DK2855496T3 - Fremgangsmåder til syntese og oprensning af phosphaplatinforbindelser og anvendelser deraf - Google Patents
Fremgangsmåder til syntese og oprensning af phosphaplatinforbindelser og anvendelser deraf Download PDFInfo
- Publication number
- DK2855496T3 DK2855496T3 DK13793812.2T DK13793812T DK2855496T3 DK 2855496 T3 DK2855496 T3 DK 2855496T3 DK 13793812 T DK13793812 T DK 13793812T DK 2855496 T3 DK2855496 T3 DK 2855496T3
- Authority
- DK
- Denmark
- Prior art keywords
- platinum
- reaction mixture
- dach
- pyrophosphate
- monomeric
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 102
- 150000001875 compounds Chemical class 0.000 title claims description 26
- 230000015572 biosynthetic process Effects 0.000 title description 24
- 238000003786 synthesis reaction Methods 0.000 title description 24
- 238000000746 purification Methods 0.000 title description 15
- 238000006243 chemical reaction Methods 0.000 claims description 68
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 68
- 239000011541 reaction mixture Substances 0.000 claims description 59
- 230000008569 process Effects 0.000 claims description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 54
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 47
- 239000007787 solid Substances 0.000 claims description 42
- 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 description 40
- 239000002244 precipitate Substances 0.000 claims description 36
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 34
- 229910017604 nitric acid Inorganic materials 0.000 claims description 34
- 229910052697 platinum Inorganic materials 0.000 claims description 33
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 27
- 229910001868 water Inorganic materials 0.000 claims description 25
- -1 aliphatic amines Chemical class 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 23
- 238000001556 precipitation Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000003446 ligand Substances 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 11
- 150000004985 diamines Chemical class 0.000 claims description 11
- 239000000706 filtrate Substances 0.000 claims description 11
- 238000001816 cooling Methods 0.000 claims description 10
- 239000003960 organic solvent Substances 0.000 claims description 10
- 239000000872 buffer Substances 0.000 claims description 8
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 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
- 238000010979 pH adjustment Methods 0.000 claims description 5
- 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
- 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
- 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
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000002156 mixing 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
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 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
- 150000007522 mineralic acids Chemical class 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- 239000000047 product Substances 0.000 description 67
- 239000000243 solution Substances 0.000 description 56
- 239000008367 deionised water Substances 0.000 description 27
- 229910021641 deionized water Inorganic materials 0.000 description 27
- 239000012535 impurity Substances 0.000 description 26
- 238000001914 filtration Methods 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 14
- 235000011180 diphosphates Nutrition 0.000 description 14
- 238000002360 preparation method Methods 0.000 description 14
- 238000002955 isolation Methods 0.000 description 13
- 229940048084 pyrophosphate Drugs 0.000 description 13
- 238000001953 recrystallisation Methods 0.000 description 13
- 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
- 238000001291 vacuum drying Methods 0.000 description 11
- 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
- 239000007864 aqueous solution Substances 0.000 description 8
- 239000007853 buffer solution Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 8
- 230000008025 crystallization Effects 0.000 description 8
- 239000000539 dimer Substances 0.000 description 8
- 150000003057 platinum Chemical class 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
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 206010028980 Neoplasm Diseases 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000003556 assay Methods 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
- 239000002002 slurry Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000004255 ion exchange chromatography Methods 0.000 description 6
- 230000001376 precipitating effect Effects 0.000 description 6
- 229940048086 sodium pyrophosphate Drugs 0.000 description 6
- 239000001577 tetrasodium phosphonato phosphate Substances 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 5
- 229960004562 carboplatin Drugs 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000010268 HPLC based assay Methods 0.000 description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000005233 alkylalcohol group Chemical group 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 238000005580 one pot reaction Methods 0.000 description 4
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 4
- 238000013341 scale-up Methods 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000012141 concentrate Substances 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
- 238000004090 dissolution Methods 0.000 description 3
- 239000008394 flocculating agent Substances 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 239000012452 mother liquor Substances 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
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000011369 resultant mixture Substances 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 229910002651 NO3 Inorganic materials 0.000 description 2
- 206010033128 Ovarian cancer Diseases 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
- 206010041067 Small cell lung cancer Diseases 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 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
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000007423 decrease Effects 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
- 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
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000011835 investigation Methods 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
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 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
- 239000000376 reactant 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
- 208000000587 small cell lung carcinoma 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
- 230000002381 testicular Effects 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
- 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
- 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
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 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
- 229910020427 K2PtCl4 Inorganic materials 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- KPDXSGZQDXNAHJ-UHFFFAOYSA-I [O-]P([O-])(=O)OP(=O)([O-])OP(=O)([O-])[O-].[Pt+5] Chemical class [O-]P([O-])(=O)OP(=O)([O-])OP(=O)([O-])[O-].[Pt+5] KPDXSGZQDXNAHJ-UHFFFAOYSA-I 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 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
- 230000009286 beneficial effect Effects 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
- 230000008859 change Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 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
- 239000012043 crude product Substances 0.000 description 1
- YMHQVDAATAEZLO-UHFFFAOYSA-N cyclohexane-1,1-diamine Chemical compound NC1(N)CCCCC1 YMHQVDAATAEZLO-UHFFFAOYSA-N 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
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 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
- 239000003937 drug carrier Substances 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
- 239000011521 glass Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 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
- 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
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- HNKLPNDFOVJIFG-UHFFFAOYSA-N oxalic acid;platinum Chemical compound [Pt].OC(=O)C(O)=O HNKLPNDFOVJIFG-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 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
- 239000010452 phosphate Substances 0.000 description 1
- NDBYXKQCPYUOMI-UHFFFAOYSA-N platinum(4+) Chemical compound [Pt+4] NDBYXKQCPYUOMI-UHFFFAOYSA-N 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 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
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)
Claims (30)
1. Fremgangsmåde til fremstilling af et monomert platin-pyrophosphat-kompleks, eller et salt deraf, hvilken fremgangsmåde omfatter: at blande en platin-dihalogenid-forbindelse med et pyrophosphatsalt i et opløsningsmiddelsystem, som omfatter vand og mindst ét vandblandbart organisk opløsningsmiddel, at opretholde en reaktionsblanding, hvor platin-dihalogenid-forbindelsen reagerer med pyrophosphatsaltet for at danne det monomere platin-pyrophosphat-kompleks; at udfælde det monomere platin-pyrophosphat-kompleks, og at isolere det monomere platinkompleks fra reaktionsblandingen.
2. Fremgangsmåde ifølge krav 1, hvor udfældningen omfatter at justere reaktionsblandingens pH til 2 ± 0,2 og at afkøle reaktionsblandingen til 20°C ± 2°C.
3. Fremgangsmåde ifølge krav 1, hvor udfældningen omfatter at justere reaktionsblandingens pH til under 2 og at afkøle reaktionsblandingen til under 20°C.
4. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 3, som yderligere omfatter at opkoncentrere reaktionsblandingen ved at afdestillere en del af opløsningsmidlet/-midlerne inden udfældningen.
5. Fremgangsmåde ifølge krav 2 eller krav 3, hvor pH-justeringen omfatter at tilsætte en påkrævet mængde af en uorganisk syre til reaktionsblandingen.
6. Fremgangsmåde ifølge krav 5, hvor den uorganiske syre er salpetersyre.
7. Fremgangsmåde ifølge krav 2 eller krav 3, hvor pH-justeringen omfatter at tilsætte reaktionsblandingen til en opløsning af en syre.
8. Fremgangsmåde ifølge krav 7, hvor syren er salpetersyre.
9. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 8, hvor det vandblandbare organiske opløsningsmiddel er en (CrCej-alkylalkohol.
10. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 9, hvor reaktionen gennemføres ved en forhøjet temperatur.
11. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 10, hvor platin-dihalogenid-forbindelsen forefindes i en sådan koncentration, at mindst 65% af platinet udfældes som det monomere platin-pyrophosphat-kompleks direkte fra reaktionsblandingen efter justering af reaktionsblandingens pH til 2 ± 0,2 ved en temperatur på 20°C ± 2°C.
12. Fremgangsmåde ifølge krav 11, hvor platin-dihalogenid-forbindelsen forefindes i en sådan koncentration, at 75-85% af platinet udfældes som det monomere platin-pyrophosphat-kompleks direkte fra reaktionsblandingen efter justering af reaktionsblandingens pH til 2 ± 0,2 ved en temperatur på 20°C ± 2°C.
13. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 10, hvor platin-dihalogenid-forbindelsen forefindes i en sådan koncentration, at mindst 65% af platinet udfældes som det monomere platin-pyrophosphat-kompleks direkte fra reaktionsblandingen efter justering afreaktionsblandingens pH til under 2 ved en temperatur på under 20°C.
14. Fremgangsmåde ifølge krav 13, hvor platin-dihalogenid-forbindelsen forefindes i en sådan koncentration, at 75% til 85% af platinet udfældes som det monomere platin-pyrophosphat-kompleks direkte fra reaktionsblandingen efter justering af reaktionsblandingens pH til under 2 ved en temperatur på under 20°C.
15. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 14, som yderligere omfatter at tilsætte et adsorptionsmiddel til reaktionsblandingen, at omrøre reaktionsblandingen i et tidsrum og at fjerne adsorptionsmidlet sammen med uopløste faste stoffer inden udfældningen.
16. Fremgangsmåde ifølge krav 15, hvor adsorptionsmidlet er aktivt kul.
17. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 14, som yderligere omfatter at lede reaktionsblandingen gennem et in-line filterelement, der omfatter et filtermedium, for at opnå en klar filtratopløsning af reaktionsblandingen inden udfældningen.
18. Fremgangsmåde ifølge krav 17, hvor den klare filtratopløsning overføres til en anden ren beholder til udfældningen.
19. Fremgangsmåde ifølge krav 17, hvor den klare filtratopløsning føres tilbage til reaktionsbeholderen, indtil hele reaktionsblandingen biiveren klar opløsning inden udfældningen.
20. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 19, hvor platin-dihalogenid-forbindelsen har formlen:
hvor R1 og R2 er to aminligander, som er uafhængigt valgt blandt NH3, substituerede eller usubstituerede alifatiske aminer og substituerede eller usubstituerede aromatiske aminer; og X er halogen valgt blandt Cl, Br og I.
21. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 19, hvor platin-dihalogenid-forbindelsen har formlen:
hvor R3 er en organisk diaminligand, og X er halogen valgt blandt Cl, Br og I.
22. Fremgangsmåde ifølge krav 21, hvor den organiske diamin er valgt blandt substituerede eller usubstituerede alifatiske 1,2-diaminer og substituerede eller usubstituerede aromatiske 1,2-diaminer.
23. Fremgangsmåde ifølge krav 21, hvor den organiske diamin er valgt blandt 1,2-ethylendiamin og cyclohexan-1,2-diamin.
24. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 23, som yderligere omfatter trinene, der går ud på at opløse det monomere platin-pyrophosphat-kompleks i en buffer og at udkrystallisere komplekset fra bufferen.
25. Fremgangsmåde ifølge et hvilket som helst af kravene 1 til 19, hvor det monomere platin-pyrophosphat-kompleks har formlen (I) eller (II): (i)
(II), eller et salt deraf, hvor R1 og R2 hver er uafhængigt valgt blandt NH3, substituerede eller usubstituerede alifatiske aminer og substituerede eller usubstituerede aromatiske aminer; og hvor R3 er valgt blandt substituerede eller usubstituerede alifatiske diaminer og substituerede eller usubstituerede aromatiske diaminer.
26. Fremgangsmåde ifølge krav 25, hvor R1 og R2 hver er uafhængigt valgt blandt NH3, methylamin, ethylamin, propylamin, isopropylamin, butylamin, cyclohexanamin, anilin, pyridin og substitueret pyridin; og R3 er valgt blandt 1,2-ethylendiamin og cyclohexan-1,2-diamin.
27. Fremgangsmåde ifølge krav 25, hvor platinkomplekset (II) er valgt blandt: /
/ t og salte og blandinger deraf.
28. Fremgangsmåde til fremstilling af et monomert platin (IV)-pyro-phosphat-kompleks eller et salt deraf, hvilken fremgangsmåde omfatter: (1) at fremstille et monomert platin (ll)-pyro-phosphat-kompleks ved fremgangsmåden ifølge et hvilket som helst af kravene 1 til 27; (2) at oxidere det i (1) dannede monomere platin (ll)-pyro-phosphat-kompleks med hydrogen peroxid, og (3) at isolere det monomere platin (IV)-pyro-phosphat-kompleks.
29. Fremgangsmåde ifølge krav 28, hvor det monomere platin (IV)-pyro-phosphat-kompleks har formlen (III) eller (IV): (HI)
(IV) eller et salt deraf, hvor R1 og R2 hver er uafhængigt valgt blandt NH3, substituerede eller usubstituerede alifatiske aminer og substituerede eller usubstituerede aromatiske aminer; og hvor R3 er valgt blandt substituerede eller usubstituerede alifatiske diaminer og substituerede eller usubstituerede aromatiske diaminer.
30. Fremgangsmåde ifølge krav 29, hvor det monomere platin (IV)-pyro-phosphat-kompleks har formlen (IV), og hvor R3 er 1,2-ethylendiamin eller cyclohexan-1,2-diamin.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261651200P | 2012-05-24 | 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 |
|---|---|
| DK2855496T3 true DK2855496T3 (da) | 2017-03-27 |
Family
ID=49624225
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK16203851T DK3202769T3 (da) | 2012-05-24 | 2013-03-15 | Fremgangsmåde til oprensning af phosphaplatinforbindelser |
| DK13793812.2T DK2855496T3 (da) | 2012-05-24 | 2013-03-15 | Fremgangsmåder til syntese og oprensning af phosphaplatinforbindelser og anvendelser deraf |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK16203851T DK3202769T3 (da) | 2012-05-24 | 2013-03-15 | Fremgangsmåde til oprensning af phosphaplatinforbindelser |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US8846964B2 (da) |
| EP (2) | EP3202769B1 (da) |
| JP (1) | JP5833795B2 (da) |
| CN (2) | CN106967124B (da) |
| CY (2) | CY1118746T1 (da) |
| DK (2) | DK3202769T3 (da) |
| ES (2) | ES2751668T3 (da) |
| HR (2) | HRP20170416T1 (da) |
| HU (2) | HUE046327T2 (da) |
| IN (1) | IN2014KN02722A (da) |
| LT (2) | LT3202769T (da) |
| PL (2) | PL2855496T3 (da) |
| PT (2) | PT2855496T (da) |
| RS (2) | RS59725B1 (da) |
| SI (2) | SI3202769T1 (da) |
| SM (2) | SMT201700168T1 (da) |
| TW (2) | TWI599361B (da) |
| WO (1) | WO2013176764A1 (da) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SMT201700168T1 (it) * | 2012-05-24 | 2017-05-08 | Phosplatin Therapeutics Llc | Metodi di sintesi e di purificazione per composti di fosfaplatino e utilizzi degli stessi |
| KR102419247B1 (ko) | 2016-04-06 | 2022-07-11 | 포스플라틴 테라퓨틱스 인코포레이티드 | 포스파플라틴 액제 제형 |
| KR102718532B1 (ko) * | 2017-01-06 | 2024-10-21 | 프로몬토리 테라퓨틱스 인코포레이티드 | 뼈 또는 혈액 암의 치료를 위한 치료제로서의 포스파플라틴 화합물 |
| JP7381083B2 (ja) * | 2017-09-08 | 2023-11-15 | フォスプラティン テラピューティクス インコーポレイテッド | 免疫調節剤としてのホスファプラチン化合物およびその治療的使用 |
| 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 |
| US7956208B2 (en) * | 2006-01-30 | 2011-06-07 | Platco Technologies (Proprietary) Limited | Preparation of platinum (II) complexes |
| AU2008254748A1 (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 |
| WO2009021081A2 (en) * | 2007-08-06 | 2009-02-12 | Ohio University | Phosphaplatins and their use in the treatment of cancers resistant to cisplatin and carboplatin |
| CN108409795B (zh) * | 2010-06-04 | 2024-09-27 | 俄亥俄大学 | 磷铂及其在治疗癌症中的用途 |
| JP6027619B2 (ja) * | 2011-10-05 | 2016-11-16 | ラシンドラ・エヌ・ボーズ | ホスファプラチン系抗腫瘍剤の大規模調製のための効率的プロセス |
| SMT201700168T1 (it) * | 2012-05-24 | 2017-05-08 | Phosplatin Therapeutics Llc | Metodi di sintesi e di purificazione per composti di fosfaplatino e utilizzi degli stessi |
-
2013
- 2013-03-15 SM SM20170168T patent/SMT201700168T1/it unknown
- 2013-03-15 ES ES16203851T patent/ES2751668T3/es active Active
- 2013-03-15 LT LT16203851T patent/LT3202769T/lt unknown
- 2013-03-15 SI SI201331598T patent/SI3202769T1/sl unknown
- 2013-03-15 CN CN201710071127.6A patent/CN106967124B/zh active Active
- 2013-03-15 ES ES13793812.2T patent/ES2619412T3/es active Active
- 2013-03-15 RS RS20191364A patent/RS59725B1/sr unknown
- 2013-03-15 HR HRP20170416TT patent/HRP20170416T1/hr unknown
- 2013-03-15 DK DK16203851T patent/DK3202769T3/da active
- 2013-03-15 JP JP2015514010A patent/JP5833795B2/ja active Active
- 2013-03-15 PL PL13793812T patent/PL2855496T3/pl unknown
- 2013-03-15 RS RS20170272A patent/RS55806B1/sr unknown
- 2013-03-15 PL PL16203851T patent/PL3202769T3/pl unknown
- 2013-03-15 PT PT137938122T patent/PT2855496T/pt unknown
- 2013-03-15 IN IN2722KON2014 patent/IN2014KN02722A/en unknown
- 2013-03-15 WO PCT/US2013/031885 patent/WO2013176764A1/en not_active Ceased
- 2013-03-15 EP EP16203851.7A patent/EP3202769B1/en active Active
- 2013-03-15 CN CN201380026289.8A patent/CN104540839B/zh active Active
- 2013-03-15 PT PT162038517T patent/PT3202769T/pt unknown
- 2013-03-15 SI SI201330565A patent/SI2855496T1/sl unknown
- 2013-03-15 HU HUE16203851A patent/HUE046327T2/hu unknown
- 2013-03-15 LT LTEP13793812.2T patent/LT2855496T/lt unknown
- 2013-03-15 HU HUE13793812A patent/HUE032197T2/en unknown
- 2013-03-15 EP EP13793812.2A patent/EP2855496B1/en active Active
- 2013-03-15 DK DK13793812.2T patent/DK2855496T3/da active
- 2013-03-15 SM SM20190617T patent/SMT201900617T1/it unknown
- 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 |
|---|---|---|
| DK2855496T3 (da) | Fremgangsmåder til syntese og oprensning af phosphaplatinforbindelser og anvendelser deraf | |
| US7956208B2 (en) | Preparation of platinum (II) complexes | |
| CN108521780B (zh) | 一锅法制备双二羧酸二氨络铂(ii)衍生物的方法 | |
| EP1680434B1 (en) | Oxaliplatin with a low content of accompanying impurities and a method for preparation thereof | |
| CN112262123B (zh) | 一种双二羧酸二氨络铂(ii)衍生物的纯化方法 | |
| HK1240939A1 (en) | Purification method for phosphaplatin compounds | |
| HK1240939B (en) | Purification method for phosphaplatin compounds | |
| HK1203202B (en) | Synthetic and purification methods for phosphaplatin compounds and uses thereof | |
| EP2330110A1 (en) | Platinum(II) complexes, preparation and use |