CZ294794A3 - Derivative of glutamic acid, process of its preparation and pharmaceutical composition containing thereof - Google Patents
Derivative of glutamic acid, process of its preparation and pharmaceutical composition containing thereof Download PDFInfo
- Publication number
- CZ294794A3 CZ294794A3 CZ942947A CZ294794A CZ294794A3 CZ 294794 A3 CZ294794 A3 CZ 294794A3 CZ 942947 A CZ942947 A CZ 942947A CZ 294794 A CZ294794 A CZ 294794A CZ 294794 A3 CZ294794 A3 CZ 294794A3
- Authority
- CZ
- Czechia
- Prior art keywords
- group
- glutamic acid
- formula
- compound
- alkyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims description 41
- 230000008569 process Effects 0.000 title claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- -1 pyrimidazolyl Chemical group 0.000 claims description 190
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 104
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 47
- 239000004220 glutamic acid Substances 0.000 claims description 46
- 235000013922 glutamic acid Nutrition 0.000 claims description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 31
- 125000006239 protecting group Chemical group 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- 125000004432 carbon atom Chemical group C* 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 239000001301 oxygen Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 239000003257 excitatory amino acid Substances 0.000 claims description 17
- 230000002461 excitatory amino acid Effects 0.000 claims description 16
- 239000004480 active ingredient Substances 0.000 claims description 15
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 14
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 229910005965 SO 2 Inorganic materials 0.000 claims description 12
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 11
- 239000011593 sulfur Substances 0.000 claims description 11
- 125000004434 sulfur atom Chemical group 0.000 claims description 11
- 150000002306 glutamic acid derivatives Chemical class 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000001425 triazolyl group Chemical group 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000003107 substituted aryl group Chemical group 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- FBQTZNBVOFPDOT-WMCAAGNKSA-N (2s)-2-amino-3-dibenzofuran-2-yloxypentanedioic acid Chemical compound C1=CC=C2C3=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C3OC2=C1 FBQTZNBVOFPDOT-WMCAAGNKSA-N 0.000 claims description 5
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- KWQFQZGMLRXMCI-LWKPJOBUSA-N (2s)-2-amino-3-(9h-fluoren-2-yloxy)pentanedioic acid Chemical compound C1=CC=C2C3=CC=C(OC(CC(O)=O)[C@H](N)C(O)=O)C=C3CC2=C1 KWQFQZGMLRXMCI-LWKPJOBUSA-N 0.000 claims description 3
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 3
- 230000005062 synaptic transmission Effects 0.000 claims description 3
- BGCPLWWYPZAURQ-UHFFFAOYSA-N 5-[[5-chloro-2-(2,2,6,6-tetramethylmorpholin-4-yl)pyrimidin-4-yl]amino]-3-(3-hydroxy-3-methylbutyl)-1-methylbenzimidazol-2-one Chemical compound ClC=1C(=NC(=NC=1)N1CC(OC(C1)(C)C)(C)C)NC1=CC2=C(N(C(N2CCC(C)(C)O)=O)C)C=C1 BGCPLWWYPZAURQ-UHFFFAOYSA-N 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims 2
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 claims 1
- 101100119135 Mus musculus Esrrb gene Proteins 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- AKZGCWXVGRRTQV-UHFFFAOYSA-N diaminomercury Chemical compound N[Hg]N AKZGCWXVGRRTQV-UHFFFAOYSA-N 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000006303 iodophenyl group Chemical group 0.000 claims 1
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 claims 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 1
- 102000018899 Glutamate Receptors Human genes 0.000 abstract description 15
- 108010027915 Glutamate Receptors Proteins 0.000 abstract description 15
- 208000012902 Nervous system disease Diseases 0.000 abstract description 6
- 208000025966 Neurological disease Diseases 0.000 abstract description 5
- 238000010189 synthetic method Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 159
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 88
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 79
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 78
- 239000000203 mixture Substances 0.000 description 77
- 238000005481 NMR spectroscopy Methods 0.000 description 71
- 238000006243 chemical reaction Methods 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 55
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 55
- 238000001819 mass spectrum Methods 0.000 description 41
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 38
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 33
- 238000004458 analytical method Methods 0.000 description 31
- 239000003921 oil Substances 0.000 description 29
- 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 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 26
- 239000012074 organic phase Substances 0.000 description 26
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
- 238000001914 filtration Methods 0.000 description 24
- 239000007787 solid Substances 0.000 description 23
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- 239000000706 filtrate Substances 0.000 description 20
- 239000000543 intermediate Substances 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
- 239000000725 suspension Substances 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000012071 phase Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 14
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 14
- 239000003960 organic solvent Substances 0.000 description 14
- 102000005962 receptors Human genes 0.000 description 14
- 108020003175 receptors Proteins 0.000 description 14
- 230000007062 hydrolysis Effects 0.000 description 13
- 238000006460 hydrolysis reaction Methods 0.000 description 13
- 239000002198 insoluble material Substances 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 239000007800 oxidant agent Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- TVPVGSSUJZWLOG-HTLJXXAVSA-N (2s)-2-amino-3-phenoxypentanedioic acid Chemical compound OC(=O)[C@@H](N)C(CC(O)=O)OC1=CC=CC=C1 TVPVGSSUJZWLOG-HTLJXXAVSA-N 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical class OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 235000011089 carbon dioxide Nutrition 0.000 description 9
- 150000002148 esters Chemical group 0.000 description 9
- UZPRGYWLTRWGFD-UHFFFAOYSA-N ethyl 4-hydroxy-5-oxopyrrolidine-2-carboxylate Chemical compound CCOC(=O)C1CC(O)C(=O)N1 UZPRGYWLTRWGFD-UHFFFAOYSA-N 0.000 description 9
- 239000004615 ingredient Substances 0.000 description 9
- 239000012286 potassium permanganate Substances 0.000 description 9
- QACXMURHOPFKFS-UMJHXOGRSA-N (2s)-2-amino-3-(4-methylphenoxy)pentanedioic acid Chemical compound CC1=CC=C(OC(CC(O)=O)[C@H](N)C(O)=O)C=C1 QACXMURHOPFKFS-UMJHXOGRSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 description 8
- ROKDJKKHBOXFHQ-UHFFFAOYSA-N 2-methoxycarbonyloxazinane-3,6-dicarboxylic acid Chemical compound COC(=O)N1OC(C(O)=O)CCC1C(O)=O ROKDJKKHBOXFHQ-UHFFFAOYSA-N 0.000 description 7
- 229920002472 Starch Polymers 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 230000002051 biphasic effect Effects 0.000 description 7
- 125000002843 carboxylic acid group Chemical group 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000000434 field desorption mass spectrometry Methods 0.000 description 7
- 229930195712 glutamate Natural products 0.000 description 7
- 210000002569 neuron Anatomy 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 6
- 239000008107 starch Substances 0.000 description 6
- WKAFQUPMTXGNLL-IAXJKZSUSA-N (2s)-2-amino-3-(1,6-dibromonaphthalen-2-yl)oxypentanedioic acid Chemical compound C1=C(Br)C=CC2=C(Br)C(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C21 WKAFQUPMTXGNLL-IAXJKZSUSA-N 0.000 description 5
- XCQZTVGZMCYTJP-YUZLPWPTSA-N (2s)-2-amino-3-(2,3-dihydro-1h-inden-5-yloxy)pentanedioic acid Chemical compound OC(=O)[C@@H](N)C(CC(O)=O)OC1=CC=C2CCCC2=C1 XCQZTVGZMCYTJP-YUZLPWPTSA-N 0.000 description 5
- TWCNTQXAQVRBFA-UMJHXOGRSA-N (2s)-2-amino-3-(4-methoxyphenoxy)pentanedioic acid Chemical compound COC1=CC=C(OC(CC(O)=O)[C@H](N)C(O)=O)C=C1 TWCNTQXAQVRBFA-UMJHXOGRSA-N 0.000 description 5
- QUXMBDGQVQBZFL-WMCAAGNKSA-N (2s)-2-amino-3-(4-phenylphenoxy)pentanedioic acid Chemical compound C1=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C1C1=CC=CC=C1 QUXMBDGQVQBZFL-WMCAAGNKSA-N 0.000 description 5
- IQXPDPGVIKHKLD-WMCAAGNKSA-N (2s)-2-amino-3-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]pentanedioic acid Chemical compound CC(C)(C)CC(C)(C)C1=CC=C(OC(CC(O)=O)[C@H](N)C(O)=O)C=C1 IQXPDPGVIKHKLD-WMCAAGNKSA-N 0.000 description 5
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Natural products OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 150000008064 anhydrides Chemical class 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000005277 cation exchange chromatography Methods 0.000 description 5
- 208000035475 disorder Diseases 0.000 description 5
- 238000006073 displacement reaction Methods 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 150000007529 inorganic bases Chemical class 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 239000000454 talc Substances 0.000 description 5
- 229910052623 talc Inorganic materials 0.000 description 5
- 235000012222 talc Nutrition 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- CMVOFPMEBRMTJL-LWKPJOBUSA-N (2s)-2-amino-3-(4-benzylphenoxy)pentanedioic acid Chemical compound C1=CC(OC(CC(O)=O)[C@H](N)C(O)=O)=CC=C1CC1=CC=CC=C1 CMVOFPMEBRMTJL-LWKPJOBUSA-N 0.000 description 4
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- 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
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- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
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- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/24—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/57—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
- C07C323/58—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups with amino groups bound to the carbon skeleton
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
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- C07D207/26—2-Pyrrolidones
- C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
- C07D207/277—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D207/28—2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/38—One sulfur atom
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
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- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/91—Dibenzofurans; Hydrogenated dibenzofurans
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- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/64—Oxygen atoms
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/10—One of the condensed rings being a six-membered aromatic ring the other ring being six-membered, e.g. tetraline
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- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/06—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members
- C07C2603/10—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings
- C07C2603/12—Ortho- or ortho- and peri-condensed systems containing three rings containing at least one ring with less than six ring members containing five-membered rings only one five-membered ring
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16183093A | 1993-12-03 | 1993-12-03 | |
| US08/322,632 US5576323A (en) | 1993-12-03 | 1994-10-13 | Excitatory amino acid receptor antagonists |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ294794A3 true CZ294794A3 (en) | 1995-12-13 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ942947A CZ294794A3 (en) | 1993-12-03 | 1994-11-29 | Derivative of glutamic acid, process of its preparation and pharmaceutical composition containing thereof |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US5576323A (en:Method) |
| EP (1) | EP0658539A1 (en:Method) |
| JP (1) | JPH07267908A (en:Method) |
| KR (1) | KR950018015A (en:Method) |
| CN (1) | CN1108240A (en:Method) |
| AU (1) | AU676781B2 (en:Method) |
| BR (1) | BR9404809A (en:Method) |
| CA (1) | CA2136904A1 (en:Method) |
| CO (1) | CO4290421A1 (en:Method) |
| CZ (1) | CZ294794A3 (en:Method) |
| FI (1) | FI945704A7 (en:Method) |
| HU (1) | HUT69181A (en:Method) |
| IL (1) | IL111789A0 (en:Method) |
| NO (1) | NO944578L (en:Method) |
| NZ (1) | NZ270009A (en:Method) |
| PE (1) | PE42595A1 (en:Method) |
| PL (1) | PL306038A1 (en:Method) |
| RU (1) | RU94042240A (en:Method) |
| TW (1) | TW287157B (en:Method) |
| YU (1) | YU70394A (en:Method) |
| ZA (1) | ZA949405B (en:Method) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5824662A (en) * | 1996-09-27 | 1998-10-20 | Guilford Pharmaceuticals Inc. | Treatment of global and focal ischemia using naaladase inhibitors |
| US6017903A (en) | 1996-09-27 | 2000-01-25 | Guilford Pharmaceuticals Inc. | Pharmaceutical compositions and methods of treating a glutamate abnormality and effecting a neuronal activity in an animal using NAALADase inhibitors |
| IL128718A0 (en) | 1996-09-27 | 2000-01-31 | Guildford Pharmaceuticals Inc | Naaldase compositions |
| JP3936418B2 (ja) * | 1996-10-25 | 2007-06-27 | サントリー株式会社 | β−ヒドロキシアスパラギン酸誘導体 |
| EP0980247A1 (en) * | 1997-05-07 | 2000-02-23 | Algos Pharmaceutical Corporation | Composition and method combining an antidepressant with an nmda receptor antagonist, for treating neuropathic pain |
| DE19801647A1 (de) | 1998-01-17 | 1999-07-22 | Bayer Ag | Substituierte beta,gamma-annellierte Lactone |
| DE19801646A1 (de) | 1998-01-17 | 1999-07-22 | Bayer Ag | Substituierte alpha,beta-annellierte Butyrolactone |
| DE19801636A1 (de) | 1998-01-17 | 1999-07-22 | Bayer Ag | Substituierte bicyclische Lactone |
| US6307090B1 (en) | 1999-01-22 | 2001-10-23 | The United States Of America As Represented By The Department Of Health And Human Services | Acylated oligopeptide derivatives having cell signal inhibiting activity |
| US7226991B1 (en) * | 1999-03-23 | 2007-06-05 | United States Of America, Represented By The Secretary, Department Of Health And Human Services | Phenylalanine derivatives |
| WO2000056760A1 (en) * | 1999-03-23 | 2000-09-28 | The United States Of America, Represented By Secretary, Department Of Health And Human Services | Phenylalanine derivatives |
| AU2241400A (en) | 1999-04-06 | 2000-10-12 | Yamanouchi Pharmaceutical Co., Ltd. | Novel thiazolobenzoimidazole derivative |
| AU780697B2 (en) | 1999-10-22 | 2005-04-14 | Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The | Inhibition of cell motility and angiogenesis by inhibitors of the GRB2 SH2-domain |
| US7871981B2 (en) * | 1999-10-22 | 2011-01-18 | The United States Of America As Represented By The Department Of Health And Human Services | Inhibition of cell motility, angiogenesis, and metastasis |
| US6362226B2 (en) | 1999-12-08 | 2002-03-26 | Vanderbilt University | Modulation of in vivo glutamine and glycine levels in the treatment of autism |
| US7425537B2 (en) * | 2000-08-22 | 2008-09-16 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | SH2 domain binding inhibitors |
| US6977241B2 (en) * | 2000-08-22 | 2005-12-20 | The United States Of America As Represented By The Department Of Health & Human Services | SH2 domain binding inhibitors |
| EP1397370B1 (en) | 2001-06-22 | 2014-07-23 | Suntory Holdings Limited | Beta-benzyloxyaspartate derivatives with amino group on benzene ring |
| US20040138104A1 (en) * | 2003-01-14 | 2004-07-15 | The Government Of The United States Of America Represented By The Secretary, | Peptides |
| US20050119163A1 (en) | 2003-09-18 | 2005-06-02 | The Government Of The United States Of America, As Represented By The Secretary, | SH2 domain binding inhibitors |
| US7423176B2 (en) * | 2004-04-13 | 2008-09-09 | Cephalon, Inc. | Bicyclic aromatic sulfinyl derivatives |
| PL2473492T3 (pl) * | 2009-08-31 | 2016-03-31 | Lonza Ag | Sposób wytwarzania (1S,4R)-2-oksa-3-azabicyklo[2.2.1]-hept-5-enów |
| AR079343A1 (es) * | 2009-12-21 | 2012-01-18 | Lilly Co Eli | Compuesto de acido 2-amino-4-(4h-1,2,4-triazol-3-ilsulfanil)biciclo[3.1.0]hexano-2,6-dicarboxilico, composicion farmaceutica que lo comprende y su uso para preparar un medicamento util para tratar un trastorno psiquiatrico |
| DK2721012T3 (en) | 2011-06-17 | 2016-08-15 | Lilly Co Eli | Biclo (3.1.0) hexane-2,6-dicarboxylic acid derivatives as MGLU2 receptor agonist |
| CN102633657B (zh) * | 2012-03-30 | 2014-05-14 | 甘肃科瑞生物科技有限公司 | 一种顺式3-氨基-环戊醇盐酸盐的制备方法 |
| CN104193612B (zh) * | 2014-08-12 | 2016-03-02 | 深圳市道尔顿电子材料有限公司 | 一种2,3,5-三羧基环戊基乙酸的制备方法 |
| CN107936040B (zh) * | 2017-12-08 | 2019-04-09 | 珠海联邦制药股份有限公司 | 一种替格瑞洛中间体的合成工艺 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4428960A (en) * | 1982-04-19 | 1984-01-31 | Merck & Co., Inc. | 3-Amino-6-substituted thio-1-azabicyclo(3.2.0)hept-6-en-2-one-7-carboxylic acids |
| DK160941C (da) * | 1988-06-28 | 1991-10-21 | Novo Nordisk As | Kondenserede 2,3-dihydroxypyraziner, fremgangsmaade til deres fremstilling og farmaceutiske praeparater, hvori forbindelserne indgaar |
| DE69019610D1 (de) * | 1989-07-06 | 1995-06-29 | Banyu Pharma Co Ltd | Cyclische Derivate des Amidinylthiocarbapenems. |
| GB9324872D0 (en) * | 1993-12-03 | 1994-01-19 | Univ Pasteur | Pharmaceutical compounds |
-
1994
- 1994-10-13 US US08/322,632 patent/US5576323A/en not_active Expired - Fee Related
- 1994-11-14 TW TW083110526A patent/TW287157B/zh active
- 1994-11-28 ZA ZA949405A patent/ZA949405B/xx unknown
- 1994-11-28 NZ NZ270009A patent/NZ270009A/en unknown
- 1994-11-28 IL IL11178994A patent/IL111789A0/xx unknown
- 1994-11-28 PE PE1994255836A patent/PE42595A1/es not_active Application Discontinuation
- 1994-11-29 NO NO944578A patent/NO944578L/no unknown
- 1994-11-29 CA CA002136904A patent/CA2136904A1/en not_active Abandoned
- 1994-11-29 PL PL94306038A patent/PL306038A1/xx unknown
- 1994-11-29 CZ CZ942947A patent/CZ294794A3/cs unknown
- 1994-11-30 CO CO94054611A patent/CO4290421A1/es unknown
- 1994-11-30 RU RU94042240/04A patent/RU94042240A/ru unknown
- 1994-11-30 AU AU79151/94A patent/AU676781B2/en not_active Ceased
- 1994-12-01 BR BR9404809A patent/BR9404809A/pt not_active Application Discontinuation
- 1994-12-01 KR KR1019940032360A patent/KR950018015A/ko not_active Withdrawn
- 1994-12-02 EP EP94308949A patent/EP0658539A1/en not_active Ceased
- 1994-12-02 JP JP6299390A patent/JPH07267908A/ja not_active Withdrawn
- 1994-12-02 YU YU70394A patent/YU70394A/sh unknown
- 1994-12-02 HU HU9403469A patent/HUT69181A/hu unknown
- 1994-12-02 FI FI945704A patent/FI945704A7/fi unknown
- 1994-12-02 CN CN94119360A patent/CN1108240A/zh active Pending
-
1996
- 1996-04-02 US US08/626,447 patent/US5843997A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US5576323A (en) | 1996-11-19 |
| FI945704A7 (fi) | 1995-06-04 |
| EP0658539A1 (en) | 1995-06-21 |
| CN1108240A (zh) | 1995-09-13 |
| BR9404809A (pt) | 1995-08-01 |
| NO944578L (no) | 1995-06-06 |
| CA2136904A1 (en) | 1995-06-04 |
| JPH07267908A (ja) | 1995-10-17 |
| AU676781B2 (en) | 1997-03-20 |
| NO944578D0 (no) | 1994-11-29 |
| US5843997A (en) | 1998-12-01 |
| CO4290421A1 (es) | 1996-04-17 |
| AU7915194A (en) | 1995-06-08 |
| PL306038A1 (en) | 1995-06-12 |
| KR950018015A (ko) | 1995-07-22 |
| IL111789A0 (en) | 1995-01-24 |
| YU70394A (sh) | 1997-12-05 |
| FI945704A0 (fi) | 1994-12-02 |
| HUT69181A (en) | 1995-08-28 |
| HU9403469D0 (en) | 1995-02-28 |
| ZA949405B (en) | 1996-05-28 |
| RU94042240A (ru) | 1996-10-10 |
| TW287157B (en:Method) | 1996-10-01 |
| PE42595A1 (es) | 1995-12-12 |
| NZ270009A (en) | 1997-01-29 |
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