SK279566B6 - Substituované pyroly a ich použitie, spôsob a medz - Google Patents

Substituované pyroly a ich použitie, spôsob a medz Download PDF

Info

Publication number: SK279566B6
Authority: SK; Slovakia
Prior art keywords: formula; methyl; solution; pyrido; alkyl
Prior art date: 1990-08-07

Application number

SK2435-91A

Other languages

English (en)

Slovak (sk)

Inventor

Peter D. Davis

Christopher H. Hill

Geoffrey Lawton

Original Assignee

F.Hoffmann-La Roche Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-08-07

Filing date

1991-08-06

Publication date

1999-01-11

1990-08-07 Priority claimed from GB909017269A external-priority patent/GB9017269D0/en

1991-05-08 Priority claimed from GB919109959A external-priority patent/GB9109959D0/en

1991-08-06 Application filed by F.Hoffmann-La Roche Ag filed Critical F.Hoffmann-La Roche Ag

1999-01-11 Publication of SK279566B6 publication Critical patent/SK279566B6/sk

Links

238000000034 method Methods 0.000 title claims description 25
150000003233 pyrroles Chemical class 0.000 title claims description 16
239000008194 pharmaceutical composition Substances 0.000 title claims description 7
238000002360 preparation method Methods 0.000 title claims description 7
239000000543 intermediate Substances 0.000 title claims description 5
150000001875 compounds Chemical class 0.000 claims abstract description 59
-1 nitro, amino Chemical group 0.000 claims abstract description 41
125000000217 alkyl group Chemical group 0.000 claims abstract description 27
239000001257 hydrogen Substances 0.000 claims abstract description 26
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
150000003839 salts Chemical class 0.000 claims abstract description 26
150000002431 hydrogen Chemical class 0.000 claims abstract description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 16
239000002253 acid Substances 0.000 claims abstract description 10
150000007513 acids Chemical class 0.000 claims abstract description 8
125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
150000007514 bases Chemical class 0.000 claims abstract description 7
229910052736 halogen Inorganic materials 0.000 claims abstract description 6
150000002367 halogens Chemical class 0.000 claims abstract description 6
125000001188 haloalkyl group Chemical group 0.000 claims abstract description 5
125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 3
125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 3
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 105
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 claims description 20
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
238000004519 manufacturing process Methods 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
208000030507 AIDS Diseases 0.000 claims description 6
208000002249 Diabetes Complications Diseases 0.000 claims description 6
206010012655 Diabetic complications Diseases 0.000 claims description 6
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 6
239000007795 chemical reaction product Substances 0.000 claims description 6
230000003779 hair growth Effects 0.000 claims description 6
230000001900 immune effect Effects 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
208000024172 Cardiovascular disease Diseases 0.000 claims description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
230000000771 oncological effect Effects 0.000 claims description 4
230000004936 stimulating effect Effects 0.000 claims description 4
239000013543 active substance Substances 0.000 claims description 3
229910021529 ammonia Inorganic materials 0.000 claims description 3
230000002526 effect on cardiovascular system Effects 0.000 claims description 3
230000002757 inflammatory effect Effects 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 2
125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims 2
230000003110 anti-inflammatory effect Effects 0.000 claims 2
125000006678 phenoxycarbonyl group Chemical group 0.000 claims 2
125000003884 phenylalkyl group Chemical group 0.000 claims 1
UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 claims 1
125000001589 carboacyl group Chemical group 0.000 abstract description 5
125000003710 aryl alkyl group Chemical group 0.000 abstract description 4
229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 abstract description 2
125000005239 aroylamino group Chemical group 0.000 abstract description 2
239000003909 protein kinase inhibitor Substances 0.000 abstract description 2
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 216
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 216
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 183
239000000243 solution Substances 0.000 description 154
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 84
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
239000000047 product Substances 0.000 description 70
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 69
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
239000002904 solvent Substances 0.000 description 45
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 34
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
230000002829 reductive effect Effects 0.000 description 29
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 27
239000000284 extract Substances 0.000 description 25
239000000725 suspension Substances 0.000 description 25
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
239000007787 solid Substances 0.000 description 23
239000012299 nitrogen atmosphere Substances 0.000 description 22
235000002639 sodium chloride Nutrition 0.000 description 22
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 21
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 20
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
238000010992 reflux Methods 0.000 description 18
238000010898 silica gel chromatography Methods 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
239000002244 precipitate Substances 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000003480 eluent Substances 0.000 description 15
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
229910000041 hydrogen chloride Inorganic materials 0.000 description 15
239000012047 saturated solution Substances 0.000 description 15
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 15
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
239000007858 starting material Substances 0.000 description 12
239000012267 brine Substances 0.000 description 11
239000012074 organic phase Substances 0.000 description 11
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
238000002844 melting Methods 0.000 description 9
230000008018 melting Effects 0.000 description 9
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 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
235000011114 ammonium hydroxide Nutrition 0.000 description 8
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 8
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 8
239000000969 carrier Substances 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
229910052763 palladium Inorganic materials 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
239000007868 Raney catalyst Substances 0.000 description 6
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
229910000564 Raney nickel Inorganic materials 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
239000012259 ether extract Substances 0.000 description 6
IAODRFIZLKITMK-UHFFFAOYSA-N furan-2,3-dione Chemical compound O=C1OC=CC1=O IAODRFIZLKITMK-UHFFFAOYSA-N 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
238000003756 stirring Methods 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 5
239000002775 capsule Substances 0.000 description 5
238000004587 chromatography analysis Methods 0.000 description 5
238000003776 cleavage reaction Methods 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000012280 lithium aluminium hydride Substances 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
230000007017 scission Effects 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 4
239000002480 mineral oil Substances 0.000 description 4
235000010446 mineral oil Nutrition 0.000 description 4
239000003208 petroleum Substances 0.000 description 4
239000000825 pharmaceutical preparation Substances 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
VUVGMQNYJPPCCC-UHFFFAOYSA-N pyrido[1,2-a]indole Chemical compound C1=CC=CC2=CC3=CC=CC=C3N21 VUVGMQNYJPPCCC-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
SFMHJRSZXNCRAM-UHFFFAOYSA-N 1-(1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1N1C(=O)C=CC1=O SFMHJRSZXNCRAM-UHFFFAOYSA-N 0.000 description 3
ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 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
239000001099 ammonium carbonate Substances 0.000 description 3
235000012501 ammonium carbonate Nutrition 0.000 description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
239000003814 drug Substances 0.000 description 3
YQZUGFCCFIEUIN-UHFFFAOYSA-N ethyl 9-hydroxy-6,7-dihydropyrido[1,2-a]indole-8-carboxylate Chemical compound C1=CC=C2N(CCC(C(=O)OCC)=C3O)C3=CC2=C1 YQZUGFCCFIEUIN-UHFFFAOYSA-N 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
230000002265 prevention Effects 0.000 description 3
239000012279 sodium borohydride Substances 0.000 description 3
229910000033 sodium borohydride Inorganic materials 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
KBSBQLOHOJDZCR-UHFFFAOYSA-N (1-benzyl-5-oxopyrrolidin-3-yl) 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OC1CC(=O)N(CC=2C=CC=CC=2)C1 KBSBQLOHOJDZCR-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
MHKQFSOWHNNEBO-UHFFFAOYSA-N 8-(carboxymethyl)-7,9-dihydro-6h-pyrido[1,2-a]indole-8-carboxylic acid Chemical compound C1=CC=C2N3CCC(C(O)=O)(CC(=O)O)CC3=CC2=C1 MHKQFSOWHNNEBO-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
FPQTVZNFABWSMU-UHFFFAOYSA-N Cl.O=C1OC=CC1=O Chemical compound Cl.O=C1OC=CC1=O FPQTVZNFABWSMU-UHFFFAOYSA-N 0.000 description 2
239000001828 Gelatine Substances 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
235000019759 Maize starch Nutrition 0.000 description 2
PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 2
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 2
206010030113 Oedema Diseases 0.000 description 2
102000003923 Protein Kinase C Human genes 0.000 description 2
108090000315 Protein Kinase C Proteins 0.000 description 2
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
241000700605 Viruses Species 0.000 description 2
YTSKEBAZYYTYGJ-KBPBESRZSA-N [(7s,8r)-7-(methylsulfonyloxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-8-yl]methyl methanesulfonate Chemical compound C1=CC=C2N(C[C@H]([C@H](COS(=O)(=O)C)C3)COS(C)(=O)=O)C3=CC2=C1 YTSKEBAZYYTYGJ-KBPBESRZSA-N 0.000 description 2
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
230000029936 alkylation Effects 0.000 description 2
238000005804 alkylation reaction Methods 0.000 description 2
125000005161 aryl oxy carbonyl group Chemical group 0.000 description 2
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000006264 debenzylation reaction Methods 0.000 description 2
230000006806 disease prevention Effects 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000008298 dragée Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
239000003925 fat Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
235000013355 food flavoring agent Nutrition 0.000 description 2
XVMKYUCBGVLGRY-UHFFFAOYSA-N formic acid 1H-indole Chemical compound C(=O)O.N1C=CC2=CC=CC=C12 XVMKYUCBGVLGRY-UHFFFAOYSA-N 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
239000008103 glucose Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000463 material Substances 0.000 description 2
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QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
125000005440 p-toluyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C(*)=O)C([H])([H])[H] 0.000 description 1
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
230000028327 secretion Effects 0.000 description 1
239000002002 slurry Substances 0.000 description 1
230000016160 smooth muscle contraction Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
YKAJWLMPUNRFOP-UHFFFAOYSA-N spiro[1,3-dihydropyrrolo[1,2-a]indole-2,3'-pyrrolidine] Chemical compound C1NCCC21CN1C3=CC=CC=C3C=C1C2 YKAJWLMPUNRFOP-UHFFFAOYSA-N 0.000 description 1
LVPXOYUHTYAQSC-UHFFFAOYSA-N spiro[1,3-dihydropyrrolo[1,2-a]indole-2,3'-pyrrolidine]-2',5'-dione Chemical compound O=C1NC(=O)CC11CN2C3=CC=CC=C3C=C2C1 LVPXOYUHTYAQSC-UHFFFAOYSA-N 0.000 description 1
REPYPUSNNJNBLM-UHFFFAOYSA-N spiro[7,9-dihydro-6h-pyrido[1,2-a]indole-8,2'-cyclopentane]-1'-amine Chemical compound NC1CCCC11CC2=CC3=CC=CC=C3N2CC1 REPYPUSNNJNBLM-UHFFFAOYSA-N 0.000 description 1
NLRXIEMQUPUXCF-UHFFFAOYSA-N spiro[7,9-dihydro-6h-pyrido[1,2-a]indole-8,2'-cyclopentane]-1'-one Chemical compound O=C1CCCC11CC2=CC3=CC=CC=C3N2CC1 NLRXIEMQUPUXCF-UHFFFAOYSA-N 0.000 description 1
HQOWZNDTZCARRM-UHFFFAOYSA-N spiro[7,9-dihydro-6h-pyrido[1,2-a]indole-8,3'-piperidine] Chemical compound C1CCNCC21CC1=CC3=CC=CC=C3N1CC2 HQOWZNDTZCARRM-UHFFFAOYSA-N 0.000 description 1
ZMENONNYGLMKMO-UHFFFAOYSA-N spiro[7,9-dihydro-6h-pyrido[1,2-a]indole-8,3'-piperidine]-2',6'-dione Chemical compound O=C1NC(=O)CCC11CC2=CC3=CC=CC=C3N2CC1 ZMENONNYGLMKMO-UHFFFAOYSA-N 0.000 description 1
KXRQVOQMZHXHOC-UHFFFAOYSA-N spiro[8,9-dihydro-6H-pyrido[1,2-a]indole-7,2'-cyclopropane]-1'-amine Chemical compound NC1CC11CN2C3=CC=CC=C3C=C2CC1 KXRQVOQMZHXHOC-UHFFFAOYSA-N 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
CFIVDZVCANWKLM-UHFFFAOYSA-N tert-butyl 2'-oxospiro[7,9-dihydro-6H-pyrido[1,2-a]indole-8,3'-cyclopentane]-1'-carboxylate Chemical compound O=C1C(C(=O)OC(C)(C)C)CCC11CC2=CC3=CC=CC=C3N2CC1 CFIVDZVCANWKLM-UHFFFAOYSA-N 0.000 description 1
HJEZRYIJNHAIGY-UHFFFAOYSA-N tert-butyl 4-bromobutanoate Chemical compound CC(C)(C)OC(=O)CCCBr HJEZRYIJNHAIGY-UHFFFAOYSA-N 0.000 description 1
QXZIXVRAVLEOOZ-UHFFFAOYSA-N tert-butyl spiro[1,3-dihydropyrrolo[1,2-a]indole-2,3'-pyrrolidine]-1'-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC21CN1C3=CC=CC=C3C=C1C2 QXZIXVRAVLEOOZ-UHFFFAOYSA-N 0.000 description 1
OFQFOTOPQKZOGP-UHFFFAOYSA-N tert-butyl spiro[7,9-dihydro-6H-pyrido[1,2-a]indole-8,3'-piperidine]-1'-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CC2=CC3=CC=CC=C3N2CC1 OFQFOTOPQKZOGP-UHFFFAOYSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000008096 xylene 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
- 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
- C07D471/12—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 three hetero rings
- C07D471/20—Spiro-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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- 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
- A61P17/00—Drugs for dermatological disorders
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
- 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
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/10—Spiro-condensed systems
- 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
- C07D471/12—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 three hetero rings
- C07D471/14—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)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Hematology (AREA)
Virology (AREA)
Cardiology (AREA)
Emergency Medicine (AREA)
Endocrinology (AREA)
Heart & Thoracic Surgery (AREA)
Obesity (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Urology & Nephrology (AREA)
AIDS & HIV (AREA)
Tropical Medicine & Parasitology (AREA)
Molecular Biology (AREA)
Rheumatology (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrrole Compounds (AREA)
Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

SK2435-91A 1990-08-07 1991-08-06 Substituované pyroly a ich použitie, spôsob a medz SK279566B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB909017269A GB9017269D0 (en)	1990-08-07	1990-08-07	Substituted pyrroles
GB919109959A GB9109959D0 (en)	1991-05-08	1991-05-08	Substituted pyrroles

Publications (1)

Publication Number	Publication Date
SK279566B6 true SK279566B6 (sk)	1999-01-11

Family

ID=26297468

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK2435-91A SK279566B6 (sk)	1990-08-07	1991-08-06	Substituované pyroly a ich použitie, spôsob a medz

Country Status (26)

Country	Link
EP (1)	EP0470490B1 (hu)
JP (1)	JPH0780880B2 (hu)
KR (1)	KR100233964B1 (hu)
AT (1)	ATE179710T1 (hu)
AU (1)	AU649699B2 (hu)
CA (1)	CA2046801C (hu)
CZ (1)	CZ280359B6 (hu)
DE (1)	DE69131190T2 (hu)
DK (1)	DK0470490T3 (hu)
DZ (1)	DZ1521A1 (hu)
ES (1)	ES2132076T3 (hu)
FI (1)	FI95909C (hu)
GR (1)	GR3030677T3 (hu)
HU (1)	HU210547B (hu)
IE (1)	IE912787A1 (hu)
IL (1)	IL99064A (hu)
IS (1)	IS1682B (hu)
MC (1)	MC2279A1 (hu)
MY (1)	MY106400A (hu)
NO (1)	NO179143C (hu)
NZ (1)	NZ239216A (hu)
PT (1)	PT98583B (hu)
RO (1)	RO112724B1 (hu)
RU (1)	RU2075474C1 (hu)
SK (1)	SK279566B6 (hu)
UA (1)	UA27100A1 (hu)

Families Citing this family (29)

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GB9123396D0 (en) *	1991-11-04	1991-12-18	Hoffmann La Roche	A process for the manufacture of substituted maleimides
EP0630241A1 (en) *	1992-03-20	1994-12-28	The Wellcome Foundation Limited	Indole derivatives with antiviral activity
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
US5723456A (en) *	1993-12-07	1998-03-03	Eli Lilly & Company	Therapeutic treatment for cardiovascular diseases
HUT69164A (en) *	1993-12-07	1995-08-28	Lilly Co Eli	Improved process for producing bis-indolyl-maleimide derivatives
US5843935A (en) *	1993-12-07	1998-12-01	Eli Lilly And Company	Protein kinase C inhibitors
ES2162843T3 (es) *	1993-12-07	2002-01-16	Lilly Co Eli	Inhibidores de la proteina quinasa c.
US5541347A (en) *	1993-12-07	1996-07-30	Eli Lilly And Company	Synthesis of bisindolylmaleimides
US5624949A (en) *	1993-12-07	1997-04-29	Eli Lilly And Company	Protein kinase C inhibitors
US6025897A (en)	1993-12-21	2000-02-15	3M Innovative Properties Co.	Display with reflective polarizer and randomizing cavity
US6804058B1 (en)	1993-12-21	2004-10-12	3M Innovative Properties Company	Electroluminescent light source and display incorporating same
DK0817627T3 (da) *	1993-12-23	2005-06-06	Lilly Co Eli	Inhibitorer af proteinkinase C
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
US5554608A (en) *	1994-09-28	1996-09-10	Ahluwalia; Gurpreet S.	Inhibition of hair growth
CA2268399C (en) *	1996-10-31	2008-08-19	Harbor Branch Oceanographic Institution, Inc.	Anti-neurogenic inflammatory compounds and compositions and methods of use thereof
ATE277010T1 (de)	1998-07-08	2004-10-15	Harbor Branch Oceanographic	Bis-indolederivate und ihre verwendung als entzündungshemmende mittel
GB9828640D0 (en) *	1998-12-23	1999-02-17	Smithkline Beecham Plc	Novel method and compounds
FR2796274B1 (fr) *	1999-07-16	2001-09-21	Oreal	Utilisation de l'acide 4,6-dimethoxy-indole 2-carboxylique ou de ses derives pour stimuler ou induire la pousse des cheveux et/ou stopper leur chute
TW201041580A (en)	2001-09-27	2010-12-01	Alcon Inc	Inhibitors of glycogen synthase kinase-3 (GSK-3) for treating glaucoma
CA2393720C (en)	2002-07-12	2010-09-14	Eli Lilly And Company	Crystalline 2,5-dione-3-(1-methyl-1h-indol-3-yl)-4-[1-(pyridin-2-ylmethyl)piperidin-4-yl]-1h-indol-3-yl]-1h-pyrrole mono-hydrochloride
TWI324604B (en) *	2003-06-18	2010-05-11	Novartis Ag	New use of staurosporine derivatives
CA2533861A1 (en)	2003-08-08	2005-02-17	Novartis Ag	Combinations comprising staurosporines
EP1734952A1 (en) *	2004-04-08	2006-12-27	Novartis AG	Protein kinase c inhibitors for the treatment of autoimmune diseases and of transplant rejection
FR2870538B1 (fr) *	2004-05-19	2006-07-14	Servier Lab	Nouveaux derives de pyrrolidines et de thiazolidines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
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

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* Cited by examiner, † Cited by third party
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
MC2096A1 (fr) *	1989-02-23	1991-02-15	Hoffmann La Roche	Pyrroles substitues
IL94274A0 (en) *	1989-05-05	1991-03-10	Goedecke Ag	Maleinimide derivatives,process for the preparation thereof and pharmaceutical compositions containing the same

1991
- 1991-07-11 CA CA002046801A patent/CA2046801C/en not_active Expired - Fee Related
- 1991-07-17 RO RO148021A patent/RO112724B1/ro unknown
- 1991-07-30 AT AT91112829T patent/ATE179710T1/de not_active IP Right Cessation
- 1991-07-30 ES ES91112829T patent/ES2132076T3/es not_active Expired - Lifetime
- 1991-07-30 EP EP91112829A patent/EP0470490B1/en not_active Expired - Lifetime
- 1991-07-30 MC MC912209A patent/MC2279A1/xx unknown
- 1991-07-30 DE DE69131190T patent/DE69131190T2/de not_active Expired - Fee Related
- 1991-07-30 DK DK91112829T patent/DK0470490T3/da active
- 1991-08-01 NZ NZ239216A patent/NZ239216A/en unknown
- 1991-08-02 HU HU912589A patent/HU210547B/hu not_active IP Right Cessation
- 1991-08-02 IS IS3741A patent/IS1682B/is unknown
- 1991-08-02 IL IL9906491A patent/IL99064A/en unknown
- 1991-08-06 NO NO913051A patent/NO179143C/no not_active IP Right Cessation
- 1991-08-06 CZ CS912435A patent/CZ280359B6/cs not_active IP Right Cessation
- 1991-08-06 KR KR1019910013605A patent/KR100233964B1/ko not_active Expired - Fee Related
- 1991-08-06 RU SU915001208A patent/RU2075474C1/ru active
- 1991-08-06 SK SK2435-91A patent/SK279566B6/sk unknown
- 1991-08-06 IE IE278791A patent/IE912787A1/en not_active IP Right Cessation
- 1991-08-06 DZ DZ910109A patent/DZ1521A1/fr active
- 1991-08-06 JP JP3219401A patent/JPH0780880B2/ja not_active Expired - Fee Related
- 1991-08-06 MY MYPI91001423A patent/MY106400A/en unknown
- 1991-08-06 PT PT98583A patent/PT98583B/pt not_active IP Right Cessation
- 1991-08-07 FI FI913754A patent/FI95909C/fi not_active IP Right Cessation
- 1991-08-07 UA UA5001208A patent/UA27100A1/uk unknown
- 1991-08-07 AU AU81672/91A patent/AU649699B2/en not_active Ceased
1999
- 1999-07-02 GR GR990401759T patent/GR3030677T3/el unknown

Also Published As

Publication number	Publication date
NZ239216A (en)	1994-05-26
HU912589D0 (en)	1992-01-28
JPH0780880B2 (ja)	1995-08-30
CA2046801A1 (en)	1992-02-08
ATE179710T1 (de)	1999-05-15
NO913051D0 (no)	1991-08-06
DE69131190D1 (de)	1999-06-10
PT98583A (pt)	1992-06-30
MC2279A1 (fr)	1993-06-23
AU649699B2 (en)	1994-06-02
IS3741A7 (is)	1992-02-08
JPH04230686A (ja)	1992-08-19
PT98583B (pt)	1999-03-31
FI95909B (fi)	1995-12-29
CA2046801C (en)	2002-02-26
RO112724B1 (ro)	1997-12-30
EP0470490B1 (en)	1999-05-06
EP0470490A1 (en)	1992-02-12
FI913754A0 (fi)	1991-08-07
FI913754L (fi)	1992-02-08
NO179143B (no)	1996-05-06
DK0470490T3 (da)	1999-11-01
UA27100A1 (uk)	2000-02-28
KR100233964B1 (ko)	1999-12-15
AU8167291A (en)	1992-02-13
KR920004380A (ko)	1992-03-27
DE69131190T2 (de)	1999-11-04
IS1682B (is)	1998-02-24
IL99064A (en)	1995-08-31
ES2132076T3 (es)	1999-08-16
NO179143C (no)	1996-08-14
CS243591A3 (en)	1992-02-19
FI95909C (fi)	1996-04-10
RU2075474C1 (ru)	1997-03-20
HU210547B (en)	1995-05-29
IL99064A0 (en)	1992-07-15
MY106400A (en)	1995-05-30
GR3030677T3 (en)	1999-11-30
DZ1521A1 (fr)	2004-09-13
HUT61542A (en)	1993-01-28
IE912787A1 (en)	1992-02-12
NO913051L (no)	1992-02-10
CZ280359B6 (cs)	1995-12-13

Publication	Publication Date	Title
SK279566B6 (sk)	1999-01-11	Substituované pyroly a ich použitie, spôsob a medz
US5292747A (en)	1994-03-08	Substituted pyrroles
US7592454B2 (en)	2009-09-22	Substituted hexahydro-pyridoindole derivatives as serotonin receptor agonists and antagonists
EP0384349B1 (de)	1994-04-27	Substituierte Pyrrole
EP0859778B1 (en)	2001-12-19	TETRAHYDROIMIDAZOPYRIDOINDOLEDIONES AS INHIBITORS OF cGMP SPECIFIC PDE
LV11690B (en)	1997-06-20	Tetracyclic derivatives, process of preparation and use
JPH06279406A (ja)	1994-10-04	６−置換−４−ジアルキルアミノテトラヒドロベンズ［ｃ，ｄ］インドール類の合成中間体
AU678435B2 (en)	1997-05-29	Substituted pyrroles
FI91410B (fi)	1994-03-15	Menetelmä terapeuttisesti aktiivisten oktahydropyrrolo-pyratsino/2,1-i/indol-2-oni-johdannaisten valmistamiseksi
US3573323A (en)	1971-03-30	1,2,3,4,5,10-hexahydroazepino(2,3-b)indoles
GB2198729A (en)	1988-06-22	8-azaspiro4.5 decane derivatives
US4973593A (en)	1990-11-27	Novel compounds for the treatment of hypertension
US4879382A (en)	1989-11-07	Pyrido(3,4-f)pyrrolo(1,2-b)(1,2,5)triazepines
US4914103A (en)	1990-04-03	Pyrido(3,4-F)pyrrolo(1,2-B)(1,2,5)triazepines