AU744633B2 - Derivatives of acyl-piperazinil-pyrimidins, preparation thereof and application as medicaments - Google Patents
Derivatives of acyl-piperazinil-pyrimidins, preparation thereof and application as medicaments Download PDFInfo
- Publication number
- AU744633B2 AU744633B2 AU83403/98A AU8340398A AU744633B2 AU 744633 B2 AU744633 B2 AU 744633B2 AU 83403/98 A AU83403/98 A AU 83403/98A AU 8340398 A AU8340398 A AU 8340398A AU 744633 B2 AU744633 B2 AU 744633B2
- Authority
- AU
- Australia
- Prior art keywords
- piperazinyl
- methoxypyrimidine
- methoxy
- chiorohydrate
- pyrimidine
- 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.)
- Ceased
Links
- 238000002360 preparation method Methods 0.000 title claims description 18
- 239000003814 drug Substances 0.000 title claims description 10
- -1 alkyl radical Chemical class 0.000 claims description 101
- 150000001875 compounds Chemical class 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000004429 atom Chemical group 0.000 claims description 20
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- 239000001301 oxygen Substances 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 239000005864 Sulphur Substances 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 230000001939 inductive effect Effects 0.000 claims description 8
- 230000007958 sleep Effects 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 7
- 150000001412 amines Chemical class 0.000 claims description 7
- 230000003387 muscular Effects 0.000 claims description 7
- 230000000202 analgesic effect Effects 0.000 claims description 6
- 230000001624 sedative effect Effects 0.000 claims description 6
- 239000002249 anxiolytic agent Substances 0.000 claims description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 5
- 239000011707 mineral Substances 0.000 claims description 5
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 150000005840 aryl radicals Chemical class 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 210000003169 central nervous system Anatomy 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 229940125681 anticonvulsant agent Drugs 0.000 claims description 3
- 239000001961 anticonvulsive agent Substances 0.000 claims description 3
- 230000000949 anxiolytic effect Effects 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 3
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000000932 sedative agent Substances 0.000 claims description 3
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- WZKSXHQDXQKIQJ-UHFFFAOYSA-N F[C](F)F Chemical compound F[C](F)F WZKSXHQDXQKIQJ-UHFFFAOYSA-N 0.000 claims description 2
- ACNPUFRLGXYSCY-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-thiophen-3-ylmethanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C2=CSC=C2)=N1 ACNPUFRLGXYSCY-UHFFFAOYSA-N 0.000 claims description 2
- 229940124326 anaesthetic agent Drugs 0.000 claims description 2
- 230000001430 anti-depressive effect Effects 0.000 claims description 2
- 239000000935 antidepressant agent Substances 0.000 claims description 2
- 229940005513 antidepressants Drugs 0.000 claims description 2
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 150000004885 piperazines Chemical class 0.000 claims description 2
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 2
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 229960002317 succinimide Drugs 0.000 claims description 2
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000002995 2-(trifluoromethyl)benzoyl group Chemical group FC(C1=C(C(=O)*)C=CC=C1)(F)F 0.000 claims 4
- XAEAFOPJORAPHJ-UHFFFAOYSA-N (2-hydroxyphenyl)-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CC=2)O)=N1 XAEAFOPJORAPHJ-UHFFFAOYSA-N 0.000 claims 2
- WHWQXBUXEZELSM-UHFFFAOYSA-N (4-chlorophenyl)-[4-(4,4-dimethoxy-1h-pyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound C1=CC(OC)(OC)NC(N2CCN(CC2)C(=O)C=2C=CC(Cl)=CC=2)=N1 WHWQXBUXEZELSM-UHFFFAOYSA-N 0.000 claims 2
- COZIABXQRYUDTN-UHFFFAOYSA-N (4-chlorophenyl)-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C=CC(Cl)=CC=2)=N1 COZIABXQRYUDTN-UHFFFAOYSA-N 0.000 claims 2
- GWOPRVSTEXYZKZ-UHFFFAOYSA-N (4-fluorophenyl)-[4-(4-propan-2-yloxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound CC(C)OC1=CC=NC(N2CCN(CC2)C(=O)C=2C=CC(F)=CC=2)=N1 GWOPRVSTEXYZKZ-UHFFFAOYSA-N 0.000 claims 2
- SDPJPFHCPZGSJA-UHFFFAOYSA-N [4-(4-ethoxypyrimidin-2-yl)piperazin-1-yl]-thiophen-2-ylmethanone Chemical compound CCOC1=CC=NC(N2CCN(CC2)C(=O)C=2SC=CC=2)=N1 SDPJPFHCPZGSJA-UHFFFAOYSA-N 0.000 claims 2
- FTZPBBKANJNASG-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-phenylmethanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C=CC=CC=2)=N1 FTZPBBKANJNASG-UHFFFAOYSA-N 0.000 claims 2
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- CCZSIFVCYJSMLQ-UHFFFAOYSA-N (3-chlorophenyl)-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C=C(Cl)C=CC=2)=N1 CCZSIFVCYJSMLQ-UHFFFAOYSA-N 0.000 claims 1
- IKPTYEDWQZPHHD-UHFFFAOYSA-N (3-chlorothiophen-2-yl)-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C2=C(C=CS2)Cl)=N1 IKPTYEDWQZPHHD-UHFFFAOYSA-N 0.000 claims 1
- YGFKQKNWPIFDAT-UHFFFAOYSA-N (4-fluorophenyl)-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C=CC(F)=CC=2)=N1 YGFKQKNWPIFDAT-UHFFFAOYSA-N 0.000 claims 1
- LOCAEJAKKVDKGA-UHFFFAOYSA-N 1-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]ethanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(C)=O)=N1 LOCAEJAKKVDKGA-UHFFFAOYSA-N 0.000 claims 1
- LNGCZSUOQHOGAY-UHFFFAOYSA-N 2-[4-(4-methoxypyrimidin-2-yl)piperazine-1-carbonyl]benzoic acid Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CC=2)C(O)=O)=N1 LNGCZSUOQHOGAY-UHFFFAOYSA-N 0.000 claims 1
- UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 claims 1
- 125000004485 2-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])C1([H])* 0.000 claims 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000002999 4-(trifluoromethyl)benzoyl group Chemical group FC(C1=CC=C(C(=O)*)C=C1)(F)F 0.000 claims 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
- ZUSWDTWYONAOPH-UHFFFAOYSA-N [2-(trifluoromethyl)phenyl]hydrazine;hydrochloride Chemical group [Cl-].[NH3+]NC1=CC=CC=C1C(F)(F)F ZUSWDTWYONAOPH-UHFFFAOYSA-N 0.000 claims 1
- OYYNOSNMCSATCG-UHFFFAOYSA-N [2-[4-(4-methoxypyrimidin-2-yl)piperazine-1-carbonyl]phenyl] acetate Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CC=2)OC(C)=O)=N1 OYYNOSNMCSATCG-UHFFFAOYSA-N 0.000 claims 1
- XPQBOJVXVCTARQ-UHFFFAOYSA-N [4-(4,4-dimethoxy-1h-pyrimidin-2-yl)piperazin-1-yl]-(2-methoxyphenyl)methanone Chemical compound COC1=CC=CC=C1C(=O)N1CCN(C=2NC(C=CN=2)(OC)OC)CC1 XPQBOJVXVCTARQ-UHFFFAOYSA-N 0.000 claims 1
- VWIITCYUQQLPGR-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-(1,3-thiazol-2-yl)methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2SC=CN=2)=N1 VWIITCYUQQLPGR-UHFFFAOYSA-N 0.000 claims 1
- WWEMTGZUYMPMMP-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-(2-methylphenyl)methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CC=2)C)=N1 WWEMTGZUYMPMMP-UHFFFAOYSA-N 0.000 claims 1
- MKXMNBMVGKHCCK-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-(3-methoxythiophen-2-yl)methanone Chemical compound C1=CSC(C(=O)N2CCN(CC2)C=2N=C(OC)C=CN=2)=C1OC MKXMNBMVGKHCCK-UHFFFAOYSA-N 0.000 claims 1
- WXLGMERILCDMDP-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-(3-methylthiophen-2-yl)methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C2=C(C=CS2)C)=N1 WXLGMERILCDMDP-UHFFFAOYSA-N 0.000 claims 1
- NQELHAAPESACKB-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-(oxolan-2-yl)methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C2OCCC2)=N1 NQELHAAPESACKB-UHFFFAOYSA-N 0.000 claims 1
- HBLIWHCJAXRHBK-UHFFFAOYSA-N [4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]-pyridin-3-ylmethanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C=2C=NC=CC=2)=N1 HBLIWHCJAXRHBK-UHFFFAOYSA-N 0.000 claims 1
- 230000002460 anti-migrenic effect Effects 0.000 claims 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims 1
- BZUCEZDSIXZHCI-UHFFFAOYSA-N cyclohexyl-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C2CCCCC2)=N1 BZUCEZDSIXZHCI-UHFFFAOYSA-N 0.000 claims 1
- RVMXZAZNYVKVED-UHFFFAOYSA-N cyclopropyl-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone Chemical compound COC1=CC=NC(N2CCN(CC2)C(=O)C2CC2)=N1 RVMXZAZNYVKVED-UHFFFAOYSA-N 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- FKLCZJNRWHQBMN-UHFFFAOYSA-N furan-2-yl-[4-(4-methoxypyrimidin-2-yl)piperazin-1-yl]methanone;hypochlorous acid Chemical compound ClO.COC1=CC=NC(N2CCN(CC2)C(=O)C=2OC=CC=2)=N1 FKLCZJNRWHQBMN-UHFFFAOYSA-N 0.000 claims 1
- 239000003193 general anesthetic agent Substances 0.000 claims 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 claims 1
- XFERWBQLDTXOLP-UHFFFAOYSA-M sodium;2-[4-(4-methoxypyrimidin-2-yl)piperazine-1-carbonyl]benzoate Chemical compound [Na+].COC1=CC=NC(N2CCN(CC2)C(=O)C=2C(=CC=CC=2)C([O-])=O)=N1 XFERWBQLDTXOLP-UHFFFAOYSA-M 0.000 claims 1
- KSMFKBFJPWHGFU-UHFFFAOYSA-N thiophen-2-yl-[4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl]methanone Chemical compound FC(F)(F)C1=CC=NC(N2CCN(CC2)C(=O)C=2SC=CC=2)=N1 KSMFKBFJPWHGFU-UHFFFAOYSA-N 0.000 claims 1
- 239000002585 base Substances 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 239000000243 solution Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/08—Antiepileptics; Anticonvulsants
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- 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
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- 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
- A61P25/20—Hypnotics; Sedatives
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- 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
- A61P25/22—Anxiolytics
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- A—HUMAN NECESSITIES
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom 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
- C07D333/30—Hetero atoms other than halogen
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- C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES009701627A ES2125206B1 (es) | 1997-07-21 | 1997-07-21 | Derivados de acil-piperazinil-pirimidinas, su preparacion y su aplicacion como medicamentos. |
| ES9701627 | 1997-07-21 | ||
| PCT/ES1998/000212 WO1999005121A1 (es) | 1997-07-21 | 1998-07-21 | Derivados de acil-piperazinil-pirimidinas, su preparacion y su aplicacion como medicamentos |
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| Publication Number | Publication Date |
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| AU8340398A AU8340398A (en) | 1999-02-16 |
| AU744633B2 true AU744633B2 (en) | 2002-02-28 |
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| AU83403/98A Ceased AU744633B2 (en) | 1997-07-21 | 1998-07-21 | Derivatives of acyl-piperazinil-pyrimidins, preparation thereof and application as medicaments |
Country Status (33)
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10035908A1 (de) | 2000-07-21 | 2002-03-07 | Asta Medica Ag | Neue Heteroaryl-Derivate und deren Verwendung als Arzneimittel |
| ES2167276B1 (es) * | 2000-10-20 | 2003-04-01 | Esteve Labor Dr | Nuevos derivados de cianoaril (o cianoheteroaril)-carbonil-piperazinil-pirimidinas, su preparacion y su aplicacion como medicamentos. |
| CA2440438C (en) | 2001-03-09 | 2011-05-03 | Ortho-Mcneil Pharmaceutical, Inc. | Heterocyclic compounds |
| US7390813B1 (en) * | 2001-12-21 | 2008-06-24 | Xenon Pharmaceuticals Inc. | Pyridylpiperazines and aminonicotinamides and their use as therapeutic agents |
| US20050119251A1 (en) * | 2001-12-21 | 2005-06-02 | Jian-Min Fu | Nicotinamide derivatives and their use as therapeutic agents |
| DK1531822T3 (da) * | 2002-06-12 | 2009-12-07 | Chemocentryx Inc | 1-aryl-4-substituerede piperazin derivater til anvendelse som CCR1 antagonister til behandlingen af inflammation og immunforstyrrelser |
| US7842693B2 (en) | 2002-06-12 | 2010-11-30 | Chemocentryx, Inc. | Substituted piperazines |
| US7589199B2 (en) | 2002-06-12 | 2009-09-15 | Chemocentryx, Inc. | Substituted piperazines |
| EP1517898A1 (de) * | 2002-06-29 | 2005-03-30 | Zentaris GmbH | Aryl- und heteroarylcarbonylpiperazine und deren verwendung zur behandlung gutartiger und b sartiger tumorerkrankungen |
| US20040127395A1 (en) * | 2002-09-06 | 2004-07-01 | Desai Pragnya J. | Use of histamine H4 receptor modulators for the treatment of allergy and asthma |
| WO2005084667A1 (en) | 2004-03-03 | 2005-09-15 | Chemocentryx, Inc. | Bicyclic and bridged nitrogen heterocycles |
| US7435831B2 (en) | 2004-03-03 | 2008-10-14 | Chemocentryx, Inc. | Bicyclic and bridged nitrogen heterocycles |
| EP2269610A3 (en) * | 2004-09-20 | 2011-03-09 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| US7829712B2 (en) * | 2004-09-20 | 2010-11-09 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives for inhibiting human stearoyl-CoA-desaturase |
| TW200626148A (en) * | 2004-09-20 | 2006-08-01 | Xenon Pharmaceuticals Inc | Heterocyclic derivatives and their use as therapeutic agents |
| CN101084211A (zh) * | 2004-09-20 | 2007-12-05 | 泽农医药公司 | 杂环衍生物及其作为治疗剂的用途 |
| BRPI0515499A (pt) * | 2004-09-20 | 2008-07-29 | Xenon Pharmaceuticals Inc | derivados de piridina para a inibição de estearoil-coa-desaturase humana |
| AU2005286793A1 (en) | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives for the treatment of diseases mediated by stearoyl-CoA desaturase enzymes |
| AR051202A1 (es) * | 2004-09-20 | 2006-12-27 | Xenon Pharmaceuticals Inc | Derivados heterociclicos y su uso como inhibidores de la estearoil-coa desaturasa |
| WO2006034338A1 (en) * | 2004-09-20 | 2006-03-30 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as mediators of stearoyl-coa desaturase |
| EP2266569A3 (en) | 2004-09-20 | 2011-03-09 | Xenon Pharmaceuticals Inc. | Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors |
| JP2009513563A (ja) * | 2005-06-03 | 2009-04-02 | ゼノン・ファーマシューティカルズ・インコーポレイテッド | ヒトのステアロイル−ＣｏＡデサチュラーゼ阻害剤としてのアミノチアゾール誘導体 |
| WO2007014851A2 (en) * | 2005-07-29 | 2007-02-08 | F. Hoffmann-La Roche Ag | Indol-3-yl-carbonyl-piperidin and piperazin derivatives |
| WO2012027495A1 (en) | 2010-08-27 | 2012-03-01 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
| DE112010005848B4 (de) * | 2010-09-06 | 2016-03-10 | Guangzhou Institutes Of Biomedicine And Health, Chinese Academy Of Sciences | Amidverbindungen |
| EP2956441A4 (en) * | 2013-02-18 | 2016-11-02 | Scripps Research Inst | MODULATORS OF VASOPRESSIN RECEPTORS WITH THERAPEUTIC POTENTIAL |
| JP2018012645A (ja) * | 2014-11-26 | 2018-01-25 | 持田製薬株式会社 | 新規ジアザビシクロ誘導体 |
| EP4377307A1 (en) * | 2021-07-30 | 2024-06-05 | Confo Therapeutics N.V. | Compounds for the treatment of pain, in particular neuropathic pain, and/or other diseases or disorders that are associated with at2r and/or at2r mediated signaling |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2535718A1 (fr) * | 1982-11-09 | 1984-05-11 | Sanofi Sa | (piperazinyl-1)-2 pyrimidines, leurs sels, procede pour leur preparation et compositions pharmaceutiques en contenant |
| US4547505A (en) * | 1983-03-25 | 1985-10-15 | Degussa Aktiengesellschaft | N-Phenyl-N-'-cycloalkylalkanoylpiperazine useful as analgetics and process for its production |
| EP0257102B1 (en) * | 1986-02-24 | 1997-11-19 | Mitsui Petrochemical Industries, Ltd. | Agents for treating neurophathy |
| FR2642759B1 (fr) * | 1989-02-09 | 1991-05-17 | Laboratorios Esteve Sa | Derives de pyrimidyl-piperazinyl-alkyl azoles avec activite anxiolytique et/ou tranquillisante |
| FR2672052B1 (fr) * | 1991-01-28 | 1995-05-24 | Esteve Labor Dr | Derives d'aryl (ou heteroaryl)-piperazinyl-alkyl-azoles, leur preparation et leur application en tant que medicaments. |
| GB9226610D0 (en) * | 1992-12-21 | 1993-02-17 | Smithkline Beecham Plc | Compounds |
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1998
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- 1998-07-20 ZA ZA986437A patent/ZA986437B/xx unknown
- 1998-07-21 UA UA2000010370A patent/UA59403C2/uk unknown
- 1998-07-21 BR BR9810772-0A patent/BR9810772A/pt not_active Application Discontinuation
- 1998-07-21 CN CNB988084589A patent/CN1202087C/zh not_active Expired - Fee Related
- 1998-07-21 PT PT98933660T patent/PT1006110E/pt unknown
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- 1998-07-21 DK DK98933660T patent/DK1006110T3/da active
- 1998-07-21 IN IN1272CA1998 patent/IN183820B/en unknown
- 1998-07-21 HU HU0002517A patent/HUP0002517A3/hu unknown
- 1998-07-21 RU RU2000104007/04A patent/RU2205827C2/ru not_active IP Right Cessation
- 1998-07-21 ES ES98933660T patent/ES2216297T3/es not_active Expired - Lifetime
- 1998-07-21 JP JP2000504120A patent/JP2001510831A/ja active Pending
- 1998-07-21 AT AT98933660T patent/ATE259357T1/de not_active IP Right Cessation
- 1998-07-21 US US09/462,880 patent/US6372746B1/en not_active Expired - Fee Related
- 1998-07-21 SI SI9820053A patent/SI20269B/sl not_active IP Right Cessation
- 1998-07-21 KR KR10-2000-7000602A patent/KR100514148B1/ko not_active Expired - Fee Related
- 1998-07-21 EP EP98933660A patent/EP1006110B8/en not_active Expired - Lifetime
- 1998-07-21 AU AU83403/98A patent/AU744633B2/en not_active Ceased
- 1998-07-21 PL PL98338143A patent/PL195632B1/pl unknown
- 1998-07-21 GE GEAP19985226A patent/GEP20033090B/en unknown
- 1998-07-21 DE DE69821623T patent/DE69821623T2/de not_active Expired - Fee Related
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2000
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- 2000-01-19 IS IS5353A patent/IS2076B/is unknown
- 2000-01-20 NO NO20000294A patent/NO314996B1/no unknown
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- 2000-01-21 LV LVP-00-08A patent/LV12457B/en unknown
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