KR20000076124A - 1,5-디히드로-피라졸로[3,4-ｄ]-피리미디논 유도체 - Google Patents
1,5-디히드로-피라졸로[3,4-ｄ]-피리미디논 유도체 Download PDFInfo
- Publication number
- KR20000076124A KR20000076124A KR1019997008213A KR19997008213A KR20000076124A KR 20000076124 A KR20000076124 A KR 20000076124A KR 1019997008213 A KR1019997008213 A KR 1019997008213A KR 19997008213 A KR19997008213 A KR 19997008213A KR 20000076124 A KR20000076124 A KR 20000076124A
- Authority
- KR
- South Korea
- Prior art keywords
- carbon atoms
- straight
- formula
- branched chain
- phenyl
- 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
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- RAEVFJQVGBSKJO-UHFFFAOYSA-N 1,2,4,7-tetrahydropyrazolo[3,4-d]pyrimidin-3-one Chemical class N1=CNCC2=C1NNC2=O RAEVFJQVGBSKJO-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 239000003814 drug Substances 0.000 claims abstract description 10
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 6
- 208000018262 Peripheral vascular disease Diseases 0.000 claims abstract description 5
- 208000025609 Urogenital disease Diseases 0.000 claims abstract description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 4
- 230000002526 effect on cardiovascular system Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 97
- 125000004432 carbon atom Chemical group C* 0.000 claims description 77
- -1 cyano, hydroxyl Chemical group 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- 239000000460 chlorine Substances 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
- 229910052794 bromium Inorganic materials 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000002541 furyl group Chemical group 0.000 claims description 12
- 239000012442 inert solvent Substances 0.000 claims description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 6
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 125000005605 benzo group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000007800 oxidant agent Substances 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 3
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 201000001881 impotence Diseases 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000004355 nitrogen functional group Chemical group 0.000 claims description 2
- 125000003386 piperidinyl group Chemical group 0.000 claims description 2
- 125000001725 pyrenyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- MIQLKTPRUZLHFE-UHFFFAOYSA-N 1,5,6,7a-tetrahydropyrano[2,3-c]pyrazol-3-amine Chemical class N1NC(C=2C1OCCC=2)=N MIQLKTPRUZLHFE-UHFFFAOYSA-N 0.000 claims 7
- 239000002671 adjuvant Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 210000002229 urogenital system Anatomy 0.000 claims 1
- 239000013543 active substance Substances 0.000 abstract 1
- 150000003217 pyrazoles Chemical class 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 300
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 207
- 239000000243 solution Substances 0.000 description 126
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 121
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 106
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 73
- 239000002904 solvent Substances 0.000 description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
- 239000012071 phase Substances 0.000 description 53
- 238000004587 chromatography analysis Methods 0.000 description 50
- 238000000746 purification Methods 0.000 description 44
- 239000007787 solid Substances 0.000 description 44
- 235000019439 ethyl acetate Nutrition 0.000 description 41
- 239000003921 oil Substances 0.000 description 41
- 229920006395 saturated elastomer Polymers 0.000 description 41
- 229940093499 ethyl acetate Drugs 0.000 description 39
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 38
- 239000011734 sodium Substances 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 35
- 235000017557 sodium bicarbonate Nutrition 0.000 description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000012074 organic phase Substances 0.000 description 28
- 238000002844 melting Methods 0.000 description 24
- 230000008018 melting Effects 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 19
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 18
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
- 239000003125 aqueous solvent Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 15
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 14
- 235000011152 sodium sulphate Nutrition 0.000 description 14
- LKXHGCAQFYIOOO-UHFFFAOYSA-N 5-amino-1-(2-hydroxy-6-phenylhexan-3-yl)pyrazole-4-carboxamide Chemical compound N1=CC(C(N)=O)=C(N)N1C(C(O)C)CCCC1=CC=CC=C1 LKXHGCAQFYIOOO-UHFFFAOYSA-N 0.000 description 13
- SSVFMICWXDVRQN-UHFFFAOYSA-N ethanol;sodium Chemical compound [Na].CCO SSVFMICWXDVRQN-UHFFFAOYSA-N 0.000 description 13
- GHVZOJONCUEWAV-UHFFFAOYSA-N [K].CCO Chemical compound [K].CCO GHVZOJONCUEWAV-UHFFFAOYSA-N 0.000 description 11
- 239000002585 base Substances 0.000 description 11
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
- HFEVEIJAYFFEBH-UHFFFAOYSA-N 5-amino-3-methyl-1-nonan-3-ylpyrazole-4-carboxamide Chemical compound CCCCCCC(CC)N1N=C(C)C(C(N)=O)=C1N HFEVEIJAYFFEBH-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- HEMYXNDMAAOTCK-UHFFFAOYSA-N methyl 2-(1,3-benzodioxol-5-yl)acetate Chemical compound COC(=O)CC1=CC=C2OCOC2=C1 HEMYXNDMAAOTCK-UHFFFAOYSA-N 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 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 description 8
- 238000009835 boiling Methods 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- LUQFHUKHDKTFNX-UHFFFAOYSA-N 5-amino-1-decan-4-yl-3-propylpyrazole-4-carboxamide Chemical compound CCCCCCC(CCC)N1N=C(CCC)C(C(N)=O)=C1N LUQFHUKHDKTFNX-UHFFFAOYSA-N 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 235000015165 citric acid Nutrition 0.000 description 7
- 238000011194 good manufacturing practice Methods 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 239000003208 petroleum Substances 0.000 description 7
- 239000011591 potassium Substances 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 6
- BOSVWXDDFBSSIZ-UHFFFAOYSA-N 2-(1-ethoxyethylidene)propanedinitrile Chemical compound CCOC(C)=C(C#N)C#N BOSVWXDDFBSSIZ-UHFFFAOYSA-N 0.000 description 6
- DTRQOKJQNZVPMZ-UHFFFAOYSA-N 5-amino-1-(2-hydroxy-6-phenylhexan-3-yl)-3-methylpyrazole-4-carboxamide Chemical compound N1=C(C)C(C(N)=O)=C(N)N1C(C(O)C)CCCC1=CC=CC=C1 DTRQOKJQNZVPMZ-UHFFFAOYSA-N 0.000 description 6
- SAJMNAAPHDISPS-UHFFFAOYSA-N 5-amino-1-decan-4-yl-3-ethylpyrazole-4-carboxamide Chemical compound CCCCCCC(CCC)N1N=C(CC)C(C(N)=O)=C1N SAJMNAAPHDISPS-UHFFFAOYSA-N 0.000 description 6
- ICXAYWYCLCNIBP-UHFFFAOYSA-N 5-amino-1-decan-4-yl-3-methylpyrazole-4-carboxamide Chemical compound CCCCCCC(CCC)N1N=C(C)C(C(N)=O)=C1N ICXAYWYCLCNIBP-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- JDAADONCQPUNRY-UHFFFAOYSA-N tert-butyl n-(5-phenylpentan-2-ylideneamino)carbamate Chemical compound CC(C)(C)OC(=O)NN=C(C)CCCC1=CC=CC=C1 JDAADONCQPUNRY-UHFFFAOYSA-N 0.000 description 6
- GXMOSBIOUZALPM-UHFFFAOYSA-N 2-(1-ethoxypropylidene)propanedinitrile Chemical compound CCOC(CC)=C(C#N)C#N GXMOSBIOUZALPM-UHFFFAOYSA-N 0.000 description 5
- TYNSUEXNGLNQSS-UHFFFAOYSA-N 6-carbamoyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(N)=O TYNSUEXNGLNQSS-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- DILOFCBIBDMHAY-UHFFFAOYSA-N methyl 2-(3,4-dimethoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(OC)C(OC)=C1 DILOFCBIBDMHAY-UHFFFAOYSA-N 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- GEDSOQMESIYDQX-UHFFFAOYSA-N 5-phenylpentan-2-ylhydrazine Chemical compound NNC(C)CCCC1=CC=CC=C1 GEDSOQMESIYDQX-UHFFFAOYSA-N 0.000 description 4
- TZYQTWHRLVDYPL-UHFFFAOYSA-N 5h-pyrimidin-4-one Chemical compound O=C1CC=NC=N1 TZYQTWHRLVDYPL-UHFFFAOYSA-N 0.000 description 4
- QAXDVKBGZRMSHF-UHFFFAOYSA-N 6-acetyl-5-hydroxy-4-methoxy-7,8-dihydro-3h-pyrrolo[3,2-e]indole-2-carboxylic acid Chemical compound C1=2C=C(C(O)=O)NC=2C(OC)=C(O)C2=C1CCN2C(C)=O QAXDVKBGZRMSHF-UHFFFAOYSA-N 0.000 description 4
- ZZNMARICFYRSPB-UHFFFAOYSA-N 6-benzyl-3-methoxy-1-(5-phenylpentan-2-yl)-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=2N=C(CC=3C=CC=CC=3)NC(=O)C=2C(OC)=NN1C(C)CCCC1=CC=CC=C1 ZZNMARICFYRSPB-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- MWNQUUNHAXFIDV-UHFFFAOYSA-N decan-4-ylhydrazine Chemical compound CCCCCCC(NN)CCC MWNQUUNHAXFIDV-UHFFFAOYSA-N 0.000 description 4
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 4
- IGXAJUPIDFDTTR-UHFFFAOYSA-N methyl 2-(3,4,5-trimethoxyphenyl)acetate Chemical compound COC(=O)CC1=CC(OC)=C(OC)C(OC)=C1 IGXAJUPIDFDTTR-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 229960005235 piperonyl butoxide Drugs 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- VQVBNWUUKLBHGI-UHFFFAOYSA-N 2-(4-bromophenyl)acetyl chloride Chemical compound ClC(=O)CC1=CC=C(Br)C=C1 VQVBNWUUKLBHGI-UHFFFAOYSA-N 0.000 description 3
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- IVCGLVZNTOAJNU-UHFFFAOYSA-N ethyl 3-[(3-methyl-1-nonan-3-yl-4-oxo-5H-pyrazolo[3,4-d]pyrimidin-6-yl)methyl]benzoate Chemical compound CCCCCCC(CC)N1N=C(C)C(C(N2)=O)=C1N=C2CC1=CC=CC(C(=O)OCC)=C1 IVCGLVZNTOAJNU-UHFFFAOYSA-N 0.000 description 1
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- NYZOHVGGRFFBEH-UHFFFAOYSA-N methyl 2-(4-morpholin-4-ylsulfonylphenyl)acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1S(=O)(=O)N1CCOCC1 NYZOHVGGRFFBEH-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- 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
-
- 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
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Vascular Medicine (AREA)
- Gynecology & Obstetrics (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19709877A DE19709877A1 (de) | 1997-03-11 | 1997-03-11 | 1,5-Dihydro-pyrazolo[3,4-d]-pyrimidinon-derivate |
| DE19709877.0 | 1997-03-11 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20000076124A true KR20000076124A (ko) | 2000-12-26 |
Family
ID=7822900
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019997008213A Ceased KR20000076124A (ko) | 1997-03-11 | 1998-02-26 | 1,5-디히드로-피라졸로[3,4-ｄ]-피리미디논 유도체 |
Country Status (17)
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|---|---|
| US (1) | US6174884B1 (enExample) |
| EP (1) | EP0973774B1 (enExample) |
| JP (1) | JP2001514638A (enExample) |
| KR (1) | KR20000076124A (enExample) |
| CN (1) | CN1151155C (enExample) |
| AT (1) | ATE231509T1 (enExample) |
| AU (1) | AU727615B2 (enExample) |
| BR (1) | BR9807995A (enExample) |
| CA (1) | CA2283211A1 (enExample) |
| DE (2) | DE19709877A1 (enExample) |
| DK (1) | DK0973774T3 (enExample) |
| ES (1) | ES2191294T3 (enExample) |
| HU (1) | HUP0001805A3 (enExample) |
| IL (1) | IL131450A0 (enExample) |
| NZ (1) | NZ337724A (enExample) |
| RU (1) | RU2219180C2 (enExample) |
| WO (1) | WO1998040384A1 (enExample) |
Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9823103D0 (en) * | 1998-10-23 | 1998-12-16 | Pfizer Ltd | Pharmaceutically active compounds |
| WO2002009713A2 (de) | 2000-08-01 | 2002-02-07 | Bayer Aktiengesellschaft | Selektive pde 2-inhibitoren als arzneimittel zur verbesserung der wahrnehmung |
| CN1481244A (zh) * | 2000-12-19 | 2004-03-10 | Ĭ��ר���ɷ�����˾ | 含有吡唑并[4,3-d]嘧啶和抗血栓形成剂、钙拮抗剂、前列腺素或前列腺素衍生物的药物制剂 |
| DE10064105A1 (de) | 2000-12-21 | 2002-06-27 | Bayer Ag | Neue Substituierte Imidazotriazinone |
| CA2437085A1 (en) * | 2001-02-02 | 2002-08-15 | Merck Patent Gesellschaft Mit Beschraenkter Haftung | Pharmaceutical formulation comprising pyrazolo[4,3-d]pyrimidines and endothelin receptor antagonists or thienopyrimidines and endothelin receptor antagonists |
| KR100393160B1 (ko) * | 2001-06-14 | 2003-07-31 | 한국과학기술연구원 | 신규한 피라졸로피리미딘티온 유도체, 그의 제법 및발기부전 치료제로서의 용도 |
| US6479493B1 (en) | 2001-08-23 | 2002-11-12 | Cell Pathways, Inc. | Methods for treatment of type I diabetes |
| WO2003072541A2 (en) * | 2001-09-27 | 2003-09-04 | Smithkline Beecham Corporation | Chemical compounds |
| FR2842809A1 (fr) * | 2002-07-26 | 2004-01-30 | Greenpharma Sas | NOUVELLES PYRAZOLO[1,5-a]-1,3,5-TRIAZINES SUBSTITUEES ET LEURS ANALOGUES, COMPOSITIONS PHARMACEUTIQUES LES CONTENANT, UTILISATION A TITRE DE MEDICAMENT ET PROCEDES POUR LEUR PREPARATION |
| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| DE10238723A1 (de) * | 2002-08-23 | 2004-03-11 | Bayer Ag | Phenyl-substituierte Pyrazolyprimidine |
| DE10238724A1 (de) * | 2002-08-23 | 2004-03-04 | Bayer Ag | Alkyl-substituierte Pyrazolpyrimidine |
| CN100397023C (zh) * | 2003-01-04 | 2008-06-25 | 胡云北 | 黄磷废渣载热量及反应尾气发热量的回收与综合利用方法 |
| EP1601675A1 (en) * | 2003-03-04 | 2005-12-07 | ALTANA Pharma AG | Purin-6-one-derivatives |
| DE10320785A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Arylmethyl-substituierte Pyrazolopyrimidine |
| US8044060B2 (en) | 2003-05-09 | 2011-10-25 | Boehringer Ingelheim International Gmbh | 6-cyclylmethyl- and 6-alkylmethyl pyrazolo[3,4-D]pyrimidines, methods for their preparation and methods for their use to treat impairments of perception, concentration learning and/or memory |
| DE102004004142A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Cyclylmethyl- und 6-Alkylmethyl-substituierte Pyrazolopyrimidine |
| DE10328479A1 (de) | 2003-06-25 | 2005-01-13 | Bayer Ag | 6-Arylamino-5-cyano-4-pyrimidinone |
| JP2007504117A (ja) * | 2003-08-28 | 2007-03-01 | アルタナ ファルマ アクチエンゲゼルシャフト | 肺サーファクタントとｐｄｅ２阻害剤とを含有する組成物 |
| DE102004001873A1 (de) | 2004-01-14 | 2005-09-29 | Bayer Healthcare Ag | Cyanopyrimidinone |
| EP1720878A1 (en) * | 2004-02-27 | 2006-11-15 | F.Hoffmann-La Roche Ag | Heteroaryl-fused pyrazolo derivatives |
| CN101397299B (zh) * | 2007-09-29 | 2011-11-16 | 温州大学 | 一种吡唑[3,4-d]嘧啶酮的合成方法 |
| PE20091211A1 (es) | 2007-11-30 | 2009-09-14 | Boehringer Ingelheim Int | Derivados de pirazolopirimidina como moduladores de pde9a |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| AP2011005672A0 (en) | 2008-09-08 | 2011-04-30 | Boehringer Ingelheim Int | Pyrazolopyrimidines and their use for the treatment of CNS disorders. |
| PE20120505A1 (es) | 2009-03-31 | 2012-05-09 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-dihidro-pirazolo[3,4-d]pirimidin-4-ona como moduladores de pde9a |
| EP2414344A1 (en) | 2009-03-31 | 2012-02-08 | ArQule, Inc. | Substituted indolo-pyridinone compounds |
| TW201118099A (en) * | 2009-08-12 | 2011-06-01 | Boehringer Ingelheim Int | New compounds for the treatment of CNS disorders |
| HUE033378T2 (en) | 2010-08-12 | 2017-11-28 | Boehringer Ingelheim Int | 6-cycloalkyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a inhibitors |
| US20130040971A1 (en) | 2011-02-14 | 2013-02-14 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of cns disorders |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| ES2602794T3 (es) | 2011-03-31 | 2017-02-22 | Pfizer Inc | Piridinonas bicíclicas novedosas |
| WO2012172449A1 (en) | 2011-06-13 | 2012-12-20 | Pfizer Inc. | Lactams as beta secretase inhibitors |
| WO2013030713A1 (en) | 2011-08-31 | 2013-03-07 | Pfizer Inc. | Hexahydropyrano [3,4-d][1,3] thiazin-2-amine compounds |
| JO3407B1 (ar) | 2012-05-31 | 2019-10-20 | Eisai R&D Man Co Ltd | مركبات رباعي هيدرو بيرازولو بيريميدين |
| UA110688C2 (uk) | 2012-09-21 | 2016-01-25 | Пфайзер Інк. | Біциклічні піридинони |
| BR112015019276A2 (pt) | 2013-02-19 | 2017-07-18 | Pfizer | compostos de azabenzimidazol como inibidores de isoenzimas de pde4 para o tratamento de distúrbios do snc e outros distúrbios |
| WO2015049616A1 (en) | 2013-10-04 | 2015-04-09 | Pfizer Inc. | Novel bicyclic pyridinones as gamma-secretase modulators |
| WO2015150957A1 (en) | 2014-04-01 | 2015-10-08 | Pfizer Inc. | Chromene and 1,1 a,2,7b-tetrahydrocyclopropa[c]chromene pyridopyrazinediones as gamma-secretase modulators |
| US10131669B2 (en) | 2014-07-24 | 2018-11-20 | Pfizer Inc. | Pyrazolopyrimidine compounds |
| EA031201B1 (ru) | 2014-08-06 | 2018-11-30 | Пфайзер Инк. | Соединения имидазопиридазина |
| WO2016125048A1 (en) | 2015-02-03 | 2016-08-11 | Pfizer Inc. | Novel cyclopropabenzofuranyl pyridopyrazinediones |
| JO3627B1 (ar) | 2015-04-30 | 2020-08-27 | H Lundbeck As | إيميدازو بيرازينونات على هيئة مثبطات pde1 |
| WO2016179059A1 (en) * | 2015-05-05 | 2016-11-10 | Merck Sharp & Dohme Corp. | Heteroaryl-pyrimidinone compounds as pde2 inhibitors |
| ES2924371T3 (es) | 2015-06-17 | 2022-10-06 | Pfizer | Compuestos tricíclicos y su uso como inhibidores de la fosfodiesterasa |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3165520A (en) * | 1965-01-12 | Certificate of correction | ||
| US3211732A (en) | 1965-10-12 | Pyrazolob:x-d]pyrlil/hdines | ||
| CH398626A (de) * | 1960-05-11 | 1966-03-15 | Ciba Geigy | Verfahren zur Herstellung neuer Pyrazolopyrimidine |
| DE1153023B (de) | 1960-05-11 | 1963-08-22 | Ciba Geigy | Verfahren zur Herstellung von 4-Hydroxy-pyrazolo[3,4-d] pyrimidinen |
| CH633297A5 (de) | 1977-09-16 | 1982-11-30 | Sandoz Ag | Verfahren zur herstellung von fluorenphosphoniten. |
| GB9121028D0 (en) | 1991-10-03 | 1991-11-13 | Pfizer Ltd | Therapeutic agents |
| US5294612A (en) * | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| EP0638080A4 (en) * | 1992-04-21 | 1995-08-23 | Biocryst Pharm Inc | 7-DISUBSTITUTED-METHYL-4-OXO-3H, 5H-PYRROLO- (3,2-d) PYRIMIDINE DERIVATIVES, THEIR PHARMACEUTICAL USE, AND COMPOSITIONS CONTAINING THESE COMPOUNDS. |
| KR19980702892A (ko) | 1995-03-10 | 1998-08-05 | 보먼 메리 피 | 6-아릴 피라졸로[3,4-디]피리미딘-4-온 및 그의 조성물 및 그의사용 방법 |
| US5656629A (en) | 1995-03-10 | 1997-08-12 | Sanofi Winthrop, Inc. | 6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof |
-
1997
- 1997-03-11 DE DE19709877A patent/DE19709877A1/de not_active Withdrawn
-
1998
- 1998-02-26 EP EP98913595A patent/EP0973774B1/de not_active Expired - Lifetime
- 1998-02-26 ES ES98913595T patent/ES2191294T3/es not_active Expired - Lifetime
- 1998-02-26 US US09/367,538 patent/US6174884B1/en not_active Expired - Fee Related
- 1998-02-26 HU HU0001805A patent/HUP0001805A3/hu unknown
- 1998-02-26 BR BR9807995-6A patent/BR9807995A/pt not_active IP Right Cessation
- 1998-02-26 RU RU99121518/04A patent/RU2219180C2/ru not_active IP Right Cessation
- 1998-02-26 DK DK98913595T patent/DK0973774T3/da active
- 1998-02-26 WO PCT/EP1998/001086 patent/WO1998040384A1/de not_active Ceased
- 1998-02-26 CN CNB988049872A patent/CN1151155C/zh not_active Expired - Fee Related
- 1998-02-26 CA CA002283211A patent/CA2283211A1/en not_active Abandoned
- 1998-02-26 AU AU68240/98A patent/AU727615B2/en not_active Ceased
- 1998-02-26 DE DE59807011T patent/DE59807011D1/de not_active Expired - Fee Related
- 1998-02-26 NZ NZ337724A patent/NZ337724A/xx unknown
- 1998-02-26 AT AT98913595T patent/ATE231509T1/de not_active IP Right Cessation
- 1998-02-26 IL IL13145098A patent/IL131450A0/xx not_active IP Right Cessation
- 1998-02-26 KR KR1019997008213A patent/KR20000076124A/ko not_active Ceased
- 1998-02-26 JP JP53913598A patent/JP2001514638A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US6174884B1 (en) | 2001-01-16 |
| AU6824098A (en) | 1998-09-29 |
| ATE231509T1 (de) | 2003-02-15 |
| BR9807995A (pt) | 2000-03-08 |
| IL131450A0 (en) | 2001-01-28 |
| HUP0001805A2 (hu) | 2000-11-28 |
| DE19709877A1 (de) | 1998-09-17 |
| JP2001514638A (ja) | 2001-09-11 |
| EP0973774B1 (de) | 2003-01-22 |
| CN1151155C (zh) | 2004-05-26 |
| DK0973774T3 (da) | 2003-05-05 |
| WO1998040384A1 (de) | 1998-09-17 |
| CA2283211A1 (en) | 1998-09-17 |
| NZ337724A (en) | 2000-08-25 |
| HUP0001805A3 (en) | 2002-09-30 |
| HK1028035A1 (en) | 2001-02-02 |
| CN1255133A (zh) | 2000-05-31 |
| AU727615B2 (en) | 2000-12-14 |
| RU2219180C2 (ru) | 2003-12-20 |
| EP0973774A1 (de) | 2000-01-26 |
| DE59807011D1 (de) | 2003-02-27 |
| ES2191294T3 (es) | 2003-09-01 |
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