ES2619412T3 - Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos - Google Patents
Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos Download PDFInfo
- Publication number
- ES2619412T3 ES2619412T3 ES13793812.2T ES13793812T ES2619412T3 ES 2619412 T3 ES2619412 T3 ES 2619412T3 ES 13793812 T ES13793812 T ES 13793812T ES 2619412 T3 ES2619412 T3 ES 2619412T3
- Authority
- ES
- Spain
- Prior art keywords
- platinum
- pyrophosphate
- reaction mixture
- dach
- monomeric
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 106
- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 230000015572 biosynthetic process Effects 0.000 title description 24
- 238000003786 synthesis reaction Methods 0.000 title description 23
- 238000000746 purification Methods 0.000 title description 17
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000011541 reaction mixture Substances 0.000 claims abstract description 61
- ZZMFAAPZGBNYRP-UHFFFAOYSA-J phosphonato phosphate platinum(4+) Chemical compound [Pt+4].[O-]P([O-])(=O)OP([O-])([O-])=O ZZMFAAPZGBNYRP-UHFFFAOYSA-J 0.000 claims abstract description 42
- 239000002244 precipitate Substances 0.000 claims abstract description 38
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 37
- 229910001868 water Inorganic materials 0.000 claims abstract description 30
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims abstract 4
- 238000006243 chemical reaction Methods 0.000 claims description 66
- 239000007787 solid Substances 0.000 claims description 42
- -1 aliphatic amines Chemical class 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- 238000001556 precipitation Methods 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 22
- 238000001914 filtration Methods 0.000 claims description 22
- 229910017604 nitric acid Inorganic materials 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 21
- 239000003446 ligand Substances 0.000 claims description 12
- 150000004985 diamines Chemical class 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 9
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 claims description 9
- 239000000872 buffer Substances 0.000 claims description 8
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical group NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 7
- 150000004982 aromatic amines Chemical class 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- NUNLBVUVTXONII-UHFFFAOYSA-J phosphonato phosphate;platinum(2+) Chemical compound [Pt+2].[Pt+2].[O-]P([O-])(=O)OP([O-])([O-])=O NUNLBVUVTXONII-UHFFFAOYSA-J 0.000 claims description 5
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 238000010979 pH adjustment Methods 0.000 claims description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000004984 aromatic diamines Chemical class 0.000 claims description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
- 150000003222 pyridines Chemical class 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 229910052740 iodine Inorganic materials 0.000 claims 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 90
- 239000000047 product Substances 0.000 description 69
- 239000000243 solution Substances 0.000 description 55
- 239000012535 impurity Substances 0.000 description 30
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 28
- 239000008367 deionised water Substances 0.000 description 27
- 229910021641 deionized water Inorganic materials 0.000 description 27
- 235000011180 diphosphates Nutrition 0.000 description 21
- 229940048084 pyrophosphate Drugs 0.000 description 20
- 238000004128 high performance liquid chromatography Methods 0.000 description 18
- 238000001953 recrystallisation Methods 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 239000007844 bleaching agent Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 238000002955 isolation Methods 0.000 description 13
- 238000002425 crystallisation Methods 0.000 description 12
- 230000008025 crystallization Effects 0.000 description 12
- VZWGHDYJGOMEKT-UHFFFAOYSA-J sodium pyrophosphate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O VZWGHDYJGOMEKT-UHFFFAOYSA-J 0.000 description 12
- 239000000725 suspension Substances 0.000 description 11
- 238000001035 drying Methods 0.000 description 10
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 10
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000008569 process Effects 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000000080 wetting agent Substances 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000007853 buffer solution Substances 0.000 description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 7
- 229960004316 cisplatin Drugs 0.000 description 7
- 239000000539 dimer Substances 0.000 description 7
- 150000003057 platinum Chemical class 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229910002651 NO3 Inorganic materials 0.000 description 6
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 6
- IYNIYQPKWZYHRQ-UHFFFAOYSA-N azane;phosphono dihydrogen phosphate Chemical class N.OP(O)(=O)OP(O)(O)=O IYNIYQPKWZYHRQ-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 230000008901 benefit Effects 0.000 description 6
- 229960004562 carboplatin Drugs 0.000 description 6
- 229940048086 sodium pyrophosphate Drugs 0.000 description 6
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 6
- 238000010268 HPLC based assay Methods 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 206010061535 Ovarian neoplasm Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 125000005233 alkylalcohol group Chemical group 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-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
- 229910019142 PO4 Inorganic materials 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 238000004255 ion exchange chromatography Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229960001756 oxaliplatin Drugs 0.000 description 3
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- YPGLWPWPVJBCEM-UHFFFAOYSA-K [Pt+3].[O-]P([O-])([O-])=O Chemical compound [Pt+3].[O-]P([O-])([O-])=O YPGLWPWPVJBCEM-UHFFFAOYSA-K 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000008394 flocculating agent Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229920001903 high density polyethylene Polymers 0.000 description 2
- 239000004700 high-density polyethylene Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- LKMWMZZOSMBNJI-UHFFFAOYSA-J phosphono phosphate platinum(4+) Chemical compound [Pt+4].OP(O)(=O)OP([O-])([O-])=O.OP(O)(=O)OP([O-])([O-])=O LKMWMZZOSMBNJI-UHFFFAOYSA-J 0.000 description 2
- NDBYXKQCPYUOMI-UHFFFAOYSA-N platinum(4+) Chemical compound [Pt+4] NDBYXKQCPYUOMI-UHFFFAOYSA-N 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- VKKIJPPZWGZEFC-UHFFFAOYSA-J tetrasodium phosphonato phosphate tetrahydrate Chemical compound O.O.O.O.[Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O VKKIJPPZWGZEFC-UHFFFAOYSA-J 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- DNIAPMSPPWPWGF-VKHMYHEASA-N (+)-propylene glycol Chemical compound C[C@H](O)CO DNIAPMSPPWPWGF-VKHMYHEASA-N 0.000 description 1
- SSJXIUAHEKJCMH-LWOQYNTDSA-N (1r)-cyclohexane-1,2-diamine Chemical compound NC1CCCC[C@H]1N SSJXIUAHEKJCMH-LWOQYNTDSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- YPFDHNVEDLHUCE-UHFFFAOYSA-N 1,3-propanediol Substances OCCCO YPFDHNVEDLHUCE-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 238000004294 195Pt NMR spectroscopy Methods 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102100028735 Dachshund homolog 1 Human genes 0.000 description 1
- 101000915055 Homo sapiens Dachshund homolog 1 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229910020427 K2PtCl4 Inorganic materials 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- RBQCRIWVHHAARW-UHFFFAOYSA-J [O-]P([O-])(=O)OP(=O)([O-])[O-].[Pt+2].NC1(CCCCC1)N.[Pt+2] Chemical compound [O-]P([O-])(=O)OP(=O)([O-])[O-].[Pt+2].NC1(CCCCC1)N.[Pt+2] RBQCRIWVHHAARW-UHFFFAOYSA-J 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000004061 bleaching Methods 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- YMHQVDAATAEZLO-UHFFFAOYSA-N cyclohexane-1,1-diamine Chemical compound NC1(N)CCCCC1 YMHQVDAATAEZLO-UHFFFAOYSA-N 0.000 description 1
- SCMHTXQHAHWVSX-UHFFFAOYSA-L cyclohexane-1,2-diamine;[hydroxy(oxido)phosphoryl] hydrogen phosphate;platinum(2+) Chemical compound [Pt+2].NC1CCCCC1N.OP([O-])(=O)OP(O)([O-])=O SCMHTXQHAHWVSX-UHFFFAOYSA-L 0.000 description 1
- PNNCIXRVXCLADM-UHFFFAOYSA-L cyclohexane-1,2-diamine;dichloroplatinum Chemical compound Cl[Pt]Cl.NC1CCCCC1N PNNCIXRVXCLADM-UHFFFAOYSA-L 0.000 description 1
- 238000000113 differential scanning calorimetry Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940000406 drug candidate Drugs 0.000 description 1
- SPFYQLKKPUBRPQ-UHFFFAOYSA-L ethane-1,2-diamine;[hydroxy(oxido)phosphoryl] hydrogen phosphate;platinum(2+) Chemical compound [Pt+2].NCCN.OP([O-])(=O)OP(O)([O-])=O SPFYQLKKPUBRPQ-UHFFFAOYSA-L 0.000 description 1
- 229940012017 ethylenediamine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- MUTQTHUBSRXFQO-UHFFFAOYSA-L oxalate;platinum(2+) Chemical class [Pt+2].[O-]C(=O)C([O-])=O MUTQTHUBSRXFQO-UHFFFAOYSA-L 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000005406 washing 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261651200P | 2012-05-24 | 2012-05-24 | |
| US201261651200P | 2012-05-24 | ||
| PCT/US2013/031885 WO2013176764A1 (en) | 2012-05-24 | 2013-03-15 | Synthetic and purification methods for phosphaplatin compounds and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2619412T3 true ES2619412T3 (es) | 2017-06-26 |
Family
ID=49624225
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13793812.2T Active ES2619412T3 (es) | 2012-05-24 | 2013-03-15 | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos |
| ES16203851T Active ES2751668T3 (es) | 2012-05-24 | 2013-03-15 | Método de purificación para compuestos de fosfaplatino |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16203851T Active ES2751668T3 (es) | 2012-05-24 | 2013-03-15 | Método de purificación para compuestos de fosfaplatino |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US8846964B2 (forum.php) |
| EP (2) | EP3202769B1 (forum.php) |
| JP (1) | JP5833795B2 (forum.php) |
| CN (2) | CN104540839B (forum.php) |
| CY (2) | CY1118746T1 (forum.php) |
| DK (2) | DK2855496T3 (forum.php) |
| ES (2) | ES2619412T3 (forum.php) |
| HR (2) | HRP20170416T1 (forum.php) |
| HU (2) | HUE046327T2 (forum.php) |
| IN (1) | IN2014KN02722A (forum.php) |
| LT (2) | LT2855496T (forum.php) |
| PL (2) | PL2855496T3 (forum.php) |
| PT (2) | PT2855496T (forum.php) |
| RS (2) | RS55806B1 (forum.php) |
| SI (2) | SI3202769T1 (forum.php) |
| SM (2) | SMT201900617T1 (forum.php) |
| TW (2) | TWI599361B (forum.php) |
| WO (1) | WO2013176764A1 (forum.php) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2619412T3 (es) * | 2012-05-24 | 2017-06-26 | Phosplatin Therapeutics Llc | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos |
| KR102419247B1 (ko) * | 2016-04-06 | 2022-07-11 | 포스플라틴 테라퓨틱스 인코포레이티드 | 포스파플라틴 액제 제형 |
| JP7023968B2 (ja) * | 2017-01-06 | 2022-02-22 | フォスプラティン・セラピューティクス・インコーポレーテッド | 骨がんまたは血液がんの治療のための治療薬としてのホスファプラチン化合物 |
| EP3679046B1 (en) * | 2017-09-08 | 2023-11-08 | Promontory Therapeutics Inc. | Phosphaplatin compounds as immuno-modulatory agents and therapeutic uses thereof |
| CN113861036B (zh) * | 2021-11-08 | 2024-04-02 | 合肥工业大学 | 一种乙二胺高氯酸铜配合物的制备及用途 |
| US11673904B1 (en) * | 2021-12-09 | 2023-06-13 | L'air Liquide, Societe Anonyme Pour L'etude Et L'exploitation Des Procedes Georges Claude | Low pressure process for synthesis of Pt(PF3)4 involving a soluble intermediate and storage of obtained Pt(PF3)4 |
| CN119822568B (zh) * | 2025-02-19 | 2025-08-19 | 扬州宏鑫环保科技有限公司 | 一种高效纯化水制备装置及制备方法 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4234500A (en) * | 1979-03-07 | 1980-11-18 | Engelhard Minerals & Chemicals Corporation | Ethylenediamine platinum(II) and 1,2-diamino-cyclohexane platinum(II) pyrophosphate complexes |
| WO2005000858A2 (en) | 2003-06-27 | 2005-01-06 | Akira Odani | Bisphosphonate complexes |
| AU2007209099A1 (en) * | 2006-01-30 | 2007-08-02 | Platco Technologies (Proprietary) Limited | Preparation of platinum (ll) complexes |
| CA2686286A1 (en) * | 2007-05-18 | 2008-11-27 | Tti Ellebeau, Inc. | Transdermal delivery devices assuring an improved release of an active principle through a biological interface |
| CN101801369B (zh) | 2007-08-06 | 2012-09-19 | 俄亥俄大学 | 磷铂及其在治疗顺铂和卡铂耐药性癌中的用途 |
| PT2575802T (pt) * | 2010-06-04 | 2016-12-27 | Univ Ohio | Fosfaplatinas e sua utilização para o tratamento de cancros |
| US9012669B2 (en) * | 2011-10-05 | 2015-04-21 | The University Of Houston System | Efficient processes for large scale preparation of phosphaplatins antitumor agents |
| ES2619412T3 (es) * | 2012-05-24 | 2017-06-26 | Phosplatin Therapeutics Llc | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos |
-
2013
- 2013-03-15 ES ES13793812.2T patent/ES2619412T3/es active Active
- 2013-03-15 EP EP16203851.7A patent/EP3202769B1/en active Active
- 2013-03-15 PL PL13793812T patent/PL2855496T3/pl unknown
- 2013-03-15 RS RS20170272A patent/RS55806B1/sr unknown
- 2013-03-15 HU HUE16203851A patent/HUE046327T2/hu unknown
- 2013-03-15 IN IN2722KON2014 patent/IN2014KN02722A/en unknown
- 2013-03-15 JP JP2015514010A patent/JP5833795B2/ja active Active
- 2013-03-15 SI SI201331598T patent/SI3202769T1/sl unknown
- 2013-03-15 HR HRP20170416TT patent/HRP20170416T1/hr unknown
- 2013-03-15 PT PT137938122T patent/PT2855496T/pt unknown
- 2013-03-15 CN CN201380026289.8A patent/CN104540839B/zh active Active
- 2013-03-15 HU HUE13793812A patent/HUE032197T2/en unknown
- 2013-03-15 CN CN201710071127.6A patent/CN106967124B/zh active Active
- 2013-03-15 SM SM20190617T patent/SMT201900617T1/it unknown
- 2013-03-15 ES ES16203851T patent/ES2751668T3/es active Active
- 2013-03-15 DK DK13793812.2T patent/DK2855496T3/en active
- 2013-03-15 LT LTEP13793812.2T patent/LT2855496T/lt unknown
- 2013-03-15 PL PL16203851T patent/PL3202769T3/pl unknown
- 2013-03-15 DK DK16203851T patent/DK3202769T3/da active
- 2013-03-15 SI SI201330565A patent/SI2855496T1/sl unknown
- 2013-03-15 WO PCT/US2013/031885 patent/WO2013176764A1/en not_active Ceased
- 2013-03-15 LT LT16203851T patent/LT3202769T/lt unknown
- 2013-03-15 PT PT162038517T patent/PT3202769T/pt unknown
- 2013-03-15 RS RS20191364A patent/RS59725B1/sr unknown
- 2013-03-15 SM SM20170168T patent/SMT201700168T1/it unknown
- 2013-03-15 EP EP13793812.2A patent/EP2855496B1/en active Active
- 2013-04-01 TW TW102111669A patent/TWI599361B/zh active
- 2013-04-01 TW TW106122720A patent/TWI653237B/zh active
- 2013-09-20 US US14/032,704 patent/US8846964B2/en active Active
-
2014
- 2014-03-18 US US14/217,883 patent/US8859796B1/en active Active
-
2017
- 2017-03-13 CY CY20171100317T patent/CY1118746T1/el unknown
-
2019
- 2019-10-21 HR HRP20191904TT patent/HRP20191904T1/hr unknown
- 2019-11-21 CY CY20191101227T patent/CY1122316T1/el unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2619412T3 (es) | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos | |
| CN103547573B (zh) | 高纯度钆布醇的制备 | |
| CN103467528A (zh) | 一种洛铂的制备方法 | |
| CN108521780B (zh) | 一锅法制备双二羧酸二氨络铂(ii)衍生物的方法 | |
| ES2320554T3 (es) | Oxaliplatino con un bajo contenido de impurezas acompañantes y un metodo para su preparacion. | |
| CN104119387B (zh) | 一种米铂的制备方法 | |
| CN113512066A (zh) | 索拉非尼-钌配合物及其制备方法和应用 | |
| JP6974788B2 (ja) | イミダゾピロロキノリン塩及びその製造方法、並びに、医薬品、化粧品及び食品 | |
| RU2367610C1 (ru) | Способ получения цис-дихлороамминметиламинплатины(ii) | |
| HK1240939A1 (en) | Purification method for phosphaplatin compounds | |
| HK1240939B (en) | Purification method for phosphaplatin compounds | |
| Aldrey et al. | A chemosensor for dihydrogenphosphate based on an oxoazamacrocycle possessing three thiourea arms | |
| HK1203202B (en) | Synthetic and purification methods for phosphaplatin compounds and uses thereof | |
| CA2934535A1 (en) | Large scale manufacture of 2,4-pyrimidinediamines and intermediates | |
| RU2703286C1 (ru) | Соли (5-гидрокси-3,4-бис(гидроксиметил)-6-метилпиридин-2-ил)метансульфокислоты и способ их получения | |
| WO2018178439A1 (es) | Procedimiento de síntesis de 9,10-bis(clorometil)antraceno | |
| CN108884119A (zh) | 一种双二羧酸二氨络铂(ii)衍生物的制备方法 | |
| CN116836206A (zh) | 一种米铂杂质c及其制备方法 | |
| CN116332843A (zh) | 一种硝酸去甲乌药碱晶体及其制备方法 | |
| RU2432351C1 (ru) | Способ получения 4-нитростирола |