DD296927A5 - Verfahren zur herstellung von 4(3h)-pteridinonen - Google Patents
Verfahren zur herstellung von 4(3h)-pteridinonen Download PDFInfo
- Publication number
- DD296927A5 DD296927A5 DD90339197A DD33919790A DD296927A5 DD 296927 A5 DD296927 A5 DD 296927A5 DD 90339197 A DD90339197 A DD 90339197A DD 33919790 A DD33919790 A DD 33919790A DD 296927 A5 DD296927 A5 DD 296927A5
- Authority
- DD
- German Democratic Republic
- Prior art keywords
- mol
- pteridinone
- general formula
- amino
- group
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- -1 alkali metal salts Chemical class 0.000 claims abstract description 23
- 229910052783 alkali metal Inorganic materials 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- SFWVULIFVPNTOF-UHFFFAOYSA-N 2-(ethoxymethyl)-1h-pteridin-4-one Chemical compound C1=CN=C2NC(COCC)=NC(=O)C2=N1 SFWVULIFVPNTOF-UHFFFAOYSA-N 0.000 claims description 6
- OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 claims description 5
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 5
- PWRHKLKFADDKHS-UHFFFAOYSA-N 5,6-diamino-1h-pyrimidin-4-one Chemical compound NC=1NC=NC(=O)C=1N PWRHKLKFADDKHS-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 229940015043 glyoxal Drugs 0.000 claims description 4
- 150000002905 orthoesters Chemical class 0.000 claims description 4
- VFATYAVSACUHHG-UHFFFAOYSA-N pteridin-4-amine Chemical compound C1=CN=C2C(N)=NC=NC2=N1 VFATYAVSACUHHG-UHFFFAOYSA-N 0.000 claims description 4
- VPVJDWCAHGQMOP-UHFFFAOYSA-N 2-(phenoxymethyl)-1h-pteridin-4-one Chemical compound N=1C2=NC=CN=C2C(=O)NC=1COC1=CC=CC=C1 VPVJDWCAHGQMOP-UHFFFAOYSA-N 0.000 claims description 3
- AAELHGKAPOOQAR-UHFFFAOYSA-N 2-(phenylmethoxymethyl)-1h-pteridin-4-one Chemical compound N=1C2=NC=CN=C2C(=O)NC=1COCC1=CC=CC=C1 AAELHGKAPOOQAR-UHFFFAOYSA-N 0.000 claims description 3
- LYENZQFRBOTNQL-UHFFFAOYSA-N 2-(propoxymethyl)-1h-pteridin-4-one Chemical compound C1=CN=C2C(=O)NC(COCCC)=NC2=N1 LYENZQFRBOTNQL-UHFFFAOYSA-N 0.000 claims description 3
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 3
- SFSMATGDLFHTHE-UHFFFAOYSA-N 3-aminopyrazine-2-carboxamide Chemical compound NC(=O)C1=NC=CN=C1N SFSMATGDLFHTHE-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- GPTKOEVRJWAAMW-UHFFFAOYSA-N 2-(ethoxymethyl)-1,8-dihydropteridine-4,7-dione Chemical compound OC1=CN=C2C(=O)NC(COCC)=NC2=N1 GPTKOEVRJWAAMW-UHFFFAOYSA-N 0.000 claims description 2
- MTSOKXKXDWKITL-UHFFFAOYSA-N 2-(methoxymethyl)-1h-pteridin-4-one Chemical group C1=CN=C2C(=O)NC(COC)=NC2=N1 MTSOKXKXDWKITL-UHFFFAOYSA-N 0.000 claims description 2
- HFMLLTVIMFEQRE-UHFFFAOYSA-N 6-amino-1h-pyrimidin-4-one Chemical compound NC1=CC(O)=NC=N1 HFMLLTVIMFEQRE-UHFFFAOYSA-N 0.000 claims description 2
- GPUANTOOPYPKGX-UHFFFAOYSA-N 6-amino-5-nitroso-1h-pyrimidin-4-one Chemical compound NC=1N=CNC(=O)C=1N=O GPUANTOOPYPKGX-UHFFFAOYSA-N 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 claims description 2
- ODUCDPQEXGNKDN-UHFFFAOYSA-N nitroxyl Chemical compound O=N ODUCDPQEXGNKDN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 125000004434 sulfur atom Chemical group 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 2
- 101100533387 Homo sapiens SCGB1D1 gene Proteins 0.000 claims 1
- 102100028659 Secretoglobin family 1D member 1 Human genes 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 6
- 230000001225 therapeutic effect Effects 0.000 abstract 2
- 239000000043 antiallergic agent Substances 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 162
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- 239000000243 solution Substances 0.000 description 64
- 238000005481 NMR spectroscopy Methods 0.000 description 58
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- 238000004458 analytical method Methods 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- 229910052757 nitrogen Inorganic materials 0.000 description 36
- 238000001914 filtration Methods 0.000 description 31
- 239000000203 mixture Substances 0.000 description 31
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 30
- 238000010992 reflux Methods 0.000 description 30
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000002244 precipitate Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 229910021529 ammonia Inorganic materials 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- GPIZLEHIVRHDAW-UHFFFAOYSA-N 3-aminopyrazine-2-carbonitrile Chemical compound NC1=NC=CN=C1C#N GPIZLEHIVRHDAW-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 230000035484 reaction time Effects 0.000 description 13
- 239000007787 solid Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- 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 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 238000001953 recrystallisation Methods 0.000 description 8
- 229910052708 sodium Inorganic materials 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000000284 extract Substances 0.000 description 7
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 230000003266 anti-allergic effect Effects 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- DVHAHPUKYBAJMJ-UHFFFAOYSA-N 2-(methoxymethoxy)ethanimidamide Chemical compound COCOCC(N)=N DVHAHPUKYBAJMJ-UHFFFAOYSA-N 0.000 description 5
- 239000000538 analytical sample Substances 0.000 description 5
- TXJURWDJHWXLSC-UHFFFAOYSA-N 2-ethoxyethanimidamide Chemical compound CCOCC(N)=N TXJURWDJHWXLSC-UHFFFAOYSA-N 0.000 description 4
- ASDRXJWNWHJARE-UHFFFAOYSA-N 5,6-diamino-2-(ethoxymethyl)-1h-pyrimidin-4-one Chemical compound CCOCC1=NC(N)=C(N)C(=O)N1 ASDRXJWNWHJARE-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- WYKXWRQUUJCTJN-UHFFFAOYSA-N 4-amino-2-(methoxymethoxymethyl)-8h-pteridin-7-one Chemical compound N1=CC(O)=NC2=NC(COCOC)=NC(N)=C21 WYKXWRQUUJCTJN-UHFFFAOYSA-N 0.000 description 3
- LDNHZINLHIXQAP-UHFFFAOYSA-N 7-methoxy-2-(methoxymethoxymethyl)pteridin-4-amine Chemical compound N1=CC(OC)=NC2=NC(COCOC)=NC(N)=C21 LDNHZINLHIXQAP-UHFFFAOYSA-N 0.000 description 3
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- FYYMOSPTRCOSBL-UHFFFAOYSA-N ethyl 2-ethoxyethanimidate Chemical compound CCOCC(=N)OCC FYYMOSPTRCOSBL-UHFFFAOYSA-N 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- TWSAQVIYYRXPCT-UHFFFAOYSA-N methyl 2-(methoxymethoxy)ethanimidate Chemical compound COCOCC(=N)OC TWSAQVIYYRXPCT-UHFFFAOYSA-N 0.000 description 3
- 229960005206 pyrazinamide Drugs 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- VEIMRILVJYYVQC-UHFFFAOYSA-N (2-ethoxy-2-iminoethyl) acetate;hydrochloride Chemical compound Cl.CCOC(=N)COC(C)=O VEIMRILVJYYVQC-UHFFFAOYSA-N 0.000 description 2
- PGNIOQWSIGBCNX-UHFFFAOYSA-N (4,7-dioxo-1,8-dihydropteridin-2-yl)methyl acetate Chemical compound OC1=CN=C2C(=O)NC(COC(=O)C)=NC2=N1 PGNIOQWSIGBCNX-UHFFFAOYSA-N 0.000 description 2
- BIXIVHKGDWTTTM-UHFFFAOYSA-N (4-oxo-1h-pteridin-2-yl)methyl acetate Chemical compound C1=CN=C2C(=O)NC(COC(=O)C)=NC2=N1 BIXIVHKGDWTTTM-UHFFFAOYSA-N 0.000 description 2
- VPYSSSUICZBLEZ-UHFFFAOYSA-N 1-[4-[(4-aminopteridin-2-yl)methoxy]-2-hydroxy-3-propylphenyl]ethanone Chemical compound C1=CC(C(C)=O)=C(O)C(CCC)=C1OCC1=NC(N)=C(N=CC=N2)C2=N1 VPYSSSUICZBLEZ-UHFFFAOYSA-N 0.000 description 2
- DZSRLWBIKNKIHO-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxy)acetonitrile Chemical compound FC(F)(F)COCC#N DZSRLWBIKNKIHO-UHFFFAOYSA-N 0.000 description 2
- UNHITYNUNDUZTD-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxy)ethanimidamide Chemical compound NC(=N)COCC(F)(F)F UNHITYNUNDUZTD-UHFFFAOYSA-N 0.000 description 2
- DYOIMRSERUBBDU-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxymethyl)-1h-pteridin-4-one Chemical compound C1=CN=C2C(=O)NC(COCC(F)(F)F)=NC2=N1 DYOIMRSERUBBDU-UHFFFAOYSA-N 0.000 description 2
- MOTCUQGKDCGFRR-UHFFFAOYSA-N 2-(2,2,2-trifluoroethoxymethyl)pteridin-4-amine Chemical compound C1=CN=C2C(N)=NC(COCC(F)(F)F)=NC2=N1 MOTCUQGKDCGFRR-UHFFFAOYSA-N 0.000 description 2
- QCUOSZDWAPHJOJ-UHFFFAOYSA-N 2-(2,3-dichlorophenoxy)ethanimidamide Chemical compound NC(=N)COC1=CC=CC(Cl)=C1Cl QCUOSZDWAPHJOJ-UHFFFAOYSA-N 0.000 description 2
- VWEPNMRHJBNTGY-UHFFFAOYSA-N 2-(2,3-dichlorophenoxy)ethanimidamide;hydrochloride Chemical compound Cl.NC(=N)COC1=CC=CC(Cl)=C1Cl VWEPNMRHJBNTGY-UHFFFAOYSA-N 0.000 description 2
- CESAAFCIFNBFCU-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethanimidamide Chemical compound NC(=N)COCCO CESAAFCIFNBFCU-UHFFFAOYSA-N 0.000 description 2
- GJGJUWHCXCEHPE-UHFFFAOYSA-N 2-(3,4-dichlorophenoxy)ethanimidamide Chemical compound NC(=N)COC1=CC=C(Cl)C(Cl)=C1 GJGJUWHCXCEHPE-UHFFFAOYSA-N 0.000 description 2
- YJAXMQZAWZOAEN-UHFFFAOYSA-N 2-(4-acetyl-3-hydroxy-2-propylphenoxy)ethanimidamide Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCC(N)=N YJAXMQZAWZOAEN-UHFFFAOYSA-N 0.000 description 2
- ZAVSPGJDAHKCPE-UHFFFAOYSA-N 2-(4-methoxyphenoxy)ethanimidamide Chemical compound COC1=CC=C(OCC(N)=N)C=C1 ZAVSPGJDAHKCPE-UHFFFAOYSA-N 0.000 description 2
- RHGGDTBUDKBQIN-UHFFFAOYSA-N 2-(benzylsulfanylmethyl)-1h-pteridin-4-one Chemical compound N=1C2=NC=CN=C2C(=O)NC=1CSCC1=CC=CC=C1 RHGGDTBUDKBQIN-UHFFFAOYSA-N 0.000 description 2
- MJMPXRQLMMSYII-UHFFFAOYSA-N 2-(ethoxymethyl)-6-methyl-1h-pteridin-4-one Chemical compound C1=C(C)N=C2C(=O)NC(COCC)=NC2=N1 MJMPXRQLMMSYII-UHFFFAOYSA-N 0.000 description 2
- UZLZCWHJWIJWKS-UHFFFAOYSA-N 2-(ethoxymethyl)-6-methylpteridin-4-amine Chemical compound N1=C(C)C=NC2=NC(COCC)=NC(N)=C21 UZLZCWHJWIJWKS-UHFFFAOYSA-N 0.000 description 2
- CTMOVSGFLPGTRS-UHFFFAOYSA-N 2-(ethoxymethyl)pteridin-4-amine Chemical compound N1=CC=NC2=NC(COCC)=NC(N)=C21 CTMOVSGFLPGTRS-UHFFFAOYSA-N 0.000 description 2
- DPOKEOQJYSCXIG-UHFFFAOYSA-N 2-(methoxymethoxymethyl)-1,8-dihydropteridine-4,7-dione Chemical compound OC1=CN=C2C(=O)NC(COCOC)=NC2=N1 DPOKEOQJYSCXIG-UHFFFAOYSA-N 0.000 description 2
- DPXPNAZMORHPDH-UHFFFAOYSA-N 2-(methoxymethoxymethyl)-1h-pteridin-4-one Chemical compound C1=CN=C2C(=O)NC(COCOC)=NC2=N1 DPXPNAZMORHPDH-UHFFFAOYSA-N 0.000 description 2
- MMPLVVHMZBGFEN-UHFFFAOYSA-N 2-(methoxymethoxymethyl)pteridin-4-amine Chemical compound N1=CC=NC2=NC(COCOC)=NC(N)=C21 MMPLVVHMZBGFEN-UHFFFAOYSA-N 0.000 description 2
- RDGWSBHVZQJWTH-UHFFFAOYSA-N 2-(propan-2-yloxymethyl)-1h-pteridin-4-one Chemical compound C1=CN=C2C(=O)NC(COC(C)C)=NC2=N1 RDGWSBHVZQJWTH-UHFFFAOYSA-N 0.000 description 2
- YSOFHMLLPADRRS-UHFFFAOYSA-N 2-[(2,3-dichlorophenoxy)methyl]-1h-pteridin-4-one Chemical compound ClC1=CC=CC(OCC=2NC(=O)C3=NC=CN=C3N=2)=C1Cl YSOFHMLLPADRRS-UHFFFAOYSA-N 0.000 description 2
- INGAAEWVEGUDDO-UHFFFAOYSA-N 2-[(2,3-dichlorophenoxy)methyl]pteridin-4-amine Chemical compound N=1C2=NC=CN=C2C(N)=NC=1COC1=CC=CC(Cl)=C1Cl INGAAEWVEGUDDO-UHFFFAOYSA-N 0.000 description 2
- DRHFAVLSICHSLF-UHFFFAOYSA-N 2-[(3,4-dichlorophenoxy)methyl]pteridin-4-amine Chemical compound N=1C2=NC=CN=C2C(N)=NC=1COC1=CC=C(Cl)C(Cl)=C1 DRHFAVLSICHSLF-UHFFFAOYSA-N 0.000 description 2
- ZMGXHJYLQJOXFG-UHFFFAOYSA-N 2-[(4-aminopteridin-2-yl)methoxy]ethanol Chemical compound C1=CN=C2C(N)=NC(COCCO)=NC2=N1 ZMGXHJYLQJOXFG-UHFFFAOYSA-N 0.000 description 2
- NQCKINRZIVYDDG-UHFFFAOYSA-N 2-[(4-chlorophenoxy)methyl]-1h-pteridin-4-one Chemical compound C1=CC(Cl)=CC=C1OCC1=NC2=NC=CN=C2C(=O)N1 NQCKINRZIVYDDG-UHFFFAOYSA-N 0.000 description 2
- QHLAMHJOLHRQLC-UHFFFAOYSA-N 2-[(4-chlorophenoxy)methyl]pteridin-4-amine Chemical compound N=1C2=NC=CN=C2C(N)=NC=1COC1=CC=C(Cl)C=C1 QHLAMHJOLHRQLC-UHFFFAOYSA-N 0.000 description 2
- ATZSZXCGUNPMHV-UHFFFAOYSA-N 2-[(4-methoxyphenoxy)methyl]-1h-pteridin-4-one Chemical compound C1=CC(OC)=CC=C1OCC1=NC2=NC=CN=C2C(=O)N1 ATZSZXCGUNPMHV-UHFFFAOYSA-N 0.000 description 2
- VYWFHHKFJPCGOW-UHFFFAOYSA-N 2-[(4-methylphenoxy)methyl]pteridin-4-amine Chemical compound C1=CC(C)=CC=C1OCC1=NC(N)=C(N=CC=N2)C2=N1 VYWFHHKFJPCGOW-UHFFFAOYSA-N 0.000 description 2
- UQNRMGKQEXLBGM-UHFFFAOYSA-N 2-[(4-oxo-1h-pteridin-2-yl)methoxy]ethyl acetate Chemical compound C1=CN=C2C(=O)NC(COCCOC(=O)C)=NC2=N1 UQNRMGKQEXLBGM-UHFFFAOYSA-N 0.000 description 2
- LTYQFHBDIKZFNI-UHFFFAOYSA-N 2-amino-6-oxo-1h-pyrazine-3-carboxamide Chemical compound NC(=O)C1=NC=C(O)N=C1N LTYQFHBDIKZFNI-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- BFRFXXVNFWXWLG-UHFFFAOYSA-N 2-propan-2-yloxyethanimidamide Chemical compound CC(C)OCC(N)=N BFRFXXVNFWXWLG-UHFFFAOYSA-N 0.000 description 2
- FSVRTOKNIQGMQP-UHFFFAOYSA-N 3-amino-5-chloropyrazine-2-carbonitrile Chemical compound NC1=NC(Cl)=CN=C1C#N FSVRTOKNIQGMQP-UHFFFAOYSA-N 0.000 description 2
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- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
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- 238000004587 chromatography analysis Methods 0.000 description 1
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- AJEHNBIPLQJTNU-UHFFFAOYSA-N cyanomethyl acetate Chemical compound CC(=O)OCC#N AJEHNBIPLQJTNU-UHFFFAOYSA-N 0.000 description 1
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- HYMXUYQKXCHWDC-UHFFFAOYSA-N ethyl 3-ethoxy-3-iminopropanoate;hydrochloride Chemical compound Cl.CCOC(=N)CC(=O)OCC HYMXUYQKXCHWDC-UHFFFAOYSA-N 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
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- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- HJFDTRFVOMRALK-UHFFFAOYSA-N methyl 2-(3,4-dichlorophenoxy)ethanimidate Chemical compound COC(=N)COC1=CC=C(Cl)C(Cl)=C1 HJFDTRFVOMRALK-UHFFFAOYSA-N 0.000 description 1
- KTXPACPJZOSRFF-UHFFFAOYSA-N methyl 2-(4-methoxyphenoxy)ethanimidate Chemical compound COC(=N)COC1=CC=C(OC)C=C1 KTXPACPJZOSRFF-UHFFFAOYSA-N 0.000 description 1
- HULAPGQHZWKPSN-UHFFFAOYSA-N methyl 2-propan-2-yloxyethanimidate Chemical compound COC(=N)COC(C)C HULAPGQHZWKPSN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 231100000683 possible toxicity Toxicity 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000000894 saliuretic effect Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D475/00—Heterocyclic compounds containing pteridine ring systems
- C07D475/02—Heterocyclic compounds containing pteridine ring systems with an oxygen atom directly attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Pulmonology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8904193A FR2645152B1 (fr) | 1989-03-30 | 1989-03-30 | 3h-pteridinones-4, procedes de preparation et medicaments les contenant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DD296927A5 true DD296927A5 (de) | 1991-12-19 |
Family
ID=9380213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DD90339197A DD296927A5 (de) | 1989-03-30 | 1990-03-29 | Verfahren zur herstellung von 4(3h)-pteridinonen |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US5167949A (he) |
| EP (1) | EP0399856B1 (he) |
| JP (1) | JPH0725761B2 (he) |
| AR (1) | AR248278A1 (he) |
| AT (1) | ATE126229T1 (he) |
| AU (1) | AU630178B2 (he) |
| CA (1) | CA2013324C (he) |
| CZ (1) | CZ284679B6 (he) |
| DD (1) | DD296927A5 (he) |
| DE (1) | DE69021444T2 (he) |
| DK (1) | DK0399856T3 (he) |
| ES (1) | ES2078324T3 (he) |
| FR (1) | FR2645152B1 (he) |
| GE (1) | GEP19971023B (he) |
| GR (1) | GR3017245T3 (he) |
| HR (1) | HRP920759B1 (he) |
| HU (1) | HU208826B (he) |
| IE (1) | IE68689B1 (he) |
| IL (1) | IL93914A (he) |
| LV (1) | LV5821B4 (he) |
| MA (1) | MA21786A1 (he) |
| NO (1) | NO175100C (he) |
| NZ (1) | NZ233130A (he) |
| OA (1) | OA09441A (he) |
| PT (1) | PT93600B (he) |
| RU (1) | RU1836344C (he) |
| SI (1) | SI9010633B (he) |
| TN (1) | TNSN90040A1 (he) |
| YU (1) | YU47346B (he) |
| ZA (1) | ZA902397B (he) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5270465A (en) * | 1989-03-30 | 1993-12-14 | Lipha, Lyonnaise Industrille Pharmaceutique | 4(3H)-pteridinone compounds |
| FR2772615B1 (fr) * | 1997-12-23 | 2002-06-14 | Lipha | Comprime multicouche pour la liberation instantanee puis prolongee de substances actives |
| US6806272B2 (en) | 2001-09-04 | 2004-10-19 | Boehringer Ingelheim Pharma Kg | Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
| CA2458699C (en) * | 2001-09-04 | 2010-10-19 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Novel dihydropteridinones, method for producing the same and the use thereof as medicaments |
| FR2831789B1 (fr) | 2001-11-07 | 2004-01-23 | Oreal | Procede et dispositif pour l'evaluation de la secheresse cutanee notamment |
| US6861422B2 (en) | 2003-02-26 | 2005-03-01 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Dihydropteridinones, processes for preparing them and their use as pharmaceutical compositions |
| DE102004029784A1 (de) | 2004-06-21 | 2006-01-05 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue 2-Benzylaminodihydropteridinone, Verfahren zur deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004033670A1 (de) * | 2004-07-09 | 2006-02-02 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Pyridodihydropyrazinone, Verfahren zu Ihrer Herstellung und Ihre Verwendung als Arzneimittel |
| US20060074088A1 (en) | 2004-08-14 | 2006-04-06 | Boehringer Ingelheim International Gmbh | Dihydropteridinones for the treatment of cancer diseases |
| US20060035903A1 (en) * | 2004-08-14 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Storage stable perfusion solution for dihydropteridinones |
| US7728134B2 (en) | 2004-08-14 | 2010-06-01 | Boehringer Ingelheim International Gmbh | Hydrates and polymorphs of 4[[(7R)-8-cyclopentyl-7-ethyl-5,6,7,8-tetrahydro-5-methyl-6-oxo-2-pteridinyl]amino]-3-methoxy-N-(1-methyl-4-piperidinyl)-benzamide, process for their manufacture and their use as medicament |
| US20060058311A1 (en) | 2004-08-14 | 2006-03-16 | Boehringer Ingelheim International Gmbh | Combinations for the treatment of diseases involving cell proliferation |
| US7759485B2 (en) | 2004-08-14 | 2010-07-20 | Boehringer Ingelheim International Gmbh | Process for the manufacture of dihydropteridinones |
| EP1630163A1 (de) | 2004-08-25 | 2006-03-01 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| EP1632493A1 (de) * | 2004-08-25 | 2006-03-08 | Boehringer Ingelheim Pharma GmbH & Co.KG | Dihydropteridinonderivative, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel |
| DE102004058337A1 (de) * | 2004-12-02 | 2006-06-14 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Verfahren zur Herstellung von annelierten Piperazin-2-on Derivaten |
| US7439358B2 (en) | 2006-02-08 | 2008-10-21 | Boehringer Ingelheim International Gmbh | Specific salt, anhydrous and crystalline form of a dihydropteridione derivative |
| EP2139895A1 (en) * | 2007-03-23 | 2010-01-06 | F. Hoffmann-Roche AG | Aza-pyridopyrimidinone derivatives |
| WO2009019205A1 (en) | 2007-08-03 | 2009-02-12 | Boehringer Ingelheim International Gmbh | Crystalline form of a dihydropteridione derivative |
| US8546566B2 (en) | 2010-10-12 | 2013-10-01 | Boehringer Ingelheim International Gmbh | Process for manufacturing dihydropteridinones and intermediates thereof |
| US9358233B2 (en) | 2010-11-29 | 2016-06-07 | Boehringer Ingelheim International Gmbh | Method for treating acute myeloid leukemia |
| US9370535B2 (en) | 2011-05-17 | 2016-06-21 | Boehringer Ingelheim International Gmbh | Method for treatment of advanced solid tumors |
| US20150031699A1 (en) | 2013-07-26 | 2015-01-29 | Boehringer Ingelheim International Gmbh | Treatment of myelodysplastic syndrome |
| US9867831B2 (en) | 2014-10-01 | 2018-01-16 | Boehringer Ingelheim International Gmbh | Combination treatment of acute myeloid leukemia and myelodysplastic syndrome |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3159628A (en) * | 1962-05-28 | 1964-12-01 | Smith Kline French Lab | Pteridine-5-oxide derivatives |
| US3426019A (en) * | 1962-06-29 | 1969-02-04 | Smithkline Corp | Derivatives of pteridine and a method for their preparation |
| SE307365B (he) * | 1966-05-28 | 1969-01-07 | Yoshitomi Pharmaceutical | |
| US3732224A (en) * | 1969-10-20 | 1973-05-08 | Sherwin Williams Co | Method of controlling plant growth and 3-substituted lumazines used in such method |
| US3819631A (en) * | 1970-12-15 | 1974-06-25 | May & Baker Ltd | Azapurinones |
| US3859287A (en) * | 1971-05-05 | 1975-01-07 | Walter Wesley Parish | Thiopteridines and process for producing same |
| DE2232098A1 (de) * | 1972-06-30 | 1974-01-17 | Boehringer Mannheim Gmbh | 2-alkyl-4(3h)-pteridinone und verfahren zu ihrer herstellung |
| US4183934A (en) * | 1978-10-16 | 1980-01-15 | Abbott Laboratories | 4-Hydroxy-7-(substituted)phenylpteridines |
| US4361700A (en) * | 1980-05-20 | 1982-11-30 | James S. Waldron | Pyridopyrimidinone derivatives |
-
1989
- 1989-03-30 FR FR8904193A patent/FR2645152B1/fr not_active Expired - Lifetime
-
1990
- 1990-03-26 AU AU52218/90A patent/AU630178B2/en not_active Ceased
- 1990-03-27 MA MA22052A patent/MA21786A1/fr unknown
- 1990-03-27 DK DK90400827.3T patent/DK0399856T3/da active
- 1990-03-27 OA OA59755A patent/OA09441A/xx unknown
- 1990-03-27 DE DE69021444T patent/DE69021444T2/de not_active Expired - Fee Related
- 1990-03-27 AT AT90400827T patent/ATE126229T1/de not_active IP Right Cessation
- 1990-03-27 IL IL9391490A patent/IL93914A/he not_active IP Right Cessation
- 1990-03-27 EP EP90400827A patent/EP0399856B1/fr not_active Expired - Lifetime
- 1990-03-27 ES ES90400827T patent/ES2078324T3/es not_active Expired - Lifetime
- 1990-03-28 ZA ZA902397A patent/ZA902397B/xx unknown
- 1990-03-28 CA CA002013324A patent/CA2013324C/fr not_active Expired - Fee Related
- 1990-03-28 CZ CS901520A patent/CZ284679B6/cs not_active IP Right Cessation
- 1990-03-29 DD DD90339197A patent/DD296927A5/de unknown
- 1990-03-29 PT PT93600A patent/PT93600B/pt not_active IP Right Cessation
- 1990-03-29 RU SU904743545A patent/RU1836344C/ru active
- 1990-03-29 IE IE115790A patent/IE68689B1/en not_active IP Right Cessation
- 1990-03-29 NZ NZ233130A patent/NZ233130A/en unknown
- 1990-03-29 AR AR90316504A patent/AR248278A1/es active
- 1990-03-29 US US07/501,104 patent/US5167949A/en not_active Expired - Fee Related
- 1990-03-29 YU YU63390A patent/YU47346B/sh unknown
- 1990-03-29 NO NO901430A patent/NO175100C/no not_active IP Right Cessation
- 1990-03-29 HU HU901898A patent/HU208826B/hu not_active IP Right Cessation
- 1990-03-29 SI SI9010633A patent/SI9010633B/sl not_active IP Right Cessation
- 1990-03-30 TN TNTNSN90040A patent/TNSN90040A1/fr unknown
- 1990-03-30 JP JP2081429A patent/JPH0725761B2/ja not_active Expired - Fee Related
-
1992
- 1992-10-01 HR HRP-633/90A patent/HRP920759B1/xx not_active IP Right Cessation
-
1993
- 1993-03-11 GE GEAP1993603A patent/GEP19971023B/en unknown
-
1995
- 1995-08-30 GR GR950402356T patent/GR3017245T3/el unknown
-
1996
- 1996-07-18 LV LV960271A patent/LV5821B4/xx unknown
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| ASS | Change of applicant or owner |
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| IF04 | In force in the year 2004 |
Expiry date: 20100330 |