CA2144049A1 - 1,2-dihydro-3h-dibenzisoquinoleine-1,3-diones, agents anticancer - Google Patents

1,2-dihydro-3h-dibenzisoquinoleine-1,3-diones, agents anticancer

Info

Publication number: CA2144049A1
Authority: CA; Canada
Prior art keywords: dihydro; dione; deh; dibenz; isoquinoline
Prior art date: 1992-09-11
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

Application number

CA002144049A

Other languages

English (en)

Inventor

David S. Alberts

Robert T. Dorr

William A. Remers

Salah M. Sami

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Research Corp Technologies Inc

Original Assignee

Individual

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.)

1992-09-11

Filing date

1993-09-13

Publication date

1994-03-31

1993-09-13 Application filed by Individual filed Critical Individual

1994-03-31 Publication of CA2144049A1 publication Critical patent/CA2144049A1/fr

Status Abandoned legal-status Critical Current

Links

239000002246 antineoplastic agent Substances 0.000 title description 8
AQLZHAWPCRYXLP-UHFFFAOYSA-N 4h-phenanthro[9,10-c]pyridine-1,3-dione Chemical compound C12=CC=CC=C2C2=CC=CC=C2C2=C1C(=O)NC(=O)C2 AQLZHAWPCRYXLP-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 205
239000001257 hydrogen Substances 0.000 claims abstract description 83
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 83
125000000217 alkyl group Chemical group 0.000 claims abstract description 71
206010028980 Neoplasm Diseases 0.000 claims abstract description 57
-1 hydroxy, mercapto Chemical group 0.000 claims abstract description 57
150000002431 hydrogen Chemical class 0.000 claims abstract description 53
125000003118 aryl group Chemical group 0.000 claims abstract description 36
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 28
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 26
125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 19
125000001589 carboacyl group Chemical group 0.000 claims abstract description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 18
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
239000000126 substance Chemical group 0.000 claims abstract description 15
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 9
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 6
229910052736 halogen Inorganic materials 0.000 claims abstract description 6
150000002367 halogens Chemical class 0.000 claims abstract description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 6
125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 5
125000005196 alkyl carbonyloxy group Chemical group 0.000 claims abstract description 5
125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims abstract description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 208
238000000034 method Methods 0.000 claims description 71
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
125000002947 alkylene group Chemical group 0.000 claims description 31
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
125000005843 halogen group Chemical group 0.000 claims description 21
230000000259 anti-tumor effect Effects 0.000 claims description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
125000005237 alkyleneamino group Chemical group 0.000 claims description 12
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 10
125000005236 alkanoylamino group Chemical group 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 5
241001465754 Metazoa Species 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000001309 chloro group Chemical group Cl* 0.000 claims description 4
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 4
239000005977 Ethylene Substances 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
229940124530 sulfonamide Drugs 0.000 claims description 3
125000004356 hydroxy functional group Chemical group O* 0.000 claims 7
BGFHMYJZJZLMHW-UHFFFAOYSA-N 4-[2-[[2-(1-benzothiophen-3-yl)-9-propan-2-ylpurin-6-yl]amino]ethyl]phenol Chemical compound N1=C(C=2C3=CC=CC=C3SC=2)N=C2N(C(C)C)C=NC2=C1NCCC1=CC=C(O)C=C1 BGFHMYJZJZLMHW-UHFFFAOYSA-N 0.000 claims 3
MAUMSNABMVEOGP-UHFFFAOYSA-N (methyl-$l^{2}-azanyl)methane Chemical group C[N]C MAUMSNABMVEOGP-UHFFFAOYSA-N 0.000 claims 2
GRHZLQBPAJAHDM-SPRQWYLLSA-N [(3as,4r,6ar)-2,3,3a,4,5,6a-hexahydrofuro[2,3-b]furan-4-yl] n-[(2s,4s,5s)-5-[[2-(2,6-dimethylphenoxy)acetyl]amino]-4-hydroxy-1,6-diphenylhexan-2-yl]carbamate Chemical compound CC1=CC=CC(C)=C1OCC(=O)N[C@H]([C@@H](O)C[C@H](CC=1C=CC=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)CC1=CC=CC=C1 GRHZLQBPAJAHDM-SPRQWYLLSA-N 0.000 claims 2
125000001475 halogen functional group Chemical group 0.000 claims 2
125000002346 iodo group Chemical group I* 0.000 claims 2
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 2
LEWNYOKWUAYXPI-UHFFFAOYSA-N 1-ethenylpiperidine Chemical group C=CN1CCCCC1 LEWNYOKWUAYXPI-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
125000003630 glycyl group Chemical group [H]N([H])C([H])([H])C(*)=O 0.000 claims 1
239000008194 pharmaceutical composition Substances 0.000 claims 1
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 196
239000000203 mixture Substances 0.000 description 151
239000002904 solvent Substances 0.000 description 111
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 94
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
239000000243 solution Substances 0.000 description 89
238000004458 analytical method Methods 0.000 description 80
238000005481 NMR spectroscopy Methods 0.000 description 76
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
230000008018 melting Effects 0.000 description 65
238000002844 melting Methods 0.000 description 65
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 63
239000000741 silica gel Substances 0.000 description 63
229910002027 silica gel Inorganic materials 0.000 description 63
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
239000007787 solid Substances 0.000 description 54
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 46
QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical class C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 description 45
210000004027 cell Anatomy 0.000 description 45
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 41
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 40
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
238000012746 preparative thin layer chromatography Methods 0.000 description 39
QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 36
WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 36
238000010992 reflux Methods 0.000 description 36
239000000725 suspension Substances 0.000 description 35
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 33
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 32
101150041968 CDC13 gene Proteins 0.000 description 30
XPNGNIFUDRPBFJ-UHFFFAOYSA-N (2-methylphenyl)methanol Chemical compound CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 description 28
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 26
229940079593 drug Drugs 0.000 description 25
239000003814 drug Substances 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 22
238000002425 crystallisation Methods 0.000 description 22
230000008025 crystallization Effects 0.000 description 22
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 21
239000000463 material Substances 0.000 description 21
238000003756 stirring Methods 0.000 description 21
DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 19
238000004440 column chromatography Methods 0.000 description 18
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 18
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 17
RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 17
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
230000000694 effects Effects 0.000 description 16
239000000706 filtrate Substances 0.000 description 16
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 16
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 16
210000004881 tumor cell Anatomy 0.000 description 16
UPALIKSFLSVKIS-UHFFFAOYSA-N 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione Chemical compound NC1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 UPALIKSFLSVKIS-UHFFFAOYSA-N 0.000 description 15
238000003556 assay Methods 0.000 description 15
150000001412 amines Chemical class 0.000 description 14
239000002244 precipitate Substances 0.000 description 14
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 13
229910003204 NH2 Inorganic materials 0.000 description 13
229960004701 amonafide Drugs 0.000 description 13
201000011510 cancer Diseases 0.000 description 13
239000000975 dye Substances 0.000 description 13
238000001704 evaporation Methods 0.000 description 13
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000013078 crystal Substances 0.000 description 12
230000008020 evaporation Effects 0.000 description 12
239000000284 extract Substances 0.000 description 12
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238000000338 in vitro Methods 0.000 description 12
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239000007858 starting material Substances 0.000 description 12
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238000004587 chromatography analysis Methods 0.000 description 11
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
150000008064 anhydrides Chemical class 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
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ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
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MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 9
KSQMWIGJIDTOFT-UHFFFAOYSA-N anthracene-1,9-dicarboxylic anhydride Chemical compound C1=CC(C(=O)OC2=O)=C3C2=C(C=CC=C2)C2=CC3=C1 KSQMWIGJIDTOFT-UHFFFAOYSA-N 0.000 description 9
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208000032839 leukemia Diseases 0.000 description 9
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102000004169 proteins and genes Human genes 0.000 description 8
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150000003839 salts Chemical class 0.000 description 8
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239000002253 acid Substances 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
231100000259 cardiotoxicity Toxicity 0.000 description 6
229940125904 compound 1 Drugs 0.000 description 6
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 6
238000010438 heat treatment Methods 0.000 description 6
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
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235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
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BRXFVYZDVQMTOX-UHFFFAOYSA-N n-anthracen-2-yl-2,2-dimethylpropanamide Chemical compound C1=CC=CC2=CC3=CC(NC(=O)C(C)(C)C)=CC=C3C=C21 BRXFVYZDVQMTOX-UHFFFAOYSA-N 0.000 description 1
MEQRPJCEQSUUTG-UHFFFAOYSA-N n-anthracen-9-ylacetamide Chemical compound C1=CC=C2C(NC(=O)C)=C(C=CC=C3)C3=CC2=C1 MEQRPJCEQSUUTG-UHFFFAOYSA-N 0.000 description 1
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230000003000 nontoxic effect Effects 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
230000000269 nucleophilic effect Effects 0.000 description 1
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239000001301 oxygen Substances 0.000 description 1
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230000002035 prolonged effect Effects 0.000 description 1
XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
238000002731 protein assay Methods 0.000 description 1
238000005086 pumping Methods 0.000 description 1
USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
HDOUGSFASVGDCS-UHFFFAOYSA-N pyridin-3-ylmethanamine Chemical compound NCC1=CC=CN=C1 HDOUGSFASVGDCS-UHFFFAOYSA-N 0.000 description 1
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000009467 reduction Effects 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
229920006395 saturated elastomer Polymers 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
230000035945 sensitivity Effects 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
YSKPDPSMMRKCND-UHFFFAOYSA-N sodium;2-(dimethylamino)ethanolate Chemical compound [Na+].CN(C)CC[O-] YSKPDPSMMRKCND-UHFFFAOYSA-N 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
230000007928 solubilization Effects 0.000 description 1
238000005063 solubilization Methods 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
238000002943 spectrophotometric absorbance Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003456 sulfonamides Chemical group 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000006228 supernatant 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
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
150000003536 tetrazoles Chemical class 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
229940033663 thimerosal Drugs 0.000 description 1
125000003396 thiol group Chemical class [H]S* 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
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
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
229960004528 vincristine Drugs 0.000 description 1
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
239000009637 wintergreen oil Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/18—Ring systems of four or more rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Other In-Based Heterocyclic Compounds (AREA)

CA002144049A 1992-09-11 1993-09-13 1,2-dihydro-3h-dibenzisoquinoleine-1,3-diones, agents anticancer Abandoned CA2144049A1 (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US94363492A	1992-09-11	1992-09-11
US943,634		1992-09-11

Publications (1)

Publication Number	Publication Date
CA2144049A1 true CA2144049A1 (fr)	1994-03-31

Family

ID=25479991

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002144049A Abandoned CA2144049A1 (fr)	1992-09-11	1993-09-13	1,2-dihydro-3h-dibenzisoquinoleine-1,3-diones, agents anticancer

Country Status (5)

Country	Link
EP (1)	EP0660824A1 (fr)
JP (1)	JP3543196B2 (fr)
AU (1)	AU5127893A (fr)
CA (1)	CA2144049A1 (fr)
WO (1)	WO1994006771A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH09512539A (ja) *	1994-04-28	1997-12-16	クノルアクチエンゲゼルシャフト	ジヒドロジベンゾ（ｄｅ，ｈ）イソキノリン誘導体および抗癌剤としての該誘導体の使用
US6291425B1 (en) *	1999-09-01	2001-09-18	Guilford Pharmaceuticals Inc.	Compounds, methods and pharmaceutical compositions for treating cellular damage, such as neural or cardiovascular tissue damage
US6376514B1 (en)	2000-10-17	2002-04-23	The Procter & Gamble Co.	Substituted six-membered heterocyclic compounds useful for treating multidrug resistance and compositions and methods thereof
US6693099B2 (en)	2000-10-17	2004-02-17	The Procter & Gamble Company	Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance
WO2009089537A2 (fr)	2008-01-11	2009-07-16	Northwestern University	Composés anticancéreux

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ES459497A1 (es) *	1977-06-04	1978-04-16	Made Labor Sa	Un metodo para la preparacion industrial de naftalimidas y sus derivados.
EP0125439B1 (fr) *	1983-04-01	1990-01-24	Warner-Lambert Company	1,8-Naphtalimides 3,6-disubstituées, leurs procédés de préparation et leur application
AU643539B2 (en) *	1990-06-26	1993-11-18	Research Corporation Technologies, Inc.	1,2-dihydro-3H-dibenzisoquinoline-1,3-dione anticancer agents

1993
- 1993-09-13 JP JP50823794A patent/JP3543196B2/ja not_active Expired - Fee Related
- 1993-09-13 CA CA002144049A patent/CA2144049A1/fr not_active Abandoned
- 1993-09-13 WO PCT/US1993/008640 patent/WO1994006771A1/fr not_active Ceased
- 1993-09-13 AU AU51278/93A patent/AU5127893A/en not_active Abandoned
- 1993-09-13 EP EP93922191A patent/EP0660824A1/fr not_active Withdrawn

Also Published As

Publication number	Publication date
WO1994006771A1 (fr)	1994-03-31
JP3543196B2 (ja)	2004-07-14
AU5127893A (en)	1994-04-12
JPH08501312A (ja)	1996-02-13
EP0660824A1 (fr)	1995-07-05

Publication	Publication Date	Title
US5635506A (en)	1997-06-03	1, 2-dihydro-3H-dibenzisoquinoline-1,3-dione anticancer agents
JP2875392B2 (ja)	1999-03-31	Ｇ−タンパク質機能の阻害および増殖性疾患の治療に有用な三環式スルホンアミド化合物
US6300338B1 (en)	2001-10-09	Tricyclic carbamate compounds useful for inhibition of g-protein function and for treatment of proliferative diseases
CN115232129B (zh)	2023-12-01	一种parp1选择性抑制剂及其制备方法和用途
DE69429438T2 (de)	2002-08-08	Tricyclische carbamat-derivate zur inhibierung der g-protein funktion und für die behandlung von proliferativen erkrankungen
JP2880576B2 (ja)	1999-04-12	Ｇ−タンパク質機能の阻害および増殖性疾患の治療に有用な三環式アミドおよび三環式尿素化合物
KR950004004B1 (ko)	1995-04-22	신규한 벤조피리도 피페리딘, 피페리딜리덴 및 피페라진 화합물, 조성물, 제조방법 및 이용방법
US6492381B1 (en)	2002-12-10	Tricyclic carbamate compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
JP2001513084A (ja)	2001-08-28	逆転写酵素の非ヌクレオシド阻害剤としての置換ベンズイミダゾール
US20030055065A1 (en)	2003-03-20	Tricyclic amide and urea compounds useful for inhibition of G-protein function and for treatment of proliferative diseases
EP0077983B1 (fr)	1987-04-29	Dérivés de triazine, leur procédé de préparation et les compositions pharmaceutiques les contenant
EP0536208B1 (fr)	1998-01-21	Agents anticancereux a base de 1,2-dihydro-3h-dibenzisoquinoline-1,3-diones
JPH01131175A (ja)	1989-05-24	イミダゾール誘導体
CA2144049A1 (fr)	1994-03-31	1,2-dihydro-3h-dibenzisoquinoleine-1,3-diones, agents anticancer
US3780035A (en)	1973-12-18	Phenothiazine and dibenzocycloheptane derivatives
WO1994006771A9 (fr)	1994-06-09	1,2 DYHYDRO-3-H-DIBENZ(de,h) ISOQUINOLINE 1,3-DIONES ET LEUR UTILISATION EN TANT QU'AGENTS ANTICANCEREUX
JPH0249727A (ja)	1990-02-20	抗潰瘍剤
HU214595B (hu)	1998-04-28	Eljárás 5,11-dihidro-6H-dipirido [3,2-b:2',3'-e][1,4] diazepinek és ezeket tartalmazó gyógyszerkészítmények előállítására

Legal Events

Date	Code	Title	Description
2000-08-16	EEER	Examination request
2008-03-31	FZDE	Discontinued
2023-05-26	FZDE	Discontinued	Effective date: 20080331