CS256392B2 - Method of phenylnonatetronic acids' derivatives production - Google Patents
Method of phenylnonatetronic acids' derivatives production Download PDFInfo
- Publication number
- CS256392B2 CS256392B2 CS855502A CS550285A CS256392B2 CS 256392 B2 CS256392 B2 CS 256392B2 CS 855502 A CS855502 A CS 855502A CS 550285 A CS550285 A CS 550285A CS 256392 B2 CS256392 B2 CS 256392B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- formula
- compound
- dimethyl
- phenyl
- nonatetraenoic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 63
- 239000002253 acid Substances 0.000 title claims description 32
- 150000007513 acids Chemical class 0.000 title description 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 279
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 57
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 26
- 239000001257 hydrogen Substances 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 20
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000000460 chlorine Substances 0.000 claims abstract description 15
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000011737 fluorine Substances 0.000 claims abstract description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 8
- -1 C1-C7alkyl Substances 0.000 claims description 77
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- 230000008569 process Effects 0.000 claims description 19
- 125000006611 nonyloxy group Chemical group 0.000 claims description 18
- 239000007858 starting material Substances 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 150000005840 aryl radicals Chemical class 0.000 claims description 2
- UZFRFMNFZWPLJT-DKGVNMKNSA-N (2E,4E,6E,8E)-9-(2-hexoxyphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCOC1=CC=CC=C1\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O UZFRFMNFZWPLJT-DKGVNMKNSA-N 0.000 claims 1
- YICSHLQWGQTKJL-UHFFFAOYSA-N 3,7-dimethyl-9-(2-nonoxyphenyl)nona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCCCCOC1=CC=CC=C1C=CC(C)=CC=CC(C)=CC(O)=O YICSHLQWGQTKJL-UHFFFAOYSA-N 0.000 claims 1
- VEMBLQMUWMQEJD-UHFFFAOYSA-N 3,7-dimethyl-9-(2-octoxyphenyl)nona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCCCOC1=CC=CC=C1C=CC(C)=CC=CC(C)=CC(O)=O VEMBLQMUWMQEJD-UHFFFAOYSA-N 0.000 claims 1
- XKQUQOQZGQFYOQ-UHFFFAOYSA-N 3,7-dimethyl-9-[2-(octoxymethyl)phenyl]nona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCCCOCC1=CC=CC=C1C=CC(C)=CC=CC(C)=CC(O)=O XKQUQOQZGQFYOQ-UHFFFAOYSA-N 0.000 claims 1
- ZMCHGPDTBOPAEG-UHFFFAOYSA-N 9-(2-chloro-6-nonoxyphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCCCCOC1=CC=CC(Cl)=C1C=CC(C)=CC=CC(C)=CC(O)=O ZMCHGPDTBOPAEG-UHFFFAOYSA-N 0.000 claims 1
- IQSXZBAQHVTNTH-UHFFFAOYSA-N 9-(2-decylphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCCCCCC1=CC=CC=C1C=CC(C)=CC=CC(C)=CC(O)=O IQSXZBAQHVTNTH-UHFFFAOYSA-N 0.000 claims 1
- RZAXMOHRXZROOM-UHFFFAOYSA-N 9-(5-methoxy-2-nonoxyphenyl)-3,7-dimethylnona-2,4,6,8-tetraenoic acid Chemical compound CCCCCCCCCOC1=CC=C(OC)C=C1C=CC(C)=CC=CC(C)=CC(O)=O RZAXMOHRXZROOM-UHFFFAOYSA-N 0.000 claims 1
- BTHCCRXBAMFUMC-UHFFFAOYSA-N C=CC=CC=CC=C(C(=O)O)C1=CC=CC=C1 Chemical class C=CC=CC=CC=C(C(=O)O)C1=CC=CC=C1 BTHCCRXBAMFUMC-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- DKNKBOCAZHQHQF-UHFFFAOYSA-N ethyl 3,7-dimethyl-9-[2-(octylamino)phenyl]nona-2,4,6,8-tetraenoate Chemical compound CCCCCCCCNC1=CC=CC=C1C=CC(C)=CC=CC(C)=CC(=O)OCC DKNKBOCAZHQHQF-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 abstract description 5
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 168
- 238000006243 chemical reaction Methods 0.000 description 143
- 239000000203 mixture Substances 0.000 description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 55
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 49
- 241000700159 Rattus Species 0.000 description 38
- 239000000243 solution Substances 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- CMSYDJVRTHCWFP-UHFFFAOYSA-N triphenylphosphane;hydrobromide Chemical compound Br.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CMSYDJVRTHCWFP-UHFFFAOYSA-N 0.000 description 33
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 26
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- 238000012360 testing method Methods 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000463 material Substances 0.000 description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
- 210000002683 foot Anatomy 0.000 description 22
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 22
- 229940126062 Compound A Drugs 0.000 description 21
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 21
- 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 21
- 230000007062 hydrolysis Effects 0.000 description 21
- 238000006460 hydrolysis reaction Methods 0.000 description 21
- 239000002671 adjuvant Substances 0.000 description 18
- 125000001033 ether group Chemical group 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 238000002425 crystallisation Methods 0.000 description 15
- 230000008025 crystallization Effects 0.000 description 15
- 206010003246 arthritis Diseases 0.000 description 13
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- 125000004185 ester group Chemical class 0.000 description 13
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- 239000000126 substance Substances 0.000 description 12
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 11
- 230000037396 body weight Effects 0.000 description 11
- 235000019359 magnesium stearate Nutrition 0.000 description 11
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
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- 238000010171 animal model Methods 0.000 description 10
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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- 239000000725 suspension Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
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- 150000002148 esters Chemical class 0.000 description 8
- 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 8
- 239000000047 product Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- SMQUZDBALVYZAC-UHFFFAOYSA-N salicylaldehyde Chemical compound OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 description 8
- 102000008946 Fibrinogen Human genes 0.000 description 7
- 108010049003 Fibrinogen Proteins 0.000 description 7
- 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 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
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- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- SAOXOQSSGYAUMP-UHFFFAOYSA-N ethyl 3,7-dimethyl-8-oxoocta-2,4,6-trienoate Chemical compound CCOC(=O)C=C(C)C=CC=C(C)C=O SAOXOQSSGYAUMP-UHFFFAOYSA-N 0.000 description 7
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- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
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- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 3
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- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
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- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 3
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- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 3
- 229920002866 paraformaldehyde Polymers 0.000 description 3
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
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- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 3
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
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- MLMLRSKLMKGKGA-DXGSGPPVSA-N ethyl (2z,4e,6e,8e)-3,7-dimethyl-9-(2-nonoxyphenyl)nona-2,4,6,8-tetraenoate Chemical compound CCCCCCCCCOC1=CC=CC=C1\C=C\C(\C)=C\C=C\C(\C)=C/C(=O)OCC MLMLRSKLMKGKGA-DXGSGPPVSA-N 0.000 description 1
- YLFXEUMFBVGYEL-GQCTYLIASA-N ethyl (e)-3-methyl-4-oxobut-2-enoate Chemical compound CCOC(=O)\C=C(/C)C=O YLFXEUMFBVGYEL-GQCTYLIASA-N 0.000 description 1
- QWFVDHNGQOSPJY-UHFFFAOYSA-N ethyl 3-methyl-8-oxoocta-2,4,6-trienoate Chemical compound CCOC(=O)C=C(C)C=CC=CC=O QWFVDHNGQOSPJY-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 150000002642 lithium compounds Chemical class 0.000 description 1
- BTAUEIDLAAYHSL-UHFFFAOYSA-M lithium;octanoate Chemical compound [Li+].CCCCCCCC([O-])=O BTAUEIDLAAYHSL-UHFFFAOYSA-M 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 229960002683 methohexital Drugs 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- JFSFZYJZNOHOOQ-UHFFFAOYSA-M methyl-(2-nonylphenyl)-diphenylphosphanium;bromide Chemical compound [Br-].CCCCCCCCCC1=CC=CC=C1[P+](C)(C=1C=CC=CC=1)C1=CC=CC=C1 JFSFZYJZNOHOOQ-UHFFFAOYSA-M 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 210000000492 nasalseptum Anatomy 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- REEZZSHJLXOIHL-UHFFFAOYSA-N octanoyl chloride Chemical compound CCCCCCCC(Cl)=O REEZZSHJLXOIHL-UHFFFAOYSA-N 0.000 description 1
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- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- PMOIAJVKYNVHQE-UHFFFAOYSA-N phosphanium;bromide Chemical class [PH4+].[Br-] PMOIAJVKYNVHQE-UHFFFAOYSA-N 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000013643 reference control Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 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
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 229940035044 sorbitan monolaurate Drugs 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229940117013 triethanolamine oleate Drugs 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 150000004794 vinyl magnesium halides Chemical class 0.000 description 1
- PGOLTJPQCISRTO-UHFFFAOYSA-N vinyllithium Chemical compound [Li]C=C PGOLTJPQCISRTO-UHFFFAOYSA-N 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
- C07C57/42—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings having unsaturation outside the rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C45/74—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups combined with dehydration
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/52—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings
- C07C47/575—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/46—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid
- C07C57/48—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings and other rings, e.g. cyclohexylphenylacetic acid having unsaturation outside the aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5456—Arylalkanephosphonium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS865454A CS256398B2 (cs) | 1984-07-27 | 1986-07-17 | Způsob výroby derivátů fonylnonatetraenových kyselin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US63510084A | 1984-07-27 | 1984-07-27 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS550285A2 CS550285A2 (en) | 1987-08-13 |
| CS256392B2 true CS256392B2 (en) | 1988-04-15 |
Family
ID=24546455
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS855502A CS256392B2 (en) | 1984-07-27 | 1985-07-25 | Method of phenylnonatetronic acids' derivatives production |
Country Status (23)
| Country | Link |
|---|---|
| EP (1) | EP0169571B1 (no) |
| JP (1) | JPH06716B2 (no) |
| KR (1) | KR930000112B1 (no) |
| AR (1) | AR242023A1 (no) |
| AT (1) | ATE32882T1 (no) |
| AU (2) | AU589130B2 (no) |
| CA (1) | CA1277332C (no) |
| CS (1) | CS256392B2 (no) |
| DE (1) | DE3561808D1 (no) |
| DK (1) | DK173287B1 (no) |
| ES (2) | ES8703825A1 (no) |
| FI (1) | FI84345C (no) |
| GR (1) | GR851841B (no) |
| HU (1) | HU195480B (no) |
| IE (1) | IE58735B1 (no) |
| IL (1) | IL75913A (no) |
| MC (1) | MC1692A1 (no) |
| NO (1) | NO161064C (no) |
| NZ (1) | NZ212868A (no) |
| PH (1) | PH21556A (no) |
| PT (1) | PT80876B (no) |
| ZA (1) | ZA854828B (no) |
| ZW (1) | ZW12185A1 (no) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ232865A (en) * | 1989-03-21 | 1992-07-28 | Hoffmann La Roche | A mixed-micelle solution comprising a micelle former and an immunomodulator |
| DE4036779A1 (de) * | 1990-11-17 | 1992-05-21 | Basf Ag | Verwendung von arylpolyencarbonsaeuren und ihren derivaten als lichtschutzmittel in kosmetischen zubereitungen |
| US7655699B1 (en) | 1992-04-22 | 2010-02-02 | Eisai Inc. | Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors |
| US5369126A (en) * | 1993-01-06 | 1994-11-29 | Hoffmann-La Roche Inc. | Nonatetraenoic acid derivative for use in treating acne |
| CA2129773C (en) * | 1993-09-02 | 2007-05-01 | Michael Klaus | Aromatic carboxylic acid derivatives |
| US7115728B1 (en) | 1995-01-30 | 2006-10-03 | Ligand Pharmaceutical Incorporated | Human peroxisome proliferator activated receptor γ |
| WO1999005161A1 (en) | 1997-07-25 | 1999-02-04 | Ligand Pharmaceuticals Incorporated | HUMAN PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA (PPARη) GENE REGULATORY SEQUENCES AND USES THEREFOR |
| US7547790B2 (en) * | 2004-10-28 | 2009-06-16 | Sankyo Company, Limited | Optically active 4,4-di-substituted oxazolidine derivative and method for producing same |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3334125A (en) * | 1964-02-26 | 1967-08-01 | Velsicol Chemical Corp | Esters of 3-6-dichloro-2-methoxy-benzyl alcohol |
| CH585166A5 (no) * | 1973-03-30 | 1977-02-28 | Hoffmann La Roche | |
| CH605562A5 (no) * | 1974-09-26 | 1978-09-29 | Hoffmann La Roche | |
| DE2933985A1 (de) * | 1979-08-22 | 1981-04-09 | Bayer Ag, 5090 Leverkusen | Neue 4-fluor-3-phenoxy-benzyl-ether und verfahren zu deren herstellung sowie neue zwischenprodukte hierfuer und verfahren zu deren herstellung |
-
1985
- 1985-06-26 ZA ZA854828A patent/ZA854828B/xx unknown
- 1985-07-25 ZW ZW121/85A patent/ZW12185A1/xx unknown
- 1985-07-25 CS CS855502A patent/CS256392B2/cs not_active IP Right Cessation
- 1985-07-25 FI FI852899A patent/FI84345C/fi not_active IP Right Cessation
- 1985-07-25 NZ NZ212868A patent/NZ212868A/xx unknown
- 1985-07-25 CA CA000487547A patent/CA1277332C/en not_active Expired - Fee Related
- 1985-07-25 GR GR851841A patent/GR851841B/el unknown
- 1985-07-25 MC MC851787A patent/MC1692A1/xx unknown
- 1985-07-25 DK DK198503404A patent/DK173287B1/da active
- 1985-07-25 AR AR85301088A patent/AR242023A1/es active
- 1985-07-25 IL IL75913A patent/IL75913A/xx not_active IP Right Cessation
- 1985-07-25 AU AU45575/85A patent/AU589130B2/en not_active Ceased
- 1985-07-26 NO NO852980A patent/NO161064C/no not_active IP Right Cessation
- 1985-07-26 DE DE8585109383T patent/DE3561808D1/de not_active Expired
- 1985-07-26 KR KR1019850005366A patent/KR930000112B1/ko not_active IP Right Cessation
- 1985-07-26 IE IE188185A patent/IE58735B1/en not_active IP Right Cessation
- 1985-07-26 JP JP60164183A patent/JPH06716B2/ja not_active Expired - Lifetime
- 1985-07-26 AT AT85109383T patent/ATE32882T1/de active
- 1985-07-26 ES ES545565A patent/ES8703825A1/es not_active Expired
- 1985-07-26 EP EP85109383A patent/EP0169571B1/de not_active Expired
- 1985-07-26 PT PT80876A patent/PT80876B/pt not_active IP Right Cessation
- 1985-07-26 PH PH32568A patent/PH21556A/en unknown
- 1985-07-26 HU HU852841A patent/HU195480B/hu not_active IP Right Cessation
-
1986
- 1986-02-17 ES ES552061A patent/ES8705355A1/es not_active Expired
-
1989
- 1989-10-05 AU AU42608/89A patent/AU619901B2/en not_active Ceased
Also Published As
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| IF00 | In force as of 2000-06-30 in czech republic | ||
| MK4A | Patent expired |
Effective date: 20000725 |