OA10103A - Indole derivatives - Google Patents
Indole derivatives Download PDFInfo
- Publication number
- OA10103A OA10103A OA60570A OA60570A OA10103A OA 10103 A OA10103 A OA 10103A OA 60570 A OA60570 A OA 60570A OA 60570 A OA60570 A OA 60570A OA 10103 A OA10103 A OA 10103A
- Authority
- OA
- OAPI
- Prior art keywords
- compound
- group
- dichloroindole
- ethenyl
- formula
- Prior art date
Links
- 150000002475 indoles Chemical class 0.000 title description 2
- 229940054051 antipsychotic indole derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 139
- -1 hydroxy, methoxy Chemical group 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 150000002148 esters Chemical class 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 20
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims abstract description 20
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 9
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 230000002461 excitatory amino acid Effects 0.000 claims abstract description 7
- 239000003257 excitatory amino acid Substances 0.000 claims abstract description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 4
- 125000003118 aryl group Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 30
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 9
- 230000000694 effects Effects 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 claims description 6
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 5
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 150000001336 alkenes Chemical class 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- QTLWFRINMXAUQZ-JXMROGBWSA-N 3-[(e)-3-anilino-2-methyl-3-oxoprop-1-enyl]-4,6-dichloro-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC(Cl)=CC(Cl)=C2C=1\C=C(/C)C(=O)NC1=CC=CC=C1 QTLWFRINMXAUQZ-JXMROGBWSA-N 0.000 claims 1
- WQVZUMRYVXXYQS-GQCTYLIASA-N 4,6-dichloro-3-[(e)-3-(3,4-dimethoxyanilino)-3-oxoprop-1-enyl]-1h-indole-2-carboxylic acid Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)\C=C\C1=C(C(O)=O)NC2=CC(Cl)=CC(Cl)=C12 WQVZUMRYVXXYQS-GQCTYLIASA-N 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 5
- 101100496169 Arabidopsis thaliana CLH1 gene Proteins 0.000 abstract 1
- 101100044057 Mesocricetus auratus SYCP3 gene Proteins 0.000 abstract 1
- 101100080600 Schizosaccharomyces pombe (strain 972 / ATCC 24843) nse6 gene Proteins 0.000 abstract 1
- 101150111293 cor-1 gene Proteins 0.000 abstract 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 66
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 239000000203 mixture Substances 0.000 description 45
- 239000007787 solid Substances 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 239000000543 intermediate Substances 0.000 description 27
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 229940093499 ethyl acetate Drugs 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 239000002244 precipitate Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 8
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 8
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 230000003389 potentiating effect Effects 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 239000004471 Glycine Substances 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
- 241000699670 Mus sp. Species 0.000 description 4
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 4
- 241001279009 Strychnos toxifera Species 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
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- 125000004494 ethyl ester group Chemical group 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
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- 238000002347 injection Methods 0.000 description 4
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- 229910052757 nitrogen Inorganic materials 0.000 description 4
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- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 229960005453 strychnine Drugs 0.000 description 4
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- UWTUEMKLYAGTNQ-UHFFFAOYSA-N 1,2-dibromoethene Chemical compound BrC=CBr UWTUEMKLYAGTNQ-UHFFFAOYSA-N 0.000 description 3
- BPXKZEMBEZGUAH-UHFFFAOYSA-N 2-(chloromethoxy)ethyl-trimethylsilane Chemical compound C[Si](C)(C)CCOCCl BPXKZEMBEZGUAH-UHFFFAOYSA-N 0.000 description 3
- CDYKOUYRAOOTCV-UHFFFAOYSA-N 3,4-dichloro-1h-indole-2-carboxylic acid Chemical compound C1=CC(Cl)=C2C(Cl)=C(C(=O)O)NC2=C1 CDYKOUYRAOOTCV-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 3
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- 125000004103 aminoalkyl group Chemical group 0.000 description 3
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
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- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
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- LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- SVOOVMQUISJERI-UHFFFAOYSA-K rhodium(3+);triacetate Chemical compound [Rh+3].CC([O-])=O.CC([O-])=O.CC([O-])=O SVOOVMQUISJERI-UHFFFAOYSA-K 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000003019 stabilising effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929208492A GB9208492D0 (en) | 1992-04-16 | 1992-04-16 | Heterocyclic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| OA10103A true OA10103A (en) | 1996-12-18 |
Family
ID=10714220
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| OA60570A OA10103A (en) | 1992-04-16 | 1994-10-10 | Indole derivatives |
Country Status (41)
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9304500D0 (en) * | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
| WO1994027964A1 (en) * | 1993-05-27 | 1994-12-08 | Merrell Dow Pharmaceuticals Inc. | 3-(indol-3-yl) propenoic acid derivatives and as nmda antagonists |
| US5519048A (en) * | 1993-05-27 | 1996-05-21 | Merrell Pharmaceuticals Inc. | 3-(indol-3-yl)-propenoic acid derivatives and pharmaceutical compositions thereof |
| GB9319243D0 (en) * | 1993-09-17 | 1993-11-03 | Glaxo Spa | Heterocyclic compounds |
| GB9321221D0 (en) * | 1993-10-14 | 1993-12-01 | Glaxo Spa | Heterocyclic compounds |
| TW280819B (enExample) * | 1993-11-17 | 1996-07-11 | Sumitomo Pharma | |
| US5563157B1 (en) * | 1994-10-31 | 1999-02-02 | Hoecst Marion Roussel Inc | Heterocycle substituted propenoic acid derivatives and pharmaceutical compositions thereof |
| GB9502695D0 (en) * | 1995-02-11 | 1995-03-29 | Glaxo Spa | Pharmaceutical composition |
| GB9504361D0 (en) * | 1995-03-04 | 1995-04-26 | Glaxo Spa | Heterocyclic compounds |
| AU4416197A (en) * | 1996-09-17 | 1998-04-14 | Regents Of The University Of California, The | Positive ampa receptor modulation to enhance brain neurotrophic factor expression |
| CN1139572C (zh) * | 1996-09-30 | 2004-02-25 | éżæž©èæŻèŻç©ć Źćž | Nmda(n-çČćș-d-怩ćŹæ°šé ž)æźæć |
| US5922752A (en) * | 1997-06-11 | 1999-07-13 | Hoechst Marion Roussell, Inc. | NMDA (n-methyl-d-aspartate) antagonists |
| AU749623B2 (en) * | 1998-03-26 | 2002-06-27 | Astellas Pharma Inc. | Sustained release preparations |
| RU2277096C2 (ru) * | 2000-07-31 | 2006-05-27 | ĐĐĐĐĐĐĐĐĐ ĐĄĐŁĐĐĐąĐĐРЀĐĐ ĐĐ ĐĐŸ., ĐĐąĐ. | ĐĄŃДЎŃŃĐČĐ° ĐżŃĐŸŃĐžĐČ ŃĐ»Đ°Đ±ĐŸŃĐŒĐžŃ, ŃĐŸĐŽĐ”ŃжаŃОД ĐżŃĐŸĐžĐ·ĐČĐŸĐŽĐœĐŸĐ” 2-Đ°ŃОл-8-ĐŸĐșŃĐŸĐŽĐžĐłĐžĐŽŃĐŸĐżŃŃĐžĐœĐ° ĐČ ĐșĐ°ŃĐ”ŃŃĐČĐ” Đ°ĐșŃĐžĐČĐœĐŸĐłĐŸ ĐžĐœĐłŃĐ”ĐŽĐžĐ”ĐœŃĐ° |
| WO2003039540A2 (en) * | 2001-11-09 | 2003-05-15 | Sepracor Inc. | D-amino acid oxidase inhibitors for learning and memory |
| MXPA04005427A (es) * | 2001-12-10 | 2005-04-19 | Amgen Inc | Ligandos de receptor vainilloide y su uso en tratamientos. |
| PA8579701A1 (es) * | 2002-08-23 | 2005-05-24 | Pfizer Prod Inc | Profarmaco inhibidor de beta-lactamasa |
| DE10306202A1 (de) | 2003-02-13 | 2004-08-26 | GrĂŒnenthal GmbH | Arzneimittel enthaltend substituierte 2-Aryl-AminoessigsĂ€ure-Verbindungen und/oder substituierte 2-Heteroaryl-AminoessigsĂ€ure-Verbindungen |
| JP2006526612A (ja) * | 2003-06-05 | 2006-11-24 | ăăĄă€ă¶ăŒă»ăăăăŻăă»ă€ăłăŻ | ăăŒăżâă©ăŻăżăăŒăŒé»ćźłć€ă»ăăăă©ăă° |
| RU2247563C1 (ru) * | 2003-06-16 | 2005-03-10 | ĐŃŃĐžĐłĐŸŃŃĐșĐ°Ń ĐłĐŸŃŃĐŽĐ°ŃŃŃĐČĐ”ĐœĐœĐ°Ń ŃĐ°ŃĐŒĐ°ŃĐ”ĐČŃĐžŃĐ”ŃĐșĐ°Ń Đ°ĐșĐ°ĐŽĐ”ĐŒĐžŃ | ĐĄĐżĐŸŃĐŸĐ± ĐżĐŸĐ»ŃŃĐ”ĐœĐžŃ ŃĐČĐ”ŃĐŽĐŸĐč лДĐșĐ°ŃŃŃĐČĐ”ĐœĐœĐŸĐč ŃĐŸŃĐŒŃ, ŃĐŸĐŽĐ”ŃжаŃĐ”Đč глŃĐșĐŸĐ·Đ°ĐŒĐžĐœĐ° гОЎŃĐŸŃ Đ»ĐŸŃОЎ |
| CA2547283C (en) * | 2003-11-26 | 2010-11-09 | Pfizer Products Inc. | Aminopyrazole derivatives as gsk-3 inhibitors |
| NZ548212A (en) * | 2003-12-29 | 2010-07-30 | Sepracor Inc | Pyrrole and pyrazole DAAO inhibitors |
| RU2281755C2 (ru) * | 2004-04-19 | 2006-08-20 | ĐŃŃĐžĐłĐŸŃŃĐșĐ°Ń ĐłĐŸŃŃĐŽĐ°ŃŃŃĐČĐ”ĐœĐœĐ°Ń ŃĐ°ŃĐŒĐ°ŃĐ”ĐČŃĐžŃĐ”ŃĐșĐ°Ń Đ°ĐșĐ°ĐŽĐ”ĐŒĐžŃ | ĐĐŸĐŒĐżĐŸĐ·ĐžŃĐžŃ - лДĐșĐ°ŃŃŃĐČĐ”ĐœĐœĐ°Ń ŃĐŸŃĐŒĐ° ĐżŃĐŸŃĐžĐČĐŸĐ°ŃŃŃĐŸĐ·ĐœĐŸĐłĐŸ ŃŃДЎŃŃĐČĐ° глŃĐșĐŸĐ·Đ°ĐŒĐžĐœĐ° гОЎŃĐŸŃ Đ»ĐŸŃОЎа ĐŽĐ»Ń ŃĐ”ĐșŃĐ°Đ»ŃĐœĐŸĐłĐŸ ĐżŃĐžĐŒĐ”ĐœĐ”ĐœĐžŃ |
| US20060002999A1 (en) * | 2004-06-17 | 2006-01-05 | Forest Laboratories, Inc. | Immediate release formulations of 1-aminocyclohexane compounds, memantine and neramexane |
| WO2007006003A2 (en) | 2005-07-06 | 2007-01-11 | Sepracor Inc. | Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders |
| US8053603B2 (en) * | 2006-01-06 | 2011-11-08 | Sunovion Pharmaceuticals Inc. | Tetralone-based monoamine reuptake inhibitors |
| KR101294014B1 (ko) | 2006-01-06 | 2013-08-09 | ì ì€ëčìš íë§ìí°ì»Źì€ ìžìœíŹë ìŽí°ë | ëȘšë žìëŻŒ ìŹíĄì ì íŽì ëĄìì ìíŽëĄìíŹìëŻŒ |
| DK2816024T3 (en) | 2006-03-31 | 2017-10-30 | Sunovion Pharmaceuticals Inc | CHIRALE AMINER |
| US7884124B2 (en) * | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
| US7579370B2 (en) * | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
| US20080082066A1 (en) * | 2006-10-02 | 2008-04-03 | Weyerhaeuser Co. | Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks |
| EP1942104A1 (en) | 2006-12-20 | 2008-07-09 | sanofi-aventis | Heteroarylcyclopropanecarboxamides and their use as pharmaceuticals |
| US20090099248A1 (en) * | 2007-01-18 | 2009-04-16 | Sepracor Inc. | Inhibitors of d-amino acid oxidase |
| US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
| MX2009012685A (es) | 2007-05-31 | 2009-12-14 | Sepracor Inc | Cicloalquilaminas sustituidas con fenilo como inhibidores de la reabsorcion de monoamina. |
| US20090247644A1 (en) * | 2008-03-28 | 2009-10-01 | Forest Laboratories Holdings Limited | Memantine formulations |
| WO2010017418A1 (en) * | 2008-08-07 | 2010-02-11 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| JP2010235597A (ja) * | 2009-03-10 | 2010-10-21 | Santen Pharmaceut Co Ltd | ïŒïŒïŒâăžăŻăăâïŒïœâă€ăłăăŒă«âïŒâă«ă«ăăłé žèȘć°äœćăŻăăźćĄ©ăæćčæćăšăăŠć«æăăèŠç„ç”éćźłăźäșéČćăŻæČ»çć€ |
| WO2011017634A2 (en) * | 2009-08-07 | 2011-02-10 | Sepracore Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
| US9737531B2 (en) | 2012-07-12 | 2017-08-22 | Glytech, Llc | Composition and method for treatment of depression and psychosis in humans |
| SG10202102125SA (en) | 2014-04-30 | 2021-04-29 | Yufeng Tseng | Use of known compounds as d-amino acid oxidase inhibitors |
| EP4289425A3 (en) | 2016-09-14 | 2024-08-07 | Yufeng Jane Tseng | Novel substituted benzimidazole derivatives as d-amino acid oxidase (daao) inhibitors |
| CA3067162A1 (en) | 2017-06-12 | 2018-12-20 | Glytech Llc. | Composition and method for treatment or depression and psychosis in humans |
| CN112707874A (zh) * | 2020-12-29 | 2021-04-27 | ćčżäžäžç§èŻç©ç 究æéć Źćž | äžç§æç æŻććç©ćć ¶ć¶ć€æčæł |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3010971A (en) * | 1960-08-04 | 1961-11-28 | Smith Kline French Lab | Cyclopropylamine derivatives and processes for their preparation |
| DK500285A (da) * | 1984-11-02 | 1986-05-03 | Glaxo Group Ltd | Cephalosporinantibiotika |
| US4960786A (en) * | 1989-04-24 | 1990-10-02 | Merrell Dow Pharmaceuticals Inc. | Excitatory amino acid antagonists |
| PT93943A (pt) * | 1989-05-05 | 1991-02-08 | Searle & Co | Processo para a preparacao de composicoes contendo compostos indole-2-carboxilato para tratamento de perturbacoes do snc |
| HU216787B (hu) * | 1990-07-16 | 1999-08-30 | Merrell Dow Pharmaceuticals Inc. | EljĂĄrĂĄs excitĂĄtoros aminosav-antagonista hatĂĄsĂș indolszĂĄrmazĂ©kok Ă©s ezeket tartalmazĂł gyĂłgyszerkĂ©szĂtmĂ©nyek elĆĂĄllĂtĂĄsĂĄra |
| US5284862A (en) * | 1991-03-18 | 1994-02-08 | Warner-Lambert Company | Derivatives of 2-carboxyindoles having pharmaceutical activity |
| US5145845A (en) * | 1991-05-14 | 1992-09-08 | Warner-Lambert Co. | Substituted 2-carboxylindoles having pharmaceutical activity |
-
1992
- 1992-04-16 GB GB929208492A patent/GB9208492D0/en active Pending
-
1993
- 1993-04-14 ZA ZA932642A patent/ZA932642B/xx unknown
- 1993-04-15 CA CA002094075A patent/CA2094075A1/en not_active Abandoned
- 1993-04-15 GR GR930100154A patent/GR1001619B/el not_active IP Right Cessation
- 1993-04-15 AT AT0075293A patent/AT403917B/de not_active IP Right Cessation
- 1993-04-15 AU AU36923/93A patent/AU666927B2/en not_active Ceased
- 1993-04-15 HU HU9402975A patent/HU217964B/hu not_active IP Right Cessation
- 1993-04-15 LU LU88248A patent/LU88248A1/fr unknown
- 1993-04-15 PL PL93305554A patent/PL176451B1/pl unknown
- 1993-04-15 RU RU94045915A patent/RU2129544C1/ru active
- 1993-04-15 SK SK1241-94A patent/SK281941B6/sk unknown
- 1993-04-15 CA CA002094073A patent/CA2094073A1/en not_active Abandoned
- 1993-04-15 EP EP93201103A patent/EP0568136A1/en not_active Withdrawn
- 1993-04-15 NZ NZ247413A patent/NZ247413A/en unknown
- 1993-04-15 FR FR9304452A patent/FR2690919B1/fr not_active Expired - Fee Related
- 1993-04-15 CA CA002094076A patent/CA2094076A1/en not_active Abandoned
- 1993-04-15 WO PCT/EP1993/000938 patent/WO1993021153A1/en not_active Ceased
- 1993-04-15 DK DK043193A patent/DK169890B1/da active
- 1993-04-15 CZ CZ942543A patent/CZ285799B6/cs not_active IP Right Cessation
- 1993-04-15 CN CN93105797A patent/CN1042331C/zh not_active Expired - Fee Related
- 1993-04-15 KR KR1019940703668A patent/KR100264114B1/ko not_active Expired - Fee Related
- 1993-04-15 GB GB9307808A patent/GB2266091B/en not_active Expired - Fee Related
- 1993-04-15 MY MYPI93000690A patent/MY112232A/en unknown
- 1993-04-15 US US08/046,947 patent/US5373018A/en not_active Expired - Fee Related
- 1993-04-15 BE BE9300371A patent/BE1006343A5/fr active
- 1993-04-15 JP JP5517997A patent/JPH07505407A/ja active Pending
- 1993-04-15 CH CH1133/93A patent/CH685630A5/fr not_active IP Right Cessation
- 1993-04-15 JP JP5088844A patent/JPH0649027A/ja active Pending
- 1993-04-15 US US08/047,430 patent/US5374649A/en not_active Expired - Fee Related
- 1993-04-15 ES ES09300771A patent/ES2105924B1/es not_active Expired - Lifetime
- 1993-04-15 IS IS3994A patent/IS3994A/is unknown
- 1993-04-15 MX MX9302195A patent/MX9302195A/es not_active IP Right Cessation
- 1993-04-15 SE SE9301241A patent/SE504336C2/sv not_active IP Right Cessation
- 1993-04-15 RO RO94-01658A patent/RO113242B1/ro unknown
- 1993-04-15 IL IL105412A patent/IL105412A/en not_active IP Right Cessation
- 1993-04-15 IT IT93RM000236A patent/IT1265325B1/it active IP Right Grant
- 1993-04-15 US US08/047,429 patent/US5374648A/en not_active Expired - Fee Related
- 1993-04-16 AP APAP/P/1993/000524A patent/AP480A/en active
- 1993-04-16 GE GEAP19932602A patent/GEP19991704B/en unknown
- 1993-05-06 TW TW082103531A patent/TW224457B/zh active
-
1994
- 1994-10-10 OA OA60570A patent/OA10103A/en unknown
- 1994-10-12 FI FI944800A patent/FI106198B/fi active
- 1994-10-14 NO NO943913A patent/NO301879B1/no not_active IP Right Cessation
- 1994-10-14 BG BG99111A patent/BG62136B1/bg unknown
- 1994-12-08 US US08/351,762 patent/US5510367A/en not_active Expired - Fee Related
-
1995
- 1995-06-29 HU HU95P/P00538P patent/HU211826A9/hu unknown
-
1997
- 1997-04-22 BR BR1100323-5A patent/BR1100323A/pt active IP Right Grant
- 1997-06-26 HK HK95797A patent/HK95797A/xx not_active IP Right Cessation
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1998
- 1998-04-30 CY CY9802038A patent/CY2038B1/xx unknown
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