FI80027B - 1,3-dioxan-5- ylalkenoylsyror. - Google Patents
1,3-dioxan-5- ylalkenoylsyror. Download PDFInfo
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- FI80027B FI80027B FI831664A FI831664A FI80027B FI 80027 B FI80027 B FI 80027B FI 831664 A FI831664 A FI 831664A FI 831664 A FI831664 A FI 831664A FI 80027 B FI80027 B FI 80027B
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- Finland
- Prior art keywords
- formula
- phenyl
- compound
- acid
- cis
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- 150000001875 compounds Chemical class 0.000 claims description 107
- -1 cyano, nitro, hydroxy, methylthio Chemical group 0.000 claims description 103
- 239000002253 acid Substances 0.000 claims description 102
- 239000000203 mixture Substances 0.000 claims description 80
- 238000000034 method Methods 0.000 claims description 78
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 56
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 36
- 239000007858 starting material Substances 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 230000008569 process Effects 0.000 claims description 31
- 229910052705 radium Inorganic materials 0.000 claims description 27
- 229910052701 rubidium Inorganic materials 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 239000002585 base Substances 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 12
- YURNCBVQZBJDAJ-UHFFFAOYSA-N 2-heptenoic acid Chemical compound CCCCC=CC(O)=O YURNCBVQZBJDAJ-UHFFFAOYSA-N 0.000 claims description 11
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- PSZDOEIIIJFCFE-OSQDELBUSA-N erythrodiol Chemical class C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(CO)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C PSZDOEIIIJFCFE-OSQDELBUSA-N 0.000 claims description 10
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 10
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 9
- 239000005977 Ethylene Substances 0.000 claims description 9
- 238000007796 conventional method Methods 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 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 claims description 7
- 239000003377 acid catalyst Substances 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- HTZRWCSRPTWJCT-UHFFFAOYSA-N erythrodiol Natural products CC1(C)CCC2(CO)CCC3C(CCC4C3(C)CCC5C(C)(C)C(O)CCC45C)C2C1 HTZRWCSRPTWJCT-UHFFFAOYSA-N 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 6
- 150000001768 cations Chemical class 0.000 claims description 6
- 125000000532 dioxanyl group Chemical group 0.000 claims description 6
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002373 hemiacetals 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
- 125000006239 protecting group Chemical group 0.000 claims description 6
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 229920002554 vinyl polymer Polymers 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 230000009435 amidation Effects 0.000 claims description 3
- 238000007112 amidation reaction Methods 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Chemical group O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 claims 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 229940102396 methyl bromide Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 134
- 239000003921 oil Substances 0.000 description 130
- 239000000243 solution Substances 0.000 description 102
- 238000005481 NMR spectroscopy Methods 0.000 description 101
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 90
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 34
- 239000007787 solid Substances 0.000 description 34
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 32
- 239000012230 colorless oil Substances 0.000 description 30
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 28
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- 235000002639 sodium chloride Nutrition 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- 239000011734 sodium Substances 0.000 description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 21
- 150000001299 aldehydes Chemical class 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 239000003085 diluting agent Substances 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- 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 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 238000003818 flash chromatography Methods 0.000 description 15
- 239000003480 eluent Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 11
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 10
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 10
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 10
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 238000002474 experimental method Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000001228 spectrum Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 238000004809 thin layer chromatography Methods 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- 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 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 239000006188 syrup Substances 0.000 description 8
- 235000020357 syrup Nutrition 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000012074 organic phase Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical group C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 239000008346 aqueous phase Substances 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
- 239000000460 chlorine Substances 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- MUPFCCVZEUACLO-UHFFFAOYSA-N hept-2-enamide Chemical compound CCCCC=CC(N)=O MUPFCCVZEUACLO-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229910052757 nitrogen Inorganic materials 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
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 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
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 5
- KCEXUGIHDXCPCJ-UHFFFAOYSA-N 2,2-dimethyl-4-phenyl-1,3-dioxane Chemical compound O1C(C)(C)OCCC1C1=CC=CC=C1 KCEXUGIHDXCPCJ-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 5
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 150000001241 acetals Chemical class 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 230000008020 evaporation Effects 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
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 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
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000012448 Lithium borohydride Substances 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 230000009471 action Effects 0.000 description 4
- 238000004458 analytical method Methods 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
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 239000012024 dehydrating agents Substances 0.000 description 4
- 238000005984 hydrogenation reaction Methods 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
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- CWXOAQXKPAENDI-UHFFFAOYSA-N sodium methylsulfinylmethylide Chemical compound [Na+].CS([CH2-])=O CWXOAQXKPAENDI-UHFFFAOYSA-N 0.000 description 4
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
- 239000012258 stirred mixture Substances 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
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- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (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)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pulmonology (AREA)
- Diabetes (AREA)
- Hematology (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)
Claims (3)
1. Förfarande för framställning av nya, terapeu-tiskt användbara 4-fenyl-l,3-dioxan-cis-5-ylalkenoylsyra-5 derivat med formeln I (CH2)n*A-Y*CO'Rc (i» 10 “k3 f| ^ 15 väri Ra och Rb oberoende av varandra är väte, vinyl eller (l-8C)alkyl, som eventuellt bär upp tili tre halogensubs-tituenter, under förutsättning av att dä bäde Ra och Rb är alkyl, är totalantalet kolatomer i Ra och Rb tillsam-mans 8 eller lägre; eller den ena av Ra och Rb är väte och 20 den andra är pentafluorfenyl, naftyl, bensyl eller fenyl, varvid fenylen eventuellt bär högst tvä substituenter som självständigt betecknar halogen, metyl, metoxi, trifluor-metyl, cyan, nitro, hydroxi, metyltio eller acetamido eller fenylgruppen eventuellt bär en metylendioxi- eller 25 metylenoximetylensubstituent; eller Ra och Rb bildar till-sammans polymetylen med 3-6 kolatomer och eventuellt bä-rande en metylsubstituent; Rc är hydroxi, (l-6C)alkoxi eller (l-6C)alkansulfonamido; n är heltalet 1 eller 2; A är etylen eller cis-vinylen; Y är polymetylen med 2-4 kol-30 atomer; bensenringen B är osubstituerad eller den bär en fluor-, klor-, metyl-, hydroxi-, metoxi-, etyl- eller iso-propylsubstitutent i orto-ställningen eller en fluor- eller klor substituent i metaställningen; och substituenterna i ställningarna 4 och 5 av dioxanringen motsvarar stereo-35 kemiskt cis-formen; eller för sädana föreningar, väri Rc 88 80027 är hydroxi, av deras fysiologiskt godtagbara bassalter, kännetecknat därav, att man a) för framställning av en förening, väri Rc är hydroxi och A är vinylen, omsätter en aldehyd med formeln
5 II (CH2)n’CH0 10 Rb I (ID 15 med ett Wittig-reagens med formeln (Rd)3 P*CH· Y*C02 M* (III) väri Rd är (l-6C)alkyl eller aryl och M* är en alkalime-20 tallkatjon; b) omsätter ett erytro-diolderivat med formeln XIII (CH2)n-A*Y-C0-Rc Qa-0 I
25 Jl Qb-O'^V^ <XIII> 30 väri den ena av Qa och Qb är väte och den andra är väte, alkansulfonyl, arensulfonyl eller en grupp med formeln -CRR1 ·0Η, väri R och R1 är sammam eller olika alkyl, med en karbonylförening med formeln RaRb*CO eller med en ace-35 tai, hemiacetal eller ett hydrat därav; 89 80027 c) för framställning av en förening med formeln I, väri Rc är hyroxi, hydrolyserar en förening med formeln XVIII 5 ^ (CH9)_-A*Y-W o δ n Ra/V0/Y\ (XVIII) Rb M B I 10 väri W är alkoxikarbonyl, fenoxikarbonyl, bensyloxikarbo-nyl, cyano eller karbamoyl; 15 d) för framställning av en förening med formeln I, väri Ra och Rb eller bensenringen B bär en hydroxisubstituent, avlägsnar skyddsgruppen i ett motsvarande derivat av den nämnda föreningen, väri hydroxisubstituenten är skyddad med en trimetylsilyl-, (l-6C)alkyl- eller acyl-20 skyddsgrupp; e) för framställning av en förening med formeln I, väri Ra och Rb vardera är väte, omsätter en erytro-diol med formeln XIII väri Qa och Qb vardera är väte, med mety-lenbromid i närvaro av en bas; eller 25 f) omsätter en förening med formeln I, väri Ra och Rb betecknar metyl eller etyl, med en karbonylförening med formeln RaRb»C0 eller med en acetal, hemiacetal eller ett hydrat därav i närvaro av en syrakatalysator; därefter 30 dä en förening med formeln I, väri Rc är (l-6)alk- oxi, önskas, förestrar en motsvarande syra med formeln I, väri Rc är hydroxi, eller ett reaktionskapabelt derivat därav, genom sedvanliga metoder, dä en förening med formeln I, väri Rc är (l-6C)al-35 kansulfonamido, önskas, omsätter en motsvarande syra med 90 80027 formeln I, väri Rc är hydroxi, med en lämplig (l-6C)alkan-sulfonamid i närvaro av ett vattenavlägsnande medel, eller omsätter ett reaktionskapabelt derivat av den nämnda syran med formreln I, med en lämplig (l-6C)alkansulfonamid eller 5 ett alkalimetallsalt därav; dä en förening med formeln I, väri A är etylen, önskas, hydrerar en motsvarande förening med formeln 1, väri A är vinylen, i närvaro av en katalysator; dä ett sait av en förening med formeln I, väri Rc 10 är hydroxi, önskas, omsätter den nämnda föreningen med en lämplig bas, vilken avger en fysiologiskt godtagbar kat-jon; och dä en optiskt aktiv form av en förening med formeln I önskas, utför vardera av de ovannämnda förfarandena ge-15 nom användande av optiskt aktivt utgängssmaterial, eller omsätter en racemisk form av en föreing med formeln I, väri Rc är hydroxi, med en optiskt aktiv form av en lämplig organisk bas, och sedan separerar den erhällna diaste-reoisomera blandningen av salterna, och frigör den önskade 20 optiskt aktiva formen av föreningen med formeln l genom behandling med en syra, och utför den ovannämnda förest-ringen eller amideringen, dä Rc är annat än hydroxi.
2. Förfarande för framställning av 5(Z)-7-[2,2-di-mety1-4-(2-mety1feny1)-1,3-dioxan-cis-5-y1]heptenoy1syra. 25
3. Förfarande för framställning av 5(Z)-7-[2,2-di- metyl-4-(2-hydroxyfenyl)-1,3-dioxan-cis-5-yl]heptenoylsy-ra.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8213702 | 1982-05-12 | ||
| GB8213702 | 1982-05-12 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI831664A0 FI831664A0 (fi) | 1983-05-12 |
| FI831664L FI831664L (fi) | 1983-11-13 |
| FI80027B true FI80027B (fi) | 1989-12-29 |
| FI80027C FI80027C (sv) | 1990-04-10 |
Family
ID=10530304
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI831664A FI80027C (sv) | 1982-05-12 | 1983-05-12 | Förfarande för framställning av nya, terapeutiskt användbara 4-fenyl-1 ,3-dioxan-cis-5-ylalkenoylsyraderivat |
Country Status (32)
| Country | Link |
|---|---|
| US (3) | US4567197A (sv) |
| EP (1) | EP0094239B1 (sv) |
| JP (1) | JPS58222081A (sv) |
| KR (1) | KR880002001B1 (sv) |
| AR (1) | AR240817A1 (sv) |
| AT (1) | ATE28329T1 (sv) |
| AU (1) | AU562056B2 (sv) |
| CA (4) | CA1258464A (sv) |
| CS (2) | CS245783B2 (sv) |
| CY (1) | CY1453A (sv) |
| DD (2) | DD219769A5 (sv) |
| DE (1) | DE3372483D1 (sv) |
| DK (1) | DK163431C (sv) |
| ES (4) | ES8407038A1 (sv) |
| FI (1) | FI80027C (sv) |
| GB (1) | GB8310407D0 (sv) |
| GR (1) | GR78138B (sv) |
| HK (1) | HK17889A (sv) |
| HU (1) | HU198705B (sv) |
| IE (1) | IE55114B1 (sv) |
| IL (1) | IL68628A0 (sv) |
| KE (1) | KE3823A (sv) |
| MW (1) | MW1583A1 (sv) |
| NO (1) | NO162383B (sv) |
| NZ (1) | NZ204202A (sv) |
| PH (1) | PH21691A (sv) |
| PL (3) | PL140462B1 (sv) |
| PT (1) | PT76684B (sv) |
| SG (1) | SG57088G (sv) |
| SU (1) | SU1277893A3 (sv) |
| ZA (1) | ZA833179B (sv) |
| ZW (1) | ZW10083A1 (sv) |
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 |
| HU198706B (en) * | 1985-05-10 | 1989-11-28 | Ici Plc | Process for producing 1,3-dioxan-ethers and pharmaceutical compositions containing them |
| GB8511891D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Alkenoic acids |
| GB8511897D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Carboxylic acids |
| GB8511895D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Heterocyclic compounds |
| GB8511892D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Fluoralkane derivatives |
| US4824858A (en) * | 1985-05-10 | 1989-04-25 | Imperial Chemical Industries Plc | 1,3-Dioxolane-5-yl-hexenoic acid derivatives |
| GB8511894D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Phenol derivatives |
| GB8511890D0 (en) * | 1985-05-10 | 1985-06-19 | Ici Plc | Benzene derivatives |
| GB8611174D0 (en) * | 1986-05-08 | 1986-06-18 | Ici Plc | Amide derivatives |
| WO1987002983A1 (en) * | 1985-11-12 | 1987-05-21 | Imperial Chemical Industries 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 |
| GB8626297D0 (en) * | 1986-11-04 | 1986-12-03 | Ici Plc | Pharmaceutical compositions |
| GB8626296D0 (en) * | 1986-11-04 | 1986-12-03 | Ici Plc | Therapeutic agents |
| 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 |
| PL1976509T3 (pl) * | 2006-01-18 | 2015-07-31 | Evolva Sa | Modulatory PPAR |
| WO2008089464A1 (en) * | 2007-01-18 | 2008-07-24 | Evolva Sa | Prodrugs of substituted 1,3-dioxanes and their uses |
| US8486994B2 (en) | 2007-01-18 | 2013-07-16 | Evolva Sa | Prodrugs of substituted 1,3-dioxanes and their uses |
| CN104302633B (zh) * | 2012-05-18 | 2016-09-07 | 赛诺菲 | 苯并[1,3]二氧杂环己烯衍生物和它们作为lpar5 拮抗剂的应用 |
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 DE DE8383302613T patent/DE3372483D1/de not_active Expired
- 1983-05-09 EP EP83302613A patent/EP0094239B1/en not_active Expired
- 1983-05-09 IL IL68628A patent/IL68628A0/xx not_active IP Right Cessation
- 1983-05-09 AT AT83302613T patent/ATE28329T1/de not_active IP Right Cessation
- 1983-05-09 HU HU831588A patent/HU198705B/hu not_active IP Right Cessation
- 1983-05-11 SU SU833596399A patent/SU1277893A3/ru active
- 1983-05-11 PL PL1983250098A patent/PL140462B1/pl unknown
- 1983-05-11 CA CA000427937A patent/CA1258464A/en not_active Expired
- 1983-05-11 PL PL1983250099A patent/PL140463B1/pl unknown
- 1983-05-11 GR GR71324A patent/GR78138B/el unknown
- 1983-05-11 DK DK211883A patent/DK163431C/da not_active IP Right Cessation
- 1983-05-11 PL PL1983241920A patent/PL140274B1/pl unknown
- 1983-05-11 PH PH28883A patent/PH21691A/en unknown
- 1983-05-11 NO NO831679A patent/NO162383B/no unknown
- 1983-05-11 NZ NZ204202A patent/NZ204202A/en unknown
- 1983-05-12 CS CS833336A patent/CS245783B2/cs unknown
- 1983-05-12 KR KR1019830002053A patent/KR880002001B1/ko not_active Expired
- 1983-05-12 CS CS847257A patent/CS245795B2/cs unknown
- 1983-05-12 JP JP58083438A patent/JPS58222081A/ja active Granted
- 1983-05-12 DD DD83264391A patent/DD219769A5/de not_active IP Right Cessation
- 1983-05-12 FI FI831664A patent/FI80027C/sv not_active IP Right Cessation
- 1983-05-12 AR AR293002A patent/AR240817A1/es active
- 1983-05-12 DD DD83250869A patent/DD212515A5/de not_active IP Right Cessation
- 1983-05-12 PT PT76684A patent/PT76684B/pt not_active IP Right Cessation
- 1983-05-12 ES ES522331A patent/ES8407038A1/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
- 1983-12-30 ES ES528577A patent/ES8608507A1/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 - Lifetime
- 1989-05-24 CA CA000600592A patent/CA1268772A/en not_active Expired - Lifetime
- 1989-05-24 CA CA000600593A patent/CA1269109A/en not_active Expired - Lifetime
- 1989-07-21 CY CY1453A patent/CY1453A/xx unknown
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