SK287161B6 - 2-Fenylsubstituované imidazotriazinóny, spôsob ich výroby, liečivá obsahujúce tieto látky a ich použitie - Google Patents
2-Fenylsubstituované imidazotriazinóny, spôsob ich výroby, liečivá obsahujúce tieto látky a ich použitie Download PDFInfo
- Publication number
- SK287161B6 SK287161B6 SK709-2000A SK7092000A SK287161B6 SK 287161 B6 SK287161 B6 SK 287161B6 SK 7092000 A SK7092000 A SK 7092000A SK 287161 B6 SK287161 B6 SK 287161B6
- Authority
- SK
- Slovakia
- Prior art keywords
- triazin
- propyl
- mmol
- methyl
- ethoxy
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 238000000034 method Methods 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title abstract description 6
- IJYHVZICHKCLMQ-UHFFFAOYSA-N imidazo[4,5-d]triazin-4-one Chemical class O=C1N=NN=C2N=CN=C12 IJYHVZICHKCLMQ-UHFFFAOYSA-N 0.000 title abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 30
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 14
- 235000019441 ethanol Nutrition 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 12
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 claims description 8
- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 201000001881 impotence Diseases 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 208000010228 Erectile Dysfunction Diseases 0.000 claims description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 230000002526 effect on cardiovascular system Effects 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
- 239000012442 inert solvent Substances 0.000 claims description 4
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 238000007039 two-step reaction Methods 0.000 claims description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 12
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 12
- 239000003112 inhibitor Substances 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 333
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 213
- -1 2-phenylsubstituted imidazotriazinones Chemical class 0.000 description 131
- 238000005160 1H NMR spectroscopy Methods 0.000 description 97
- 238000004128 high performance liquid chromatography Methods 0.000 description 89
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 83
- QMNWYGTWTXOQTP-UHFFFAOYSA-N 1h-triazin-6-one Chemical compound O=C1C=CN=NN1 QMNWYGTWTXOQTP-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 51
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 48
- 229940092714 benzenesulfonic acid Drugs 0.000 description 48
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 44
- 239000011541 reaction mixture Substances 0.000 description 42
- 239000002904 solvent Substances 0.000 description 37
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 150000001408 amides Chemical class 0.000 description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 238000010992 reflux Methods 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- 229910052938 sodium sulfate Inorganic materials 0.000 description 22
- 235000011152 sodium sulphate Nutrition 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 239000012074 organic phase Substances 0.000 description 21
- 239000000047 product Substances 0.000 description 17
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 13
- 229910052799 carbon Inorganic materials 0.000 description 13
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
- 235000017557 sodium bicarbonate Nutrition 0.000 description 13
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 8
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000011194 good manufacturing practice Methods 0.000 description 7
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 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 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000004927 clay Substances 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 5
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 4
- DTIMTCJMOWXMGT-UHFFFAOYSA-N 2-(butanoylamino)propanoic acid Chemical compound CCCC(=O)NC(C)C(O)=O DTIMTCJMOWXMGT-UHFFFAOYSA-N 0.000 description 4
- UYCUMNRCCJNSBR-UHFFFAOYSA-N 2-ethoxy-2-oxoacetic acid;hydrochloride Chemical compound Cl.CCOC(=O)C(O)=O UYCUMNRCCJNSBR-UHFFFAOYSA-N 0.000 description 4
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- 210000000709 aorta Anatomy 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 3
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- 241000283690 Bos taurus Species 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 230000000747 cardiac effect Effects 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- GGRAUDKKGGVZAD-UHFFFAOYSA-N tert-butyl 4-(5-hydroxy-2-methyl-1,2,5-oxadiazole-3-carbonyl)piperazine-1-carboxylate Chemical compound CN1ON(O)C=C1C(=O)N1CCN(C(=O)OC(C)(C)C)CC1 GGRAUDKKGGVZAD-UHFFFAOYSA-N 0.000 description 3
- NGMHLSBQVIXGNZ-UHFFFAOYSA-N (2-ethoxybenzenecarboximidoyl)azanium;chloride Chemical compound Cl.CCOC1=CC=CC=C1C(N)=N NGMHLSBQVIXGNZ-UHFFFAOYSA-N 0.000 description 2
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 2
- ZSPLZWJOLZTDHW-UHFFFAOYSA-N 1H-triazin-6-one hydrochloride Chemical compound Cl.OC1=NN=NC=C1 ZSPLZWJOLZTDHW-UHFFFAOYSA-N 0.000 description 2
- IJCQPYVFQIZZSO-UHFFFAOYSA-N 2-(2-ethoxyphenyl)-5,7-dimethyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCOC1=CC=CC=C1C(NC1=O)=NN2C1=C(C)N=C2C IJCQPYVFQIZZSO-UHFFFAOYSA-N 0.000 description 2
- YRRWQMBIMZMVDB-UHFFFAOYSA-N 2-(2-ethoxyphenyl)-5-methyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCC1=NC(C)=C(C(N=2)=O)N1NC=2C1=CC=CC=C1OCC YRRWQMBIMZMVDB-UHFFFAOYSA-N 0.000 description 2
- BBIGEIYZKFRRMH-UHFFFAOYSA-N 2-(butanoylamino)butanoic acid Chemical compound CCCC(=O)NC(CC)C(O)=O BBIGEIYZKFRRMH-UHFFFAOYSA-N 0.000 description 2
- JRMGZDWJZHJQCY-UHFFFAOYSA-N 2-(prop-2-enylamino)ethanol Chemical compound OCCNCC=C JRMGZDWJZHJQCY-UHFFFAOYSA-N 0.000 description 2
- BCLSJHWBDUYDTR-UHFFFAOYSA-N 2-(propylamino)ethanol Chemical compound CCCNCCO BCLSJHWBDUYDTR-UHFFFAOYSA-N 0.000 description 2
- ZMJKETTWHDMJKT-UHFFFAOYSA-N 2-[2-ethoxy-4-methoxy-5-(4-methylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCC1=NC(C)=C(C(N2)=O)N1N=C2C(C(=CC=1OC)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 ZMJKETTWHDMJKT-UHFFFAOYSA-N 0.000 description 2
- YBYSAURRFYGCPI-UHFFFAOYSA-N 2-[2-ethoxy-5-(3-hydroxypyrrolidin-1-yl)sulfonylphenyl]-5,7-dimethyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound C1=C(C=2NC(=O)C3=C(C)N=C(C)N3N=2)C(OCC)=CC=C1S(=O)(=O)N1CCC(O)C1 YBYSAURRFYGCPI-UHFFFAOYSA-N 0.000 description 2
- MSZKWBWZTVILRH-UHFFFAOYSA-N 2-[2-ethoxy-5-(4-pyrimidin-2-ylpiperazin-1-yl)sulfonylphenyl]-5,7-dimethyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound C1=C(C=2NC(=O)C3=C(C)N=C(C)N3N=2)C(OCC)=CC=C1S(=O)(=O)N(CC1)CCN1C1=NC=CC=N1 MSZKWBWZTVILRH-UHFFFAOYSA-N 0.000 description 2
- CSXGBYZQWMVGTD-UHFFFAOYSA-N 2-[2-ethoxy-5-[4-(hydroxymethyl)piperidin-1-yl]sulfonylphenyl]-5-ethyl-7-propyl-1h-imidazo[5,1-f][1,2,4]triazin-4-one Chemical compound CCCC1=NC(CC)=C(C(N2)=O)N1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCC(CO)CC1 CSXGBYZQWMVGTD-UHFFFAOYSA-N 0.000 description 2
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- UYXJYVCFRHGEBO-UHFFFAOYSA-N 2-ethoxy-4-methoxybenzenecarboximidamide;hydrochloride Chemical compound Cl.CCOC1=CC(OC)=CC=C1C(N)=N UYXJYVCFRHGEBO-UHFFFAOYSA-N 0.000 description 2
- ARCIRLBUCOJLBV-UHFFFAOYSA-N 2-ethoxy-4-methoxybenzonitrile Chemical compound CCOC1=CC(OC)=CC=C1C#N ARCIRLBUCOJLBV-UHFFFAOYSA-N 0.000 description 2
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 2
- IBZKBSXREAQDTO-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)ethanamine Chemical compound COCCNCCOC IBZKBSXREAQDTO-UHFFFAOYSA-N 0.000 description 2
- ASUDFOJKTJLAIK-UHFFFAOYSA-N 2-methoxyethanamine Chemical compound COCCN ASUDFOJKTJLAIK-UHFFFAOYSA-N 0.000 description 2
- WLODJVVNLOYYEE-UHFFFAOYSA-N 2-propoxybenzonitrile Chemical compound CCCOC1=CC=CC=C1C#N WLODJVVNLOYYEE-UHFFFAOYSA-N 0.000 description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 description 2
- JNZYADHPGVZMQK-UHFFFAOYSA-N 3-(aminomethyl)phenol Chemical compound NCC1=CC=CC(O)=C1 JNZYADHPGVZMQK-UHFFFAOYSA-N 0.000 description 2
- ZYRXTFQJXOMBOD-UHFFFAOYSA-N 3-butyl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine Chemical compound CCCC[N+]1=CC(=N)O[N-]1 ZYRXTFQJXOMBOD-UHFFFAOYSA-N 0.000 description 2
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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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
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Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19750085A DE19750085A1 (de) | 1997-11-12 | 1997-11-12 | 2-Phenyl-substituierte Imidazotriazinone |
DE1998112462 DE19812462A1 (de) | 1998-03-23 | 1998-03-23 | 2-[2-Ethoxy-5(4-ethyl-piperazin-1-sulfonyl) -phenyl]-5-methyl-7-prophyl-3H-imidazo[5,1-f][1,2,4]triazin-4-on Dihydrochlorid |
DE1998140289 DE19840289A1 (de) | 1998-09-04 | 1998-09-04 | 2-Phenyl-substituierte Imidazotriazinone |
PCT/EP1998/006910 WO1999024433A1 (de) | 1997-11-12 | 1998-10-31 | 2-phenyl-substituierte imidazotriazinone als phosphodiesterase inhibitoren |
Publications (2)
Publication Number | Publication Date |
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SK7092000A3 SK7092000A3 (en) | 2001-03-12 |
SK287161B6 true SK287161B6 (sk) | 2010-02-08 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK709-2000A SK287161B6 (sk) | 1997-11-12 | 1998-10-31 | 2-Fenylsubstituované imidazotriazinóny, spôsob ich výroby, liečivá obsahujúce tieto látky a ich použitie |
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- 2000-05-05 BG BG104406A patent/BG65257B1/bg unknown
- 2000-05-09 FI FI20001086A patent/FI113772B/fi not_active IP Right Cessation
- 2000-05-09 DK DK200000766A patent/DK176852B1/da not_active IP Right Cessation
- 2000-05-11 HR HR20000292A patent/HRP20000292B1/xx not_active IP Right Cessation
- 2000-05-11 NO NO20002444A patent/NO314940B1/no not_active IP Right Cessation
- 2000-05-11 SE SE0001745A patent/SE522809C2/sv not_active IP Right Cessation
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2001
- 2001-04-02 HK HK01102357A patent/HK1031730A1/xx not_active IP Right Cessation
- 2001-08-30 US US09/943,530 patent/US6566360B1/en not_active Expired - Lifetime
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2002
- 2002-04-11 NO NO20021714A patent/NO20021714D0/no not_active Application Discontinuation
- 2002-05-02 JP JP2002130480A patent/JP4388729B2/ja not_active Expired - Lifetime
- 2002-05-15 AR ARP020101786A patent/AR035972A2/es active IP Right Grant
- 2002-07-09 HR HRP20020585AA patent/HRP20020585B1/hr not_active IP Right Cessation
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2003
- 2003-02-12 US US10/365,740 patent/US6890922B2/en not_active Expired - Lifetime
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2004
- 2004-08-12 IL IL163475A patent/IL163475A/en not_active IP Right Cessation
- 2004-08-20 US US10/923,544 patent/US7122540B2/en not_active Expired - Lifetime
- 2004-12-23 HK HK04110195.8A patent/HK1067124A1/xx not_active IP Right Cessation
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2006
- 2006-04-21 US US11/409,417 patent/US7314871B2/en not_active Expired - Fee Related
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2007
- 2007-12-21 US US12/004,933 patent/US7704999B2/en not_active Expired - Fee Related
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2009
- 2009-09-29 US US12/569,720 patent/US7696206B2/en not_active Expired - Fee Related
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2010
- 2010-03-04 US US12/717,443 patent/US20110009367A1/en not_active Abandoned
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2012
- 2012-03-26 US US13/429,588 patent/US20130059844A1/en not_active Abandoned
- 2012-08-03 CY CY20121100695T patent/CY1112949T1/el unknown
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