-yl)acetonitrile Chemical compound N#CCC1=CC=C2C3=CC(Cl)=CC=C3OC2=C1 KJNBXCPVUPRFSZ-UHFFFAOYSA-N 0.000 description 1
- CUQSPIQQVXMDLH-UHFFFAOYSA-N 2-(8-fluorodibenzofuran-3-yl)acetic acid Chemical class C1=C(F)C=C2C3=CC=C(CC(=O)O)C=C3OC2=C1 CUQSPIQQVXMDLH-UHFFFAOYSA-N 0.000 description 1
- UUUYAVXPERPSAI-UHFFFAOYSA-N 2-(furan-3-yl)acetic acid Chemical compound OC(=O)CC=1C=COC=1 UUUYAVXPERPSAI-UHFFFAOYSA-N 0.000 description 1
- DOGYSAWVOSELAN-UHFFFAOYSA-N 2-dibenzofuran-2-ylacetic acid Chemical class C1=CC=C2C3=CC(CC(=O)O)=CC=C3OC2=C1 DOGYSAWVOSELAN-UHFFFAOYSA-N 0.000 description 1
- PVQCXOIBLHYLNV-UHFFFAOYSA-N 2-dibenzofuran-3-ylacetic acid Chemical compound C1=CC=C2C3=CC=C(CC(=O)O)C=C3OC2=C1 PVQCXOIBLHYLNV-UHFFFAOYSA-N 0.000 description 1
- LQLJZSJKRYTKTP-UHFFFAOYSA-N 2-dimethylaminoethyl chloride hydrochloride Chemical compound Cl.CN(C)CCCl LQLJZSJKRYTKTP-UHFFFAOYSA-N 0.000 description 1
- VRGCYEIGVVTZCC-UHFFFAOYSA-N 3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione Chemical compound ClC1=C(Cl)C(=O)C(=O)C(Cl)=C1Cl VRGCYEIGVVTZCC-UHFFFAOYSA-N 0.000 description 1
- WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
- RHMPLDJJXGPMEX-UHFFFAOYSA-N 4-fluorophenol Chemical compound OC1=CC=C(F)C=C1 RHMPLDJJXGPMEX-UHFFFAOYSA-N 0.000 description 1
- HQGMHBDFAHXWNY-UHFFFAOYSA-N 8-bromodibenzofuran-3-carboxylic acid Chemical compound C1=C(Br)C=C2C3=CC=C(C(=O)O)C=C3OC2=C1 HQGMHBDFAHXWNY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WKGHHMBVWQUEEL-UHFFFAOYSA-N C1=CC=C2C(=C1)C3=C(O2)C=C(C=C3)OC(=O)C=O Chemical compound C1=CC=C2C(=C1)C3=C(O2)C=C(C=C3)OC(=O)C=O WKGHHMBVWQUEEL-UHFFFAOYSA-N 0.000 description 1
- MGABRVBZGQFDAJ-UHFFFAOYSA-N C1C=C2C3=CC=CC=C3OC2=CC1(C(=O)Cl)Cl Chemical compound C1C=C2C3=CC=CC=C3OC2=CC1(C(=O)Cl)Cl MGABRVBZGQFDAJ-UHFFFAOYSA-N 0.000 description 1
- AFJIVKSIZODFDM-UHFFFAOYSA-N CCOC(=O)C(C)(C)C1=C2C(=CC=C1)OC3=C2C=C(C=C3)Cl Chemical compound CCOC(=O)C(C)(C)C1=C2C(=CC=C1)OC3=C2C=C(C=C3)Cl AFJIVKSIZODFDM-UHFFFAOYSA-N 0.000 description 1
- HPWWEGGBPXINDE-UHFFFAOYSA-N CCOC(=O)CC1=C(C=CC2=C1C3=CC=CC=C3O2)C Chemical compound CCOC(=O)CC1=C(C=CC2=C1C3=CC=CC=C3O2)C HPWWEGGBPXINDE-UHFFFAOYSA-N 0.000 description 1
- HPQCRJQTJQHBGM-UHFFFAOYSA-N CCOC(=O)CC1=CC2=C(C(=C1)C)C3=C(O2)C=CC(=C3)OF Chemical compound CCOC(=O)CC1=CC2=C(C(=C1)C)C3=C(O2)C=CC(=C3)OF HPQCRJQTJQHBGM-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 150000000994 L-ascorbates Chemical class 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 101100290429 Mus musculus Mcm3 gene Proteins 0.000 description 1
- 241000186359 Mycobacterium Species 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- UEUWUINNHVBBPS-UHFFFAOYSA-N OC(CC(C=C1)=CC2=C1C(C=C(CCl)C=C1)=C1O2)=O Chemical compound OC(CC(C=C1)=CC2=C1C(C=C(CCl)C=C1)=C1O2)=O UEUWUINNHVBBPS-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- ZLMJMSJWJFRBEC-LZFNBGRKSA-N Potassium-45 Chemical compound [45K] ZLMJMSJWJFRBEC-LZFNBGRKSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 239000004133 Sodium thiosulphate Substances 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 238000005672 Willgerodt-Kindler rearrangement reaction Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- FKCBLVCOSCZFHV-UHFFFAOYSA-N acetonitrile;ethanol Chemical compound CCO.CC#N FKCBLVCOSCZFHV-UHFFFAOYSA-N 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000002579 anti-swelling effect Effects 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000005228 aryl sulfonate group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000012320 chlorinating reagent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- QBKFLYWZRMHHRS-UHFFFAOYSA-N chloroform;1,4-dioxane Chemical compound ClC(Cl)Cl.C1COCCO1 QBKFLYWZRMHHRS-UHFFFAOYSA-N 0.000 description 1
- QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- GCIDAUVMQWKJLE-UHFFFAOYSA-N cyclohexane;1,4-dioxane Chemical compound C1CCCCC1.C1COCCO1 GCIDAUVMQWKJLE-UHFFFAOYSA-N 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 150000004826 dibenzofurans Chemical class 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 1
- XHNJFNLTFMAPQB-UHFFFAOYSA-N ethyl 2-(4-oxocyclohexyl)acetate Chemical compound CCOC(=O)CC1CCC(=O)CC1 XHNJFNLTFMAPQB-UHFFFAOYSA-N 0.000 description 1
- RRUJMJLHOSVNCM-UHFFFAOYSA-N ethyl 2-(4-oxocyclohexyl)propanoate Chemical compound CCOC(=O)C(C)C1CCC(=O)CC1 RRUJMJLHOSVNCM-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005496 eutectics Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000010729 leg swelling Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 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 1
- 239000000376 reactant Substances 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- FENGEGUDMXHOBU-UHFFFAOYSA-M sodium;4-fluorophenolate Chemical compound [Na+].[O-]C1=CC=C(F)C=C1 FENGEGUDMXHOBU-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- 230000001562 ulcerogenic effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
-
- 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)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US44885374A | 1974-03-07 | 1974-03-07 | |
| US44885374 | 1974-03-07 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI750646A7 FI750646A7 (en, 2012) | 1975-09-08 |
| FI66857B FI66857B (fi) | 1984-08-31 |
| FI66857C true FI66857C (fi) | 1984-12-10 |
Family
ID=23781916
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI750646A FI66857C (fi) | 1974-03-07 | 1975-03-06 | Foerfarande foer framstaellning av nya farmaceutiskt anvaendbara 3-substituerade dibensofuranderivat |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US4022805A (en, 2012) |
| JP (1) | JPS5910356B2 (en, 2012) |
| AR (1) | AR223797A1 (en, 2012) |
| AT (4) | AT353257B (en, 2012) |
| AU (1) | AU500749B2 (en, 2012) |
| BE (1) | BE826345A (en, 2012) |
| BR (1) | BR7501324A (en, 2012) |
| CA (1) | CA1041106A (en, 2012) |
| CH (1) | CH618165A5 (en, 2012) |
| CU (1) | CU34216A (en, 2012) |
| DD (1) | DD118424A5 (en, 2012) |
| DE (1) | DE2510001A1 (en, 2012) |
| DK (1) | DK143133C (en, 2012) |
| ES (1) | ES435341A1 (en, 2012) |
| FI (1) | FI66857C (en, 2012) |
| FR (1) | FR2262979B1 (en, 2012) |
| GB (1) | GB1471847A (en, 2012) |
| HK (1) | HK19680A (en, 2012) |
| IE (1) | IE40760B1 (en, 2012) |
| IL (1) | IL46729A (en, 2012) |
| KE (1) | KE3036A (en, 2012) |
| LU (1) | LU71971A1 (en, 2012) |
| MY (1) | MY8100033A (en, 2012) |
| NL (1) | NL7502477A (en, 2012) |
| NO (1) | NO143664C (en, 2012) |
| PH (1) | PH13826A (en, 2012) |
| SE (1) | SE419646B (en, 2012) |
| YU (2) | YU39465B (en, 2012) |
| ZA (1) | ZA751101B (en, 2012) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4102816A (en) * | 1976-10-18 | 1978-07-25 | The United States Of America As Represented By The Secretary Of The Interior | Adsorbent for polynuclear aromatic compounds |
| US4501908A (en) * | 1981-03-12 | 1985-02-26 | Hoffmann-La Roche Inc. | 2,3-Isopropylidene ribonic acid, 1,4-lactones |
| JPS6115350U (ja) * | 1984-06-28 | 1986-01-29 | 日本鋪道株式会社 | 掘削装置のバケツト装置 |
| EG17620A (en) * | 1984-11-15 | 1990-10-30 | Wellcome Found | A process for the preparation of polycyclic biocidal compounds their preparation and formulations containing them |
| GB8428930D0 (en) * | 1984-11-15 | 1984-12-27 | Wellcome Found | Polycyclic biocidal compounds |
| JPS645951U (en, 2012) * | 1987-06-26 | 1989-01-13 | ||
| US5019573A (en) * | 1989-09-19 | 1991-05-28 | Euroceltique, S.A. | Substituted dibenzofurans and methods of using same |
| US7601856B2 (en) | 2006-07-27 | 2009-10-13 | Wyeth | Benzofurans as potassium ion channel modulators |
| US7662831B2 (en) | 2006-07-27 | 2010-02-16 | Wyeth Llc | Tetracyclic indoles as potassium channel modulators |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH532629A (de) | 1969-12-17 | 1973-01-15 | Ciba Geigy Ag | Verfahren zum optischen Aufhellen mit neuen Bis-aroxazolyl-Verbindungen |
| US3803180A (en) * | 1971-03-26 | 1974-04-09 | L Berger | Tricyclic compounds |
| NL7305520A (en, 2012) * | 1972-05-13 | 1973-11-15 |
-
1975
- 1975-02-10 US US05/548,658 patent/US4022805A/en not_active Expired - Lifetime
- 1975-02-17 CH CH195675A patent/CH618165A5/de not_active IP Right Cessation
- 1975-02-21 ZA ZA00751101A patent/ZA751101B/xx unknown
- 1975-02-28 IL IL46729A patent/IL46729A/xx unknown
- 1975-02-28 CA CA220,990A patent/CA1041106A/en not_active Expired
- 1975-03-01 CU CU34216A patent/CU34216A/es unknown
- 1975-03-03 PH PH16854A patent/PH13826A/en unknown
- 1975-03-03 YU YU499/75A patent/YU39465B/xx unknown
- 1975-03-03 AU AU78737/75A patent/AU500749B2/en not_active Expired
- 1975-03-03 NL NL7502477A patent/NL7502477A/xx not_active Application Discontinuation
- 1975-03-05 DD DD184587A patent/DD118424A5/xx unknown
- 1975-03-05 LU LU71971A patent/LU71971A1/xx unknown
- 1975-03-05 SE SE7502468A patent/SE419646B/xx unknown
- 1975-03-05 JP JP50026124A patent/JPS5910356B2/ja not_active Expired
- 1975-03-05 FR FR7506848A patent/FR2262979B1/fr not_active Expired
- 1975-03-06 IE IE490/75A patent/IE40760B1/xx unknown
- 1975-03-06 BR BR1324/75A patent/BR7501324A/pt unknown
- 1975-03-06 FI FI750646A patent/FI66857C/fi not_active IP Right Cessation
- 1975-03-06 ES ES435341A patent/ES435341A1/es not_active Expired
- 1975-03-06 AR AR257869A patent/AR223797A1/es active
- 1975-03-06 BE BE154047A patent/BE826345A/xx not_active IP Right Cessation
- 1975-03-06 GB GB938075A patent/GB1471847A/en not_active Expired
- 1975-03-06 DK DK91375A patent/DK143133C/da not_active IP Right Cessation
- 1975-03-06 NO NO750746A patent/NO143664C/no unknown
- 1975-03-06 AT AT173175A patent/AT353257B/de not_active IP Right Cessation
- 1975-03-07 DE DE19752510001 patent/DE2510001A1/de not_active Ceased
-
1978
- 1978-04-07 US US05/894,282 patent/US4192809A/en not_active Expired - Lifetime
- 1978-07-14 AT AT513478A patent/AT356099B/de not_active IP Right Cessation
- 1978-07-14 AT AT513278A patent/AT356097B/de not_active IP Right Cessation
- 1978-07-14 AT AT513378A patent/AT356098B/de not_active IP Right Cessation
-
1980
- 1980-03-19 KE KE3036A patent/KE3036A/xx unknown
- 1980-04-10 HK HK196/80A patent/HK19680A/xx unknown
-
1981
- 1981-04-10 YU YU00934/81A patent/YU93481A/xx unknown
- 1981-12-30 MY MY33/81A patent/MY8100033A/xx unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR900007780B1 (ko) | 축합된 피롤리논 유도체의 제조방법 | |
| US3420851A (en) | Novel dibenzoxepines | |
| US4148897A (en) | 1,2-Dihydronaphthalene derivatives and pharmaceutical composition | |
| CS241015B2 (en) | Method of 2-benzyl-1,2-dihydro-1-oxophthalazine-4-ylacetic acid's derivatives production | |
| US4188486A (en) | 2-Substituted benzimidazole compounds | |
| FI66857B (fi) | Foerfarande foer framstaellning av nya farmaceutiskt anvaendbara 3-substituerade dibensofuranderivat | |
| PL119501B1 (en) | Process for manufacturing novel,condensed pyrimidine derivatives pirimidina | |
| US4092325A (en) | 5,6-Dihydro-4-oxo-4H-thieno[2,3-b]thiopyran-5-carboxamides, and process for the preparation thereof | |
| US4192880A (en) | 2-Substituted benzimidazole compounds | |
| US4356186A (en) | Acetic acid derivatives and composition containing the same | |
| US4222944A (en) | Halo-3-dibenzofuran alkanonitriles | |
| US4219657A (en) | Dibenzothiophenes | |
| JPH01319479A (ja) | ５―アミノメチル―２―フラノメタノールの新規な誘導体、その製造及び使用 | |
| US4353923A (en) | Pharmaceutical composition containing a benzofurancarboxamide derivative as the active ingredient | |
| CA1104144A (en) | Dibenzothiophenes derivatives | |
| JPH0710863B2 (ja) | エーテル化若しくはエステル化しうるジヒドロキシ基により位置２で置換された４―ｏｈキノリンカルボン酸の新規の誘導体、その製造方法、及び医薬としてのその使用 | |
| RU2090559C1 (ru) | Рацемические или оптически активные производные изохинолина, способ их получения, фармацевтическая композиция на их основе и способ получения фармацевтической композиции | |
| US4334078A (en) | Dibenzothiophenes | |
| US4097497A (en) | Amides of 2-(3-dibenzofuran) alkanoic acids | |
| IL34468A (en) | Acidic salt salts of the history of indonopyridine, their preparation and pharmaceutical preparations containing them | |
| EP0036773B1 (en) | 2,3-dihydrobenzofurans, process for their preparation and pharmaceutical compositions containing them | |
| KR790001069B1 (ko) | 피리도 벤조디아제피논류의 제조방법 | |
| CA1189078A (en) | Process for producing 4-oximino-1,2,3,4- tetrahydroquinoline derivatives and said derivatives produced thereby | |
| NO147561B (no) | Analogifremgangsmaater for fremstilling av 6,11-dihydro-11-oksodibenz(b,e)oksepinalkan-syrer, estere og salter derav | |
| US3989689A (en) | 4-Carbamoyl-1-benzazepines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed |
Owner name: F. HOFFMANN-LA ROCHE & CO. AG |