SK53594A3 - Substituted pyroles method of their production and medicines on their base - Google Patents

Substituted pyroles method of their production and medicines on their base Download PDF

Info

Publication number: SK53594A3
Authority: SK; Slovakia
Prior art keywords: methyl; indol; indolyl; dione; pyrrole
Prior art date: 1993-05-10

Application number

SK535-94A

Other languages

English (en)

Slovak (sk)

Inventor

William Harris

Christopher H Hill

Geoffrey Lawton

Original Assignee

Hoffmann La Roche

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.)

1993-05-10

Filing date

1994-05-09

Publication date

1995-02-08

1993-05-10 Priority claimed from GB939309602A external-priority patent/GB9309602D0/en

1994-05-09 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1995-02-08 Publication of SK53594A3 publication Critical patent/SK53594A3/sk

Links

238000000034 method Methods 0.000 title claims description 15
239000003814 drug Substances 0.000 title claims description 14
238000004519 manufacturing process Methods 0.000 title claims description 6
229940079593 drug Drugs 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 70
150000003839 salts Chemical class 0.000 claims abstract description 31
125000000217 alkyl group Chemical group 0.000 claims abstract description 24
239000002253 acid Substances 0.000 claims abstract description 16
150000007513 acids Chemical class 0.000 claims abstract description 9
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 9
208000030507 AIDS Diseases 0.000 claims abstract description 8
125000003118 aryl group Chemical group 0.000 claims abstract description 8
208000006673 asthma Diseases 0.000 claims abstract description 8
230000003779 hair growth Effects 0.000 claims abstract description 8
208000002249 Diabetes Complications Diseases 0.000 claims abstract description 7
206010012655 Diabetic complications Diseases 0.000 claims abstract description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 7
230000001900 immune effect Effects 0.000 claims abstract description 7
125000004423 acyloxy group Chemical group 0.000 claims abstract description 6
150000007514 bases Chemical class 0.000 claims abstract description 6
230000000771 oncological effect Effects 0.000 claims abstract description 6
208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 5
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
239000001257 hydrogen Substances 0.000 claims abstract description 5
230000002757 inflammatory effect Effects 0.000 claims abstract description 5
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 3
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 2
-1 lower cycloacyl Chemical group 0.000 claims description 42
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 11
230000008569 process Effects 0.000 claims description 7
125000004432 carbon atom Chemical group C* 0.000 claims description 5
239000013543 active substance Substances 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
230000004936 stimulating effect Effects 0.000 claims description 4
JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 4
230000002526 effect on cardiovascular system Effects 0.000 claims description 3
150000003233 pyrroles Chemical class 0.000 claims description 3
125000001424 substituent group Chemical group 0.000 claims description 3
239000004480 active ingredient Substances 0.000 claims description 2
208000027866 inflammatory disease Diseases 0.000 claims description 2
125000006239 protecting group Chemical group 0.000 claims description 2
230000003110 anti-inflammatory effect Effects 0.000 claims 2
206010012601 diabetes mellitus Diseases 0.000 claims 1
230000002265 prevention Effects 0.000 abstract description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 4
125000000753 cycloalkyl group Chemical group 0.000 abstract description 3
230000000638 stimulation Effects 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
239000000243 solution Substances 0.000 description 78
239000007787 solid Substances 0.000 description 77
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
239000000203 mixture Substances 0.000 description 33
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
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 30
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
239000007858 starting material Substances 0.000 description 22
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 20
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 20
239000002904 solvent Substances 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 17
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
229910052943 magnesium sulfate Inorganic materials 0.000 description 14
235000019341 magnesium sulphate Nutrition 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 14
229940086542 triethylamine Drugs 0.000 description 14
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000003208 petroleum Substances 0.000 description 13
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
238000004128 high performance liquid chromatography Methods 0.000 description 10
239000000725 suspension Substances 0.000 description 10
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 10
239000003480 eluent Substances 0.000 description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
238000010828 elution Methods 0.000 description 8
150000002576 ketones Chemical class 0.000 description 8
239000011347 resin Substances 0.000 description 8
229920005989 resin Polymers 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
239000000969 carrier Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
239000012299 nitrogen atmosphere Substances 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 6
JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 6
238000003756 stirring Methods 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 5
GXBDUKNALWQPMX-UHFFFAOYSA-N hydron;pyrrole-2,5-dione;chloride Chemical compound Cl.O=C1NC(=O)C=C1 GXBDUKNALWQPMX-UHFFFAOYSA-N 0.000 description 5
239000012280 lithium aluminium hydride Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
150000003141 primary amines Chemical class 0.000 description 5
238000012360 testing method Methods 0.000 description 5
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 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 0.000 description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
238000009833 condensation Methods 0.000 description 4
230000005494 condensation Effects 0.000 description 4
239000006260 foam Substances 0.000 description 4
229910052736 halogen Inorganic materials 0.000 description 4
150000002367 halogens Chemical class 0.000 description 4
IUYHWZFSGMZEOG-UHFFFAOYSA-M magnesium;propane;chloride Chemical compound [Mg+2].[Cl-].C[CH-]C IUYHWZFSGMZEOG-UHFFFAOYSA-M 0.000 description 4
150000002825 nitriles Chemical class 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000010898 silica gel chromatography Methods 0.000 description 4
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 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
GUKDTFJMXRYGFL-UHFFFAOYSA-N 3-(1H-indol-2-yl)-1-methylpyrrole-2,5-dione Chemical compound CN1C(C(=CC1=O)C=1NC2=CC=CC=C2C=1)=O GUKDTFJMXRYGFL-UHFFFAOYSA-N 0.000 description 3
XIRFXORWGKTRJI-UHFFFAOYSA-N 6,7,8,9-tetrahydropyrido[1,2-a]indole-8-carbonitrile Chemical compound C1=CC=C2N3CCC(C#N)CC3=CC2=C1 XIRFXORWGKTRJI-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 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
239000008346 aqueous phase Substances 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
238000003776 cleavage reaction Methods 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
230000006806 disease prevention Effects 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000011065 in-situ storage Methods 0.000 description 3
125000001041 indolyl group Chemical group 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
150000002923 oximes Chemical class 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
229920006395 saturated elastomer Polymers 0.000 description 3
230000007017 scission Effects 0.000 description 3
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
XCFTZNYGACLFHH-JTQLQIEISA-N (8s)-6,7,8,9-tetrahydropyrido[1,2-a]indole-8-carboxylic acid Chemical compound C1=CC=C2N3CC[C@H](C(=O)O)CC3=CC2=C1 XCFTZNYGACLFHH-JTQLQIEISA-N 0.000 description 2
PWLOCYPSIHEJPO-LBPRGKRZSA-N (8s)-n-methoxy-n-methyl-6,7,8,9-tetrahydropyrido[1,2-a]indole-8-carboxamide Chemical compound C1=CC=C2N3CC[C@H](C(=O)N(C)OC)CC3=CC2=C1 PWLOCYPSIHEJPO-LBPRGKRZSA-N 0.000 description 2
MLWVXRFGMRAYDX-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolo[1,2-a]indole-2-carboxylic acid Chemical compound C1=CC=C2N(CC(C(=O)O)C3)C3=CC2=C1 MLWVXRFGMRAYDX-UHFFFAOYSA-N 0.000 description 2
PWQOKENMGJNGKV-UHFFFAOYSA-N 2-(1-phenylindol-3-yl)acetic acid Chemical compound C12=CC=CC=C2C(CC(=O)O)=CN1C1=CC=CC=C1 PWQOKENMGJNGKV-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
INIZQHSIRKWIQR-UHFFFAOYSA-N 6,7,8,9-tetrahydropyrido[1,2-a]indole-8-carboxamide Chemical compound C1=CC=C2N3CCC(C(=O)N)CC3=CC2=C1 INIZQHSIRKWIQR-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-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
239000007818 Grignard reagent Substances 0.000 description 2
108010033040 Histones Proteins 0.000 description 2
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
235000019759 Maize starch Nutrition 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
102000003923 Protein Kinase C Human genes 0.000 description 2
108090000315 Protein Kinase C Proteins 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000000654 additive Substances 0.000 description 2
230000000996 additive effect Effects 0.000 description 2
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
238000003556 assay Methods 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000004093 cyano group Chemical group *C#N 0.000 description 2
150000004292 cyclic ethers Chemical class 0.000 description 2
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 2
ODCCJTMPMUFERV-UHFFFAOYSA-N ditert-butyl carbonate Chemical compound CC(C)(C)OC(=O)OC(C)(C)C ODCCJTMPMUFERV-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
YQSQQTUEYUKCQW-UHFFFAOYSA-N ethyl 2-oxo-2-(1-phenylindol-3-yl)acetate Chemical compound C12=CC=CC=C2C(C(=O)C(=O)OCC)=CN1C1=CC=CC=C1 YQSQQTUEYUKCQW-UHFFFAOYSA-N 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000003925 fat Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
IAODRFIZLKITMK-UHFFFAOYSA-N furan-2,3-dione Chemical class O=C1OC=CC1=O IAODRFIZLKITMK-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
239000003365 glass fiber Substances 0.000 description 2
239000008103 glucose Substances 0.000 description 2
150000004795 grignard reagents Chemical class 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
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230000037361 pathway Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
239000003909 protein kinase inhibitor Substances 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
VUVGMQNYJPPCCC-UHFFFAOYSA-N pyrido[1,2-a]indole Chemical compound C1=CC=CC2=CC3=CC=CC=C3N21 VUVGMQNYJPPCCC-UHFFFAOYSA-N 0.000 description 1
230000002285 radioactive effect Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000028327 secretion Effects 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
FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 1
229940048086 sodium pyrophosphate Drugs 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
239000012258 stirred mixture Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository 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
150000003892 tartrate salts Chemical class 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
229940066528 trichloroacetate Drugs 0.000 description 1
238000005406 washing Methods 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
- A61P11/08—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
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Diabetes (AREA)
Virology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Endocrinology (AREA)
Communicable Diseases (AREA)
Emergency Medicine (AREA)
Pulmonology (AREA)
Hematology (AREA)
Obesity (AREA)
Oncology (AREA)
Rheumatology (AREA)
Molecular Biology (AREA)
Immunology (AREA)
Tropical Medicine & Parasitology (AREA)
AIDS & HIV (AREA)
Pain & Pain Management (AREA)
Vascular Medicine (AREA)
Dermatology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrrole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Saccharide Compounds (AREA)
Cephalosporin Compounds (AREA)

SK535-94A 1993-05-10 1994-05-09 Substituted pyroles method of their production and medicines on their base SK53594A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB939309602A GB9309602D0 (en)	1993-05-10	1993-05-10	Substituted pyrroles
GB9403249A GB9403249D0 (en)	1993-05-10	1994-02-21	Substituted pyrroles

Publications (1)

Publication Number	Publication Date
SK53594A3 true SK53594A3 (en)	1995-02-08

Family

ID=26302877

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK535-94A SK53594A3 (en)	1993-05-10	1994-05-09	Substituted pyroles method of their production and medicines on their base

Country Status (25)

Country	Link
EP (1)	EP0624586B1 (zh)
JP (1)	JP2668818B2 (zh)
CN (1)	CN1048014C (zh)
AT (1)	ATE184007T1 (zh)
AU (1)	AU678435B2 (zh)
BG (1)	BG98761A (zh)
BR (1)	BR9401935A (zh)
CA (1)	CA2121567A1 (zh)
CZ (1)	CZ112894A3 (zh)
DE (1)	DE69420310T2 (zh)
DK (1)	DK0624586T3 (zh)
ES (1)	ES2137281T3 (zh)
FI (1)	FI106961B (zh)
GR (1)	GR3031901T3 (zh)
HR (1)	HRP940287B1 (zh)
HU (1)	HU215954B (zh)
IL (1)	IL109547A (zh)
IS (1)	IS1690B (zh)
LT (1)	LT3288B (zh)
LV (1)	LV11173B (zh)
NO (1)	NO301230B1 (zh)
NZ (1)	NZ260475A (zh)
RU (1)	RU2141960C1 (zh)
SI (1)	SI0624586T1 (zh)
SK (1)	SK53594A3 (zh)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA44690C2 (uk) *	1993-12-07	2002-03-15	Елі Ліллі Енд Компані	Макроциклічна сполука іміду біс-індол-малеїнової кислоти, спосіб її одержання та фармацевтична композиція, макроциклічні сполуки іміду біс-індол-малеїнової кислоти та біс-індол-малеїнового ангідриду, спосіб одержання (варіанти)
US5624949A (en) *	1993-12-07	1997-04-29	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
AU1339895A (en) *	1993-12-23	1995-07-10	Eli Lilly And Company	Protein kinase c inhibitors
EP0695755B1 (en) *	1994-08-04	1998-10-21	F. Hoffmann-La Roche AG	Pyrrolocarbazole
CA2249205A1 (en) *	1996-03-20	1997-09-25	Eli Lilly And Company	Synthesis of indolylmaleimides
KR100499190B1 (ko) *	1996-03-29	2006-04-17	교와 핫꼬 고교 가부시끼가이샤	육모제
US5859261A (en) *	1997-03-20	1999-01-12	Eli Lilly And Company	Synthesis of indolylmaleimides
PL366701A1 (en)	2000-07-27	2005-02-07	F.Hoffmann-La Roche Ag	3-indolyl-4-phenyl-1h-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta
HU230798B1 (hu)	2001-10-30	2018-06-28	Novartis Ag	Staurosporin-származékok mint az FLT3 receptor tirozin-kináz aktivitás inhibitorai
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
EP1653973A1 (en)	2003-08-08	2006-05-10	Novartis AG	Combinations comprising staurosporines

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3803620A1 (de) *	1988-02-06	1989-08-17	Goedecke Ag	Indolocarbazol-derivate, verfahren zu deren herstellung und diese enthaltende arzneimittel
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
DE3833008A1 (de) *	1988-09-29	1990-04-05	Goedecke Ag	Pyrrolocarbozol-derivate, verfahren zu deren herstellung und deren verwendung als arzneimittel
MC2096A1 (fr) *	1989-02-23	1991-02-15	Hoffmann La Roche	Pyrroles substitues
CA2046801C (en) *	1990-08-07	2002-02-26	Peter D. Davis	Substituted pyrroles

1994
- 1994-04-15 AU AU60555/94A patent/AU678435B2/en not_active Ceased
- 1994-04-26 CA CA002121567A patent/CA2121567A1/en not_active Abandoned
- 1994-05-02 DK DK94106812T patent/DK0624586T3/da active
- 1994-05-02 EP EP94106812A patent/EP0624586B1/en not_active Expired - Lifetime
- 1994-05-02 SI SI9430273T patent/SI0624586T1/xx unknown
- 1994-05-02 AT AT94106812T patent/ATE184007T1/de not_active IP Right Cessation
- 1994-05-02 DE DE69420310T patent/DE69420310T2/de not_active Expired - Fee Related
- 1994-05-02 ES ES94106812T patent/ES2137281T3/es not_active Expired - Lifetime
- 1994-05-04 IL IL10954794A patent/IL109547A/en not_active IP Right Cessation
- 1994-05-04 HU HU9401298A patent/HU215954B/hu not_active IP Right Cessation
- 1994-05-05 HR HR9309602.2A patent/HRP940287B1/xx not_active IP Right Cessation
- 1994-05-05 RU RU94015830A patent/RU2141960C1/ru active
- 1994-05-06 NO NO941682A patent/NO301230B1/no not_active IP Right Cessation
- 1994-05-06 NZ NZ260475A patent/NZ260475A/en unknown
- 1994-05-06 CZ CZ941128A patent/CZ112894A3/cs unknown
- 1994-05-09 BR BR9401935A patent/BR9401935A/pt not_active Application Discontinuation
- 1994-05-09 SK SK535-94A patent/SK53594A3/sk unknown
- 1994-05-09 CN CN94105846A patent/CN1048014C/zh not_active Expired - Fee Related
- 1994-05-09 JP JP6119542A patent/JP2668818B2/ja not_active Expired - Fee Related
- 1994-05-09 LV LVP-94-100A patent/LV11173B/en unknown
- 1994-05-09 LT LTIP1927A patent/LT3288B/lt not_active IP Right Cessation
- 1994-05-09 IS IS4162A patent/IS1690B/is unknown
- 1994-05-10 BG BG98761A patent/BG98761A/xx unknown
- 1994-05-10 FI FI942158A patent/FI106961B/fi not_active IP Right Cessation
1999
- 1999-11-18 GR GR990402995T patent/GR3031901T3/el unknown

Also Published As

Publication number	Publication date
AU678435B2 (en)	1997-05-29
JP2668818B2 (ja)	1997-10-27
DE69420310D1 (de)	1999-10-07
IL109547A0 (en)	1994-08-26
FI942158A0 (fi)	1994-05-10
HRP940287A2 (en)	1996-12-31
CZ112894A3 (en)	1994-12-15
BR9401935A (pt)	1995-03-07
GR3031901T3 (en)	2000-02-29
LV11173A (lv)	1996-04-20
EP0624586A1 (en)	1994-11-17
NO941682D0 (no)	1994-05-06
FI942158A7 (fi)	1994-11-11
LV11173B (en)	1996-06-20
FI106961B (fi)	2001-05-15
CA2121567A1 (en)	1994-11-11
AU6055594A (en)	1994-11-17
LTIP1927A (en)	1994-11-25
EP0624586B1 (en)	1999-09-01
CN1048014C (zh)	2000-01-05
NZ260475A (en)	1996-02-27
NO941682L (no)	1994-11-11
DK0624586T3 (da)	2000-03-27
HU9401298D0 (en)	1994-08-29
ES2137281T3 (es)	1999-12-16
LT3288B (en)	1995-06-26
HUT71492A (en)	1995-11-28
RU2141960C1 (ru)	1999-11-27
HRP940287B1 (en)	2000-02-29
DE69420310T2 (de)	2000-04-13
CN1103402A (zh)	1995-06-07
IS4162A (is)	1994-11-11
IS1690B (is)	1998-04-20
HU215954B (hu)	1999-03-29
NO301230B1 (no)	1997-09-29
SI0624586T1 (en)	1999-12-31
ATE184007T1 (de)	1999-09-15
JPH06329672A (ja)	1994-11-29
BG98761A (en)	1995-03-31
IL109547A (en)	1998-07-15

Publication	Publication Date	Title
AU592983B2 (en)	1990-02-01	Imidazoquinoline antithrombogenic cardiotonicagents
EP0384349B1 (de)	1994-04-27	Substituierte Pyrrole
AU603577B2 (en)	1990-11-22	Imidazoquinolinylether derivatives
RU2100357C1 (ru)	1997-12-27	Гетероариламины или их фармацевтически приемлемые соли и фармацевтическая композиция на их основе
KR102851932B1 (ko)	2025-08-27	Pad4 억제제로서의 치환된 티에노피롤
FI95909B (fi)	1995-12-29	Menetelmä terapeuttisesti käyttökelpoisten 3,4-bis(3-indolyyli)-1H-pyrroli-2,5-dionijohdannaisten valmistamiseksi sekä menetelmässä käyttökelpoiset välituotteet
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AU2006259572A1 (en)	2006-12-28	Aspartyl protease inhibitors
AU2003279230A1 (en)	2004-05-04	AZAINDOLE DERIVATIVES AS INHIBITORS OF p38 KINASE
SK53594A3 (en)	1995-02-08	Substituted pyroles method of their production and medicines on their base
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WO2002044181A1 (en)	2002-06-06	Hydantoin compounds useful as anti-inflammatory agents
IE871767L (en)	1988-01-04	PYRROLO £1,2-c\| THIAZOLE DERIVATIVES
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US5521181A (en)	1996-05-28	Bicyclic substituted hexahydrobenz[e]isoindole α-1 adrenergic antagonists
US5721230A (en)	1998-02-24	Substituted pyrroles
US6057340A (en)	2000-05-02	Oxazole derivatives as serotonin-1A receptor agonists
HU198937B (en)	1989-12-28	Process for producing indolopyrazino benzodiazepine derivatives and pharmaceutical compositions comprising same
WO2013001498A1 (en)	2013-01-03	Amidoalkylpiperazinyl derivatives for the treatment of central nervous system diseases
KR100331515B1 (ko)	2002-08-19	치환된피롤
EP0145304B1 (en)	1988-04-20	Tetrahydro-beta-carboline derivatives and process for the preparation thereof
NO811376L (no)	1981-10-26	Fremgangsmaate ved fremstilling av antihypertensive lactamer
EP0912511A1 (en)	1999-05-06	5-indolyl-2,4-pentadienoic acid derivatives useful as inhibitors of bone resorption