CS329691A3 - Synergistic agent - Google Patents
Synergistic agent Download PDFInfo
- Publication number
- CS329691A3 CS329691A3 CS913296A CS329691A CS329691A3 CS 329691 A3 CS329691 A3 CS 329691A3 CS 913296 A CS913296 A CS 913296A CS 329691 A CS329691 A CS 329691A CS 329691 A3 CS329691 A3 CS 329691A3
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- methyl
- fluoro
- methoxy
- oxo
- phenyl
- Prior art date
Links
- 239000012747 synergistic agent Substances 0.000 title claims description 9
- 239000000203 mixture Substances 0.000 claims description 107
- 239000003112 inhibitor Substances 0.000 claims description 42
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 35
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 35
- 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 claims description 34
- -1 4-methyl-3-oxo-2,3-dihydro-4H- 1,4-benzoxazin-7-ylthio Chemical group 0.000 claims description 33
- 230000002195 synergetic effect Effects 0.000 claims description 30
- 230000002757 inflammatory effect Effects 0.000 claims description 25
- 239000000867 Lipoxygenase Inhibitor Substances 0.000 claims description 24
- 229940124125 5 Lipoxygenase inhibitor Drugs 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 21
- 230000002917 arthritic effect Effects 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 229960000905 indomethacin Drugs 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 229960001259 diclofenac Drugs 0.000 claims description 13
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 229960002390 flurbiprofen Drugs 0.000 claims description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- HLDFFDCGHUCLMU-UHFFFAOYSA-N 6-[3-fluoro-5-(4-methoxyoxan-4-yl)phenyl]sulfanyl-1-methyl-3,4-dihydroquinolin-2-one Chemical compound C=1C(F)=CC(SC=2C=C3CCC(=O)N(C)C3=CC=2)=CC=1C1(OC)CCOCC1 HLDFFDCGHUCLMU-UHFFFAOYSA-N 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- KISROBRRFKHWAD-UHFFFAOYSA-N 6-[5-(4-methoxyoxan-4-yl)thiophen-2-yl]sulfanyl-1-methyl-3,4-dihydroquinolin-2-one Chemical compound C=1C=C(SC=2C=C3CCC(=O)N(C)C3=CC=2)SC=1C1(OC)CCOCC1 KISROBRRFKHWAD-UHFFFAOYSA-N 0.000 claims description 4
- OPHGQYRYTLTLFC-UHFFFAOYSA-N 4-[3-[4-[difluoro-(4-fluorophenyl)methyl]phenyl]sulfanyl-5-fluorophenyl]-4-methoxyoxane Chemical compound C=1C(F)=CC(SC=2C=CC(=CC=2)C(F)(F)C=2C=CC(F)=CC=2)=CC=1C1(OC)CCOCC1 OPHGQYRYTLTLFC-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- SLZBEPLWGGRZAY-UHFFFAOYSA-N 6-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]-1-methylquinolin-2-one Chemical compound C=1C(F)=CC(OCC=2C=C3C=CC(=O)N(C)C3=CC=2)=CC=1C1(OC)CCOCC1 SLZBEPLWGGRZAY-UHFFFAOYSA-N 0.000 claims description 2
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 3
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 claims 1
- 229940121363 anti-inflammatory agent Drugs 0.000 claims 1
- 239000002260 anti-inflammatory agent Substances 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 49
- 239000000243 solution Substances 0.000 description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 150000001875 compounds Chemical class 0.000 description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000004480 active ingredient Substances 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- 102100022364 Polyunsaturated fatty acid 5-lipoxygenase Human genes 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 16
- 101710156627 Polyunsaturated fatty acid 5-lipoxygenase Proteins 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 14
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000007858 starting material Substances 0.000 description 11
- 239000003480 eluent Substances 0.000 description 10
- 239000012267 brine Substances 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 238000004440 column chromatography Methods 0.000 description 8
- 150000002617 leukotrienes Chemical class 0.000 description 8
- 235000019359 magnesium stearate Nutrition 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- 229940114079 arachidonic acid Drugs 0.000 description 6
- 235000021342 arachidonic acid Nutrition 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000002411 adverse Effects 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 210000005069 ears Anatomy 0.000 description 4
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- CMLFRMDBDNHMRA-UHFFFAOYSA-N 2h-1,2-benzoxazine Chemical compound C1=CC=C2C=CNOC2=C1 CMLFRMDBDNHMRA-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 3
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 230000002456 anti-arthritic effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- XFEBRUWAGDHHFT-UHFFFAOYSA-N (4-fluorophenyl)-(4-iodophenyl)methanone Chemical compound C1=CC(F)=CC=C1C(=O)C1=CC=C(I)C=C1 XFEBRUWAGDHHFT-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 2
- QYEMNJMSULGQRD-UHFFFAOYSA-N 1-methyl-2-quinolone Chemical compound C1=CC=C2C=CC(=O)N(C)C2=C1 QYEMNJMSULGQRD-UHFFFAOYSA-N 0.000 description 2
- DASYEPCWJXEIDF-UHFFFAOYSA-N 1-methyl-6-[(1-methyl-2-oxo-3,4-dihydroquinolin-6-yl)disulfanyl]-3,4-dihydroquinolin-2-one Chemical compound CN1C(=O)CCC2=CC(SSC=3C=C4CCC(=O)N(C4=CC=3)C)=CC=C21 DASYEPCWJXEIDF-UHFFFAOYSA-N 0.000 description 2
- NYCDFHQOYLMAGZ-UHFFFAOYSA-N 1-methyl-6-sulfanyl-3,4-dihydroquinolin-2-one Chemical compound SC1=CC=C2N(C)C(=O)CCC2=C1 NYCDFHQOYLMAGZ-UHFFFAOYSA-N 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- WLJXULCDIKXOGT-UHFFFAOYSA-N 3-fluoro-5-(4-methoxyoxan-4-yl)benzenethiol Chemical compound C=1C(F)=CC(S)=CC=1C1(OC)CCOCC1 WLJXULCDIKXOGT-UHFFFAOYSA-N 0.000 description 2
- HEABCAMWOVYMHZ-UHFFFAOYSA-N 4-(3,5-difluorophenyl)-4-methoxyoxane Chemical compound C=1C(F)=CC(F)=CC=1C1(OC)CCOCC1 HEABCAMWOVYMHZ-UHFFFAOYSA-N 0.000 description 2
- OTPOPGAXHKBKDO-UHFFFAOYSA-N 4-(5-bromothiophen-2-yl)-4-methoxyoxane Chemical compound C=1C=C(Br)SC=1C1(OC)CCOCC1 OTPOPGAXHKBKDO-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 235000019759 Maize starch Nutrition 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000004795 grignard reagents Chemical class 0.000 description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 2
- 229960001680 ibuprofen Drugs 0.000 description 2
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- 239000011777 magnesium Substances 0.000 description 2
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- 238000002844 melting Methods 0.000 description 2
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- 239000007922 nasal spray Substances 0.000 description 2
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- JMJRYTGVHCAYCT-UHFFFAOYSA-N oxan-4-one Chemical compound O=C1CCOCC1 JMJRYTGVHCAYCT-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
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- 230000008569 process Effects 0.000 description 2
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- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
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- 229940083466 soybean lecithin Drugs 0.000 description 2
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- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
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- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 2
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
- 229940029284 trichlorofluoromethane Drugs 0.000 description 2
- CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- VYMPLPIFKRHAAC-UHFFFAOYSA-N 1,2-ethanedithiol Chemical compound SCCS VYMPLPIFKRHAAC-UHFFFAOYSA-N 0.000 description 1
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
- SMXMJQPIBZFCEK-UHFFFAOYSA-N 1,3-dimethylquinolin-2-one Chemical compound C1=CC=C2N(C)C(=O)C(C)=CC2=C1 SMXMJQPIBZFCEK-UHFFFAOYSA-N 0.000 description 1
- IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
- LFMWZTSOMGDDJU-UHFFFAOYSA-N 1,4-diiodobenzene Chemical compound IC1=CC=C(I)C=C1 LFMWZTSOMGDDJU-UHFFFAOYSA-N 0.000 description 1
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- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP90403144 | 1990-11-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS329691A3 true CS329691A3 (en) | 1992-05-13 |
Family
ID=8205772
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS913296A CS329691A3 (en) | 1990-11-06 | 1991-10-30 | Synergistic agent |
Country Status (12)
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994029297A1 (en) * | 1993-06-07 | 1994-12-22 | Zeneca Limited | 2-oxo-1,2,3,4-tetrahydroquinoline derivatives |
| IL110280A0 (en) * | 1993-07-27 | 1994-10-21 | Zeneca Ltd | Thiazole derivatives |
| EP0636624A1 (en) * | 1993-07-27 | 1995-02-01 | Zeneca Limited | Thiazole derivatives as lipoxygenase inhibitors |
| ZA945250B (en) * | 1993-07-27 | 1995-01-27 | Zeneca Ltd | Thiazole derivatives |
| US5643933A (en) * | 1995-06-02 | 1997-07-01 | G. D. Searle & Co. | Substituted sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors |
| EP0833622B8 (en) * | 1995-06-12 | 2005-10-12 | G.D. Searle & Co. | Compositions comprising a cyclooxygenase-2 inhibitor and a 5-lipoxygenase inhibitor |
| CA2224563A1 (en) | 1995-06-12 | 1996-12-27 | G.D. Searle & Co. | Combination of a cyclooxygenase-2 inhibitor and a leukotriene b4 receptor antagonist for the treatment of inflammations |
| US5700816A (en) * | 1995-06-12 | 1997-12-23 | Isakson; Peter C. | Treatment of inflammation and inflammation-related disorders with a combination of a cyclooxygenase-2 inhibitor and a leukotriene A4 hydrolase inhibitor |
| DK0880363T3 (da) | 1996-02-13 | 2003-01-20 | Searle & Co | Kombinationer der omfatter en cyclooxygenase-2 hæmmer samt en leukotrien A4 hydrolasehæmmer, som har immunsuppressive virkninger |
| ATE296114T1 (de) | 1996-02-13 | 2005-06-15 | Searle & Co | Zubereitungen, enthaltend einen cyclooxygenase-2- inhibitor und einen leukotrien-b4-rezeptor- antagonisten |
| DE69709069T2 (de) | 1996-02-13 | 2002-07-04 | G.D. Searle & Co., Chicago | Zusammensetzungen mit immunosuppressiven wirkungen, welche 5-lipoxygenase-inhibitoren und cyclooxygenase-2-inhibitoren enthalten |
| US6087446A (en) * | 1996-03-20 | 2000-07-11 | Hercules Incorporated | Masterbatch formulations for polyolefin applications |
| US6677364B2 (en) | 1998-04-20 | 2004-01-13 | G.D. Searle & Co. | Substituted sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors |
| EP0891772A3 (en) * | 1997-06-18 | 1999-05-19 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for rheumatic disease comprising nonsteroidal anti-inflamatory drug and phenylpropionic acid derivative |
| EP1385835A1 (en) | 2001-04-23 | 2004-02-04 | Astrazeneca AB | Benzoxazinone derivatives for use in the treatment of angiogenesis |
| US7294118B2 (en) | 2001-10-24 | 2007-11-13 | Becton, Dickinson And Company | Retractable needle assembly |
| US8377906B2 (en) | 2004-06-04 | 2013-02-19 | Ethicon, Inc. | Compositions and methods for preventing or reducing postoperative ileus and gastric stasis |
| US8129359B2 (en) | 2004-06-04 | 2012-03-06 | Ethicon, Inc. | Composition and method for treating post-surgical pain |
| GB0513058D0 (en) * | 2005-06-27 | 2005-08-03 | Sandoz Ag | Organic compounds |
| EP2335703B1 (en) | 2006-06-13 | 2014-09-24 | Ethicon, Incorporated | Compositions and methods for preventing or reducing postoperative ileus and gastric stasis in mammals |
| CN113943294A (zh) * | 2020-07-15 | 2022-01-18 | 成都海博为药业有限公司 | 一种作为btk抑制剂的化合物及其制备方法与用途 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8006488A (nl) * | 1979-12-19 | 1981-07-16 | Upjohn Co | Werkwijze voor het bereiden van arylpropionzuren. |
| IE70521B1 (en) * | 1989-02-28 | 1996-12-11 | Zeneca Pharma Sa | Heterocycles with inhibitory activity of 5-lipoxygenase |
| GB9018134D0 (en) * | 1989-09-29 | 1990-10-03 | Ici Plc | Heterocyclic derivatives |
| AU637500B2 (en) * | 1990-06-21 | 1993-05-27 | Zeneca Limited | Bicyclic heterocyclic compounds |
-
1991
- 1991-10-17 IE IE365591A patent/IE913655A1/en not_active Application Discontinuation
- 1991-10-18 IL IL99792A patent/IL99792A0/xx unknown
- 1991-10-21 ZA ZA918387A patent/ZA918387B/xx unknown
- 1991-10-21 NZ NZ240297A patent/NZ240297A/xx unknown
- 1991-10-22 AU AU86049/91A patent/AU649729B2/en not_active Ceased
- 1991-10-28 CA CA002054312A patent/CA2054312A1/en not_active Abandoned
- 1991-10-30 CS CS913296A patent/CS329691A3/cs unknown
- 1991-10-31 EP EP19910310059 patent/EP0485111A3/en not_active Withdrawn
- 1991-11-05 PT PT99426A patent/PT99426A/pt not_active Application Discontinuation
- 1991-11-05 KR KR1019910019567A patent/KR920009396A/ko not_active Withdrawn
- 1991-11-06 JP JP3289610A patent/JPH04264028A/ja active Pending
- 1991-11-07 TW TW080108799A patent/TW216772B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| IE913655A1 (en) | 1992-05-22 |
| TW216772B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1993-12-01 |
| IL99792A0 (en) | 1992-08-18 |
| NZ240297A (en) | 1993-11-25 |
| EP0485111A3 (en) | 1993-08-18 |
| AU649729B2 (en) | 1994-06-02 |
| JPH04264028A (ja) | 1992-09-18 |
| PT99426A (pt) | 1992-09-30 |
| AU8604991A (en) | 1992-05-14 |
| KR920009396A (ko) | 1992-06-25 |
| CA2054312A1 (en) | 1992-05-07 |
| EP0485111A2 (en) | 1992-05-13 |
| ZA918387B (en) | 1992-07-29 |
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