IL101380A - Bis-naphthalimides and pharmaceutical compositions containing them - Google Patents

Bis-naphthalimides and pharmaceutical compositions containing them

Info

Publication number: IL101380A
Authority: IL; Israel
Prior art keywords: nitro; bis; benz; isoquinoline; dione
Prior art date: 1991-03-27

Application number

IL10138092A

Other languages

English (en)

Hebrew (he)

Other versions

IL101380A0 (en

Original Assignee

Du Pont Merck Pharma

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.)

1991-03-27

Filing date

1992-03-26

Publication date

1996-10-31

1992-03-26 Application filed by Du Pont Merck Pharma filed Critical Du Pont Merck Pharma

1992-11-15 Publication of IL101380A0 publication Critical patent/IL101380A0/xx

1996-10-31 Publication of IL101380A publication Critical patent/IL101380A/en

Links

239000000825 pharmaceutical preparation Substances 0.000 title 1
238000002360 preparation method Methods 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 57
239000000203 mixture Substances 0.000 claims description 45
-1 1-methyl-2, 1-ethanediyl Chemical group 0.000 claims description 19
125000001841 imino group Chemical group [H]N=* 0.000 claims description 18
150000003839 salts Chemical class 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 6
PXBZKHOQHTVCSQ-UHFFFAOYSA-N 5-nitro-2-[1-[2-[2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propylamino]ethylamino]propan-2-yl]benzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(C(CNCCNCC(C)N2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 PXBZKHOQHTVCSQ-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
ATCLJHDWROMCIV-QZTJIDSGSA-N 5-nitro-2-[(2r)-2-[2-[[(2r)-1-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propan-2-yl]amino]ethylamino]propyl]benzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(C[C@@H](C)NCCN[C@@H](CN2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 ATCLJHDWROMCIV-QZTJIDSGSA-N 0.000 claims 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 58
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
125000003118 aryl group Chemical group 0.000 description 42
206010028980 Neoplasm Diseases 0.000 description 36
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 22
239000007787 solid Substances 0.000 description 22
239000002904 solvent Substances 0.000 description 20
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000004480 active ingredient Substances 0.000 description 18
239000000243 solution Substances 0.000 description 16
238000005160 1H NMR spectroscopy Methods 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
230000000694 effects Effects 0.000 description 13
239000007788 liquid Substances 0.000 description 13
238000012360 testing method Methods 0.000 description 13
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
238000001914 filtration Methods 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
229910001868 water Inorganic materials 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 10
239000012458 free base Substances 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
208000026310 Breast neoplasm Diseases 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
238000010992 reflux Methods 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
241000699670 Mus sp. Species 0.000 description 8
201000011510 cancer Diseases 0.000 description 8
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 7
238000001816 cooling Methods 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
206010006187 Breast cancer Diseases 0.000 description 6
GRSMWKLPSNHDHA-UHFFFAOYSA-N Naphthalic anhydride Chemical compound C1=CC(C(=O)OC2=O)=C3C2=CC=CC3=C1 GRSMWKLPSNHDHA-UHFFFAOYSA-N 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 6
150000008064 anhydrides Chemical class 0.000 description 6
238000004440 column chromatography Methods 0.000 description 6
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
238000000034 method Methods 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
239000000047 product Substances 0.000 description 6
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
239000000725 suspension Substances 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
238000000023 Kugelrohr distillation Methods 0.000 description 5
241001529936 Murinae Species 0.000 description 5
241000699660 Mus musculus Species 0.000 description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
XJHABGPPCLHLLV-UHFFFAOYSA-N benzo[de]isoquinoline-1,3-dione Chemical group C1=CC(C(=O)NC2=O)=C3C2=CC=CC3=C1 XJHABGPPCLHLLV-UHFFFAOYSA-N 0.000 description 5
239000002775 capsule Substances 0.000 description 5
208000029742 colonic neoplasm Diseases 0.000 description 5
239000003814 drug Substances 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
BYVCTYDTPSKPRM-UHFFFAOYSA-N naphthalene-1-carbonyl naphthalene-1-carboxylate Chemical compound C1=CC=C2C(C(OC(=O)C=3C4=CC=CC=C4C=CC=3)=O)=CC=CC2=C1 BYVCTYDTPSKPRM-UHFFFAOYSA-N 0.000 description 5
239000011734 sodium Substances 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000003826 tablet Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
238000002835 absorbance Methods 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
208000037841 lung tumor Diseases 0.000 description 4
239000002609 medium Substances 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
238000011830 transgenic mouse model Methods 0.000 description 4
230000004614 tumor growth Effects 0.000 description 4
239000003981 vehicle Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
QGNQEODJYRGEJX-UHFFFAOYSA-N 4h-isoquinoline-1,3-dione Chemical compound C1=CC=C2C(=O)NC(=O)CC2=C1 QGNQEODJYRGEJX-UHFFFAOYSA-N 0.000 description 3
QNAYBMKLOCPYGJ-UHFFFAOYSA-N D-alpha-Ala Natural products CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-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
229960003767 alanine Drugs 0.000 description 3
230000000259 anti-tumor effect Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
210000001072 colon Anatomy 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000013415 human tumor xenograft model Methods 0.000 description 3
239000008101 lactose Substances 0.000 description 3
125000005647 linker group Chemical group 0.000 description 3
239000008297 liquid dosage form Substances 0.000 description 3
208000020816 lung neoplasm Diseases 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
RBZHDBMXRKHHMV-UHFFFAOYSA-N propane-1,2-diamine;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.CC(N)CN RBZHDBMXRKHHMV-UHFFFAOYSA-N 0.000 description 3
AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 3
108700042226 ras Genes Proteins 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
IVOYGHSAULJATN-UHFFFAOYSA-N CS(O)(=O)=O.[O-][N+](=O)c1cc2C(=O)NC(=O)c3cccc(c1)c23 Chemical compound CS(O)(=O)=O.[O-][N+](=O)c1cc2C(=O)NC(=O)c3cccc(c1)c23 IVOYGHSAULJATN-UHFFFAOYSA-N 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
206010058467 Lung neoplasm malignant Diseases 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
239000012980 RPMI-1640 medium Substances 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000001093 anti-cancer Effects 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
229910000085 borane Inorganic materials 0.000 description 2
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
210000000481 breast Anatomy 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
239000000969 carrier Substances 0.000 description 2
OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
239000007891 compressed tablet Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
230000012010 growth Effects 0.000 description 2
230000009036 growth inhibition Effects 0.000 description 2
BTJRKNUKPQBLAL-UHFFFAOYSA-N hydron;4-methylmorpholine;chloride Chemical compound Cl.CN1CCOCC1 BTJRKNUKPQBLAL-UHFFFAOYSA-N 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000002347 injection Methods 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
201000005296 lung carcinoma Diseases 0.000 description 2
239000000463 material Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
IYUKFAFDFHZKPI-DFWYDOINSA-N methyl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](C)N IYUKFAFDFHZKPI-DFWYDOINSA-N 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000011707 mineral Substances 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000003182 parenteral nutrition solution Substances 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
102000004196 processed proteins & peptides Human genes 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000003381 stabilizer Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
239000012730 sustained-release form Substances 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
238000005303 weighing Methods 0.000 description 2
XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
UNGHXBFOHKKVKV-WWHJSGOESA-N (2S)-2-N-[(2S)-2-[[(2S)-2-aminopropyl]amino]propyl]propane-1,2-diamine tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.NC[C@H](C)NC[C@H](C)NC[C@H](C)N UNGHXBFOHKKVKV-WWHJSGOESA-N 0.000 description 1
ZQARFKGNOGUQDW-CIUDSAMLSA-N (2s)-2-n-[(2s)-2-[[(2s)-2-aminopropyl]amino]propyl]propane-1,2-diamine Chemical compound C[C@H](N)CN[C@@H](C)CN[C@@H](C)CN ZQARFKGNOGUQDW-CIUDSAMLSA-N 0.000 description 1
125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 description 1
PDCDOUBVZNSPJG-FKLPMGAJSA-N 2-[(2s)-2-[2-[[(2s)-1-(1,3-dioxobenzo[de]isoquinolin-2-yl)propan-2-yl]amino]ethylamino]propyl]benzo[de]isoquinoline-1,3-dione;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=CC(C(N(C[C@H](C)NCCN[C@H](CN2C(C=3C=CC=C4C=CC=C(C=34)C2=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 PDCDOUBVZNSPJG-FKLPMGAJSA-N 0.000 description 1
XFKYKTBPRBZDFG-UHFFFAOYSA-N 2-aminoacetonitrile;hydrochloride Chemical compound Cl.NCC#N XFKYKTBPRBZDFG-UHFFFAOYSA-N 0.000 description 1
JBECEVVDUANREC-UHFFFAOYSA-N 2-aminopropanamide;dihydrochloride Chemical compound Cl.Cl.CC(N)C(N)=O JBECEVVDUANREC-UHFFFAOYSA-N 0.000 description 1
PXBZKHOQHTVCSQ-ROUUACIJSA-N 5-nitro-2-[(2s)-1-[2-[[(2s)-2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propyl]amino]ethylamino]propan-2-yl]benzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N([C@H](CNCCNC[C@H](C)N2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 PXBZKHOQHTVCSQ-ROUUACIJSA-N 0.000 description 1
ATCLJHDWROMCIV-ROUUACIJSA-N 5-nitro-2-[(2s)-2-[2-[[(2s)-1-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propan-2-yl]amino]ethylamino]propyl]benzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(C[C@H](C)NCCN[C@H](CN2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 ATCLJHDWROMCIV-ROUUACIJSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
238000011725 BALB/c mouse Methods 0.000 description 1
101150041968 CDC13 gene Proteins 0.000 description 1
201000009030 Carcinoma Diseases 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
QNAYBMKLOCPYGJ-UWTATZPHSA-N D-alanine Chemical compound C[C@@H](N)C(O)=O QNAYBMKLOCPYGJ-UWTATZPHSA-N 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
208000007093 Leukemia L1210 Diseases 0.000 description 1
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
241000713333 Mouse mammary tumor virus Species 0.000 description 1
239000007868 Raney catalyst Substances 0.000 description 1
NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
229910000564 Raney nickel Inorganic materials 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
238000005903 acid hydrolysis reaction Methods 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
125000002947 alkylene group Chemical group 0.000 description 1
230000003064 anti-oxidating effect Effects 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
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238000011717 athymic nude mouse Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
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239000012267 brine Substances 0.000 description 1
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239000003054 catalyst Substances 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
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229960004926 chlorobutanol Drugs 0.000 description 1
238000000576 coating method Methods 0.000 description 1
229940075614 colloidal silicon dioxide Drugs 0.000 description 1
201000010897 colon adenocarcinoma Diseases 0.000 description 1
238000004040 coloring Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000004590 computer program Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 1
229910003460 diamond Inorganic materials 0.000 description 1
239000010432 diamond Substances 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
150000002334 glycols Chemical class 0.000 description 1
239000001963 growth medium Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 1
239000010410 layer Substances 0.000 description 1
210000004072 lung Anatomy 0.000 description 1
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239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
JZLALHHQECURLW-APTPAJQOSA-N methanesulfonic acid;5-nitro-2-[(2s)-1-[2-[[(2s)-2-(5-nitro-1,3-dioxobenzo[de]isoquinolin-2-yl)propyl]amino]ethylamino]propan-2-yl]benzo[de]isoquinoline-1,3-dione Chemical compound CS(O)(=O)=O.[O-][N+](=O)C1=CC(C(N([C@H](CNCCNC[C@H](C)N2C(C=3C=C(C=C4C=CC=C(C=34)C2=O)[N+]([O-])=O)=O)C)C2=O)=O)=C3C2=CC=CC3=C1 JZLALHHQECURLW-APTPAJQOSA-N 0.000 description 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
230000003278 mimic effect Effects 0.000 description 1
238000002156 mixing Methods 0.000 description 1
VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
238000011580 nude mouse model Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
235000019629 palatability Nutrition 0.000 description 1
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
238000000746 purification Methods 0.000 description 1
BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
238000011160 research Methods 0.000 description 1
238000012552 review Methods 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
239000004299 sodium benzoate Substances 0.000 description 1
235000010234 sodium benzoate Nutrition 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
208000024891 symptom Diseases 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
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000009261 transgenic effect Effects 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
238000013414 tumor xenograft model Methods 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- C07D221/06—Ring systems of three rings
- C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
- C07C209/44—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers
- C07C209/50—Preparation of compounds containing amino groups bound to a carbon skeleton by reduction of carboxylic acids or esters thereof in presence of ammonia or amines, or by reduction of nitriles, carboxylic acid amides, imines or imino-ethers by reduction of carboxylic acid amides

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

IL10138092A 1991-03-27 1992-03-26 Bis-naphthalimides and pharmaceutical compositions containing them IL101380A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US67606191A	1991-03-27	1991-03-27
US07/805,044 US5206249A (en)	1991-03-27	1991-12-11	Bis-naphthalimides containing amino-acid derived linkers as anticancer agents

Publications (2)

Publication Number	Publication Date
IL101380A0 IL101380A0 (en)	1992-11-15
IL101380A true IL101380A (en)	1996-10-31

Family

ID=27101469

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL10138092A IL101380A (en)	1991-03-27	1992-03-26	Bis-naphthalimides and pharmaceutical compositions containing them

Country Status (17)

Country	Link
US (1)	US5206249A (no)
EP (2)	EP0577753A1 (no)
JP (1)	JPH06506229A (no)
CZ (1)	CZ281868B6 (no)
FI (1)	FI934225L (no)
HU (1)	HUT68969A (no)
IE (1)	IE920958A1 (no)
IL (1)	IL101380A (no)
MA (1)	MA22476A1 (no)
MX (1)	MX9201355A (no)
MY (1)	MY108433A (no)
NO (1)	NO180584C (no)
NZ (1)	NZ242126A (no)
SK (1)	SK107193A3 (no)
TW (1)	TW205547B (no)
WO (1)	WO1992017453A1 (no)
YU (1)	YU30092A (no)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5461176A (en) *	1991-03-27	1995-10-24	The Du Pont Merck Pharmaceutical Company	Processes for preparing bis-naphthalimides containing amino-acid derived linkers
US5329048A (en) *	1991-03-27	1994-07-12	The Dupont Merck Pharmaceutical Company	Process of preparing tetraamino intermediates
AU3241593A (en) *	1991-12-11	1993-07-19	Du Pont Merck Pharmaceutical Company, The	Highly water soluble bis-naphthalimides useful as anticancer agents
US5235045A (en) *	1992-03-19	1993-08-10	Microbiomed Corporation	Non-azo naphthalimide dyes
US5376664A (en) *	1992-07-27	1994-12-27	The Du Pont Merck Pharmaceutical Company	Unsymmetrical mono-3-nitro bis-naphthalimides as anticancer agents
US5364867A (en) *	1992-11-30	1994-11-15	Sterling Winthrop Inc.	4-phenylpiperdine agents for treating cns disorders
US5359070A (en) *	1993-02-11	1994-10-25	The Du Pont Merck Pharmaceutical Company	Unsymmetrical bis-imides as anticancer agents
US5416089A (en) *	1993-06-24	1995-05-16	The Du Pont Merck Pharmaceutical Company	Polycyclic and heterocyclic chromophores for bis-imide tumoricidals
US5766600A (en) *	1993-08-09	1998-06-16	Microbiomed Corporation	Non-azo naphtalimide dyes and uses for same
IL110460A (en) *	1993-08-18	2001-01-11	Basf Ag	Bis-naphthalimides, their preparation and pharmaceutical compositions containing them
US6204243B1 (en)	1993-09-01	2001-03-20	Novatis Ag	Pharmaceutical preparations for the targeted treatment of crohn's disease and ulcerative colitis
WO1995008539A1 (en) *	1993-09-24	1995-03-30	The Du Pont Merck Pharmaceutical Company	Improved methods for preparing bis-imide compounds
US5604095A (en) *	1994-07-22	1997-02-18	Cancer Therapy & Research Center	Unsymmetrically linked bisnaphthalimides as antitumor agents
US5561042A (en) *	1994-07-22	1996-10-01	Cancer Therapy And Research Center	Diamine platinum naphthalimide complexes as antitumor agents
US5641782A (en) *	1995-02-16	1997-06-24	The Dupont Merck Pharmaceutical Company	3-aromatic and 3-heteroaromatic substituted bisnaphthalimides
FR2751655B1 (fr) *	1996-07-26	1998-08-28	Adir	Nouveaux derives de bis-imides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
GB9723407D0 (en)	1997-11-05	1998-01-07	Ciba Geigy Ag	Organic compounds
ATE320417T1 (de)	1998-07-03	2006-04-15	Taiho Pharmaceutical Co Ltd	Naphthimidobenzamid-derivate
EP1159273A1 (en)	1999-03-02	2001-12-05	Boehringer Ingelheim Pharmaceuticals Inc.	Compounds useful as reversible inhibitors of cathepsin s
AU3883600A (en)	1999-03-16	2000-10-04	Regents Of The University Of California, The	Glycosylated polyamines
US6420364B1 (en)	1999-09-13	2002-07-16	Boehringer Ingelheim Pharmaceuticals, Inc.	Compound useful as reversible inhibitors of cysteine proteases
GB0003111D0 (en)	2000-02-10	2000-03-29	Novartis Ag	Organic compounds
JP2005533088A (ja) *	2002-07-08	2005-11-04	ケムジェネックス・ファーマシューティカルズ・リミテッド	アモナフィドを含むナフタルイミドの製造およびその医薬製剤
US20050192312A1 (en) *	2004-01-30	2005-09-01	Brown Dennis M.	Naphthalimide dosing by N-acetyl transferase genotyping
WO2005117893A2 (en) *	2004-06-04	2005-12-15	Chemgenex Pharmaceuticals, Inc.	Methods of treating cellular proliferative disease using naphthalimide and parp-1 inhibitors
US7947839B2 (en) *	2004-12-01	2011-05-24	Genentech, Inc.	Heterocyclic-substituted bis-1,8 naphthalimide compounds, antibody drug conjugates, and methods of use
WO2009089537A2 (en)	2008-01-11	2009-07-16	Northwestern University	Anti-cancer compounds
WO2011044472A1 (en) *	2009-10-08	2011-04-14	Angus Chemical Company	Low-voc polyamines
CN109490291B (zh) *	2018-11-20	2021-05-11	上海应用技术大学	基于吸电子基取代的1,8-萘酰亚胺类化合物作为氟离子的显色试剂的用途
WO2020139971A2 (en) *	2018-12-27	2020-07-02	Alucent Biomedical, Inc.	Methods for making dimeric naphthalimides and solid state forms of the same

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4146720A (en) *	1976-10-27	1979-03-27	Laboratorios Made, S.A.	N-aminoethyl-substituted-3-nitronaphthalimides
EP0125439B1 (en) *	1983-04-01	1990-01-24	Warner-Lambert Company	3,6-disubstituted-1,8-naphthalimides and methods for their production and use
US4665071A (en) *	1984-02-21	1987-05-12	Warner-Lambert Company	3,6-disubstituted-1,8-naphthalimides and methods for their production and use
DE3535496A1 (de) *	1985-10-04	1987-04-16	Bayer Ag	Verfahren zur fluoreszenzloeschung und neue kationische naphthalin-peri-dicarbonsaeureimid-derivate
DE3707651A1 (de) *	1987-03-10	1988-09-22	Knoll Ag	Bis-naphthalimide, ihre herstellung und verwendung
US5086059A (en) *	1990-06-07	1992-02-04	Du Pont Merck Pharmaceutical Company	Bis-naphthalimides as anticancer agents

1991
- 1991-12-11 US US07/805,044 patent/US5206249A/en not_active Expired - Fee Related
1992
- 1992-03-25 WO PCT/US1992/002134 patent/WO1992017453A1/en not_active Application Discontinuation
- 1992-03-25 CZ CS932060A patent/CZ281868B6/cs unknown
- 1992-03-25 TW TW081102277A patent/TW205547B/zh active
- 1992-03-25 EP EP92910566A patent/EP0577753A1/en not_active Withdrawn
- 1992-03-25 JP JP4509685A patent/JPH06506229A/ja active Pending
- 1992-03-25 HU HU9302719A patent/HUT68969A/hu unknown
- 1992-03-25 EP EP92105120A patent/EP0506008A1/en active Pending
- 1992-03-25 MA MA22765A patent/MA22476A1/fr unknown
- 1992-03-25 NZ NZ242126A patent/NZ242126A/en unknown
- 1992-03-25 MY MYPI92000501A patent/MY108433A/en unknown
- 1992-03-25 SK SK1071-93A patent/SK107193A3/sk unknown
- 1992-03-26 IL IL10138092A patent/IL101380A/en not_active IP Right Cessation
- 1992-03-26 YU YU30092A patent/YU30092A/sh unknown
- 1992-03-26 MX MX9201355A patent/MX9201355A/es unknown
- 1992-03-26 IE IE095892A patent/IE920958A1/en not_active Application Discontinuation
1993
- 1993-09-27 NO NO933455A patent/NO180584C/no unknown
- 1993-09-27 FI FI934225A patent/FI934225L/fi unknown

Also Published As

Publication number	Publication date
MX9201355A (es)	1992-10-01
US5206249A (en)	1993-04-27
FI934225A0 (fi)	1993-09-27
NO180584C (no)	1997-05-14
AU666847B2 (en)	1996-02-29
IE920958A1 (en)	1992-10-07
MA22476A1 (fr)	1992-10-01
CZ281868B6 (cs)	1997-03-12
YU30092A (sr)	1996-01-09
SK107193A3 (en)	1994-08-10
TW205547B (no)	1993-05-11
EP0506008A1 (en)	1992-09-30
WO1992017453A1 (en)	1992-10-15
FI934225L (fi)	1993-10-15
CZ206093A3 (en)	1994-03-16
NO933455L (no)	1993-11-26
MY108433A (en)	1996-09-30
JPH06506229A (ja)	1994-07-14
IL101380A0 (en)	1992-11-15
NO180584B (no)	1997-02-03
EP0577753A1 (en)	1994-01-12
AU1767692A (en)	1992-11-02
HU9302719D0 (en)	1993-12-28
NZ242126A (en)	1996-09-25
HUT68969A (en)	1995-08-28
NO933455D0 (no)	1993-09-27

Publication	Publication Date	Title
US5206249A (en)	1993-04-27	Bis-naphthalimides containing amino-acid derived linkers as anticancer agents
US5376664A (en)	1994-12-27	Unsymmetrical mono-3-nitro bis-naphthalimides as anticancer agents
AU640888B2 (en)	1993-09-02	Bis-naphthalimides as anticancer agents
US5461176A (en)	1995-10-24	Processes for preparing bis-naphthalimides containing amino-acid derived linkers
IL110460A (en)	2001-01-11	Bis-naphthalimides, their preparation and pharmaceutical compositions containing them
US5488110A (en)	1996-01-30	Highly water soluble bis-naphthalimides useful as anticancer agents
US5329048A (en)	1994-07-12	Process of preparing tetraamino intermediates
US5206250A (en)	1993-04-27	Bis-naphthalimides containing amide and thioamide linkers as anticancer agents
AU666847C (en)	1996-12-12	Bis-naphthalimides containing amino-acid derived linkers as anticancer agents
US5641782A (en)	1997-06-24	3-aromatic and 3-heteroaromatic substituted bisnaphthalimides
CA2106999A1 (en)	1992-09-28	Bis-naphthalimides containing amino-acid derived linkers as anticancer agents
LV10045B (en)	1995-08-20	Bis-naphthalimides with a bond derived from amino acids, their use as anti-cancer agents
RU2066316C1 (ru)	1996-09-10	Производные бис-нафталимидов, их энантиомерные или диастереомерные формы, или их смеси, или их фармацевтически приемлемые соли, противоопухолевая композиция и способ лечения
JPH09512539A (ja)	1997-12-16	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
US5359070A (en)	1994-10-25	Unsymmetrical bis-imides as anticancer agents
HU210345A9 (hu)	1995-03-28	Aminosav eredetű linkereket tartalmazó bisz-naftálimid rákellenes szerek

Legal Events

Date	Code	Title
1997-03-18	FF	Patent granted
1997-07-13	KB	Patent renewed
1999-03-12	RH	Patent void