NO300135B1 - Heterocyklisk substituerte 2-acylamino-5-tiazoler, og mellomprodukter for fremstilling derav - Google Patents
Heterocyklisk substituerte 2-acylamino-5-tiazoler, og mellomprodukter for fremstilling derav Download PDFInfo
- Publication number
- NO300135B1 NO300135B1 NO922215A NO922215A NO300135B1 NO 300135 B1 NO300135 B1 NO 300135B1 NO 922215 A NO922215 A NO 922215A NO 922215 A NO922215 A NO 922215A NO 300135 B1 NO300135 B1 NO 300135B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- alkyl
- constitutes
- formula
- phenyl
- Prior art date
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- 125000000623 heterocyclic group Chemical group 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title description 13
- 239000000543 intermediate Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 54
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- -1 phenyl carbon Chemical compound 0.000 claims description 21
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 239000000460 chlorine Substances 0.000 claims description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract description 3
- 125000004103 aminoalkyl group Chemical group 0.000 abstract description 2
- 125000005842 heteroatom Chemical group 0.000 abstract 2
- 229910052760 oxygen Inorganic materials 0.000 abstract 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 abstract 1
- 125000005242 carbamoyl alkyl group Chemical group 0.000 abstract 1
- 125000004181 carboxyalkyl group Chemical group 0.000 abstract 1
- 125000004966 cyanoalkyl group Chemical group 0.000 abstract 1
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract 1
- 125000003884 phenylalkyl group Chemical group 0.000 abstract 1
- KGFYHTZWPPHNLQ-AWEZNQCLSA-N rivaroxaban Chemical compound S1C(Cl)=CC=C1C(=O)NC[C@@H]1OC(=O)N(C=2C=CC(=CC=2)N2C(COCC2)=O)C1 KGFYHTZWPPHNLQ-AWEZNQCLSA-N 0.000 abstract 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 abstract 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- 239000000203 mixture Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- 239000012074 organic phase Substances 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 238000000034 method Methods 0.000 description 24
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 21
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 19
- 239000002253 acid Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 229940107137 cholecystokinin Drugs 0.000 description 16
- 101800001982 Cholecystokinin Proteins 0.000 description 15
- 102100025841 Cholecystokinin Human genes 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 14
- 239000011734 sodium Substances 0.000 description 13
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 12
- 239000002244 precipitate Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 239000000047 product Substances 0.000 description 10
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 9
- 239000003480 eluent Substances 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- KXHBYSRUWPZBMF-UHFFFAOYSA-N 1-acetylindole-2-carboxylic acid Chemical compound C1=CC=C2N(C(=O)C)C(C(O)=O)=CC2=C1 KXHBYSRUWPZBMF-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
- 239000005557 antagonist Substances 0.000 description 8
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 8
- 150000003557 thiazoles Chemical class 0.000 description 8
- 102400000921 Gastrin Human genes 0.000 description 7
- 108010052343 Gastrins Proteins 0.000 description 7
- 239000007853 buffer solution Substances 0.000 description 7
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 102000005962 receptors Human genes 0.000 description 6
- 108020003175 receptors Proteins 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 229910052938 sodium sulfate Inorganic materials 0.000 description 6
- 235000011152 sodium sulphate Nutrition 0.000 description 6
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 230000008878 coupling Effects 0.000 description 5
- 238000010168 coupling process Methods 0.000 description 5
- 238000010908 decantation Methods 0.000 description 5
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- 238000003786 synthesis reaction Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 108010089335 Cholecystokinin A Receptor Proteins 0.000 description 4
- 108010089448 Cholecystokinin B Receptor Proteins 0.000 description 4
- 102100034927 Cholecystokinin receptor type A Human genes 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 229950003476 aminothiazole Drugs 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
- 210000003169 central nervous system Anatomy 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- SYYLBTHATZNOSE-UHFFFAOYSA-N 1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]indole-2-carboxylic acid Chemical compound C1=CC=C2N(CC(=O)OC(C)(C)C)C(C(O)=O)=CC2=C1 SYYLBTHATZNOSE-UHFFFAOYSA-N 0.000 description 3
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
- YUMHQQUMURQNOP-UHFFFAOYSA-N 5-benzyl-4-(2,4-dimethoxyphenyl)-1,3-thiazol-2-amine Chemical compound COC1=CC(OC)=CC=C1C1=C(CC=2C=CC=CC=2)SC(N)=N1 YUMHQQUMURQNOP-UHFFFAOYSA-N 0.000 description 3
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- 238000005727 Friedel-Crafts reaction Methods 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
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- 238000009835 boiling Methods 0.000 description 3
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- 210000002784 stomach Anatomy 0.000 description 3
- WOAKYNXITKJPIU-UHFFFAOYSA-N 1-(2-amino-4-phenyl-1,3-thiazol-5-yl)ethyl adamantane-1-carboxylate Chemical compound C1C(C2)CC(C3)CC2CC13C(=O)OC(C)C=1SC(N)=NC=1C1=CC=CC=C1 WOAKYNXITKJPIU-UHFFFAOYSA-N 0.000 description 2
- BPPBQXDRYMAPPZ-UHFFFAOYSA-N 2-[2-[[5-(2-acetyloxyethyl)-4-phenyl-1,3-thiazol-2-yl]carbamoyl]indol-1-yl]acetic acid Chemical compound CC(=O)OCCC=1SC(NC(=O)C=2N(C3=CC=CC=C3C=2)CC(O)=O)=NC=1C1=CC=CC=C1 BPPBQXDRYMAPPZ-UHFFFAOYSA-N 0.000 description 2
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- OTCFHGIJKQWKTL-UHFFFAOYSA-N 5-(2-aminoethyl)-4-phenyl-1,3-thiazol-2-amine Chemical compound S1C(N)=NC(C=2C=CC=CC=2)=C1CCN OTCFHGIJKQWKTL-UHFFFAOYSA-N 0.000 description 2
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- 239000007832 Na2SO4 Substances 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
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- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- PBQBMNVQZCXYEU-UHFFFAOYSA-N ethyl 2-[2-[(1-acetylindole-2-carbonyl)amino]-4-(2,4-dimethoxyphenyl)-1,3-thiazol-5-yl]acetate Chemical compound CCOC(=O)CC=1SC(NC(=O)C=2N(C3=CC=CC=C3C=2)C(C)=O)=NC=1C1=CC=C(OC)C=C1OC PBQBMNVQZCXYEU-UHFFFAOYSA-N 0.000 description 2
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- SANBIBGFRRCPOZ-UHFFFAOYSA-N tert-butyl 2-[2-[[5-(2-acetyloxyethyl)-4-phenyl-1,3-thiazol-2-yl]carbamoyl]indol-1-yl]acetate Chemical compound CC(=O)OCCC=1SC(NC(=O)C=2N(C3=CC=CC=C3C=2)CC(=O)OC(C)(C)C)=NC=1C1=CC=CC=C1 SANBIBGFRRCPOZ-UHFFFAOYSA-N 0.000 description 1
- XCTWTDDJJOPQRI-UHFFFAOYSA-N tert-butyl 2-[2-[[5-(2-hydroxyethyl)-4-phenyl-1,3-thiazol-2-yl]carbamoyl]indol-1-yl]acetate Chemical compound C(C)(C)(C)OC(=O)CN1C(=CC2=CC=CC=C12)C(=O)NC=1SC(=C(N1)C1=CC=CC=C1)CCO XCTWTDDJJOPQRI-UHFFFAOYSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 150000003585 thioureas Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/08—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D277/12—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/18—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/40—Unsubstituted amino or imino radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR9106814A FR2677356B1 (fr) | 1991-06-05 | 1991-06-05 | Derives heterocycliques d'acylamino-2 thiazoles-5 substitues, leur preparation et compositions pharmaceutiques en contenant. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO922215D0 NO922215D0 (no) | 1992-06-04 |
| NO922215L NO922215L (no) | 1992-12-07 |
| NO300135B1 true NO300135B1 (no) | 1997-04-14 |
Family
ID=9413505
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO922215A NO300135B1 (no) | 1991-06-05 | 1992-06-04 | Heterocyklisk substituerte 2-acylamino-5-tiazoler, og mellomprodukter for fremstilling derav |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US5314889A (cs) |
| EP (1) | EP0518731B1 (cs) |
| JP (1) | JP3199451B2 (cs) |
| KR (1) | KR100222309B1 (cs) |
| AT (1) | ATE170186T1 (cs) |
| AU (1) | AU650754B2 (cs) |
| BR (2) | BR9202156A (cs) |
| CA (1) | CA2070526A1 (cs) |
| CZ (1) | CZ289003B6 (cs) |
| DE (1) | DE69226729T2 (cs) |
| ES (1) | ES2121575T3 (cs) |
| FI (1) | FI922589A7 (cs) |
| FR (1) | FR2677356B1 (cs) |
| HU (1) | HU221312B1 (cs) |
| IE (1) | IE921814A1 (cs) |
| IL (1) | IL102004A (cs) |
| MX (1) | MX9202662A (cs) |
| NO (1) | NO300135B1 (cs) |
| NZ (1) | NZ243009A (cs) |
| RU (1) | RU2059637C1 (cs) |
| TW (1) | TW202448B (cs) |
| UA (1) | UA26899C2 (cs) |
| ZA (1) | ZA923981B (cs) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4303676A1 (de) * | 1993-02-09 | 1994-08-11 | Bayer Ag | 1-Aryltriazolin(thi)one |
| FR2701708B1 (fr) * | 1993-02-19 | 1995-05-19 | Sanofi Elf | Dérivés de 2-amido-4-phénylthiazoles polysubstitués, procédé de préparation, composition pharmaceutique et utilisation de ces dérivés pour la préparation d'un médicament. |
| FR2703995B1 (fr) * | 1993-04-16 | 1995-07-21 | Sanofi Elf | 5-acylamino 1,2,4-thiadiazoles, leur preparation et compositions pharmaceutiques en contenant. |
| WO1995032963A1 (en) * | 1994-06-01 | 1995-12-07 | Yoshitomi Pharmaceutical Industries, Ltd. | Thienylazole compound and thienotriazolodiazepine compound |
| MX9604483A (es) * | 1994-09-08 | 1998-02-28 | Jean-Francois Rossignol | Derivados de benzamida, composiciones que contienen dicho derivado y uso de las mismas. |
| JP3404749B2 (ja) * | 1996-06-27 | 2003-05-12 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | Ｎ―［４―（ヘテロアリールメチル）フェニル］―ヘテロアリールアミン |
| WO1998035707A1 (en) | 1997-02-18 | 1998-08-20 | Thomas Jefferson University | Compositions that bind to pancreatic cancer cells and methods of using the same |
| CO4970713A1 (es) | 1997-09-19 | 2000-11-07 | Sanofi Synthelabo | Derivados de carboxamidotiazoles, su preparacion, composiciones farmaceuticas que los contienen |
| FR2768737B1 (fr) * | 1997-09-19 | 2000-05-19 | Sanofi Sa | Derives de carboxamidothiazoles, leur preparation, les compositions pharmaceutiques en contenant |
| GB0028383D0 (en) * | 2000-11-21 | 2001-01-03 | Novartis Ag | Organic compounds |
| EP1361220A4 (en) * | 2001-01-26 | 2005-09-07 | Shionogi & Co | CYCLIC COMPOUNDS WITH THROMBOPOIETIN RECEPTAGONISM |
| EP1357116A4 (en) * | 2001-02-02 | 2005-06-01 | Yamanouchi Pharma Co Ltd | 2-ACYLAMINOTHIAZOLE DERIVATIVE OR SALT THEREOF |
| ES2610611T3 (es) * | 2002-01-18 | 2017-04-28 | Astellas Pharma Inc. | Derivado de 2-acilaminotiazol o sal del mismo |
| US20030225054A1 (en) * | 2002-06-03 | 2003-12-04 | Jingwu Duan | Combined use of tace inhibitors and COX2 inhibitors as anti-inflammatory agents |
| FR2854158B1 (fr) * | 2003-04-25 | 2006-11-17 | Sanofi Synthelabo | Derives de 2-acylamino-4-phenylethiazole, leur preparation et leur application en therapeutique |
| KR100907317B1 (ko) * | 2003-07-17 | 2009-07-13 | 아스텔라스세이야쿠 가부시키가이샤 | 2-아실아미노티아졸 유도체 또는 그의 염 |
| AR045651A1 (es) * | 2003-09-19 | 2005-11-02 | Solvay Pharm Bv | Derivados de tiazol como moduladores del receptor de cannabinoide |
| RU2361868C2 (ru) * | 2003-12-08 | 2009-07-20 | Ф.Хоффманн-Ля Рош Аг | Новые производные тиазола |
| SI3002283T1 (en) * | 2003-12-26 | 2018-06-29 | Kyowa Hakko Kirin Co., Ltd. | Thiazole derivatives |
| GB0401336D0 (en) * | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
| ES2777924T3 (es) | 2004-05-23 | 2020-08-06 | Hmi Medical Innovations Llc | Moduladores de teramuteína |
| FR2872813B1 (fr) * | 2004-07-09 | 2007-01-19 | Sanofi Synthelabo | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| AU2005272815A1 (en) * | 2004-08-13 | 2006-02-23 | Genentech, Inc. | Thiazole based inhibitors of ATP-utilizing enzymes |
| FR2876692B1 (fr) * | 2004-10-19 | 2007-02-23 | Sanofi Aventis Sa | Derives de 2-amido-4-phenylthiazole, leur preparation et leur application en therapeutique |
| JP4774995B2 (ja) * | 2005-01-12 | 2011-09-21 | アステラス製薬株式会社 | アシルアミノチアゾール誘導体を有効成分とする医薬組成物 |
| MX2007015216A (es) * | 2005-06-03 | 2008-02-22 | Xenon Pharmaceuticals Inc | Derivados de aminotiazol y sus usos como agentes terapeuticos. |
| JPWO2006137527A1 (ja) * | 2005-06-23 | 2009-01-22 | 協和発酵キリン株式会社 | チアゾール誘導体 |
| HUE034666T2 (hu) | 2005-08-02 | 2018-02-28 | Kyowa Hakko Kirin Co Ltd | Szer alvászavar kezelésére és/vagy megelõzésére |
| EP1971368A4 (en) * | 2005-11-08 | 2009-08-05 | Astellas Pharma Inc | COMPOSITIONS AND METHODS FOR TREATING THROMBOCYTOPENIA |
| FR2895989B1 (fr) * | 2006-01-06 | 2010-04-30 | Sanofi Aventis | Derives de 2-carbamide-4-phenylthiazole, leur preparation et leur application en therapeutique |
| WO2007087427A2 (en) * | 2006-01-25 | 2007-08-02 | Synta Pharmaceuticals Corp. | Thiazole and thiadiazole compounds for inflammation and immune-related uses |
| CN101096363B (zh) * | 2006-06-27 | 2011-05-11 | 中国人民解放军军事医学科学院毒物药物研究所 | 2,4,5-三取代噻唑类化合物、其制备方法、药物组合物及其制药用途 |
| AU2007284644B2 (en) * | 2006-08-08 | 2011-09-01 | Akarx, Inc. | Compositions and methods for increasing blood platelet levels in humans |
| JP2011509261A (ja) * | 2008-01-07 | 2011-03-24 | シンタ ファーマシューティカルズ コーポレーション | 炎症および免疫関連用途向けの化合物 |
| CL2009000780A1 (es) | 2008-03-31 | 2010-01-15 | Genentech Inc | Compuestos derivados de heterociclil-pirano-heterociclilo, heterociclil-oxepina-heterociclilo, benzopirano-heterociclilo y benzoxepina-heterociclilo sustituidos; composicion farmaceutica; procedimiento de preparacion de la composicion; kit farmaceutico; y su uso en el tratamiento del cancer, mediado por la inhibicion de pi3k. |
| EP2464352A1 (en) * | 2009-08-14 | 2012-06-20 | Eisai Inc. | Use of e5501 for stimulating platelet production |
| JP5546636B2 (ja) | 2009-09-28 | 2014-07-09 | エフ・ホフマン−ラ・ロシュ・アクチェンゲゼルシャフト | ベンゾキセピンｐｉ３ｋ阻害剤化合物及び使用方法 |
| PL2483278T3 (pl) | 2009-09-28 | 2014-05-30 | Hoffmann La Roche | Związki benzoksazepinowe stanowiące inhibitor pi3k i ich zastosowanie w leczeniu nowotworu |
| KR101609856B1 (ko) * | 2010-03-17 | 2016-04-07 | 타이벡스 세라피틱스 코포레이션 | Ｈｅｃ１ 활성의 조절인자 및 이의 방법 |
| CA2825966A1 (en) | 2011-03-21 | 2012-09-27 | F. Hoffmann-La Roche Ag | Benzoxazepin compounds selective for pi3k p110 delta and methods of use |
| MX2014009624A (es) | 2012-02-17 | 2015-03-19 | Hoffmann La Roche | Compuestos triciclicos y metodos para el uso de los mismos. |
| JP2022500499A (ja) | 2018-09-07 | 2022-01-04 | ピク セラピューティクス， インコーポレイテッド | Ｅｉｆ４ｅ阻害剤およびその使用 |
| WO2021178488A1 (en) | 2020-03-03 | 2021-09-10 | PIC Therapeutics, Inc. | Eif4e inhibitors and uses thereof |
| CA3229560A1 (en) | 2021-08-25 | 2023-03-02 | Christopher L. Vandeusen | Eif4e inhibitors and uses thereof |
| JP2024532276A (ja) | 2021-08-25 | 2024-09-05 | ピク セラピューティクス， インコーポレイテッド | ｅＩＦ４Ｅ阻害剤及びその使用 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3210368A (en) * | 1964-09-29 | 1965-10-05 | Ciba Geigy Corp | Certain 2-amino-4-aryl-5-n, n-disubstituted amino-lower alkyl-thiazole compounds |
| EP0208510B1 (en) * | 1985-07-09 | 1991-09-11 | Pfizer Inc. | 1-substituted oxindole-3-carboxamines as antiinflammatory and analgesic agents |
| DE3705934A1 (de) * | 1987-02-25 | 1988-09-08 | Nattermann A & Cie | Indolyl-derivate, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US4971978A (en) * | 1987-09-21 | 1990-11-20 | Nadzan Alex M | Derivatives of D-glutamic acid and D-aspartic acid |
| US4992437A (en) * | 1987-12-22 | 1991-02-12 | Yoshitomi Pharmaceutical Industries, Ltd. | Thienodiazepine compounds and their pharmaceutical use |
| IE68593B1 (en) * | 1989-12-06 | 1996-06-26 | Sanofi Sa | Heterocyclic substituted acylaminothiazoles their preparation and pharmaceutical compositions containing them |
-
1991
- 1991-06-05 FR FR9106814A patent/FR2677356B1/fr not_active Expired - Fee Related
-
1992
- 1992-05-26 IL IL102004A patent/IL102004A/xx not_active IP Right Cessation
- 1992-05-28 AU AU17279/92A patent/AU650754B2/en not_active Ceased
- 1992-05-29 US US07/889,910 patent/US5314889A/en not_active Expired - Fee Related
- 1992-06-01 ZA ZA923981A patent/ZA923981B/xx unknown
- 1992-06-01 TW TW081104270A patent/TW202448B/zh active
- 1992-06-03 AT AT92401518T patent/ATE170186T1/de not_active IP Right Cessation
- 1992-06-03 NZ NZ243009A patent/NZ243009A/en unknown
- 1992-06-03 ES ES92401518T patent/ES2121575T3/es not_active Expired - Lifetime
- 1992-06-03 DE DE69226729T patent/DE69226729T2/de not_active Expired - Fee Related
- 1992-06-03 EP EP92401518A patent/EP0518731B1/fr not_active Expired - Lifetime
- 1992-06-04 FI FI922589A patent/FI922589A7/fi not_active Application Discontinuation
- 1992-06-04 JP JP14415092A patent/JP3199451B2/ja not_active Expired - Fee Related
- 1992-06-04 CA CA002070526A patent/CA2070526A1/en not_active Abandoned
- 1992-06-04 CZ CS19921693A patent/CZ289003B6/cs not_active IP Right Cessation
- 1992-06-04 HU HU9201870A patent/HU221312B1/hu not_active IP Right Cessation
- 1992-06-04 RU SU5011874/04A patent/RU2059637C1/ru not_active IP Right Cessation
- 1992-06-04 MX MX9202662A patent/MX9202662A/es not_active IP Right Cessation
- 1992-06-04 NO NO922215A patent/NO300135B1/no not_active IP Right Cessation
- 1992-06-05 BR BR929202156A patent/BR9202156A/pt not_active Application Discontinuation
- 1992-06-05 KR KR1019920009859A patent/KR100222309B1/ko not_active Expired - Fee Related
- 1992-07-01 IE IE181492A patent/IE921814A1/en not_active IP Right Cessation
-
1993
- 1993-06-15 UA UA93002939A patent/UA26899C2/uk unknown
-
1994
- 1994-03-03 US US08/205,408 patent/US5380736A/en not_active Expired - Fee Related
-
1997
- 1997-05-12 BR BR1100786-9A patent/BR1100786A/pt active IP Right Grant
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