NO301230B1 - Substituerte pyrroler - Google Patents
Substituerte pyrroler Download PDFInfo
- Publication number
- NO301230B1 NO301230B1 NO941682A NO941682A NO301230B1 NO 301230 B1 NO301230 B1 NO 301230B1 NO 941682 A NO941682 A NO 941682A NO 941682 A NO941682 A NO 941682A NO 301230 B1 NO301230 B1 NO 301230B1
- Authority
- NO
- Norway
- Prior art keywords
- indol
- methyl
- tetrahydropyrido
- pyrrole
- indolyl
- Prior art date
Links
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 58
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 13
- 150000007513 acids Chemical class 0.000 claims abstract description 10
- 208000030507 AIDS Diseases 0.000 claims abstract description 6
- 208000002249 Diabetes Complications Diseases 0.000 claims abstract description 6
- 206010012655 Diabetic complications Diseases 0.000 claims abstract description 6
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 150000007514 bases Chemical class 0.000 claims abstract description 6
- 230000003779 hair growth Effects 0.000 claims abstract description 6
- 230000001900 immune effect Effects 0.000 claims abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 4
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 4
- 230000000771 oncological effect Effects 0.000 claims abstract description 4
- 230000000638 stimulation Effects 0.000 claims abstract description 4
- 239000012876 carrier material Substances 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 claims description 3
- MMCDXUBLCGTHBR-UHFFFAOYSA-N 3-[7-(1-amino-2-methylpropyl)-6,7,8,9-tetrahydropyrido[1,2-a]indol-9-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione Chemical compound C1=CC=C2N(CC(C(N)C(C)C)CC3C=4C(NC(=O)C=4C=4C5=CC=CC=C5N(C)C=4)=O)C3=CC2=C1 MMCDXUBLCGTHBR-UHFFFAOYSA-N 0.000 claims description 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 2
- KIMGSERZPUILOK-SOKVYYICSA-N 3-[(8s)-8-[(1s)-1-amino-2-methylpropyl]-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=C2N2CC[C@H]([C@@H](N)C(C)C)CC2=C1C1=C(C=2C3=CC=CC=C3N(C)C=2)C(=O)NC1=O KIMGSERZPUILOK-SOKVYYICSA-N 0.000 claims 1
- UHFUPZMCUMRGEQ-MNAQKMTRSA-N 3-[(8s)-8-[(1s)-1-amino-2-methylpropyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-phenylindol-3-yl)pyrrole-2,5-dione Chemical compound C([C@@H](C1)[C@@H](N)C(C)C)CN(C2=CC=CC=C22)C1=C2C(C(NC1=O)=O)=C1C(C1=CC=CC=C11)=CN1C1=CC=CC=C1 UHFUPZMCUMRGEQ-MNAQKMTRSA-N 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 claims 1
- 230000004936 stimulating effect Effects 0.000 claims 1
- 230000002265 prevention Effects 0.000 abstract description 5
- 125000003118 aryl group Chemical group 0.000 abstract description 4
- 125000004423 acyloxy group Chemical group 0.000 abstract description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 3
- 125000003710 aryl alkyl group Chemical group 0.000 abstract description 2
- 239000001257 hydrogen Substances 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
- 239000000243 solution Substances 0.000 description 77
- 239000007787 solid Substances 0.000 description 71
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 230000008018 melting Effects 0.000 description 35
- 238000002844 melting Methods 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- -1 methoxy, ethoxy, propoxy, isopropoxy, butoxy Chemical group 0.000 description 23
- 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 22
- 239000007858 starting material Substances 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000010828 elution Methods 0.000 description 18
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
- 235000019341 magnesium sulphate Nutrition 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 239000000741 silica gel Substances 0.000 description 14
- 229910002027 silica gel Inorganic materials 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
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2,3-Dihydro-1H-pyrrole Natural products C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 12
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 10
- 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 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
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 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
- 239000000706 filtrate Substances 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
- 239000000047 product Substances 0.000 description 6
- 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 5
- 241000700159 Rattus Species 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- HHLFWLYXYJOTON-UHFFFAOYSA-N glyoxylic acid Chemical class OC(=O)C=O HHLFWLYXYJOTON-UHFFFAOYSA-N 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 150000003141 primary amines Chemical class 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241001480079 Corymbia calophylla Species 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 235000006552 Liquidambar styraciflua Nutrition 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
- 206010030113 Oedema Diseases 0.000 description 4
- 125000003545 alkoxy group Chemical group 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
- 210000002683 foot Anatomy 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 150000002576 ketones Chemical class 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 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
- 238000004519 manufacturing process Methods 0.000 description 4
- 150000002825 nitriles Chemical class 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- BQJRUJTZSGYBEZ-YVQNUNKESA-N phorbol 12,13-dibutanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCC)C1(C)C BQJRUJTZSGYBEZ-YVQNUNKESA-N 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
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- 238000012360 testing method Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
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- 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
- 150000004292 cyclic ethers Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 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
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- 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
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- MLICRUTZSXNCBZ-UHFFFAOYSA-N 2-methyl-1-(6,7,8,9-tetrahydropyrido[1,2-a]indol-7-yl)propan-1-one Chemical compound C1=CC=C2N(CC(C(=O)C(C)C)CC3)C3=CC2=C1 MLICRUTZSXNCBZ-UHFFFAOYSA-N 0.000 description 2
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- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 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
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 159000000001 potassium salts Chemical class 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
- 150000003233 pyrroles Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 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
- 159000000000 sodium salts Chemical class 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 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
- 125000001424 substituent group Chemical group 0.000 description 1
- 108010013480 succinylated gelatin Proteins 0.000 description 1
- 229940007079 succinylated gelatin Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 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
- 238000010998 test method Methods 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 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)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Virology (AREA)
- Endocrinology (AREA)
- Communicable Diseases (AREA)
- Emergency Medicine (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Urology & Nephrology (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Cephalosporin Compounds (AREA)
- Saccharide Compounds (AREA)
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 (3)
| Publication Number | Publication Date |
|---|---|
| NO941682D0 NO941682D0 (no) | 1994-05-06 |
| NO941682L NO941682L (no) | 1994-11-11 |
| NO301230B1 true NO301230B1 (no) | 1997-09-29 |
Family
ID=26302877
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO941682A NO301230B1 (no) | 1993-05-10 | 1994-05-06 | Substituerte pyrroler |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP0624586B1 (de) |
| JP (1) | JP2668818B2 (de) |
| CN (1) | CN1048014C (de) |
| AT (1) | ATE184007T1 (de) |
| AU (1) | AU678435B2 (de) |
| BG (1) | BG98761A (de) |
| BR (1) | BR9401935A (de) |
| CA (1) | CA2121567A1 (de) |
| CZ (1) | CZ112894A3 (de) |
| DE (1) | DE69420310T2 (de) |
| DK (1) | DK0624586T3 (de) |
| ES (1) | ES2137281T3 (de) |
| FI (1) | FI106961B (de) |
| GR (1) | GR3031901T3 (de) |
| HR (1) | HRP940287B1 (de) |
| HU (1) | HU215954B (de) |
| IL (1) | IL109547A (de) |
| IS (1) | IS1690B (de) |
| LT (1) | LT3288B (de) |
| LV (1) | LV11173B (de) |
| NO (1) | NO301230B1 (de) |
| NZ (1) | NZ260475A (de) |
| RU (1) | RU2141960C1 (de) |
| SI (1) | SI0624586T1 (de) |
| SK (1) | SK53594A3 (de) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| RU2147304C1 (ru) * | 1993-12-07 | 2000-04-10 | Эли Лилли Энд Компани | Бис-индолмалеимидные макроциклические производные, способ их получения (варианты) и фармацевтическая композиция |
| EP1449529B1 (de) * | 1993-12-23 | 2010-01-27 | Eli Lilly And Company | Proteinkinase C Inhibitoren |
| DK0695755T3 (da) * | 1994-08-04 | 1999-06-28 | Hoffmann La Roche | Pyrrolocarbazoler |
| US5919946A (en) * | 1996-03-20 | 1999-07-06 | 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 |
| HUP0301431A2 (hu) | 2000-07-27 | 2003-08-28 | F. Hoffmann-La Roche Ag. | 3-Indolil-4-fenil-1H-pirrol-2,5-dion-származékok, mint glikogén szintáz kináz-3béta inhibitorok, eljárás az előállításukra és ezeket tartalmazó gyógyszerkészítmények |
| ATE335490T1 (de) | 2001-10-30 | 2006-09-15 | Novartis Pharma Gmbh | Staurosporin-derivate als hemmer der flt3- rezeptor-tyrosinkinase-wirkung |
| 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 |
| CN100536850C (zh) | 2003-08-08 | 2009-09-09 | 诺瓦提斯公司 | 包含星孢素的组合 |
Family Cites Families (5)
| 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 |
| NZ227850A (en) * | 1988-02-10 | 1991-11-26 | Hoffmann La Roche | Indole substituted pyrrole derivatives; preparatory process and medicaments for use against inflammatory immunological, bronchopulmonary or vascular disorders |
| 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 DE DE69420310T patent/DE69420310T2/de not_active Expired - Fee Related
- 1994-05-02 DK DK94106812T patent/DK0624586T3/da active
- 1994-05-02 AT AT94106812T patent/ATE184007T1/de not_active IP Right Cessation
- 1994-05-02 EP EP94106812A patent/EP0624586B1/de not_active Expired - Lifetime
- 1994-05-02 ES ES94106812T patent/ES2137281T3/es not_active Expired - Lifetime
- 1994-05-02 SI SI9430273T patent/SI0624586T1/xx unknown
- 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 CZ CZ941128A patent/CZ112894A3/cs unknown
- 1994-05-06 NZ NZ260475A patent/NZ260475A/en unknown
- 1994-05-06 NO NO941682A patent/NO301230B1/no not_active IP Right Cessation
- 1994-05-09 JP JP6119542A patent/JP2668818B2/ja not_active Expired - Fee Related
- 1994-05-09 BR BR9401935A patent/BR9401935A/pt not_active Application Discontinuation
- 1994-05-09 CN CN94105846A patent/CN1048014C/zh not_active Expired - Fee Related
- 1994-05-09 LV LVP-94-100A patent/LV11173B/en unknown
- 1994-05-09 SK SK535-94A patent/SK53594A3/sk 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
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |
Free format text: LAPSED IN NOVEMBER 2001 |