DE60313156T2 - Amonafidsalze - Google Patents
Amonafidsalze Download PDFInfo
- Publication number
- DE60313156T2 DE60313156T2 DE60313156T DE60313156T DE60313156T2 DE 60313156 T2 DE60313156 T2 DE 60313156T2 DE 60313156 T DE60313156 T DE 60313156T DE 60313156 T DE60313156 T DE 60313156T DE 60313156 T2 DE60313156 T2 DE 60313156T2
- Authority
- DE
- Germany
- Prior art keywords
- acid
- aliphatic
- compound
- amonafide
- salt
- 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.)
- Expired - Lifetime
Links
- -1 carboxylate anion Chemical class 0.000 claims abstract description 57
- 150000001875 compounds Chemical class 0.000 claims abstract description 57
- 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 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 49
- 229960004701 amonafide Drugs 0.000 claims abstract description 46
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 12
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 5
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 239000002253 acid Substances 0.000 claims description 47
- 125000001931 aliphatic group Chemical group 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 37
- 229910001868 water Inorganic materials 0.000 claims description 33
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 30
- XXVLKDRPHSFIIB-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-5-nitrobenzo[de]isoquinoline-1,3-dione Chemical compound [O-][N+](=O)C1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 XXVLKDRPHSFIIB-UHFFFAOYSA-N 0.000 claims description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 25
- 229940049920 malate Drugs 0.000 claims description 21
- 229950001745 mitonafide Drugs 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 17
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 16
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 15
- 238000005984 hydrogenation reaction Methods 0.000 claims description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 14
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 14
- KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 claims description 13
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 13
- YYPNJNDODFVZLE-UHFFFAOYSA-N 3-methylbut-2-enoic acid Chemical compound CC(C)=CC(O)=O YYPNJNDODFVZLE-UHFFFAOYSA-N 0.000 claims description 11
- CQJHAULYLJXJNL-UHFFFAOYSA-N 4-methylpent-3-enoic acid Chemical compound CC(C)=CCC(O)=O CQJHAULYLJXJNL-UHFFFAOYSA-N 0.000 claims description 11
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 11
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 11
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 claims description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 10
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 239000002243 precursor Substances 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims description 8
- 235000011054 acetic acid Nutrition 0.000 claims description 8
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 8
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 7
- 239000001630 malic acid Substances 0.000 claims description 7
- 235000011090 malic acid Nutrition 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 claims description 6
- YIYBQIKDCADOSF-UHFFFAOYSA-N alpha-Butylen-alpha-carbonsaeure Natural products CCC=CC(O)=O YIYBQIKDCADOSF-UHFFFAOYSA-N 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 6
- 239000001384 succinic acid Substances 0.000 claims description 6
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 5
- 239000001361 adipic acid Substances 0.000 claims description 5
- HWXBTNAVRSUOJR-UHFFFAOYSA-N alpha-hydroxyglutaric acid Natural products OC(=O)C(O)CCC(O)=O HWXBTNAVRSUOJR-UHFFFAOYSA-N 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 5
- 239000001530 fumaric acid Substances 0.000 claims description 5
- 239000004310 lactic acid Substances 0.000 claims description 5
- 235000014655 lactic acid Nutrition 0.000 claims description 5
- 239000011976 maleic acid Substances 0.000 claims description 5
- 150000004701 malic acid derivatives Chemical class 0.000 claims description 5
- 229960002510 mandelic acid Drugs 0.000 claims description 5
- 235000019260 propionic acid Nutrition 0.000 claims description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 5
- 239000011975 tartaric acid Substances 0.000 claims description 5
- YIYBQIKDCADOSF-ONEGZZNKSA-N trans-pent-2-enoic acid Chemical compound CC\C=C\C(O)=O YIYBQIKDCADOSF-ONEGZZNKSA-N 0.000 claims description 5
- UIUWNILCHFBLEQ-NSCUHMNNSA-N trans-pent-3-enoic acid Chemical compound C\C=C\CC(O)=O UIUWNILCHFBLEQ-NSCUHMNNSA-N 0.000 claims description 5
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims description 4
- 239000000174 gluconic acid Substances 0.000 claims description 4
- 235000012208 gluconic acid Nutrition 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 claims description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 3
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims description 3
- 235000011037 adipic acid Nutrition 0.000 claims description 3
- 229940009533 alpha-ketoglutaric acid Drugs 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 3
- 235000015165 citric acid Nutrition 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 229940076788 pyruvate Drugs 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
- 229940107700 pyruvic acid Drugs 0.000 claims description 2
- 229960001860 salicylate Drugs 0.000 claims description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 claims 4
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 claims 2
- OZDAOHVKBFBBMZ-UHFFFAOYSA-N 2-aminopentanedioic acid;hydrate Chemical compound O.OC(=O)C(N)CCC(O)=O OZDAOHVKBFBBMZ-UHFFFAOYSA-N 0.000 claims 2
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 claims 2
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 claims 2
- CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims 2
- 229960005261 aspartic acid Drugs 0.000 claims 2
- 235000011087 fumaric acid Nutrition 0.000 claims 2
- 229960002989 glutamic acid Drugs 0.000 claims 2
- UJVRLOMJDXYDHD-UHFFFAOYSA-N 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.NC1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 UJVRLOMJDXYDHD-UHFFFAOYSA-N 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 150000003839 salts Chemical class 0.000 abstract description 58
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
- 230000015572 biosynthetic process Effects 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- 229940079593 drug Drugs 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 150000007524 organic acids Chemical class 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 238000003786 synthesis reaction Methods 0.000 description 15
- 235000005985 organic acids Nutrition 0.000 description 13
- 150000007513 acids Chemical class 0.000 description 12
- 239000012458 free base Substances 0.000 description 12
- 150000001735 carboxylic acids Chemical class 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 229910052500 inorganic mineral Inorganic materials 0.000 description 10
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 238000009835 boiling Methods 0.000 description 9
- 239000011707 mineral Substances 0.000 description 9
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 8
- JNZBHHQBPHSOMU-WNQIDUERSA-N 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione;(2s)-2-hydroxybutanedioic acid Chemical class OC(=O)[C@@H](O)CC(O)=O.NC1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 JNZBHHQBPHSOMU-WNQIDUERSA-N 0.000 description 8
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 239000012043 crude product Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000012010 growth Effects 0.000 description 7
- 239000012510 hollow fiber Substances 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 230000009467 reduction Effects 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 238000007912 intraperitoneal administration Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000000835 fiber Substances 0.000 description 5
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 241001212017 Brana Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000009036 growth inhibition Effects 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000000376 reactant Substances 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 241000894007 species Species 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 229910052717 sulfur Inorganic materials 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 150000003628 tricarboxylic acids Chemical class 0.000 description 4
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 150000001242 acetic acid derivatives Chemical class 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 3
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 239000007943 implant Substances 0.000 description 3
- 239000000138 intercalating agent Substances 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- IOOMXAQUNPWDLL-UHFFFAOYSA-N 2-[6-(diethylamino)-3-(diethyliminiumyl)-3h-xanthen-9-yl]-5-sulfobenzene-1-sulfonate Chemical compound C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=C(S(O)(=O)=O)C=C1S([O-])(=O)=O IOOMXAQUNPWDLL-UHFFFAOYSA-N 0.000 description 2
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- C—CHEMISTRY; METALLURGY
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Lubricants (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US128129 | 2002-04-22 | ||
| US10/128,129 US6693198B2 (en) | 2002-04-22 | 2002-04-22 | Amonafide salts |
| PCT/US2003/012619 WO2003089415A1 (en) | 2002-04-22 | 2003-04-22 | Amonafide salts |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60313156D1 DE60313156D1 (de) | 2007-05-24 |
| DE60313156T2 true DE60313156T2 (de) | 2007-12-13 |
Family
ID=29248438
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60313156T Expired - Lifetime DE60313156T2 (de) | 2002-04-22 | 2003-04-22 | Amonafidsalze |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6693198B2 (https=) |
| EP (1) | EP1499595B1 (https=) |
| JP (2) | JP4630518B2 (https=) |
| AT (1) | ATE359273T1 (https=) |
| AU (1) | AU2003221771B2 (https=) |
| CA (1) | CA2482445A1 (https=) |
| DE (1) | DE60313156T2 (https=) |
| ES (1) | ES2287463T3 (https=) |
| WO (1) | WO2003089415A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050239816A1 (en) * | 2002-04-22 | 2005-10-27 | Xanthus Life Sciences, Inc. | Amonafide salts |
| US6693198B2 (en) | 2002-04-22 | 2004-02-17 | Xanthus Life Sciences, Inc. | Amonafide salts |
| WO2004004716A1 (en) * | 2002-07-08 | 2004-01-15 | Chemgenex Pharmaceuticals Limited | Naphthalimide synthesis including amonafide synthesis and pharmaceutical preparations thereof |
| AU2005209845A1 (en) * | 2004-01-30 | 2005-08-18 | Chemgenex Pharmaceuticals, Inc. | Naphthalimide dosing by N-acetyl transferase genotyping |
| BRPI0510719A (pt) * | 2004-05-05 | 2007-11-20 | Unibioscreen Sa | derivados de naftalimida, composição farmacêutica, uso e método de preparação dos mesmos |
| WO2005117893A2 (en) * | 2004-06-04 | 2005-12-15 | Chemgenex Pharmaceuticals, Inc. | Methods of treating cellular proliferative disease using naphthalimide and parp-1 inhibitors |
| FR2898902B1 (fr) * | 2006-03-24 | 2010-09-10 | Oreal | Colorants particuliers de type naphtalimide, composition tinctoriale comprenant au moins un tel colorant, procede de mise en oeuvre et utilisations |
| ES2338193B8 (es) * | 2008-02-25 | 2011-07-19 | Centro Atlantico Del Medicamento, S.A. | Nuevas sales de amonafide. |
| NZ779754A (en) | 2009-01-16 | 2023-04-28 | Exelixis Inc | Malate salt of n-(4-{ [6,7-bis(methyloxy)quinolin-4-yl] oxy} phenyl)-n’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer |
| CN102718709A (zh) * | 2011-03-30 | 2012-10-10 | 北京德众万全药物技术开发有限公司 | 一种制备氨萘非特的新方法 |
| 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 |
Family Cites Families (13)
| 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. |
| US4614820A (en) * | 1983-04-01 | 1986-09-30 | Warner-Lambert Co. | 3,6-disubstituted-1,8-naphthalimides |
| US4499266A (en) * | 1983-04-01 | 1985-02-12 | Warner-Lambert Company | 3,6-Dinitro-1,8-naphthalimides |
| US5183821A (en) | 1983-09-19 | 1993-02-02 | Laboratories Knoll, S.A. | Method for treating leukemias using N-(2-dimethylaminoethyl)-3-amino-1,8-naphthalimide for treating leukemias and solid tumors |
| US4665071A (en) | 1984-02-21 | 1987-05-12 | Warner-Lambert Company | 3,6-disubstituted-1,8-naphthalimides and methods for their production and use |
| DE3614414A1 (de) * | 1986-04-29 | 1987-11-05 | Knoll Ag | Neue benzo(de)isochinolin-1,3-dione, ihre herstellung und verwendung |
| DE3635711A1 (de) * | 1986-10-21 | 1988-04-28 | Knoll Ag | 5-nitrobenzo(de)isochinolin-1,3-dione, ihre herstellung und verwendung |
| DE3922771A1 (de) * | 1989-07-11 | 1991-01-24 | Knoll Ag | Amonafide-salze |
| US5420137A (en) | 1989-07-11 | 1995-05-30 | Knoll Ag | Amonafide salts |
| DE4106122A1 (de) * | 1991-02-27 | 1992-09-03 | Bayer Ag | Neue naphthalimide, diese enthaltende toner und die verwendung der neuen naphthalimide als additive fuer toner |
| CN1330638A (zh) * | 1998-11-25 | 2002-01-09 | 默克专利股份公司 | 取代的苯并[de]异哇啉－1,3－二酮 |
| EP1274458B1 (en) | 2000-04-12 | 2005-09-28 | ChemGenex Pharmaceuticals, Inc. | Compositions containing a naphthalmide and an antiproliferative agent |
| US6693198B2 (en) | 2002-04-22 | 2004-02-17 | Xanthus Life Sciences, Inc. | Amonafide salts |
-
2002
- 2002-04-22 US US10/128,129 patent/US6693198B2/en not_active Expired - Fee Related
- 2002-07-05 JP JP2002197809A patent/JP4630518B2/ja not_active Expired - Fee Related
-
2003
- 2003-04-22 CA CA002482445A patent/CA2482445A1/en not_active Abandoned
- 2003-04-22 EP EP03718511A patent/EP1499595B1/en not_active Expired - Lifetime
- 2003-04-22 AT AT03718511T patent/ATE359273T1/de not_active IP Right Cessation
- 2003-04-22 WO PCT/US2003/012619 patent/WO2003089415A1/en not_active Ceased
- 2003-04-22 AU AU2003221771A patent/AU2003221771B2/en not_active Ceased
- 2003-04-22 DE DE60313156T patent/DE60313156T2/de not_active Expired - Lifetime
- 2003-04-22 ES ES03718511T patent/ES2287463T3/es not_active Expired - Lifetime
- 2003-10-20 US US10/690,458 patent/US6989390B2/en not_active Expired - Fee Related
-
2009
- 2009-08-27 JP JP2009197462A patent/JP2010006831A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| EP1499595B1 (en) | 2007-04-11 |
| JP2003321452A (ja) | 2003-11-11 |
| AU2003221771A1 (en) | 2003-11-03 |
| JP2010006831A (ja) | 2010-01-14 |
| ES2287463T3 (es) | 2007-12-16 |
| WO2003089415A1 (en) | 2003-10-30 |
| JP4630518B2 (ja) | 2011-02-09 |
| CA2482445A1 (en) | 2003-10-30 |
| US6693198B2 (en) | 2004-02-17 |
| AU2003221771B2 (en) | 2007-02-15 |
| US20030203932A1 (en) | 2003-10-30 |
| US20040132763A1 (en) | 2004-07-08 |
| DE60313156D1 (de) | 2007-05-24 |
| US6989390B2 (en) | 2006-01-24 |
| ATE359273T1 (de) | 2007-05-15 |
| EP1499595A1 (en) | 2005-01-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8327 | Change in the person/name/address of the patent owner |
Owner name: XANTHUS PHARMACEUTICALS, INC., MONTREAL, QUEBE, CA |
|
| 8364 | No opposition during term of opposition |