CS245783B2 - Production method of 4-phenyl-1,3-dioxan-cis-5-ylalkene acids - Google Patents
Production method of 4-phenyl-1,3-dioxan-cis-5-ylalkene acids Download PDFInfo
- Publication number
- CS245783B2 CS245783B2 CS833336A CS333683A CS245783B2 CS 245783 B2 CS245783 B2 CS 245783B2 CS 833336 A CS833336 A CS 833336A CS 333683 A CS333683 A CS 333683A CS 245783 B2 CS245783 B2 CS 245783B2
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- CS
- Czechoslovakia
- Prior art keywords
- formula
- group
- phenyl
- cis
- carbon atoms
- Prior art date
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- 239000002253 acid Substances 0.000 title claims abstract description 43
- 150000007513 acids Chemical class 0.000 title claims description 15
- 238000004519 manufacturing process Methods 0.000 title description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 92
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 59
- 238000000034 method Methods 0.000 claims abstract description 38
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 32
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 28
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 229910052705 radium Inorganic materials 0.000 claims abstract description 20
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 20
- 230000008569 process Effects 0.000 claims abstract description 15
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 13
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 10
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000000532 dioxanyl group Chemical group 0.000 claims abstract description 7
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000005977 Ethylene Substances 0.000 claims abstract description 5
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 3
- -1 nitro, hydroxyl Chemical group 0.000 claims description 104
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 85
- 150000001875 compounds Chemical class 0.000 claims description 67
- 239000000203 mixture Substances 0.000 claims description 55
- 125000004432 carbon atom Chemical group C* 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 239000007858 starting material Substances 0.000 claims description 38
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 15
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 10
- 239000002585 base Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 239000012024 dehydrating agents Substances 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- 239000003849 aromatic solvent Substances 0.000 claims description 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 230000009435 amidation Effects 0.000 claims 1
- 238000007112 amidation reaction Methods 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims 1
- 239000011833 salt mixture Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 7
- 201000010099 disease Diseases 0.000 abstract description 6
- DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 abstract description 6
- 230000009471 action Effects 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- RCJRILMVFLGCJY-UHFFFAOYSA-N 4-phenyl-1,3-dioxane Chemical compound O1COCCC1C1=CC=CC=C1 RCJRILMVFLGCJY-UHFFFAOYSA-N 0.000 abstract 1
- 238000012824 chemical production Methods 0.000 abstract 1
- 125000001188 haloalkyl group Chemical group 0.000 abstract 1
- 125000003107 substituted aryl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
- 239000003921 oil Substances 0.000 description 95
- 239000000243 solution Substances 0.000 description 83
- 238000005481 NMR spectroscopy Methods 0.000 description 77
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 37
- 238000001819 mass spectrum Methods 0.000 description 33
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 24
- 235000002639 sodium chloride Nutrition 0.000 description 23
- 239000000047 product Substances 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000012230 colorless oil Substances 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 17
- 150000001299 aldehydes Chemical class 0.000 description 17
- 238000004440 column chromatography Methods 0.000 description 17
- 239000003480 eluent Substances 0.000 description 16
- 238000003756 stirring Methods 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- 230000003287 optical effect Effects 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- 229910052731 fluorine Inorganic materials 0.000 description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 description 7
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 239000011737 fluorine Substances 0.000 description 7
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 6
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 230000003042 antagnostic effect Effects 0.000 description 6
- 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 6
- 229910052786 argon Inorganic materials 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 6
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- 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 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 230000001631 hypertensive effect Effects 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- 238000005325 percolation Methods 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 4
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 4
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 4
- MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-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
- 239000012448 Lithium borohydride Substances 0.000 description 4
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 125000005236 alkanoylamino group Chemical group 0.000 description 4
- 125000005530 alkylenedioxy group Chemical group 0.000 description 4
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 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
- 238000001035 drying Methods 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 238000004452 microanalysis Methods 0.000 description 4
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 3
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 3
- OCOBFMZGRJOSOU-UHFFFAOYSA-N 3-o-tert-butyl 1-o-ethyl propanedioate Chemical compound CCOC(=O)CC(=O)OC(C)(C)C OCOBFMZGRJOSOU-UHFFFAOYSA-N 0.000 description 3
- OAKURXIZZOAYBC-UHFFFAOYSA-N 3-oxopropanoic acid Chemical class OC(=O)CC=O OAKURXIZZOAYBC-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- PSZDOEIIIJFCFE-UHFFFAOYSA-N Oleanolic alcohol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(CO)CCC(C)(C)CC5C4=CCC3C21C PSZDOEIIIJFCFE-UHFFFAOYSA-N 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
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- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical class [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 1
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- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
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- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 description 1
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- SJMCLWCCNYAWRQ-UHFFFAOYSA-N propane-2-sulfonamide Chemical class CC(C)S(N)(=O)=O SJMCLWCCNYAWRQ-UHFFFAOYSA-N 0.000 description 1
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- NKAAEMMYHLFEFN-ZVGUSBNCSA-M sodium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical class [Na+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O NKAAEMMYHLFEFN-ZVGUSBNCSA-M 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
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- 239000000021 stimulant Substances 0.000 description 1
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- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- GIZSHQYTTBQKOQ-UHFFFAOYSA-N threo-Syringoylglycerol Chemical compound COC1=CC(C(O)C(O)CO)=CC(OC)=C1O GIZSHQYTTBQKOQ-UHFFFAOYSA-N 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
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- 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 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/06—1,3-Dioxanes; Hydrogenated 1,3-dioxanes not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pulmonology (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)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CS847257A CS245795B2 (en) | 1982-05-12 | 1983-05-12 | Production method of 4-phenyl-1,3-dioxan-cis-5-ylalkene acids |
| CS847258A CS245796B2 (cs) | 1983-05-12 | 1983-05-12 | Způsob výroby derivátů 4-hydroxyfenyl-l,3-dioxan-cis-5-ylalkenovýeh kyselin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8213702 | 1982-05-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CS333683A2 CS333683A2 (en) | 1985-09-17 |
| CS245783B2 true CS245783B2 (en) | 1986-10-16 |
Family
ID=10530304
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS833336A CS245783B2 (en) | 1982-05-12 | 1983-05-12 | Production method of 4-phenyl-1,3-dioxan-cis-5-ylalkene acids |
| CS847257A CS245795B2 (en) | 1982-05-12 | 1983-05-12 | Production method of 4-phenyl-1,3-dioxan-cis-5-ylalkene acids |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS847257A CS245795B2 (en) | 1982-05-12 | 1983-05-12 | Production method of 4-phenyl-1,3-dioxan-cis-5-ylalkene acids |
Country Status (32)
| Country | Link |
|---|---|
| US (3) | US4567197A (en, 2012) |
| EP (1) | EP0094239B1 (en, 2012) |
| JP (1) | JPS58222081A (en, 2012) |
| KR (1) | KR880002001B1 (en, 2012) |
| AR (1) | AR240817A1 (en, 2012) |
| AT (1) | ATE28329T1 (en, 2012) |
| AU (1) | AU562056B2 (en, 2012) |
| CA (4) | CA1258464A (en, 2012) |
| CS (2) | CS245783B2 (en, 2012) |
| CY (1) | CY1453A (en, 2012) |
| DD (2) | DD219769A5 (en, 2012) |
| DE (1) | DE3372483D1 (en, 2012) |
| DK (1) | DK163431C (en, 2012) |
| ES (4) | ES522331A0 (en, 2012) |
| FI (1) | FI80027C (en, 2012) |
| GB (1) | GB8310407D0 (en, 2012) |
| GR (1) | GR78138B (en, 2012) |
| HK (1) | HK17889A (en, 2012) |
| HU (1) | HU198705B (en, 2012) |
| IE (1) | IE55114B1 (en, 2012) |
| IL (1) | IL68628A0 (en, 2012) |
| KE (1) | KE3823A (en, 2012) |
| MW (1) | MW1583A1 (en, 2012) |
| NO (1) | NO162383B (en, 2012) |
| NZ (1) | NZ204202A (en, 2012) |
| PH (1) | PH21691A (en, 2012) |
| PL (3) | PL140462B1 (en, 2012) |
| PT (1) | PT76684B (en, 2012) |
| SG (1) | SG57088G (en, 2012) |
| SU (1) | SU1277893A3 (en, 2012) |
| ZA (1) | ZA833179B (en, 2012) |
| ZW (1) | ZW10083A1 (en, 2012) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8310407D0 (en) * | 1982-05-12 | 1983-05-25 | Ici Plc | 1 3 - dioxan -5- ylalkenoic acids |
| FR2551446B1 (fr) * | 1983-08-31 | 1987-03-20 | Elf Aquitaine | Compositions de resines ayant une resistance amelioree au choc renfermant un polymere thermoplastique, un additif choc du type copolymere greffe, et eventuellement d'autres additifs, et copolymere greffe correspondant, a caractere d'additif choc |
| GB8330094D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Diphenyl compounds |
| GB8330120D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Chemical process |
| GB8330097D0 (en) * | 1983-11-11 | 1983-12-21 | Ici Plc | Cyclic ethers |
| GB8417314D0 (en) * | 1984-07-06 | 1984-08-08 | Ici Plc | Carboxylic acid derivatives |
| GB8511891D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Alkenoic acids |
| GR861209B (en) * | 1985-05-10 | 1986-08-29 | Ici Plc | Process for preparing novel alkene derivatives |
| GB8511895D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Heterocyclic compounds |
| GB8511890D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Benzene derivatives |
| DK212786A (da) * | 1985-05-10 | 1986-11-11 | Ici Plc | 1,3-dioxanethere |
| GB8511894D0 (en) | 1985-05-10 | 1985-06-19 | Ici Plc | Phenol derivatives |
| GB8511892D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Fluoralkane derivatives |
| GB8511897D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Carboxylic acids |
| WO1987002983A1 (en) * | 1985-11-12 | 1987-05-21 | Imperial Chemical Industries Plc | Amide derivatives |
| GB8611174D0 (en) * | 1986-05-08 | 1986-06-18 | Ici Plc | Amide derivatives |
| GB8531892D0 (en) * | 1985-12-30 | 1986-02-05 | Ici Plc | Carboxylic acids |
| DE3603662A1 (de) * | 1986-02-06 | 1987-08-13 | Basf Ag | Acetalisierte oder ketalisierte dihydroxyaldehyde, verfahren zu ihrer herstellung und diese enthaltende loesungen |
| GB8626296D0 (en) * | 1986-11-04 | 1986-12-03 | Ici Plc | Therapeutic agents |
| GB8626297D0 (en) * | 1986-11-04 | 1986-12-03 | Ici Plc | Pharmaceutical compositions |
| GB8709794D0 (en) * | 1987-04-24 | 1987-05-28 | Ici Plc | Heterocyclic acids |
| US5248780A (en) * | 1988-02-16 | 1993-09-28 | Imperial Chemical Industries, Plc | Pyridyl substituted alkenoic acid derivatives |
| GB8901201D0 (en) * | 1988-02-16 | 1989-03-15 | Ici Plc | Pyridine derivatives |
| EP0346511A1 (en) * | 1988-06-15 | 1989-12-20 | Fujisawa Pharmaceutical Co., Ltd. | Oxygen-containing hererocyclic compound, processes for their preparation and pharmaceutical compositions comprising them |
| IE81170B1 (en) * | 1988-10-21 | 2000-05-31 | Zeneca Ltd | Pyridine derivatives |
| CN1034120C (zh) * | 1988-10-21 | 1997-02-26 | 曾尼卡有限公司 | 制备二噁烷链烯酸衍生物的方法 |
| GB9021571D0 (en) * | 1990-10-04 | 1990-11-21 | Ici Plc | Heterocyclic acids |
| US5925795A (en) * | 1996-09-16 | 1999-07-20 | Zeneca Limited | Processes for the preparation of aryl-β-diketones, arylpyrimidine ketones and crop protection intermediates |
| GB0413970D0 (en) * | 2004-06-22 | 2004-07-28 | Syngenta Participations Ag | Chemical compounds |
| IN2015DN00502A (en, 2012) * | 2006-01-18 | 2015-06-26 | Evolva Sa | |
| CA2676444C (en) * | 2007-01-18 | 2013-07-30 | Evolva Sa | Prodrugs of substituted 1,3-dioxanes and their uses |
| AU2008206047B2 (en) * | 2007-01-18 | 2014-07-10 | Evolva Sa | Substituted 1,3-dioxanes useful as PPAR modulators |
| MX354521B (es) * | 2012-05-18 | 2018-03-08 | Sanofi Sa | Derivados de benzo [1,3] dioxina y su uso como antagonistas de lpar5. |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4243592A (en) * | 1979-03-12 | 1981-01-06 | The Upjohn Company | 9,11-Dideoxy-10-oxa-TXB compounds |
| GB8310407D0 (en) * | 1982-05-12 | 1983-05-25 | Ici Plc | 1 3 - dioxan -5- ylalkenoic acids |
| GB8417314D0 (en) * | 1984-07-06 | 1984-08-08 | Ici Plc | Carboxylic acid derivatives |
-
1983
- 1983-04-18 GB GB838310407A patent/GB8310407D0/en active Pending
- 1983-04-29 ZW ZW100/83A patent/ZW10083A1/xx unknown
- 1983-05-02 IE IE1005/83A patent/IE55114B1/en not_active IP Right Cessation
- 1983-05-04 MW MW15/83A patent/MW1583A1/xx unknown
- 1983-05-04 AU AU14223/83A patent/AU562056B2/en not_active Ceased
- 1983-05-04 ZA ZA833179A patent/ZA833179B/xx unknown
- 1983-05-06 US US06/492,247 patent/US4567197A/en not_active Expired - Fee Related
- 1983-05-09 HU HU831588A patent/HU198705B/hu not_active IP Right Cessation
- 1983-05-09 EP EP83302613A patent/EP0094239B1/en not_active Expired
- 1983-05-09 AT AT83302613T patent/ATE28329T1/de not_active IP Right Cessation
- 1983-05-09 IL IL68628A patent/IL68628A0/xx not_active IP Right Cessation
- 1983-05-09 DE DE8383302613T patent/DE3372483D1/de not_active Expired
- 1983-05-11 PL PL1983250098A patent/PL140462B1/pl unknown
- 1983-05-11 NO NO831679A patent/NO162383B/no unknown
- 1983-05-11 PH PH28883A patent/PH21691A/en unknown
- 1983-05-11 PL PL1983250099A patent/PL140463B1/pl unknown
- 1983-05-11 DK DK211883A patent/DK163431C/da not_active IP Right Cessation
- 1983-05-11 NZ NZ204202A patent/NZ204202A/en unknown
- 1983-05-11 CA CA000427937A patent/CA1258464A/en not_active Expired
- 1983-05-11 SU SU833596399A patent/SU1277893A3/ru active
- 1983-05-11 PL PL1983241920A patent/PL140274B1/pl unknown
- 1983-05-11 GR GR71324A patent/GR78138B/el unknown
- 1983-05-12 DD DD83264391A patent/DD219769A5/de not_active IP Right Cessation
- 1983-05-12 AR AR293002A patent/AR240817A1/es active
- 1983-05-12 ES ES522331A patent/ES522331A0/es active Granted
- 1983-05-12 JP JP58083438A patent/JPS58222081A/ja active Granted
- 1983-05-12 PT PT76684A patent/PT76684B/pt not_active IP Right Cessation
- 1983-05-12 CS CS833336A patent/CS245783B2/cs unknown
- 1983-05-12 FI FI831664A patent/FI80027C/fi not_active IP Right Cessation
- 1983-05-12 CS CS847257A patent/CS245795B2/cs unknown
- 1983-05-12 KR KR1019830002053A patent/KR880002001B1/ko not_active Expired
- 1983-05-12 DD DD83250869A patent/DD212515A5/de not_active IP Right Cessation
- 1983-12-30 ES ES528577A patent/ES8608507A1/es not_active Expired
- 1983-12-30 ES ES528575A patent/ES8700249A1/es not_active Expired
- 1983-12-30 ES ES528576A patent/ES8700250A1/es not_active Expired
-
1985
- 1985-11-12 US US06/797,204 patent/US4745198A/en not_active Expired - Fee Related
-
1988
- 1988-02-09 US US07/153,928 patent/US5166377A/en not_active Expired - Fee Related
- 1988-08-18 KE KE3823A patent/KE3823A/xx unknown
- 1988-08-31 SG SG570/88A patent/SG57088G/en unknown
-
1989
- 1989-03-02 HK HK178/89A patent/HK17889A/xx unknown
- 1989-05-24 CA CA000600591A patent/CA1268771A/en not_active Expired - Fee Related
- 1989-05-24 CA CA000600592A patent/CA1268772A/en not_active Expired - Fee Related
- 1989-05-24 CA CA000600593A patent/CA1269109A/en not_active Expired - Fee Related
- 1989-07-21 CY CY1453A patent/CY1453A/xx unknown
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