SK278711B6 - Indolylsubstituované pyroly, ich použitie ako tera - Google Patents
Indolylsubstituované pyroly, ich použitie ako tera Download PDFInfo
- Publication number
- SK278711B6 SK278711B6 SK855-90A SK85590A SK278711B6 SK 278711 B6 SK278711 B6 SK 278711B6 SK 85590 A SK85590 A SK 85590A SK 278711 B6 SK278711 B6 SK 278711B6
- Authority
- SK
- Slovakia
- Prior art keywords
- formula
- indolyl
- solution
- methyl
- indol
- Prior art date
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- -1 Indolylsubstituted pyrroles Chemical class 0.000 title claims description 124
- 238000000034 method Methods 0.000 title claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 239000000126 substance Substances 0.000 title abstract description 3
- 239000013067 intermediate product Substances 0.000 title abstract 2
- 238000004519 manufacturing process Methods 0.000 title description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 177
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000012280 lithium aluminium hydride Substances 0.000 claims abstract description 13
- 150000003233 pyrroles Chemical class 0.000 claims abstract description 11
- 239000013543 active substance Substances 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 7
- 239000000203 mixture Substances 0.000 claims description 160
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 43
- 150000007513 acids Chemical class 0.000 claims description 32
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 125000004442 acylamino group Chemical group 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 150000007514 bases Chemical class 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 208000030507 AIDS Diseases 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 229910052721 tungsten Inorganic materials 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 5
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000004682 aminothiocarbonyl group Chemical group NC(=S)* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 230000001900 immune effect Effects 0.000 claims description 4
- 125000004954 trialkylamino group Chemical group 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 3
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 3
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 3
- 239000000543 intermediate Substances 0.000 claims description 3
- 230000000771 oncological effect Effects 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- FXGHOAZJQNLNFD-UHFFFAOYSA-N 3-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N2CCC(CN(C)C)CC2=C1C1=C(C=2C3=CC=CC=C3N(C)C=2)C(=O)NC1=O FXGHOAZJQNLNFD-UHFFFAOYSA-N 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- HFSBFDMMLPZISX-UHFFFAOYSA-N [10-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-7-yl]methyl carbamimidothioate Chemical compound C12=CC=CC=C2N(C)C=C1C1=C(C=2C3=CC=CC=C3N3CC(CSC(N)=N)CCC3=2)C(=O)NC1=O HFSBFDMMLPZISX-UHFFFAOYSA-N 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
- 229940125692 cardiovascular agent Drugs 0.000 claims 1
- 239000002327 cardiovascular agent Substances 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000004971 nitroalkyl group Chemical group 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 claims 1
- 230000002829 reductive effect Effects 0.000 abstract description 53
- 238000006243 chemical reaction Methods 0.000 abstract description 23
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
- 125000001041 indolyl group Chemical group 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 486
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 306
- 239000000243 solution Substances 0.000 description 246
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 227
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 117
- 239000000047 product Substances 0.000 description 97
- 239000002904 solvent Substances 0.000 description 95
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 90
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 67
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 57
- 239000000741 silica gel Substances 0.000 description 57
- 229910002027 silica gel Inorganic materials 0.000 description 57
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 56
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- 239000012299 nitrogen atmosphere Substances 0.000 description 52
- 238000002425 crystallisation Methods 0.000 description 51
- 230000008025 crystallization Effects 0.000 description 51
- 238000004587 chromatography analysis Methods 0.000 description 39
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 36
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 35
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 34
- 239000003480 eluent Substances 0.000 description 31
- 239000003208 petroleum Substances 0.000 description 31
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 30
- 238000003756 stirring Methods 0.000 description 29
- 239000012074 organic phase Substances 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 25
- 235000011114 ammonium hydroxide Nutrition 0.000 description 25
- 239000007858 starting material Substances 0.000 description 25
- 239000000725 suspension Substances 0.000 description 25
- NAIPEFIYIQFVFC-UHFFFAOYSA-N 2-(1-methylindol-3-yl)acetic acid Chemical compound C1=CC=C2N(C)C=C(CC(O)=O)C2=C1 NAIPEFIYIQFVFC-UHFFFAOYSA-N 0.000 description 24
- 239000000284 extract Substances 0.000 description 24
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 24
- IAODRFIZLKITMK-UHFFFAOYSA-N furan-2,3-dione Chemical compound O=C1OC=CC1=O IAODRFIZLKITMK-UHFFFAOYSA-N 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 21
- 238000010898 silica gel chromatography Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 102000003923 Protein Kinase C Human genes 0.000 description 11
- 108090000315 Protein Kinase C Proteins 0.000 description 11
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 8
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 8
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 7
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 239000000969 carrier Substances 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 6
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- IZDROVVXIHRYMH-UHFFFAOYSA-N methanesulfonic anhydride Chemical compound CS(=O)(=O)OS(C)(=O)=O IZDROVVXIHRYMH-UHFFFAOYSA-N 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 125000001544 thienyl group Chemical group 0.000 description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 6
- AZRRZGIBBLWSSQ-UHFFFAOYSA-N 4-ethyl-7-phenyl-3,5-diazabicyclo[2.2.2]octane-2,6-dione Chemical compound N1C(=O)C2C(=O)NC1(CC)CC2C1=CC=CC=C1 AZRRZGIBBLWSSQ-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 239000002027 dichloromethane extract Substances 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
- CTPZDTIWANLKQZ-UHFFFAOYSA-N 6,7,8,9-tetrahydropyrido[1,2-a]indol-8-ylmethyl acetate Chemical compound C1=CC=C2N3CCC(COC(=O)C)CC3=CC2=C1 CTPZDTIWANLKQZ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 239000012298 atmosphere Substances 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- RAFNCPHFRHZCPS-UHFFFAOYSA-N di(imidazol-1-yl)methanethione Chemical compound C1=CN=CN1C(=S)N1C=CN=C1 RAFNCPHFRHZCPS-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 208000027775 Bronchopulmonary disease Diseases 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000010908 decantation Methods 0.000 description 3
- 229940043279 diisopropylamine Drugs 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 3
- 208000026278 immune system disease Diseases 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
-
- 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
- A61P11/06—Antiasthmatics
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Virology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pain & Pain Management (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Polyoxymethylene Polymers And Polymers With Carbon-To-Carbon Bonds (AREA)
- Pyridine Compounds (AREA)
- Saccharide Compounds (AREA)
- Cephalosporin Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB898904161A GB8904161D0 (en) | 1989-02-23 | 1989-02-23 | Substituted pyrroles |
| GB898928210A GB8928210D0 (en) | 1989-02-23 | 1989-12-13 | Substituted pyrroles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK85590A3 SK85590A3 (en) | 1998-01-14 |
| SK278711B6 true SK278711B6 (sk) | 1998-01-14 |
Family
ID=26295005
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK855-90A SK278711B6 (sk) | 1989-02-23 | 1990-02-22 | Indolylsubstituované pyroly, ich použitie ako tera |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0384349B1 (cs) |
| JP (1) | JPH06102661B2 (cs) |
| AT (1) | ATE104972T1 (cs) |
| AU (1) | AU633051B2 (cs) |
| CA (1) | CA2010636C (cs) |
| CZ (1) | CZ284587B6 (cs) |
| DE (1) | DE59005491D1 (cs) |
| DK (1) | DK0384349T3 (cs) |
| DZ (1) | DZ1399A1 (cs) |
| ES (1) | ES2052995T3 (cs) |
| FI (1) | FI93447C (cs) |
| HU (1) | HU206351B (cs) |
| IE (1) | IE64184B1 (cs) |
| IL (1) | IL93433A (cs) |
| MC (1) | MC2096A1 (cs) |
| NO (1) | NO174891C (cs) |
| NZ (1) | NZ232589A (cs) |
| PT (1) | PT93246B (cs) |
| RU (2) | RU2014332C1 (cs) |
| SK (1) | SK278711B6 (cs) |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5292747A (en) * | 1990-08-07 | 1994-03-08 | Hoffman-La Roche Inc. | Substituted pyrroles |
| CA2046801C (en) * | 1990-08-07 | 2002-02-26 | Peter D. Davis | Substituted pyrroles |
| DE4128015A1 (de) * | 1991-08-23 | 1993-02-25 | Kali Chemie Pharma Gmbh | 1,7-anellierte 2-(piperazinoalkyl)indol-derivate sowie verfahren und zwischenprodukte zu ihrer herstellung und diese verbindugnen enthaltende arzneimittel |
| GB9123396D0 (en) * | 1991-11-04 | 1991-12-18 | Hoffmann La Roche | A process for the manufacture of substituted maleimides |
| JPH07504673A (ja) * | 1992-03-20 | 1995-05-25 | ザ・ウエルカム・ファウンデーション・リミテッド | 抗ウイルス活性を有するインドール誘導体 |
| AU678435B2 (en) | 1993-05-10 | 1997-05-29 | F. Hoffmann-La Roche Ag | Substituted pyrroles |
| US5721230A (en) * | 1993-05-10 | 1998-02-24 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| US5405864A (en) * | 1993-10-15 | 1995-04-11 | Syntex (U.S.A.) Inc. | Chemotherapeutic maleimides |
| US5541347A (en) * | 1993-12-07 | 1996-07-30 | Eli Lilly And Company | Synthesis of bisindolylmaleimides |
| DK0657411T3 (da) * | 1993-12-07 | 1999-11-15 | Lilly Co Eli | Forbedret syntese af bisindolylmaleimider |
| AU687909B2 (en) * | 1993-12-07 | 1998-03-05 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5843935A (en) * | 1993-12-07 | 1998-12-01 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5723456A (en) * | 1993-12-07 | 1998-03-03 | Eli Lilly & Company | Therapeutic treatment for cardiovascular diseases |
| US5624949A (en) * | 1993-12-07 | 1997-04-29 | Eli Lilly And Company | Protein kinase C inhibitors |
| ATE290378T1 (de) | 1993-12-23 | 2005-03-15 | Lilly Co Eli | Proteinkinase c-inhibitoren |
| US5491242A (en) * | 1994-06-22 | 1996-02-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5481003A (en) * | 1994-06-22 | 1996-01-02 | Eli Lilly And Company | Protein kinase C inhibitors |
| EP0695755B1 (en) * | 1994-08-04 | 1998-10-21 | F. Hoffmann-La Roche AG | Pyrrolocarbazole |
| US5591855A (en) * | 1994-10-14 | 1997-01-07 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5475110A (en) * | 1994-10-14 | 1995-12-12 | Cephalon, Inc. | Fused Pyrrolocarbazoles |
| US5594009A (en) * | 1994-10-14 | 1997-01-14 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| US5705511A (en) * | 1994-10-14 | 1998-01-06 | Cephalon, Inc. | Fused pyrrolocarbazoles |
| BR9509998A (pt) * | 1994-12-13 | 1997-12-30 | Hoffmann La Roche | Derivados imidazol como inibidores de proteína quinase em particular egf-r tirosina quinase |
| US5616724A (en) * | 1996-02-21 | 1997-04-01 | Cephalon, Inc. | Fused pyrrolo[2,3-c]carbazole-6-ones |
| EP0935463B1 (en) * | 1996-10-31 | 2004-01-21 | Harbor Branch Oceanographic Institution, Inc. | Use of anti-neurogenic inflammatory compounds and compositions |
| GB9819035D0 (en) * | 1998-09-01 | 1998-10-28 | Cerebrus Res Ltd | Chemical compounds VII |
| AU6593600A (en) * | 1999-08-20 | 2001-03-19 | Rei Asakai | Drugs inhibiting cell death |
| US6313143B1 (en) * | 1999-12-16 | 2001-11-06 | Hoffmann-La Roche Inc. | Substituted pyrroles |
| WO2002010158A2 (en) | 2000-07-27 | 2002-02-07 | F. Hoffmann-La Roche Ag | 3-indolyl-4-phenyl-1h-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta |
| DK1362047T3 (da) | 2000-12-08 | 2006-09-04 | Ortho Mcneil Pharm Inc | Indazolylsubstituerede pyrrolinforbindelser som kinaseinhibitorer |
| TW201041580A (en) | 2001-09-27 | 2010-12-01 | Alcon Inc | Inhibitors of glycogen synthase kinase-3 (GSK-3) for treating glaucoma |
| BR0215360A (pt) * | 2001-12-27 | 2004-12-14 | Theravance Inc | Derivados de indolina úteis como inibidores de proteìna quinase |
| TW200918046A (en) * | 2002-04-03 | 2009-05-01 | Novartis Ag | Indolylmaleimide derivatives |
| US7452913B2 (en) * | 2003-02-24 | 2008-11-18 | Pharmacia & Upjohn Company | Polymorphs of pyrrole substituted 2-indolinone protein kinase inhibitors |
| EP2305265A1 (en) | 2003-08-08 | 2011-04-06 | Novartis AG | Combinations comprising staurosporines |
| CA2552738A1 (en) * | 2004-01-19 | 2005-07-28 | Novartis Ag | Indolylmaleimide derivatives |
| EP1814882A1 (en) * | 2004-11-22 | 2007-08-08 | Vertex Pharmaceuticals Incorporated | Pyrrolopyrazines and pyrazolopyrazines useful as inhibitors of protein kinases |
| EP1819697B1 (en) | 2004-12-08 | 2012-08-01 | Johannes Gutenberg-Universität Mainz | 3-(indolyl)-4-arylmaleimide derivatives and their use as angiogenesis inhibitors |
| HRP20100650T2 (hr) | 2005-02-09 | 2012-02-29 | Arqule | Derivati maleimida, farmaceutski pripravci i postupci liječenja raka |
| EP1904482B1 (en) | 2005-07-11 | 2011-01-19 | Novartis AG | Indolylmaleimide derivatives |
| CA2618550C (en) * | 2005-08-12 | 2013-12-17 | Merck Frosst Canada Ltd. | Indole derivatives as crth2 receptor antagonists |
| EP1980561B1 (en) | 2007-03-30 | 2013-10-09 | Nerviano Medical Sciences S.R.L. | Substituted 1h-pyrazolo[3,4-b] pyridine derivatives active as kinase inhibitors |
| JP5425060B2 (ja) * | 2007-06-22 | 2014-02-26 | アークル インコーポレイテッド | ピロリジノン、ピロリジン−２，５−ジオン、ピロリジンおよびチオスクシンイミド誘導体、癌の治療のための組成物および方法 |
| WO2009002807A2 (en) | 2007-06-22 | 2008-12-31 | Arqule, Inc. | Indolyl pyrrolidines for the treatment of cancer |
| BRPI0813355A2 (pt) | 2007-06-22 | 2014-12-30 | Arqule Inc | Compostos de quinazolinona e métodos de uso dos mesmos |
| CA2737483A1 (en) * | 2008-09-22 | 2010-03-25 | Merck Frosst Canada Ltd. | Indole derivatives as crth2 receptor antagonists |
| EP2343291A1 (en) | 2009-12-18 | 2011-07-13 | Johannes Gutenberg-Universität Mainz | 3-(Indolyl)- or 3-(Azaindolyl)-4-arylmaleimide compounds and their use in tumor treatment |
| US8563567B2 (en) | 2009-12-30 | 2013-10-22 | Arqule, Inc. | Substituted heterocyclic compounds |
| EP2474541A1 (en) | 2010-12-23 | 2012-07-11 | Johannes- Gutenberg-Universität Mainz | Conjugated 3-(indolyl)- and 3-(azaindolyl)-4-arylmaleimide compounds and their use in tumor treatment |
| AU2014257578B2 (en) * | 2013-04-23 | 2017-11-16 | Laboratorios Del Dr. Esteve, S.A. | Pyrazino[1,2-a]indole compounds, their preparation and use in medicaments |
| US20170209488A1 (en) | 2014-07-17 | 2017-07-27 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods for treating neuromuscular junction-related diseases |
| WO2016207366A1 (en) | 2015-06-26 | 2016-12-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of viral infections |
| EP3187495A1 (en) | 2015-12-30 | 2017-07-05 | Johannes Gutenberg-Universität Mainz | 3-(5-fluoroindolyl)-4-arylmaleimide compounds and their use in tumor treatment |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ280738B6 (cs) * | 1988-02-10 | 1996-04-17 | F. Hoffmann - La Roche And Co., Aktiengesellschaft | Substituované pyrroly, jejich použití pro výrobu léčiv a léčiva na jejich bázi |
| US5049563A (en) * | 1988-07-07 | 1991-09-17 | Duphar International Research B.V. | Annelated indoleketones with an imidazolylalkyl substituent |
-
1990
- 1990-02-16 MC MC902110A patent/MC2096A1/fr unknown
- 1990-02-19 EP EP90103142A patent/EP0384349B1/de not_active Expired - Lifetime
- 1990-02-19 ES ES90103142T patent/ES2052995T3/es not_active Expired - Lifetime
- 1990-02-19 AT AT9090103142T patent/ATE104972T1/de not_active IP Right Cessation
- 1990-02-19 NZ NZ232589A patent/NZ232589A/xx unknown
- 1990-02-19 HU HU90846A patent/HU206351B/hu not_active IP Right Cessation
- 1990-02-19 DK DK90103142.7T patent/DK0384349T3/da active
- 1990-02-19 IL IL9343390A patent/IL93433A/en not_active IP Right Cessation
- 1990-02-19 DE DE59005491T patent/DE59005491D1/de not_active Expired - Fee Related
- 1990-02-21 DZ DZ900033A patent/DZ1399A1/fr active
- 1990-02-21 FI FI900863A patent/FI93447C/fi not_active IP Right Cessation
- 1990-02-21 AU AU50033/90A patent/AU633051B2/en not_active Ceased
- 1990-02-22 SK SK855-90A patent/SK278711B6/sk unknown
- 1990-02-22 CZ CS90855A patent/CZ284587B6/cs not_active IP Right Cessation
- 1990-02-22 NO NO900855A patent/NO174891C/no unknown
- 1990-02-22 CA CA002010636A patent/CA2010636C/en not_active Expired - Fee Related
- 1990-02-22 JP JP2042286A patent/JPH06102661B2/ja not_active Expired - Fee Related
- 1990-02-22 RU SU904743198A patent/RU2014332C1/ru active
- 1990-02-22 IE IE64790A patent/IE64184B1/en not_active IP Right Cessation
- 1990-02-22 RU RU93033479A patent/RU2142460C1/ru active
- 1990-02-22 PT PT93246A patent/PT93246B/pt not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SK85590A3 (en) | 1998-01-14 |
| NO174891C (no) | 1994-07-27 |
| IE64184B1 (en) | 1995-07-12 |
| AU5003390A (en) | 1990-08-30 |
| FI93447C (fi) | 1995-04-10 |
| FI93447B (fi) | 1994-12-30 |
| NO900855D0 (no) | 1990-02-22 |
| HU900846D0 (en) | 1990-04-28 |
| PT93246A (pt) | 1990-08-31 |
| EP0384349A1 (de) | 1990-08-29 |
| EP0384349B1 (de) | 1994-04-27 |
| ATE104972T1 (de) | 1994-05-15 |
| CA2010636A1 (en) | 1990-08-23 |
| HU206351B (en) | 1992-10-28 |
| MC2096A1 (fr) | 1991-02-15 |
| DE59005491D1 (de) | 1994-06-01 |
| AU633051B2 (en) | 1993-01-21 |
| NO900855L (no) | 1990-08-24 |
| FI900863A0 (fi) | 1990-02-21 |
| IL93433A (en) | 1996-11-14 |
| ES2052995T3 (es) | 1994-07-16 |
| PT93246B (pt) | 1996-01-31 |
| HUT53369A (en) | 1990-10-28 |
| DZ1399A1 (fr) | 2004-09-13 |
| CA2010636C (en) | 1999-12-14 |
| JPH06102661B2 (ja) | 1994-12-14 |
| RU2142460C1 (ru) | 1999-12-10 |
| JPH02264776A (ja) | 1990-10-29 |
| CZ284587B6 (cs) | 1999-01-13 |
| NO174891B (no) | 1994-04-18 |
| DK0384349T3 (da) | 1994-09-05 |
| IL93433A0 (en) | 1990-11-29 |
| IE900647L (en) | 1990-08-23 |
| CZ85590A3 (cs) | 1998-10-14 |
| NZ232589A (en) | 1992-09-25 |
| RU2014332C1 (ru) | 1994-06-15 |
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