CA2310008A1 - 1,3,4-thiadiazoles derivatives as kyn-oh inhibitors - Google Patents
1,3,4-thiadiazoles derivatives as kyn-oh inhibitors Download PDFInfo
- Publication number
- CA2310008A1 CA2310008A1 CA002310008A CA2310008A CA2310008A1 CA 2310008 A1 CA2310008 A1 CA 2310008A1 CA 002310008 A CA002310008 A CA 002310008A CA 2310008 A CA2310008 A CA 2310008A CA 2310008 A1 CA2310008 A1 CA 2310008A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- alkyl
- group
- thiadiazole
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000004869 1,3,4-thiadiazoles Chemical class 0.000 title description 3
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 94
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 61
- 239000001257 hydrogen Substances 0.000 claims abstract description 60
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 45
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 43
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 34
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 29
- 239000001301 oxygen Substances 0.000 claims abstract description 29
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 27
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 27
- 239000011593 sulfur Substances 0.000 claims abstract description 27
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 18
- 108010033242 Kynurenine 3-monooxygenase Proteins 0.000 claims abstract description 15
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims abstract description 12
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 11
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 30
- -1 nitro, formylamino Chemical group 0.000 claims description 38
- 238000000034 method Methods 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 19
- 125000004423 acyloxy group Chemical group 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 102100037652 Kynurenine 3-monooxygenase Human genes 0.000 claims description 13
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims description 9
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 8
- 239000002532 enzyme inhibitor Substances 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 229940125532 enzyme inhibitor Drugs 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 4
- LYGIGUPIAFUWJV-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(5-imidazol-1-yl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1N1C=NC=C1 LYGIGUPIAFUWJV-UHFFFAOYSA-N 0.000 claims description 3
- ZHTLPWXEXRGOTB-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1C1=CC=CC=C1 ZHTLPWXEXRGOTB-UHFFFAOYSA-N 0.000 claims description 3
- IMYZRRDTZGTBJK-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(5-pyridin-4-yl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1C1=CC=NC=C1 IMYZRRDTZGTBJK-UHFFFAOYSA-N 0.000 claims description 3
- KGKMXEXDMWNIKI-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-(4-methylpiperazin-1-yl)-1,3,4-thiadiazol-2-yl]carbamate Chemical compound C1CN(C)CCN1C1=NN=C(NC(=O)OCC(Cl)(Cl)Cl)S1 KGKMXEXDMWNIKI-UHFFFAOYSA-N 0.000 claims description 3
- VZGYERPUJWZKET-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-[4-(3,6-dihydro-2h-pyridin-1-yl)phenyl]-1,3,4-thiadiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1C1=CC=C(N2CC=CCC2)C=C1 VZGYERPUJWZKET-UHFFFAOYSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- XDLRNUUYTHQPDP-UHFFFAOYSA-N benzyl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound C=1C=CC=CC=1COC(=O)NC(S1)=NN=C1C1=CC=CC=C1 XDLRNUUYTHQPDP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 230000000626 neurodegenerative effect Effects 0.000 claims description 3
- WRZDSDNQWXDTTH-UHFFFAOYSA-N o-benzyl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamothioate Chemical compound C=1C=CC=CC=1COC(=S)NC(S1)=NN=C1C1=CC=CC=C1 WRZDSDNQWXDTTH-UHFFFAOYSA-N 0.000 claims description 3
- 230000007170 pathology Effects 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- ROKPXGYIMNGEED-UHFFFAOYSA-N 1-(5-phenyl-1,3,4-thiadiazol-2-yl)-3-(2,2,2-trichloroethyl)urea Chemical compound S1C(NC(=O)NCC(Cl)(Cl)Cl)=NN=C1C1=CC=CC=C1 ROKPXGYIMNGEED-UHFFFAOYSA-N 0.000 claims description 2
- JQRLAWQPNSPNPH-UHFFFAOYSA-N 1-phenyl-3-(5-phenyl-1,3,4-thiadiazol-2-yl)urea Chemical compound C=1C=CC=CC=1NC(=O)NC(S1)=NN=C1C1=CC=CC=C1 JQRLAWQPNSPNPH-UHFFFAOYSA-N 0.000 claims description 2
- WJEGHQOMLGXQQP-UHFFFAOYSA-N 1-phenyl-3-(5-pyridin-3-yl-1,3,4-thiadiazol-2-yl)urea Chemical compound C=1C=CC=CC=1NC(=O)NC(S1)=NN=C1C1=CC=CN=C1 WJEGHQOMLGXQQP-UHFFFAOYSA-N 0.000 claims description 2
- QNRJWRQLWGFXEI-UHFFFAOYSA-N 2,2,2-trichloroethyl N-[5-(1H-imidazol-5-yl)-1,3,4-thiadiazol-2-yl]carbamate Chemical compound ClC(COC(=O)NC=1SC(=NN1)C=1N=CNC1)(Cl)Cl QNRJWRQLWGFXEI-UHFFFAOYSA-N 0.000 claims description 2
- NUDUCFCNOIGTFW-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(5-pyridin-3-yl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1C1=CC=CN=C1 NUDUCFCNOIGTFW-UHFFFAOYSA-N 0.000 claims description 2
- GUKFPFLTAQTPQN-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(5-pyrrolidin-1-yl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1N1CCCC1 GUKFPFLTAQTPQN-UHFFFAOYSA-N 0.000 claims description 2
- XLOOPENIVSBRLR-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-(3,4-difluorophenyl)-1,3,4-thiadiazol-2-yl]carbamate Chemical compound C1=C(F)C(F)=CC=C1C1=NN=C(NC(=O)OCC(Cl)(Cl)Cl)S1 XLOOPENIVSBRLR-UHFFFAOYSA-N 0.000 claims description 2
- NQTIJYAPUNFOIL-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-(3-azabicyclo[3.2.2]nonan-3-yl)-1,3,4-thiadiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1N1CC(CC2)CCC2C1 NQTIJYAPUNFOIL-UHFFFAOYSA-N 0.000 claims description 2
- BTJXWKWFDHFORA-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]carbamate Chemical compound C1=CC(F)=CC=C1C1=NN=C(NC(=O)OCC(Cl)(Cl)Cl)S1 BTJXWKWFDHFORA-UHFFFAOYSA-N 0.000 claims description 2
- OSFYVRYOORHEJE-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-(imidazol-1-ylmethyl)-1,3,4-thiadiazol-2-yl]carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1CN1C=NC=C1 OSFYVRYOORHEJE-UHFFFAOYSA-N 0.000 claims description 2
- ATXZILXEKIQCMI-UHFFFAOYSA-N 2,2,2-trichloroethyl n-[5-[4-(methanesulfonamido)phenyl]-1,3,4-thiadiazol-2-yl]carbamate Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=NN=C(NC(=O)OCC(Cl)(Cl)Cl)S1 ATXZILXEKIQCMI-UHFFFAOYSA-N 0.000 claims description 2
- PMSGEOLYLKYLQC-UHFFFAOYSA-N 2,2,2-trifluoroethyl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(F)(F)F)=NN=C1C1=CC=CC=C1 PMSGEOLYLKYLQC-UHFFFAOYSA-N 0.000 claims description 2
- 208000002381 Brain Hypoxia Diseases 0.000 claims description 2
- 201000006474 Brain Ischemia Diseases 0.000 claims description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 229940122439 Hydroxylase inhibitor Drugs 0.000 claims description 2
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 208000018737 Parkinson disease Diseases 0.000 claims description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 206010008118 cerebral infarction Diseases 0.000 claims description 2
- 206010015037 epilepsy Diseases 0.000 claims description 2
- 125000002757 morpholinyl group Chemical group 0.000 claims description 2
- APUSPAVNNZSCPD-UHFFFAOYSA-N o-naphthalen-2-yl n-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-n-naphthalen-2-yloxycarbothioylcarbamothioate Chemical compound C1=CC(F)=CC=C1C1=NN=C(N(C(=S)OC=2C=C3C=CC=CC3=CC=2)C(=S)OC=2C=C3C=CC=CC3=CC=2)S1 APUSPAVNNZSCPD-UHFFFAOYSA-N 0.000 claims description 2
- NSDKKEKKHQMCAI-UHFFFAOYSA-N o-phenyl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamothioate Chemical compound C=1C=CC=CC=1OC(=S)NC(S1)=NN=C1C1=CC=CC=C1 NSDKKEKKHQMCAI-UHFFFAOYSA-N 0.000 claims description 2
- GFQMNCKABOMRNI-UHFFFAOYSA-N o-pyridin-4-yl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamothioate Chemical compound C=1C=NC=CC=1OC(=S)NC(S1)=NN=C1C1=CC=CC=C1 GFQMNCKABOMRNI-UHFFFAOYSA-N 0.000 claims description 2
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 claims description 2
- ZJNRXZXODSHXDU-UHFFFAOYSA-N phenyl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NC(S1)=NN=C1C1=CC=CC=C1 ZJNRXZXODSHXDU-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 15
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- ZUEHVXUZUYMPPF-UHFFFAOYSA-N 2,2,2-trichloroethyl n-(5-pyridin-2-yl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound S1C(NC(=O)OCC(Cl)(Cl)Cl)=NN=C1C1=CC=CC=N1 ZUEHVXUZUYMPPF-UHFFFAOYSA-N 0.000 claims 1
- 206010019196 Head injury Diseases 0.000 claims 1
- QHXXXKWGRPFQMC-UHFFFAOYSA-N pyridin-4-yl n-(5-phenyl-1,3,4-thiadiazol-2-yl)carbamate Chemical compound C=1C=NC=CC=1OC(=O)NC(S1)=NN=C1C1=CC=CC=C1 QHXXXKWGRPFQMC-UHFFFAOYSA-N 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- 150000002431 hydrogen Chemical group 0.000 description 22
- YGPSJZOEDVAXAB-UHFFFAOYSA-N kynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC=C1N YGPSJZOEDVAXAB-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- CCPHAMSKHBDMDS-UHFFFAOYSA-N Chetoseminudin B Natural products C=1NC2=CC=CC=C2C=1CC1(SC)NC(=O)C(CO)(SC)N(C)C1=O CCPHAMSKHBDMDS-UHFFFAOYSA-N 0.000 description 14
- HCZHHEIFKROPDY-UHFFFAOYSA-N kynurenic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC(=O)C2=C1 HCZHHEIFKROPDY-UHFFFAOYSA-N 0.000 description 14
- 239000000725 suspension Substances 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
- GJAWHXHKYYXBSV-UHFFFAOYSA-N quinolinic acid Chemical compound OC(=O)C1=CC=CN=C1C(O)=O GJAWHXHKYYXBSV-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 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
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- WJXSWCUQABXPFS-UHFFFAOYSA-N 3-hydroxyanthranilic acid Chemical compound NC1=C(O)C=CC=C1C(O)=O WJXSWCUQABXPFS-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- VCKPUUFAIGNJHC-UHFFFAOYSA-N 3-hydroxykynurenine Chemical compound OC(=O)C(N)CC(=O)C1=CC=CC(O)=C1N VCKPUUFAIGNJHC-UHFFFAOYSA-N 0.000 description 4
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- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
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- 235000011149 sulphuric acid Nutrition 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
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- 238000001816 cooling Methods 0.000 description 3
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- 238000001914 filtration Methods 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 3
- 238000003760 magnetic stirring Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- YPLIFKZBNCNJJN-UHFFFAOYSA-N n,n-bis(ethylamino)ethanamine Chemical compound CCNN(CC)NCC YPLIFKZBNCNJJN-UHFFFAOYSA-N 0.000 description 1
- BOGNGKDURDUBMC-UHFFFAOYSA-N n-[4-(5-amino-1,3,4-thiadiazol-2-yl)phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1C1=NN=C(N)S1 BOGNGKDURDUBMC-UHFFFAOYSA-N 0.000 description 1
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- 239000002581 neurotoxin Substances 0.000 description 1
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- 230000007935 neutral effect Effects 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
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- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- 230000008506 pathogenesis Effects 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
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- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
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- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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- 229920003109 sodium starch glycolate Polymers 0.000 description 1
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- 239000008109 sodium starch glycolate Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
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- 238000009495 sugar coating Methods 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000004867 thiadiazoles Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—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
- A61K31/433—Thidiazoles
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- 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
-
- 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
- C07D417/04—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 directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
- C07F9/6539—Five-membered rings
- C07F9/65392—Five-membered rings containing two nitrogen atoms
- C07F9/65395—Five-membered rings containing two nitrogen atoms having the two nitrogen atoms in positions 1 and 2
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9725055.9 | 1997-11-26 | ||
| GBGB9725055.9A GB9725055D0 (en) | 1997-11-26 | 1997-11-26 | 1,3,4-thiadiazoles compounds |
| PCT/EP1998/006995 WO1999028309A1 (en) | 1997-11-26 | 1998-10-27 | 1,3,4-thiadiazoles derivatives as kyn-oh inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2310008A1 true CA2310008A1 (en) | 1999-06-10 |
Family
ID=10822700
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002310008A Abandoned CA2310008A1 (en) | 1997-11-26 | 1998-10-27 | 1,3,4-thiadiazoles derivatives as kyn-oh inhibitors |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1054876A1 (ja) |
| JP (1) | JP2001524547A (ja) |
| AU (1) | AU1487599A (ja) |
| CA (1) | CA2310008A1 (ja) |
| GB (1) | GB9725055D0 (ja) |
| WO (1) | WO1999028309A1 (ja) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL204750B1 (pl) * | 2004-03-26 | 2010-02-26 | Univ Przyrodniczy W Lublinie | Pochodna 1,3,4-tiadiazolu , zastosowanie pochodnej 1,3,4-tiadiazolu w leczeniu chorób neurologicznych oraz sposób otrzymywania pochodnej 1,3,4-tiadiazolu |
| WO2008022286A2 (en) | 2006-08-16 | 2008-02-21 | The J. David Gladstone Institutes, A Testamentary Trust Established Under The Will Of J. David Gladstone | Small molecule inhibitors of kynurenine-3-monooxygenase |
| EP2054397B1 (en) | 2006-08-16 | 2015-10-07 | The J. David Gladstone Institutes, A Testamentary Trust Established under The Will of J. David Gladstone | Small molecule inhibitors of kynurenine-3-monooxygenase |
| CN103119034B (zh) * | 2010-04-16 | 2016-08-03 | 拜耳知识产权有限责任公司 | 作为害虫防治剂的杂环化合物 |
| WO2014060381A1 (de) | 2012-10-18 | 2014-04-24 | Bayer Cropscience Ag | Heterocyclische verbindungen als schädlingsbekämpfungsmittel |
| WO2022026823A1 (en) * | 2020-07-31 | 2022-02-03 | Chan Zuckerberg Biohub, Inc. | Cdk19-selective inhibitors, and methods of use thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1265101B1 (it) * | 1993-07-23 | 1996-10-30 | Erba Carlo Spa | Derivati dell'acido 2-ammino-4-fenil-4-osso butirrico |
| US5519055A (en) * | 1993-08-06 | 1996-05-21 | University Of Maryland At Baltimore | Substituted kynurenines and process for their preparation |
| GB9522617D0 (en) * | 1995-11-03 | 1996-01-03 | Pharmacia Spa | 4-Phenyl-4-oxo-butenoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity |
| GB9522615D0 (en) * | 1995-11-03 | 1996-01-03 | Pharmacia Spa | 4-Phenyl-4-oxo-butanoic acid derivatives with kynurenine-3-hydroxylase inhibiting activity |
| GB9618349D0 (en) * | 1996-09-03 | 1996-10-16 | Pharmacia Spa | N-substituted 2-amino-4-phenyl-4-oxo-butanoic acid derivatives with kynurenine-3-hydroxylase inhibitory activity |
-
1997
- 1997-11-26 GB GBGB9725055.9A patent/GB9725055D0/en not_active Ceased
-
1998
- 1998-10-27 JP JP2000523201A patent/JP2001524547A/ja not_active Withdrawn
- 1998-10-27 CA CA002310008A patent/CA2310008A1/en not_active Abandoned
- 1998-10-27 WO PCT/EP1998/006995 patent/WO1999028309A1/en not_active Application Discontinuation
- 1998-10-27 EP EP98958896A patent/EP1054876A1/en not_active Withdrawn
- 1998-10-27 AU AU14875/99A patent/AU1487599A/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1054876A1 (en) | 2000-11-29 |
| GB9725055D0 (en) | 1998-01-28 |
| AU1487599A (en) | 1999-06-16 |
| JP2001524547A (ja) | 2001-12-04 |
| WO1999028309A1 (en) | 1999-06-10 |
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| Date | Code | Title | Description |
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| FZDE | Dead |