CA2389312A1 - Agents cytotoxiques heterocycliques - Google Patents
Agents cytotoxiques heterocycliques Download PDFInfo
- Publication number
- CA2389312A1 CA2389312A1 CA002389312A CA2389312A CA2389312A1 CA 2389312 A1 CA2389312 A1 CA 2389312A1 CA 002389312 A CA002389312 A CA 002389312A CA 2389312 A CA2389312 A CA 2389312A CA 2389312 A1 CA2389312 A1 CA 2389312A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- alkyl
- alkoxy
- hydrogen
- hydroxy
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 229940127089 cytotoxic agent Drugs 0.000 title description 5
- 239000002254 cytotoxic agent Substances 0.000 title description 4
- 231100000599 cytotoxic agent Toxicity 0.000 title description 4
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 31
- 201000011510 cancer Diseases 0.000 claims abstract description 25
- 238000000034 method Methods 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 238000002560 therapeutic procedure Methods 0.000 claims abstract 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 202
- -1 nitro, hydroxy Chemical group 0.000 claims description 99
- 239000001257 hydrogen Substances 0.000 claims description 80
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
- 125000005843 halogen group Chemical group 0.000 claims description 43
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 241000124008 Mammalia Species 0.000 claims description 10
- 230000000844 anti-bacterial effect Effects 0.000 claims description 9
- 230000000843 anti-fungal effect Effects 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000005505 thiomorpholino group Chemical group 0.000 claims description 8
- 229940121375 antifungal agent Drugs 0.000 claims description 7
- 230000000842 anti-protozoal effect Effects 0.000 claims description 6
- 239000003904 antiprotozoal agent Substances 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- DZPAHDGQIJWIKC-UHFFFAOYSA-N 2,3,8-trimethoxynaphtho[1,2-c]cinnolin-9-ol Chemical compound COC1=C(OC)C=C2C=CC3=C(C=C(C(OC)=C4)O)C4=NN=C3C2=C1 DZPAHDGQIJWIKC-UHFFFAOYSA-N 0.000 claims description 5
- BNKLNOIJZZDUHZ-UHFFFAOYSA-N 2,3-dimethoxy-8,9-methylenedioxy-dibenzo[c,h]cinnoline Chemical compound C1=C2N=NC3=C(C=C(C(OC)=C4)OC)C4=CC=C3C2=CC2=C1OCO2 BNKLNOIJZZDUHZ-UHFFFAOYSA-N 0.000 claims description 5
- YFFVOLMHDPWYHI-UHFFFAOYSA-N 3-methoxy-8,9-methylenedioxydibenzo[c,h]cinnoline Chemical compound C1=C2OCOC2=CC2=NN=C(C=3C(=CC=C(C=3)OC)C=C3)C3=C21 YFFVOLMHDPWYHI-UHFFFAOYSA-N 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- OMUIGKAGIWPDCY-UHFFFAOYSA-N 2,3,8,9-tetramethoxynaphtho[1,2-c]cinnoline Chemical compound COC1=C(OC)C=C2N=NC3=C(C=C(C(OC)=C4)OC)C4=CC=C3C2=C1 OMUIGKAGIWPDCY-UHFFFAOYSA-N 0.000 claims description 4
- DZVDICCNYQNJJC-UHFFFAOYSA-N 2,3,8-trimethoxy-9-phenylmethoxynaphtho[1,2-c]cinnoline Chemical compound COC=1C=C2N=NC3=C4C=C(OC)C(OC)=CC4=CC=C3C2=CC=1OCC1=CC=CC=C1 DZVDICCNYQNJJC-UHFFFAOYSA-N 0.000 claims description 4
- YPLVCEDAZWQZQO-UHFFFAOYSA-N 2,3,8-trimethoxynaphtho[1,2-c]cinnoline Chemical compound C1=C(OC)C(OC)=CC2=CC=C3C4=CC=C(OC)C=C4N=NC3=C21 YPLVCEDAZWQZQO-UHFFFAOYSA-N 0.000 claims description 4
- IMPABAXTBFQROU-UHFFFAOYSA-N 2-methoxy-8,9-methylenedioxydibenzo[c,h]cinnoline Chemical compound C1=C2OCOC2=CC2=NN=C3C4=CC=C(OC)C=C4C=CC3=C21 IMPABAXTBFQROU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 230000010261 cell growth Effects 0.000 claims description 4
- 238000001727 in vivo Methods 0.000 claims description 4
- CTZYGJFBHJAZBE-UHFFFAOYSA-N 2,3-dimethoxynaphtho[1,2-c]cinnoline Chemical compound C1=CC=C2N=NC3=C(C=C(C(OC)=C4)OC)C4=CC=C3C2=C1 CTZYGJFBHJAZBE-UHFFFAOYSA-N 0.000 claims description 3
- 230000000840 anti-viral effect Effects 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 238000013160 medical therapy Methods 0.000 claims description 2
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims 6
- YUYRZQOQHINLNO-UHFFFAOYSA-N 2,3,9-trimethoxynaphtho[1,2-c]cinnoline Chemical compound C1=C(OC)C(OC)=CC2=CC=C(C=3C(=CC=C(C=3)OC)N=N3)C3=C21 YUYRZQOQHINLNO-UHFFFAOYSA-N 0.000 claims 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 2
- 239000000543 intermediate Substances 0.000 abstract description 22
- 230000008569 process Effects 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 252
- 239000000243 solution Substances 0.000 description 90
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 80
- 239000000203 mixture Substances 0.000 description 75
- 238000005481 NMR spectroscopy Methods 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- 125000003545 alkoxy group Chemical group 0.000 description 28
- 239000012044 organic layer Substances 0.000 description 27
- 239000012043 crude product Substances 0.000 description 23
- 239000012267 brine Substances 0.000 description 22
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 22
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 18
- 229910002027 silica gel Inorganic materials 0.000 description 18
- 102000003915 DNA Topoisomerases Human genes 0.000 description 16
- 108090000323 DNA Topoisomerases Proteins 0.000 description 16
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 16
- 101150041968 CDC13 gene Proteins 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 239000003054 catalyst Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 231100000614 poison Toxicity 0.000 description 12
- 239000002574 poison Substances 0.000 description 12
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 12
- 239000007788 liquid Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 9
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
- 238000004587 chromatography analysis Methods 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 8
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 235000010288 sodium nitrite Nutrition 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 7
- 125000001589 carboacyl group Chemical group 0.000 description 7
- 239000010410 layer Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- RPRQHHJLRLEIOK-UHFFFAOYSA-N 2-(6,7-dimethoxynaphthalen-2-yl)aniline Chemical compound C1=C2C=C(OC)C(OC)=CC2=CC=C1C1=CC=CC=C1N RPRQHHJLRLEIOK-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- KKMPSGJPCCJYRV-UHFFFAOYSA-N Nitidine Chemical compound C1=C2C3=[N+](C)C=C4C=C(OC)C(OC)=CC4=C3C=CC2=CC2=C1OCO2 KKMPSGJPCCJYRV-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000012954 diazonium Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 6
- 239000011698 potassium fluoride Substances 0.000 description 6
- 235000003270 potassium fluoride Nutrition 0.000 description 6
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 6
- KCOBIBRGPCFIGF-UHFFFAOYSA-N 1-bromo-4-methoxy-2-nitrobenzene Chemical compound COC1=CC=C(Br)C([N+]([O-])=O)=C1 KCOBIBRGPCFIGF-UHFFFAOYSA-N 0.000 description 5
- MVXFWIJIPARTPT-UHFFFAOYSA-N 2-(6,7-dimethoxynaphthalen-2-yl)-4,5-dimethoxyaniline Chemical compound C1=C(OC)C(OC)=CC(N)=C1C1=CC=C(C=C(OC)C(OC)=C2)C2=C1 MVXFWIJIPARTPT-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 101710183280 Topoisomerase Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 229940127093 camptothecin Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
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- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 5
- 229910000080 stannane Inorganic materials 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- DJLDZTLFZFWEPH-UHFFFAOYSA-N trimethyl-(6-nitro-1,3-benzodioxol-5-yl)stannane Chemical compound C1=C([N+]([O-])=O)C([Sn](C)(C)C)=CC2=C1OCO2 DJLDZTLFZFWEPH-UHFFFAOYSA-N 0.000 description 5
- DUHXKKFPSASCAQ-UHFFFAOYSA-N 2-(6,7-dimethoxynaphthalen-2-yl)-4-methoxyaniline Chemical compound COC1=CC=C(N)C(C=2C=C3C=C(OC)C(OC)=CC3=CC=2)=C1 DUHXKKFPSASCAQ-UHFFFAOYSA-N 0.000 description 4
- PXMNNSNFKYHGSG-UHFFFAOYSA-N 2-(6,7-dimethoxynaphthalen-2-yl)-5-methoxyaniline Chemical compound NC1=CC(OC)=CC=C1C1=CC=C(C=C(OC)C(OC)=C2)C2=C1 PXMNNSNFKYHGSG-UHFFFAOYSA-N 0.000 description 4
- KBTMGSMZIKLAHN-UHFFFAOYSA-N 4-bromo-1,2-dimethoxybenzene Chemical compound COC1=CC=C(Br)C=C1OC KBTMGSMZIKLAHN-UHFFFAOYSA-N 0.000 description 4
- OIAMIMPHJVFABE-UHFFFAOYSA-N 6-(6,7-dimethoxynaphthalen-2-yl)-1,3-benzodioxol-5-amine Chemical compound C1=C2C=C(OC)C(OC)=CC2=CC=C1C(C(=C1)N)=CC2=C1OCO2 OIAMIMPHJVFABE-UHFFFAOYSA-N 0.000 description 4
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 4
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- PDYBUYVOPAJLKP-UHFFFAOYSA-M 2,3,10,11-tetramethoxy-8-methylisoquinolino[2,1-b]isoquinolin-7-ium;chloride Chemical compound [Cl-].C1=C(OC)C(OC)=CC2=CC3=C(C=C(C(OC)=C4)OC)C4=CC=[N+]3C(C)=C21 PDYBUYVOPAJLKP-UHFFFAOYSA-M 0.000 description 3
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- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
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- 229910052720 vanadium Inorganic materials 0.000 description 1
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- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- A61P31/10—Antimycotics
-
- 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
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
- A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
L'invention concerne des composés de la formule (I) dans laquelle R¿1?-R¿8? et A-G ont n'importe laquelle des définitions décrites dans le mémorandum descriptif, et leurs sels pharmaceutiquement acceptables. L'invention concerne en outre des compositions pharmaceutiques comprenant un composé de la formule (I), des méthodes de préparation de composés de la formule (I), des intermédiaires utiles pour la préparation de composés de la formule (I), et des méthodes thérapeutiques pour le traitement du cancer utilisant des composés de la formule (I).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16254099P | 1999-10-29 | 1999-10-29 | |
| US60/162,540 | 1999-10-29 | ||
| PCT/US2000/029583 WO2001032631A2 (fr) | 1999-10-29 | 2000-10-26 | Agents cytotoxiques heterocycliques |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2389312A1 true CA2389312A1 (fr) | 2001-05-10 |
Family
ID=22586069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002389312A Abandoned CA2389312A1 (fr) | 1999-10-29 | 2000-10-26 | Agents cytotoxiques heterocycliques |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1228045A2 (fr) |
| JP (1) | JP2003513079A (fr) |
| AR (1) | AR026267A1 (fr) |
| AU (1) | AU1236401A (fr) |
| CA (1) | CA2389312A1 (fr) |
| WO (1) | WO2001032631A2 (fr) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1453812B1 (fr) | 2001-11-14 | 2008-08-20 | Rutgers, The State University | Agents cytotoxiques |
| MXPA04004607A (es) * | 2001-11-14 | 2004-09-10 | Univ Rutgers | Agentes de venenos de topoisomerasa solubilizados. |
| AU2002364953A1 (en) | 2001-11-14 | 2003-06-17 | Edmond J. Lavoie | Topoisomerase poison agents |
| DE60235287D1 (de) * | 2001-11-14 | 2010-03-25 | Univ Rutgers | Löslich gemachte topoisomerase-gifte |
| US6989387B2 (en) | 2002-08-09 | 2006-01-24 | Rutgers, The State University Of New Jersey | Nitro and amino substituted topoisomerase agents |
| AU2003268075A1 (en) * | 2002-08-09 | 2004-02-25 | Edmond J. Lavoie | Nitro and amino substituted dibenzonaphthyridines as topoisomerase agents |
| US6992088B2 (en) | 2002-08-09 | 2006-01-31 | Rutgers, The State University Of New Jersey | Nitro and amino substituted heterocycles as topoisomerase I targeting agents |
| CA2510337C (fr) | 2002-11-12 | 2013-01-08 | Rutgers, The State University Of New Jersey | Agents ciblant les topoisomerases |
| CA2512000C (fr) * | 2002-12-26 | 2011-08-09 | Eisai Co., Ltd. | Modulateurs selectifs des recepteurs d'oestrogene |
| DE102008022221A1 (de) | 2008-05-06 | 2009-11-12 | Universität des Saarlandes | Inhibitoren der humanen Aldosteronsynthase CYP11B2 |
| TW201038578A (en) | 2009-01-30 | 2010-11-01 | Univ Rutgers | Methods to treat cancer |
| DK2403856T3 (da) | 2009-03-06 | 2013-04-08 | Univ Rutgers | Methylendioxybenzo[i]phenanthridinderivater anvendt til behandling af cancer |
| WO2010127363A1 (fr) | 2009-05-01 | 2010-11-04 | Rutgers, The State University Of New Jersey | Inhibiteurs de topoisomérase |
| US8541404B2 (en) | 2009-11-09 | 2013-09-24 | Elexopharm Gmbh | Inhibitors of the human aldosterone synthase CYP11B2 |
| US9421264B2 (en) | 2014-03-28 | 2016-08-23 | Duke University | Method of treating cancer using selective estrogen receptor modulators |
| FI3834824T3 (fi) | 2014-03-28 | 2025-12-05 | Univ Duke | Estrogeenireseptoripositiivisen rintasyövän hoito selektiivisellä estrogeenireseptorin modulaattorilla |
| US11091498B2 (en) | 2016-04-04 | 2021-08-17 | Rutgers, The State University Of New Jersey | Topoisomerase poisons |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998045272A1 (fr) * | 1997-04-07 | 1998-10-15 | Latrobe University | Inhibiteurs de la topoisomerase |
-
2000
- 2000-10-26 WO PCT/US2000/029583 patent/WO2001032631A2/fr not_active Ceased
- 2000-10-26 AU AU12364/01A patent/AU1236401A/en not_active Abandoned
- 2000-10-26 JP JP2001534782A patent/JP2003513079A/ja not_active Withdrawn
- 2000-10-26 CA CA002389312A patent/CA2389312A1/fr not_active Abandoned
- 2000-10-26 EP EP00973917A patent/EP1228045A2/fr not_active Withdrawn
- 2000-10-27 AR ARP000105664A patent/AR026267A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AR026267A1 (es) | 2003-02-05 |
| JP2003513079A (ja) | 2003-04-08 |
| EP1228045A2 (fr) | 2002-08-07 |
| WO2001032631A3 (fr) | 2002-02-21 |
| WO2001032631A2 (fr) | 2001-05-10 |
| AU1236401A (en) | 2001-05-14 |
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