FI87572B - Foerfarande foer framstaellning av platinakomplex med terapeutisk effekt - Google Patents
Foerfarande foer framstaellning av platinakomplex med terapeutisk effekt Download PDFInfo
- Publication number
- FI87572B FI87572B FI882130A FI882130A FI87572B FI 87572 B FI87572 B FI 87572B FI 882130 A FI882130 A FI 882130A FI 882130 A FI882130 A FI 882130A FI 87572 B FI87572 B FI 87572B
- Authority
- FI
- Finland
- Prior art keywords
- groups
- group
- alkyl group
- platinum
- diaminocyclohexane
- Prior art date
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- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 title claims description 24
- 229910052697 platinum Inorganic materials 0.000 title claims description 8
- 238000005057 refrigeration Methods 0.000 title 1
- 230000001225 therapeutic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 113
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 100
- 125000001424 substituent group Chemical group 0.000 claims description 71
- -1 2-methoxyethoxy Chemical group 0.000 claims description 53
- 238000000034 method Methods 0.000 claims description 43
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 40
- 238000006243 chemical reaction Methods 0.000 claims description 24
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 18
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical group [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 claims description 11
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 11
- 229910052710 silicon Inorganic materials 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- PGXWQVAXEKBIOE-UHFFFAOYSA-L 4-oxoazetidine-2,2-dicarboxylate;platinum(2+) Chemical compound [Pt+2].[O-]C(=O)C1(C([O-])=O)CC(=O)N1 PGXWQVAXEKBIOE-UHFFFAOYSA-L 0.000 claims description 2
- WZEXMEUHMNNBBY-UHFFFAOYSA-L COCN1C(CC1(C(=O)[O-])C(=O)[O-])=O.[Pt+2] Chemical compound COCN1C(CC1(C(=O)[O-])C(=O)[O-])=O.[Pt+2] WZEXMEUHMNNBBY-UHFFFAOYSA-L 0.000 claims description 2
- RMHDPTJPWMCAKH-UHFFFAOYSA-L cyclohexane-1,2-diamine 1-methyl-4-oxoazetidine-2,2-dicarboxylate platinum(2+) Chemical compound [Pt+2].NC1CCCCC1N.CN1C(=O)CC1(C([O-])=O)C([O-])=O RMHDPTJPWMCAKH-UHFFFAOYSA-L 0.000 claims description 2
- SGLJYTWMWIAGEU-UHFFFAOYSA-N cyclohexane-1,2-diamine;platinum(2+) Chemical compound [Pt+2].NC1CCCCC1N SGLJYTWMWIAGEU-UHFFFAOYSA-N 0.000 claims description 2
- HWESRJQMCGXFOM-UHFFFAOYSA-N 3-(1-octanoyloxyethyl)-4-oxoazetidine-2-carboxylic acid Chemical compound CCCCCCCC(=O)OC(C)C1C(C(O)=O)NC1=O HWESRJQMCGXFOM-UHFFFAOYSA-N 0.000 claims 1
- DBBVUTFTBVQUBO-UHFFFAOYSA-N 3-[1-[tert-butyl(dimethyl)silyl]oxyethyl]-4-oxoazetidine-2-carboxylic acid Chemical compound CC(C)(C)[Si](C)(C)OC(C)C1C(C(O)=O)NC1=O DBBVUTFTBVQUBO-UHFFFAOYSA-N 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- WEGYSHUDTRKDQC-YIXJLRDRSA-L C(CCCCCCC)(=O)O[C@H](C)[C@H]1C(N[C@@H]1C(=O)[O-])=O.[Pt+2].C(CCCCCCC)(=O)O[C@H](C)[C@H]1C(N[C@@H]1C(=O)[O-])=O Chemical compound C(CCCCCCC)(=O)O[C@H](C)[C@H]1C(N[C@@H]1C(=O)[O-])=O.[Pt+2].C(CCCCCCC)(=O)O[C@H](C)[C@H]1C(N[C@@H]1C(=O)[O-])=O WEGYSHUDTRKDQC-YIXJLRDRSA-L 0.000 claims 1
- ROFHTDLFMWOFRA-UHFFFAOYSA-L CN1C(C(C1(C(=O)[O-])C(=O)[O-])C(C)C)=O.[Pt+2] Chemical compound CN1C(C(C1(C(=O)[O-])C(=O)[O-])C(C)C)=O.[Pt+2] ROFHTDLFMWOFRA-UHFFFAOYSA-L 0.000 claims 1
- YVKZJLVLJZUNHQ-UHFFFAOYSA-L CN1C(CC1(C(=O)[O-])C(=O)[O-])=O.[Pt+2] Chemical compound CN1C(CC1(C(=O)[O-])C(=O)[O-])=O.[Pt+2] YVKZJLVLJZUNHQ-UHFFFAOYSA-L 0.000 claims 1
- ABKPEKKFENHSQB-UHFFFAOYSA-L COCCOCN1C(CC1(C(=O)[O-])C(=O)[O-])=O.[Pt+2] Chemical compound COCCOCN1C(CC1(C(=O)[O-])C(=O)[O-])=O.[Pt+2] ABKPEKKFENHSQB-UHFFFAOYSA-L 0.000 claims 1
- 229910052783 alkali metal Inorganic materials 0.000 claims 1
- 150000001340 alkali metals Chemical class 0.000 claims 1
- SXMPLHNWGJICOQ-UHFFFAOYSA-L cyclohexane-1,2-diamine 1-methyl-4-oxo-3-propan-2-ylazetidine-2,2-dicarboxylate platinum(2+) Chemical compound [Pt+2].NC1CCCCC1N.CC(C)C1C(=O)N(C)C1(C([O-])=O)C([O-])=O SXMPLHNWGJICOQ-UHFFFAOYSA-L 0.000 claims 1
- XHHAKXDPLOLVCO-UHFFFAOYSA-L cyclohexane-1,2-diamine;4-oxoazetidine-2,2-dicarboxylate;platinum(2+) Chemical compound [Pt+2].NC1CCCCC1N.[O-]C(=O)C1(C([O-])=O)CC(=O)N1 XHHAKXDPLOLVCO-UHFFFAOYSA-L 0.000 claims 1
- 125000001893 nitrooxy group Chemical group [O-][N+](=O)O* 0.000 claims 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 34
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 31
- 239000000203 mixture Substances 0.000 description 30
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- 125000003277 amino group Chemical group 0.000 description 20
- NWAHZABTSDUXMJ-UHFFFAOYSA-N platinum(2+);dinitrate Chemical compound [Pt+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O NWAHZABTSDUXMJ-UHFFFAOYSA-N 0.000 description 17
- 239000013078 crystal Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 14
- 238000001914 filtration Methods 0.000 description 11
- 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 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 125000004103 aminoalkyl group Chemical group 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 150000001334 alicyclic compounds Chemical class 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 230000000259 anti-tumor effect Effects 0.000 description 5
- 239000002246 antineoplastic agent Substances 0.000 description 5
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 5
- 229960004316 cisplatin Drugs 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 5
- 150000003057 platinum Chemical class 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 235000017557 sodium bicarbonate Nutrition 0.000 description 5
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 4
- 229960004562 carboplatin Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000011347 resin Substances 0.000 description 4
- 229920005989 resin Polymers 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- YMHQVDAATAEZLO-UHFFFAOYSA-N cyclohexane-1,1-diamine Chemical compound NC1(N)CCCCC1 YMHQVDAATAEZLO-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 2
- ZUYYQGFCSKJGDO-UHFFFAOYSA-N 2-(aminomethyl)cyclohexan-1-amine Chemical compound NCC1CCCCC1N ZUYYQGFCSKJGDO-UHFFFAOYSA-N 0.000 description 2
- BQDDMUZICLSWRG-UHFFFAOYSA-N 4-oxoazetidine-2,2-dicarboxylic acid Chemical compound OC(=O)C1(C(O)=O)CC(=O)N1 BQDDMUZICLSWRG-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- 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 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- XZAHJRZBUWYCBM-UHFFFAOYSA-N [1-(aminomethyl)cyclohexyl]methanamine Chemical compound NCC1(CN)CCCCC1 XZAHJRZBUWYCBM-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 125000002723 alicyclic group Chemical group 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- 229940045985 antineoplastic platinum compound Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- MRSXAYGJYKDUHG-MFAVDMRSSA-N benzyl 3-[(1r)-1-hydroxyethyl]-4-oxoazetidine-2-carboxylate Chemical compound N1C(=O)C([C@H](O)C)C1C(=O)OCC1=CC=CC=C1 MRSXAYGJYKDUHG-MFAVDMRSSA-N 0.000 description 2
- JSMRMEYFZHIPJV-UHFFFAOYSA-N bicyclo[2.1.1]hexane Chemical compound C1C2CC1CC2 JSMRMEYFZHIPJV-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- DBBUVLSRTWYISN-UHFFFAOYSA-N cycloheptane-1,2-diamine Chemical compound NC1CCCCCC1N DBBUVLSRTWYISN-UHFFFAOYSA-N 0.000 description 2
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 2
- 239000004914 cyclooctane Substances 0.000 description 2
- 229940111685 dibasic potassium phosphate Drugs 0.000 description 2
- GBVVJYJSVRBGDL-UHFFFAOYSA-N diethyl 1-[(2,4-dimethoxyphenyl)methyl]-4-oxoazetidine-2,2-dicarboxylate Chemical compound CCOC(=O)C1(C(=O)OCC)CC(=O)N1CC1=CC=C(OC)C=C1OC GBVVJYJSVRBGDL-UHFFFAOYSA-N 0.000 description 2
- GEVPUOKCAPKLLP-UHFFFAOYSA-N diethyl 2-(3-bromopropanoylamino)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)NC(=O)CCBr GEVPUOKCAPKLLP-UHFFFAOYSA-N 0.000 description 2
- PVULNIOVRWYXIK-UHFFFAOYSA-N diethyl 4-oxoazetidine-2,2-dicarboxylate Chemical compound CCOC(=O)C1(C(=O)OCC)CC(=O)N1 PVULNIOVRWYXIK-UHFFFAOYSA-N 0.000 description 2
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- RBJZSJZUOCLCHB-UHFFFAOYSA-L disodium;4-oxoazetidine-2,2-dicarboxylate Chemical compound [Na+].[Na+].[O-]C(=O)C1(C([O-])=O)CC(=O)N1 RBJZSJZUOCLCHB-UHFFFAOYSA-L 0.000 description 2
- QDENWSJNTCZMTB-UHFFFAOYSA-L disodium;5-oxopyrrolidine-2,2-dicarboxylate Chemical compound [Na+].[Na+].[O-]C(=O)C1(C([O-])=O)CCC(=O)N1 QDENWSJNTCZMTB-UHFFFAOYSA-L 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 2
- 231100000417 nephrotoxicity Toxicity 0.000 description 2
- 150000003058 platinum compounds Chemical class 0.000 description 2
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- XFNJVJPLKCPIBV-UHFFFAOYSA-N trimethylenediamine Chemical compound NCCCN XFNJVJPLKCPIBV-UHFFFAOYSA-N 0.000 description 2
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- YSPMLLKKKHCTBN-REOHCLBHSA-N (2s)-4-oxoazetidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CC(=O)N1 YSPMLLKKKHCTBN-REOHCLBHSA-N 0.000 description 1
- RVZXVWXLFWWDQA-NJUXHZRNSA-N (2s,3s)-3-[(1r)-1-butanoyloxyethyl]-4-oxoazetidine-2-carboxylic acid Chemical compound CCCC(=O)O[C@H](C)[C@@H]1[C@@H](C(O)=O)NC1=O RVZXVWXLFWWDQA-NJUXHZRNSA-N 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- BTTRRUWBZXHEEA-UHFFFAOYSA-N 1,3-dimethyl-4-oxoazetidine-2,2-dicarboxylic acid Chemical compound CC1C(=O)N(C)C1(C(O)=O)C(O)=O BTTRRUWBZXHEEA-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
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- 0 C[C@](N(C)C1C=CCCC1N)P(C)COC(*C(*)(C1)N(C)C1=O)=O Chemical compound C[C@](N(C)C1C=CCCC1N)P(C)COC(*C(*)(C1)N(C)C1=O)=O 0.000 description 1
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- 101100062121 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cyc-1 gene Proteins 0.000 description 1
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- PVGDTRYBROZOIA-UHFFFAOYSA-N [5-(aminomethyl)-1,3-dioxan-5-yl]methanamine Chemical compound NCC1(CN)COCOC1 PVGDTRYBROZOIA-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
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- 238000010171 animal model Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 150000001539 azetidines Chemical class 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
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- 150000007942 carboxylates Chemical class 0.000 description 1
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- 125000004122 cyclic group Chemical group 0.000 description 1
- MVTAAUNISXMHJU-UHFFFAOYSA-N cyclooctane-1,2-diamine Chemical compound NC1CCCCCCC1N MVTAAUNISXMHJU-UHFFFAOYSA-N 0.000 description 1
- UEIMXRCPSILWLM-UHFFFAOYSA-N cyclooctane-1,3-diamine Chemical compound NC1CCCCCC(N)C1 UEIMXRCPSILWLM-UHFFFAOYSA-N 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- MYJQGGALXPHWLV-UHFFFAOYSA-N cyclopentane-1,2-diamine Chemical compound NC1CCCC1N MYJQGGALXPHWLV-UHFFFAOYSA-N 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- NHKVBPRGGXQNHS-UHFFFAOYSA-N diethyl 2-[(2,4-dimethoxyphenyl)methylamino]propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)NCC1=CC=C(OC)C=C1OC NHKVBPRGGXQNHS-UHFFFAOYSA-N 0.000 description 1
- GLFVNTDRBTZJIY-UHFFFAOYSA-N diethyl 2-aminopropanedioate;hydron;chloride Chemical compound Cl.CCOC(=O)C(N)C(=O)OCC GLFVNTDRBTZJIY-UHFFFAOYSA-N 0.000 description 1
- GRAPLOUUXSQOTQ-UHFFFAOYSA-N diethyl 5-oxopyrrolidine-2,2-dicarboxylate Chemical compound CCOC(=O)C1(C(=O)OCC)CCC(=O)N1 GRAPLOUUXSQOTQ-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- HEXCQMKXCQEUOL-UHFFFAOYSA-L disodium;1-(methoxymethyl)-4-oxo-3-propan-2-ylazetidine-2,2-dicarboxylate Chemical compound [Na+].[Na+].COCN1C(=O)C(C(C)C)C1(C([O-])=O)C([O-])=O HEXCQMKXCQEUOL-UHFFFAOYSA-L 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 125000000268 heptanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 150000002763 monocarboxylic acids Chemical class 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002801 octanoyl group Chemical group C(CCCCCCC)(=O)* 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- NFOHLBHARAZXFQ-UHFFFAOYSA-L platinum(2+);dihydroxide Chemical compound O[Pt]O NFOHLBHARAZXFQ-UHFFFAOYSA-L 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- AUKXFNABVHIUAC-UHFFFAOYSA-N pyrrolidin-2-ylmethylamine Chemical compound NCC1CCCN1 AUKXFNABVHIUAC-UHFFFAOYSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
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- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/28—Compounds containing heavy metals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Claims (20)
1. Analogiförfarande för framställning av ett terapeutiskt verkande platinakomplex med formeln (I) : 5 A t dl 10 aX ^ [där: 15. och B är likadana eller olika och vardera avser en ammingrupp, eller A och B avser tillsammans en diamino-C3_9-cykloalkylgrupp, och Z avser en grupp med formeln (II): 20 0 //
0-C (CH2)n / \ / \ , C CS-R1 (II) \ / \ / Ο-c N-C \\ l \\ 25. a2 o eller en grupp med formeln (III): O 30 tl o-c 7 xx (III) \ / N-C- H II
35 C-CH * X , o R1 67 8 7 5 7 2 där: R1 avser en väteatom eller en C1-C4-alkygrupp, en C^-C^-alkoxigrupp, en substituerad C1-CA-alkylgrupp med ätminstone en av följande substi-5 tuenter, vilka substituenter är valda frän hydroxigrupper, silyloxigrupper med 1-3 C1-CA-alkylsubstituenter pä kiselatomen, Cj-CA-alkoxigrupper, grup-per med formeln -OPO(OR3)2, där R3 avser en C^-C^-alkylgrupp, eller en 10 fenylgrupp och -O-COR*1, där R*1 avser en C1-C9-alkylgrupp, C2-C5-alkoxi-alkoxigrupper och C3-C7-alkoxialkoxialkoxigrupper; R2 avser en väteatom, en C^C^-alkylgrupp, en substituerad Cl-CA-alkyl -grupp med ätminstone en av substituenterna, som är valda frän C1-CA-15 alkoxigrupper och C2-C5-alkoxialkoxigrupper; X avser en enda kol-kolbindning eller en metylengrupp; n är 0 eller 1; 20 kännetecknat därav, att man vid förfarandet bringar en förening med formeln (Va):
25 A 5* \ / A <Va> B 8a 30 (där A och B är definierade som ovan, och R* avser en hydroxigrupp eller en nitrooxigrupp) att reagera med en förening med formeln (VI), (VII) eller (IX): 35 68 8 7 572 MOOC (CH2)a \ / \ c CH-R1 (VI) / \ /
5 MOOC N-C I W R2 0 X-COOH 10 / (VII) C-CH // \ O R1 15 HOOC (CH2)a \ / \ c CH-R1 (1χ) / \ / HOOC N-C
20 I R2 0 (där R1, R2, X och n är definierade son ovan och M avser en alkali-metall), vid behov i närvaro av ett alkali. 25
2. Förfarande enligt patentkrav 1, kännetecknat därav, att reagenterna och reaktionsförhdllandena väljes för att framställa en förening med formeln (Ia): O 30 // A O-C (CH2)Q \ / \ / \ Pc C CH-R1 (Ia) / \ / \ / B 0-C N-C \\ | \\
36. O där A, B, R1, R2 och n är definierade som i patentkrav 1. 69 87 572
3. Förfarande enligt patentkrav 1, kännetecknat därav, att reagenterna och reaktionsförhällandena väljes för att framställa en förening med formeln (Ib): 5 0 // A 0-C ' / \ Λ / Hb, B N-C-H 10. j C-CH rt \ O H1 där A, B, R1 och X är definierade som i patentkrav 1. 15
4. Förfarande enligt patentkrav 1 eller 2, kännetecknat därav, att n är 0.
5. Förfarande enligt patentkrav 2, kännetecknat därav, 20 att: R1 avser: en väteatom, en C^C^-alkylgrupp; en substituerad C1-C4-al-kylgrupp med ätminstone en substituent som är vald frän C1-C3-alkoxi-grupper, C2-C5-alkoxialkoxigrupper och silyloxigrupper med 3 substi-. . 25 tuenter pä kiselatomen valda frän Cj-C^-alkylgrupper; R2 avser en väteatom, en Cj-C^alkylgrupp eller en substituerad C1-C2-alkylgrupp med ätminstone en substituent som är vald frän C1-C2-alko-xigrupper och C2-C5-alkoxialkoxigrupper; och 30 n är 0.
6. Förfarande enligt patentkrav 2, kännetecknat därav, att: R1 avser en väteatom, en C^-C^-alkylgrupp, en substituerad C1-CA-alkyl-grupp med ätminstone en substituent som är vald frän C1-C2-alkoxigrup- 35
70 B 7 5 7 2 per, C2-C5-alkoxialkoxigrupper och silyloxigrupper med tre substituen-ter pä kiselatomen som är valda frän C1-C4-alkylgrupper; R2 avser en väteatom, en C1-C2-alkylgrupp eller en substituerad C1-C2-5 alkylgrupp med ätminstone en substituent som är vald frän C1-C2-alko-xigrupper och C2-C5-alkoxialkoxigrupper; och n är 0, 10 7. Förfarande enligt patentkrav 3, kännetecknat därav, att: R1 avser en väteatom, en Cj-C^-alkylgrupp, en Cj-C^,-alkoxigrupp, en substituerad alkylgrupp med ätminstone en av substituenterna 15 (a"'), som definieras nedan; substituenterna (a"') är valda frän silyloxigrupper med tre substi-tuenter pä kiselatomen vald frän C1-Ci|-alkylgrupper, eller substituenterna (a''') är valda frän C1-C3-alkoxigrupper, C2-C5-alkoxialkoxigrup-20 per, C3-C7-alkoxialkoxialkoxigrupper och grupper med formeln -OPO(OR3)2 och -0- COR4; där:
25 R3 avser en C1-C3-alkylgrupp eller en fenylgrupp, och R* avser en Cx-C8-alkylgrupp.
8. Förfarande enligt patentkrav 3, kännetecknat därav, 30 att:
1 R1 avser en väteatom, en Cx-C2-alkylgrupp, en C1-C2-alkoxigrupp, en substituerad C1-Cil-alkylgrupp med ätminstone en av substituenterna (aiv) , som definieras nedan; substituenterna (aiv) är valda frän silyloxigrupper med tre Cj-C^-al-kylsubstituenter pä kiselatomen, C1-C3-alkoxigrupper, C2-C5-alkoxi- 35 7i 87572 alkoxigrupper, C3-C7*alkoxialkoxialkoxigrupper och grupper med formeln -OPO(OR3)2 och -0- COR4; där: 5 R3 avser en C1-C3-alkylgrupp eller en fenylgrupp, och R* avser en Cj-Cg-alkylgrupp. 10 9. Förfarande enligt patentkrav 1, kännetecknat därav, att reagenterna och reaktionsförhällandena väljes för att framställa: 1.2- diaminocyklohexanplatina(II) 2-oxoazetidin-4,4-dikarboxylat; 15 1,2-diaminocyklohexanplatina(II) (1-metyl-2-oxoazetidin-4,4-dikarb oxylat ; 1.2- diaminocyklohexanplatina(II) (1-metoximetyl-2-oxoazetidin-4,4- dikarboxylat; 70 1 , 2 - diani i nocykl ohexanpla t ina( Li) (l - (2 - inet.ox ietoxl )inety 1 - 2 -oxoaze L I din-4,4-dikarboxylat; 1.2- diaminocyklohexanplatina(II) (1-metyl-3-isopropyl-2-oxoazetidin- 25 4,4-dikarboxylat); 1.2- diaminocyklohexanplatina(II) 3-[1-(metoximetoxi)etyl]-2-oxoaze-tidin-4-ylasetat; 30 1,2-diaminocyklohexanplatina(II) 3-[1-(2-metoxietoximetoxi)etyl]-2- oxoazetidin-4-ylasetat; 1 , 7. - di am i nooyk 1 ohoxnnplnt i iwi( TI) 3 - (1 -oktnnoyloxietyl) -7 - oxoazet. Id i n -4-ylkarboxy1 at; eller 35 72 8 7 5 7 2 1,2-diaminocyklohexanplatina(II) 3-(1-t-butyldimetylsilyloxietyl)-2-oxoazetidin-4-ylkarboxylat.
10. Förfarande enligt patentkrav 1, kännetecknat därav, 5 att reagenterna och reaktionsförhAllandena väljes för att framställa: cis-Γ trans-(2)-1,2-diaminocyklohexan]platina(II) 2-oxoazetidin-4,4-dikarboxylat; 10 cis-[trans-(2)-l,2-diarainocyklohexan]platina(II) (l-metyl-2-oxoaze-tidin-4,4-dikarboxylat); cis-f trans-(2)-1,2-diaminocyklohexan]platina(II) (1-metoximetyl-2-oxoazetidin-4,4-dikarboxylat); 15 cis-[trans-(2)-1,2-diaminocyklohexan]platina(II) [1-(2-metoxietoxi)-metyl-2-oxoazetidin-4,4-dikarboxylat]; cis-f trans-(2)-1,2-diaminocyklohexan]platina(Il) (1-metyl-3-isopropyl-20 2-oxoazetidin-4,4-dikarboxylat); cis-f trans-(2)-1,2-diaminocyklohexan]platina(II) {(3S,4R)-3-[(R)-1-(metoximetoxi)etyl]-2-oxoazetidin-4-yl}acetat; 25 cis-f trans-(£)-1.2-diaminocyklohexan1platina(II) {(3S,4R)-3-[(R)-1-(2-metoxietoximetoxi)etyl]-2-oxoazetidin-4-yl)acetat; cis-[trans-(2)-1.2-diaminocyklohexan]platina(II) ((3S,4S)-3-[(R)-1-oktanoyloxietyl]- 2-oxoazetidin-4-ylJkarboxylat; 30 eller cis-Γ trans -(i)-1.2-diaminocvklohekxan]platina(II) ((3S,4S)-3-[(R)-l-t-butyldimetylsilyloxietyl]-2-oxoazetidin-4-yl}karboxylat.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP11218187 | 1987-05-08 | ||
| JP11218187 | 1987-05-08 | ||
| JP11450087 | 1987-05-13 | ||
| JP11450087 | 1987-05-13 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI882130A0 FI882130A0 (fi) | 1988-05-06 |
| FI882130A FI882130A (fi) | 1988-11-09 |
| FI87572B true FI87572B (fi) | 1992-10-15 |
| FI87572C FI87572C (sv) | 1993-01-25 |
Family
ID=26451415
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI882130A FI87572C (sv) | 1987-05-08 | 1988-05-06 | Förfarande för framställning av platinakomplex med terapeutisk effekt |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US5527905A (sv) |
| EP (1) | EP0290280B1 (sv) |
| KR (1) | KR950008372B1 (sv) |
| CN (1) | CN1017803B (sv) |
| AU (1) | AU617314B2 (sv) |
| CA (1) | CA1308723C (sv) |
| DE (1) | DE3887194T2 (sv) |
| DK (1) | DK252688A (sv) |
| ES (1) | ES2061646T3 (sv) |
| FI (1) | FI87572C (sv) |
| HU (1) | HU199492B (sv) |
| NO (1) | NO178069C (sv) |
| RU (1) | RU2039064C1 (sv) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0164460B1 (ko) * | 1995-10-02 | 1999-03-20 | 김은영 | 고분자 백금 착화합물, 그의 제조방법 및 그를 유효성분으로 하는 항암제 |
| US6235776B1 (en) | 1998-11-12 | 2001-05-22 | Cell Pathways, Inc. | Method for treating a patient with neoplasia by treatment with a paclitaxel derivative |
| US6235782B1 (en) | 1998-11-12 | 2001-05-22 | Rifat Pamukcu | Method for treating a patient with neoplasia by treatment with a platinum coordination complex |
| AU775373B2 (en) | 1999-10-01 | 2004-07-29 | Immunogen, Inc. | Compositions and methods for treating cancer using immunoconjugates and chemotherapeutic agents |
| WO2001036007A2 (en) * | 1999-11-12 | 2001-05-25 | Angiotech Pharmaceuticals, Inc. | Compositions of a combination of radioactive therapy and cell-cycle inhibitors |
| KR100363394B1 (ko) | 2000-08-21 | 2002-12-05 | 한국과학기술연구원 | 온도감응성을 갖는 포스파젠삼량체-백금착물 복합체, 그의제조방법 및 그를 함유하는 항암제 조성물 |
| AU2003300076C1 (en) | 2002-12-30 | 2010-03-04 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
| US7138520B2 (en) * | 2003-01-13 | 2006-11-21 | Massachusetts Institute Of Technology | Coordination complexes having tethered therapeutic agents and/or targeting moieties, and methods of making and using the same |
| ES2588979T3 (es) | 2010-08-24 | 2016-11-08 | Dana-Farber Cancer Institute, Inc. | Procedimientos para la predicción de una respuesta contra el cáncer |
| WO2012174378A2 (en) | 2011-06-17 | 2012-12-20 | Myriad Genetics, Inc. | Methods and materials for assessing allelic imbalance |
| FI2794907T4 (sv) | 2011-12-21 | 2023-03-27 | Förfaranden och material för bedömning av heterozygotförlust | |
| CA3080441A1 (en) | 2012-02-23 | 2013-09-06 | The Children's Hospital Corporation | Methods for predicting anti-cancer response |
| AU2013273466B2 (en) | 2012-06-07 | 2018-11-01 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Methods for detecting inactivation of the homologous recombination pathway (BRCA1/2) in human tumors |
| WO2014160080A1 (en) | 2013-03-14 | 2014-10-02 | Children's Medical Center Corporation | Cancer diagnosis, treatment selection and treatment |
| CA2931181C (en) | 2013-12-09 | 2023-01-24 | Institut Curie | Methods for detecting inactivation of the homologous recombination pathway (brca1/2) in human tumors |
| PT3180447T (pt) | 2014-08-15 | 2020-06-18 | Myriad Genetics Inc | Métodos e materiais para avaliar a deficiência de recombinação homóloga |
| CN111721842B (zh) * | 2019-03-19 | 2022-07-12 | 海南长安国际制药有限公司 | 洛铂中有关物质的检测方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6041077B2 (ja) * | 1976-09-06 | 1985-09-13 | 喜徳 喜谷 | １，２‐ジアミノシクロヘキサン異性体のシス白金（２）錯体 |
| GB2019397B (en) * | 1978-04-20 | 1982-10-27 | Johnson Matthey Co Ltd | Pt 2 and 4 complexes with amino-acids |
| IL67789A (en) * | 1983-01-31 | 1986-09-30 | Yissum Res Dev Co | Amino-substituted malonato platinum(ii)complexes and method for their preparation |
| SU1565347A3 (ru) * | 1985-09-06 | 1990-05-15 | Санкио Компани Лимитед (Фирма) | Способ получени производных мочевины, содержащих платину |
| DE3630497A1 (de) * | 1986-09-08 | 1988-03-10 | Behringwerke Ag | Cis-platin-komplexe, verfahren zu ihrer herstellung und diese verbindungen enthaltende pharmazeutische mittel |
-
1988
- 1988-05-06 HU HU882309A patent/HU199492B/hu not_active IP Right Cessation
- 1988-05-06 ES ES88304140T patent/ES2061646T3/es not_active Expired - Lifetime
- 1988-05-06 DE DE3887194T patent/DE3887194T2/de not_active Expired - Fee Related
- 1988-05-06 FI FI882130A patent/FI87572C/sv not_active IP Right Cessation
- 1988-05-06 EP EP88304140A patent/EP0290280B1/en not_active Expired - Lifetime
- 1988-05-06 DK DK252688A patent/DK252688A/da not_active Application Discontinuation
- 1988-05-07 KR KR1019880005324A patent/KR950008372B1/ko not_active IP Right Cessation
- 1988-05-07 CN CN88103597A patent/CN1017803B/zh not_active Expired
- 1988-05-09 NO NO882012A patent/NO178069C/no unknown
- 1988-05-09 CA CA000566294A patent/CA1308723C/en not_active Expired - Fee Related
- 1988-05-09 AU AU15813/88A patent/AU617314B2/en not_active Ceased
-
1992
- 1992-05-19 RU SU925011706A patent/RU2039064C1/ru active
-
1994
- 1994-11-18 US US08/341,702 patent/US5527905A/en not_active Expired - Fee Related
-
1995
- 1995-06-07 US US08/472,128 patent/US5633243A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1034544A (zh) | 1989-08-09 |
| NO882012L (no) | 1989-02-27 |
| EP0290280B1 (en) | 1994-01-19 |
| AU1581388A (en) | 1988-11-10 |
| HU199492B (en) | 1990-02-28 |
| CA1308723C (en) | 1992-10-13 |
| DK252688A (da) | 1988-11-09 |
| CN1017803B (zh) | 1992-08-12 |
| NO882012D0 (no) | 1988-05-09 |
| FI882130A (fi) | 1988-11-09 |
| KR880013961A (ko) | 1988-12-22 |
| HUT47301A (en) | 1989-02-28 |
| DK252688D0 (da) | 1988-05-06 |
| RU2039064C1 (ru) | 1995-07-09 |
| AU617314B2 (en) | 1991-11-28 |
| US5527905A (en) | 1996-06-18 |
| DE3887194T2 (de) | 1994-07-28 |
| US5633243A (en) | 1997-05-27 |
| EP0290280A3 (en) | 1990-07-25 |
| NO178069B (no) | 1995-10-09 |
| FI882130A0 (fi) | 1988-05-06 |
| FI87572C (sv) | 1993-01-25 |
| KR950008372B1 (ko) | 1995-07-28 |
| ES2061646T3 (es) | 1994-12-16 |
| NO178069C (no) | 1996-01-17 |
| EP0290280A2 (en) | 1988-11-09 |
| DE3887194D1 (de) | 1994-03-03 |
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| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: SANKYO COMPANY LIMITED |