CA2130878C - 4-aminopyrimidine derivatives - Google Patents
4-aminopyrimidine derivativesInfo
- Publication number
- CA2130878C CA2130878C CA002130878A CA2130878A CA2130878C CA 2130878 C CA2130878 C CA 2130878C CA 002130878 A CA002130878 A CA 002130878A CA 2130878 A CA2130878 A CA 2130878A CA 2130878 C CA2130878 C CA 2130878C
- Authority
- CA
- Canada
- Prior art keywords
- imidazolyl
- thienyl
- formula
- pyrimidine
- alkyl
- 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.)
- Expired - Fee Related
Links
- 150000005007 4-aminopyrimidines Chemical class 0.000 title claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 239000001257 hydrogen Substances 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 19
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 17
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 12
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 11
- 239000005864 Sulphur Substances 0.000 claims abstract description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 5
- 125000005702 oxyalkylene group Chemical group 0.000 claims abstract description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 86
- -1 cyano, ethynyl Chemical group 0.000 claims description 27
- 239000000460 chlorine Substances 0.000 claims description 24
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 15
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 13
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- BQNXHDSGGRTFNX-UHFFFAOYSA-N n-methylpyrimidin-2-amine Chemical compound CNC1=NC=CC=N1 BQNXHDSGGRTFNX-UHFFFAOYSA-N 0.000 claims description 11
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000002883 imidazolyl group Chemical group 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 206010030113 Oedema Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 206010002383 Angina Pectoris Diseases 0.000 claims description 5
- 241000282414 Homo sapiens Species 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 5
- 229930192474 thiophene Chemical group 0.000 claims description 5
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 4
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000004060 metabolic process Effects 0.000 claims description 4
- 208000010125 myocardial infarction Diseases 0.000 claims description 4
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 3
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical group C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000009447 Cardiac Edema Diseases 0.000 claims description 3
- 206010020772 Hypertension Diseases 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 3
- 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 108010069102 Thromboxane-A synthase Proteins 0.000 claims description 3
- 230000002490 cerebral effect Effects 0.000 claims description 3
- 206010008118 cerebral infarction Diseases 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 230000002440 hepatic effect Effects 0.000 claims description 3
- 201000006370 kidney failure Diseases 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- HICTVWSLWMSGQS-UHFFFAOYSA-N 2-[2-[[2-imidazol-1-yl-5-(3-methoxyphenyl)-6-methylpyrimidin-4-yl]amino]ethoxy]ethanol Chemical compound COC1=CC=CC(C=2C(=NC(=NC=2C)N2C=NC=C2)NCCOCCO)=C1 HICTVWSLWMSGQS-UHFFFAOYSA-N 0.000 claims description 2
- WSNKLMCLTOHXEA-UHFFFAOYSA-N 2-imidazol-1-yl-n-(2-methoxyethyl)pyrimidin-4-amine Chemical compound COCCNC1=CC=NC(N2C=NC=C2)=N1 WSNKLMCLTOHXEA-UHFFFAOYSA-N 0.000 claims description 2
- SMJJLSJVVHQEOZ-UHFFFAOYSA-N 6-(3h-benzimidazol-5-yl)-2-imidazol-1-yl-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3NC=NC3=CC=2)=C1C1=CC=CS1 SMJJLSJVVHQEOZ-UHFFFAOYSA-N 0.000 claims description 2
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 2
- 206010012289 Dementia Diseases 0.000 claims description 2
- 206010061598 Immunodeficiency Diseases 0.000 claims description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 208000006011 Stroke Diseases 0.000 claims description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 206010006451 bronchitis Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000007813 immunodeficiency Effects 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- JFHHKIKFDMEQCN-UHFFFAOYSA-N n,5-dibenzyl-2-imidazol-1-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC1=NC(N2C=NC=C2)=NC=C1CC1=CC=CC=C1 JFHHKIKFDMEQCN-UHFFFAOYSA-N 0.000 claims description 2
- DEXBJDYTILITIS-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5,6-dimethylpyrimidin-4-amine Chemical compound CC=1C(C)=NC(N2C=NC=C2)=NC=1NCC1=CC=CC=C1 DEXBJDYTILITIS-UHFFFAOYSA-N 0.000 claims description 2
- OYPHRJNZVAUEEV-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-[(4-methoxyphenyl)methyl]pyrimidin-4-amine Chemical compound C1=CC(OC)=CC=C1CC1=CN=C(N2C=NC=C2)N=C1NCC1=CC=CC=C1 OYPHRJNZVAUEEV-UHFFFAOYSA-N 0.000 claims description 2
- ZOQGANUYHAUGMO-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-methylpyrimidin-4-amine Chemical compound CC1=CN=C(N2C=NC=C2)N=C1NCC1=CC=CC=C1 ZOQGANUYHAUGMO-UHFFFAOYSA-N 0.000 claims description 2
- BHLSDEMYHGXDEB-UHFFFAOYSA-N n-benzyl-2-imidazol-1-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CNC(N=1)=CC=NC=1N1C=CN=C1 BHLSDEMYHGXDEB-UHFFFAOYSA-N 0.000 claims description 2
- VMXDVIPVHZVXJP-UHFFFAOYSA-N n-benzyl-5-ethyl-2-imidazol-1-ylpyrimidin-4-amine Chemical compound CCC1=CN=C(N2C=NC=C2)N=C1NCC1=CC=CC=C1 VMXDVIPVHZVXJP-UHFFFAOYSA-N 0.000 claims description 2
- 239000008016 pharmaceutical coating Substances 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims 1
- RFMKUWJJIQLQOB-UHFFFAOYSA-N 2-(benzimidazol-1-yl)-6-(1,3-benzodioxol-5-yl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound CNC1=NC(N2C3=CC=CC=C3N=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CS1 RFMKUWJJIQLQOB-UHFFFAOYSA-N 0.000 claims 1
- KIENUZLCJVIMNJ-UHFFFAOYSA-N 2-[2-(6-amino-2-imidazol-1-yl-5-thiophen-2-ylpyrimidin-4-yl)ethoxy]ethanol Chemical compound NC1=NC(N2C=NC=C2)=NC(CCOCCO)=C1C1=CC=CS1 KIENUZLCJVIMNJ-UHFFFAOYSA-N 0.000 claims 1
- KQUISXLVZIBKSN-UHFFFAOYSA-N 2-[2-[6-amino-2-imidazol-1-yl-5-[(4-methoxyphenyl)methyl]pyrimidin-4-yl]ethoxy]ethanol Chemical compound C1=CC(OC)=CC=C1CC1=C(N)N=C(N2C=NC=C2)N=C1CCOCCO KQUISXLVZIBKSN-UHFFFAOYSA-N 0.000 claims 1
- UDBZTAAZKCFULU-UHFFFAOYSA-N 2-imidazol-1-yl-6-(2-methoxyethyl)-5-thiophen-2-ylpyrimidin-4-amine Chemical compound COCCC1=NC(N2C=NC=C2)=NC(N)=C1C1=CC=CS1 UDBZTAAZKCFULU-UHFFFAOYSA-N 0.000 claims 1
- GNZWOKRRXWMIDK-UHFFFAOYSA-N 2-imidazol-1-yl-6-(3-methoxyphenyl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=CC(OC)=C1 GNZWOKRRXWMIDK-UHFFFAOYSA-N 0.000 claims 1
- ZJSAXCMSIZBQLN-UHFFFAOYSA-N 2-imidazol-1-yl-6-(4-imidazol-1-ylphenyl)-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C(C=C1)=CC=C1N1C=CN=C1 ZJSAXCMSIZBQLN-UHFFFAOYSA-N 0.000 claims 1
- QLFGUSQOQSNXIL-UHFFFAOYSA-N 2-imidazol-1-yl-n-phenylmethoxy-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CC=CC=1CONC1=NC(N2C=NC=C2)=NC=C1C1=CC=CS1 QLFGUSQOQSNXIL-UHFFFAOYSA-N 0.000 claims 1
- KIPWHTUWFFGRHP-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-imidazol-1-yl-5-(4-methoxyphenyl)-n-methylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=C(OC)C=C1 KIPWHTUWFFGRHP-UHFFFAOYSA-N 0.000 claims 1
- SLGAFWFUSUTTFH-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-imidazol-1-yl-n-methyl-5-(4-methylphenyl)pyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=C(C)C=C1 SLGAFWFUSUTTFH-UHFFFAOYSA-N 0.000 claims 1
- ZAQXWRSCILOFCP-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-imidazol-1-yl-n-methyl-5-naphthalen-2-ylpyrimidin-4-amine Chemical compound N=1C(C=2C=C3OCOC3=CC=2)=C(C=2C=C3C=CC=CC3=CC=2)C(NC)=NC=1N1C=CN=C1 ZAQXWRSCILOFCP-UHFFFAOYSA-N 0.000 claims 1
- UKNRRUGIGXYFKT-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-imidazol-1-yl-n-methyl-5-pyridin-3-ylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CN=C1 UKNRRUGIGXYFKT-UHFFFAOYSA-N 0.000 claims 1
- ZOTVQOQEEGIXNJ-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-2-imidazol-1-yl-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CS1 ZOTVQOQEEGIXNJ-UHFFFAOYSA-N 0.000 claims 1
- WPIASDUYUDJBEI-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-5-(furan-3-yl)-2-imidazol-1-yl-n-methylpyrimidin-4-amine Chemical compound CNC1=NC(N2C=NC=C2)=NC(C=2C=C3OCOC3=CC=2)=C1C=1C=COC=1 WPIASDUYUDJBEI-UHFFFAOYSA-N 0.000 claims 1
- MPBORPSIMRCJPW-UHFFFAOYSA-N 6-(1,3-benzodioxol-5-yl)-n-methyl-2-pyridin-3-yl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound CNC1=NC(C=2C=NC=CC=2)=NC(C=2C=C3OCOC3=CC=2)=C1C1=CC=CS1 MPBORPSIMRCJPW-UHFFFAOYSA-N 0.000 claims 1
- FOSQODJYRAMXHJ-UHFFFAOYSA-N 6-(4-chlorophenyl)-2-imidazol-1-yl-n-methyl-5-thiophen-2-ylpyrimidin-4-amine Chemical compound C=1C=CSC=1C=1C(NC)=NC(N2C=NC=C2)=NC=1C1=CC=C(Cl)C=C1 FOSQODJYRAMXHJ-UHFFFAOYSA-N 0.000 claims 1
- KDVGNFQFXLZNRD-UHFFFAOYSA-N N-benzyl-2,5-di(imidazol-1-yl)-6-methylpyrimidin-4-amine Chemical compound N1(C=NC=C1)C1=NC(=C(C(=N1)NCC1=CC=CC=C1)N1C=NC=C1)C KDVGNFQFXLZNRD-UHFFFAOYSA-N 0.000 claims 1
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- XDKIWKBPMAEDGN-UHFFFAOYSA-N n-benzyl-2-imidazol-1-yl-5-thiophen-2-ylpyrimidin-4-amine;hydrochloride Chemical compound Cl.C=1C=CC=CC=1CNC1=NC(N2C=NC=C2)=NC=C1C1=CC=CS1 XDKIWKBPMAEDGN-UHFFFAOYSA-N 0.000 description 1
- WLQRJGNUUYRQPF-UHFFFAOYSA-N n-benzyl-5-(1-chloroethenyl)-2-imidazol-1-ylpyrimidin-4-amine;hydrochloride Chemical compound Cl.ClC(=C)C1=CN=C(N2C=NC=C2)N=C1NCC1=CC=CC=C1 WLQRJGNUUYRQPF-UHFFFAOYSA-N 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
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- WSDQIHATCCOMLH-UHFFFAOYSA-N phenyl n-(3,5-dichlorophenyl)carbamate Chemical compound ClC1=CC(Cl)=CC(NC(=O)OC=2C=CC=CC=2)=C1 WSDQIHATCCOMLH-UHFFFAOYSA-N 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- SGUKUZOVHSFKPH-YNNPMVKQSA-N prostaglandin G2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](OO)CCCCC)[C@H]2C\C=C/CCCC(O)=O SGUKUZOVHSFKPH-YNNPMVKQSA-N 0.000 description 1
- YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
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- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
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- 239000008223 sterile water Substances 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
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- 239000001117 sulphuric acid Substances 0.000 description 1
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- 210000000225 synapse Anatomy 0.000 description 1
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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- 230000001988 toxicity Effects 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
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- REZGGXNDEMKIQB-UHFFFAOYSA-N zaprinast Chemical compound CCCOC1=CC=CC=C1C1=NC(=O)C2=NNNC2=N1 REZGGXNDEMKIQB-UHFFFAOYSA-N 0.000 description 1
- 229950005371 zaprinast Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/14—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 three or more hetero rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- 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
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11190693A | 1993-08-26 | 1993-08-26 | |
| US08/111,906 | 1993-08-26 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2130878A1 CA2130878A1 (en) | 1995-02-27 |
| CA2130878C true CA2130878C (en) | 1999-03-23 |
Family
ID=22341063
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002130878A Expired - Fee Related CA2130878C (en) | 1993-08-26 | 1994-08-25 | 4-aminopyrimidine derivatives |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US5525604A (OSRAM) |
| EP (1) | EP0640599B1 (OSRAM) |
| JP (1) | JPH0789958A (OSRAM) |
| KR (1) | KR100204433B1 (OSRAM) |
| CN (1) | CN1109055A (OSRAM) |
| AT (1) | ATE163647T1 (OSRAM) |
| CA (1) | CA2130878C (OSRAM) |
| DE (1) | DE69408750T2 (OSRAM) |
| DK (1) | DK0640599T3 (OSRAM) |
| ES (1) | ES2114662T3 (OSRAM) |
| TW (1) | TW273548B (OSRAM) |
Families Citing this family (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9325217D0 (en) * | 1993-12-09 | 1994-02-09 | Zeneca Ltd | Pyrimidine derivatives |
| JP2000507224A (ja) * | 1996-03-08 | 2000-06-13 | スミスクライン・ビーチャム・コーポレイション | Ｃｓａｉｄ化合物の血管形成の抑制物質としての使用 |
| DE19644228A1 (de) * | 1996-10-24 | 1998-04-30 | Merck Patent Gmbh | Thienopyrimidine |
| KR100239800B1 (ko) * | 1996-11-28 | 2000-03-02 | 손경식 | 4,5-디아미노 피리미딘 유도체 및 이의 제조방법 |
| US6432947B1 (en) | 1997-02-19 | 2002-08-13 | Berlex Laboratories, Inc. | N-heterocyclic derivatives as NOS inhibitors |
| PL335235A1 (en) * | 1997-02-19 | 2000-04-10 | Berlex Lab | N-heterocyclic derivatives as nos inhibitors |
| IN188411B (OSRAM) | 1997-03-27 | 2002-09-21 | Yuhan Corp | |
| US6440965B1 (en) * | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
| BR9908004A (pt) | 1998-02-17 | 2001-12-18 | Tularik Inc | Composto, composição e método para prevençãoou supressão de uma infecção viral |
| DE19819023A1 (de) * | 1998-04-29 | 1999-11-04 | Merck Patent Gmbh | Thienopyrimidine |
| KR100272471B1 (ko) | 1998-11-17 | 2000-11-15 | 김선진 | 신규의 피리미딘 유도체 및 그의 제조방법 |
| JP4709388B2 (ja) * | 1999-01-25 | 2011-06-22 | 全薬工業株式会社 | 複素環式化合物及びそれを有効成分とする抗腫瘍剤 |
| US6583148B1 (en) | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
| KR100546992B1 (ko) * | 1999-04-09 | 2006-02-01 | 씨제이 주식회사 | 4,5-다이아미노 피리미딘 유도체 및 이의 제조방법 |
| US7037916B2 (en) | 1999-07-15 | 2006-05-02 | Pharmacopeia Drug Discovery, Inc. | Pyrimidine derivatives as IL-8 receptor antagonists |
| CA2383466C (en) * | 1999-09-16 | 2009-08-25 | Tanabe Seiyaku Co., Ltd. | Aromatic nitrogen-containing 6-membered cyclic compounds |
| ATE314362T1 (de) | 1999-10-12 | 2006-01-15 | Takeda Pharmaceutical | Pyrimidin-5-carboximidverbindungen, verfahren zur herstellung derselben und deren verwendung |
| JP2003519153A (ja) * | 1999-12-24 | 2003-06-17 | バイエル アクチェンゲゼルシャフト | イソオキサゾロピリミジノン類及びその使用 |
| US6943161B2 (en) * | 1999-12-28 | 2005-09-13 | Pharmacopela Drug Discovery, Inc. | Pyrimidine and triazine kinase inhibitors |
| US6410726B1 (en) | 2000-01-12 | 2002-06-25 | Tularik Inc. | Arylsulfonic acid salts of pyrimidine-based antiviral |
| US6525051B2 (en) | 2000-03-27 | 2003-02-25 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| DE60142236D1 (de) | 2000-07-24 | 2010-07-08 | Krenitsky Pharmaceuticals Inc | Substituierte 5-alkinyl-pyrimidine mit neurotropher wirkung |
| IT1318674B1 (it) * | 2000-08-08 | 2003-08-27 | Nicox Sa | Faramaci per l'incontinenza. |
| WO2002047690A1 (en) * | 2000-12-12 | 2002-06-20 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators of caspases and inducers of apoptosis and the use thereof |
| US6716851B2 (en) | 2000-12-12 | 2004-04-06 | Cytovia, Inc. | Substituted 2-aryl-4-arylaminopyrimidines and analogs as activators or caspases and inducers of apoptosis and the use thereof |
| US20040127502A1 (en) | 2001-01-31 | 2004-07-01 | Synaptic Pharmaceutical Corporation | Use of GAL3 antagonist for treatment of depression |
| US7081470B2 (en) | 2001-01-31 | 2006-07-25 | H. Lundbeck A/S | Use of GALR3 receptor antagonists for the treatment of depression and/or anxiety and compounds useful in such methods |
| NZ527741A (en) * | 2001-02-26 | 2005-02-25 | Tanabe Seiyaku Co | Pyridopyrimidine or naphthyridine derivative |
| AU2002253619B2 (en) | 2001-04-27 | 2007-05-17 | Zenyaku Kogyo Kabushiki Kaisha | Heterocyclic compound and antitumor agent containing the same active ingredients |
| US6982259B2 (en) | 2002-04-30 | 2006-01-03 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
| CN1665506A (zh) | 2002-07-02 | 2005-09-07 | 霍夫曼-拉罗奇有限公司 | 作为ccr－3受体拮抗剂ⅸ的2,5－取代的嘧啶衍生物 |
| WO2005110416A2 (en) * | 2004-05-08 | 2005-11-24 | Neurogen Corporation | 4,5-disubstituted-2-aryl pyrimidines |
| CA2587427A1 (en) | 2004-11-17 | 2006-05-26 | Miikana Therapeutics, Inc. | Kinase inhibitors |
| ES2395196T3 (es) * | 2005-03-11 | 2013-02-11 | Zenyaku Kogyo Kabushikikaisha | Agente inmunosupresor que comprende un compuesto heterocíclico como ingrediente activo |
| WO2006123639A1 (ja) * | 2005-05-18 | 2006-11-23 | Asahi Kasei Pharma Corporation | ピリミジン誘導体 |
| US20060293343A1 (en) * | 2005-05-18 | 2006-12-28 | Asahi Kasei Pharma Corporation | Pyrimidine derivatives |
| JP5597353B2 (ja) * | 2005-09-30 | 2014-10-01 | ミイカナ セラピューティクス インコーポレイテッド | 置換ピラゾール化合物 |
| GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
| US20090029992A1 (en) * | 2007-06-11 | 2009-01-29 | Agoston Gregory E | Substituted pyrazole compounds |
| WO2009064388A2 (en) * | 2007-11-09 | 2009-05-22 | Liu Jun O | Inhibitors of human methionine aminopeptidase 1 and methods of treating disorders |
| WO2010027097A1 (en) * | 2008-09-04 | 2010-03-11 | Mitsubishi Tanabe Pharma Corporation | Tri-substituted pyrimidine compounds and their use as pde10 inhibitors |
| CA2799579A1 (en) | 2010-05-21 | 2011-11-24 | Intellikine, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| CA2840883C (en) * | 2011-07-07 | 2019-07-16 | Merck Patent Gmbh | Substituted azaheterocycles |
| CN103998442B (zh) | 2011-08-29 | 2016-09-14 | 无限药品股份有限公司 | 杂环化合物及其用途 |
| US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
| EP3080101A1 (en) * | 2013-12-10 | 2016-10-19 | Cleave Biosciences, Inc. | Monocyclic pyrimidine/pyridine compounds as inhibitors of p97 complex |
| CN109045032A (zh) | 2014-01-01 | 2018-12-21 | 麦迪威森技术有限责任公司 | 氨基吡啶类化合物和使用方法 |
| JP6387111B2 (ja) | 2014-01-20 | 2018-09-05 | クリーブ バイオサイエンシズ インコーポレイテッド | ｐ９７複合体の阻害剤としての縮合ピリミジン |
| CN105294661B (zh) * | 2015-07-27 | 2017-10-24 | 西南大学 | 5‑氟尿嘧啶苯并咪唑类化合物及其制备方法和应用 |
| GB201705263D0 (en) | 2017-03-31 | 2017-05-17 | Probiodrug Ag | Novel inhibitors |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3992320A (en) * | 1974-08-24 | 1976-11-16 | Basf Aktiengesellschaft | Manufacture of a modified titanium component for catalysts of the Ziegler-Natta type |
| US4018770A (en) * | 1975-03-03 | 1977-04-19 | Sterling Drug Inc. | N-(2-(pyridinyl)-4-pyrimidinyl)-aminomethylenemalonates and analogs |
| US4032523A (en) * | 1975-03-03 | 1977-06-28 | Sterling Drug Inc. | 4-amino (or halo or hydroxy or hydrazino)-2-(pyridinyl)pyrimidines |
| US3992380A (en) * | 1975-03-03 | 1976-11-16 | Sterling Drug Inc. | 5,8-Dihydro-5-oxo-2-(4-or 3-pyridinyl)pyrido[2,3-d]pyrimidine-6-carboxylic acids and esters |
| DE3922735A1 (de) * | 1989-07-11 | 1991-01-24 | Hoechst Ag | Aminopyrimidin-derivate, verfahren zu ihrer herstellung, sie enthaltende mittel und ihre verwendung als fungizide |
| AU683620B2 (en) * | 1992-09-28 | 1997-11-20 | Pfizer Inc. | Substituted pyrimidines for control of diabetic complications |
| US5318975A (en) * | 1993-02-16 | 1994-06-07 | Berlex Laboratories, Inc. | 5-pyrimdineamine derivatives |
-
1994
- 1994-08-12 ES ES94305973T patent/ES2114662T3/es not_active Expired - Lifetime
- 1994-08-12 EP EP94305973A patent/EP0640599B1/en not_active Expired - Lifetime
- 1994-08-12 AT AT94305973T patent/ATE163647T1/de not_active IP Right Cessation
- 1994-08-12 DE DE69408750T patent/DE69408750T2/de not_active Expired - Fee Related
- 1994-08-12 DK DK94305973T patent/DK0640599T3/da active
- 1994-08-24 US US08/295,377 patent/US5525604A/en not_active Expired - Fee Related
- 1994-08-24 JP JP6222654A patent/JPH0789958A/ja active Pending
- 1994-08-25 CA CA002130878A patent/CA2130878C/en not_active Expired - Fee Related
- 1994-08-25 CN CN94109363A patent/CN1109055A/zh active Pending
- 1994-08-25 KR KR1019940021017A patent/KR100204433B1/ko not_active Expired - Fee Related
- 1994-08-29 TW TW083107897A patent/TW273548B/zh active
Also Published As
| Publication number | Publication date |
|---|---|
| CN1109055A (zh) | 1995-09-27 |
| ES2114662T3 (es) | 1998-06-01 |
| DE69408750T2 (de) | 1998-07-23 |
| DK0640599T3 (da) | 1998-09-28 |
| CA2130878A1 (en) | 1995-02-27 |
| KR950005825A (ko) | 1995-03-20 |
| JPH0789958A (ja) | 1995-04-04 |
| US5525604A (en) | 1996-06-11 |
| ATE163647T1 (de) | 1998-03-15 |
| TW273548B (OSRAM) | 1996-04-01 |
| KR100204433B1 (ko) | 1999-06-15 |
| DE69408750D1 (de) | 1998-04-09 |
| EP0640599A1 (en) | 1995-03-01 |
| EP0640599B1 (en) | 1998-03-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed | ||
| MKLA | Lapsed |
Effective date: 20000825 |