HUE032197T2 - Synthetic and purification methods for phosphaplatin compounds and uses thereof - Google Patents
Synthetic and purification methods for phosphaplatin compounds and uses thereof Download PDFInfo
- Publication number
- HUE032197T2 HUE032197T2 HUE13793812A HUE13793812A HUE032197T2 HU E032197 T2 HUE032197 T2 HU E032197T2 HU E13793812 A HUE13793812 A HU E13793812A HU E13793812 A HUE13793812 A HU E13793812A HU E032197 T2 HUE032197 T2 HU E032197T2
- Authority
- HU
- Hungary
- Prior art keywords
- platinum
- complex
- dach
- reaction mixture
- pyrophosphate
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 130
- 150000001875 compounds Chemical class 0.000 title claims abstract description 30
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 238000000746 purification Methods 0.000 title claims abstract description 18
- 230000015572 biosynthetic process Effects 0.000 title description 22
- 238000003786 synthesis reaction Methods 0.000 title description 22
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 121
- 238000006243 chemical reaction Methods 0.000 claims description 70
- 239000011541 reaction mixture Substances 0.000 claims description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 61
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 48
- 229910052697 platinum Inorganic materials 0.000 claims description 45
- 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 42
- 230000008569 process Effects 0.000 claims description 40
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 39
- 239000002244 precipitate Substances 0.000 claims description 37
- -1 aliphatic amines Chemical class 0.000 claims description 36
- 229910017604 nitric acid Inorganic materials 0.000 claims description 35
- 235000011180 diphosphates Nutrition 0.000 claims description 31
- 229940048084 pyrophosphate Drugs 0.000 claims description 30
- 229910001868 water Inorganic materials 0.000 claims description 29
- 238000003756 stirring Methods 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 23
- 238000001556 precipitation Methods 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 19
- 150000004985 diamines Chemical class 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 13
- 239000003960 organic solvent Substances 0.000 claims description 13
- 238000001816 cooling Methods 0.000 claims description 12
- 239000000872 buffer Substances 0.000 claims description 11
- 150000004982 aromatic amines Chemical class 0.000 claims description 10
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 9
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 7
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 7
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 239000003463 adsorbent Substances 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 6
- 239000011707 mineral Substances 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 239000012141 concentrate Substances 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 239000000178 monomer Substances 0.000 claims 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- 229920002472 Starch Polymers 0.000 claims 1
- 229910052785 arsenic Inorganic materials 0.000 claims 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims 1
- 239000012803 melt mixture Substances 0.000 claims 1
- 239000003921 oil Substances 0.000 claims 1
- 230000001175 peptic effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000011347 resin Substances 0.000 claims 1
- 229920005989 resin Polymers 0.000 claims 1
- 235000019698 starch Nutrition 0.000 claims 1
- 239000008107 starch Substances 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 238000010189 synthetic method Methods 0.000 abstract description 5
- 239000008177 pharmaceutical agent Substances 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- 239000000243 solution Substances 0.000 description 68
- 239000000047 product Substances 0.000 description 67
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 42
- 239000007787 solid Substances 0.000 description 42
- 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
- 238000002955 isolation Methods 0.000 description 16
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 15
- 239000003446 ligand Substances 0.000 description 15
- 238000001953 recrystallisation Methods 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 14
- 230000001376 precipitating effect Effects 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 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
- 235000019818 tetrasodium diphosphate Nutrition 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
- 239000000706 filtrate Substances 0.000 description 9
- 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
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 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
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 7
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 229940048086 sodium pyrophosphate Drugs 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 239000001577 tetrasodium phosphonato phosphate 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
- 125000005233 alkylalcohol group Chemical group 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000004255 ion exchange chromatography Methods 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- 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
- 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 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
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 235000010755 mineral Nutrition 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
- 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
- 150000004984 aromatic diamines Chemical class 0.000 description 3
- 201000011510 cancer Diseases 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
- 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
- 230000001590 oxidative effect Effects 0.000 description 3
- 238000010979 pH adjustment Methods 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
- 238000013341 scale-up Methods 0.000 description 3
- 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
- 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
- YMHQVDAATAEZLO-UHFFFAOYSA-N cyclohexane-1,1-diamine Chemical compound NC1(N)CCCCC1 YMHQVDAATAEZLO-UHFFFAOYSA-N 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
- 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
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 2
- 230000002611 ovarian Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 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
- 150000003222 pyridines Chemical class 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
- 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
- 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
- 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
- 238000013019 agitation Methods 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
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 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
- 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
- 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
- 238000000655 nuclear magnetic resonance spectrum Methods 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
- 230000003647 oxidation Effects 0.000 description 1
- 239000002245 particle 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
- 239000000758 substrate Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 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 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)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261651200P | 2012-05-24 | 2012-05-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HUE032197T2 true HUE032197T2 (en) | 2017-09-28 |
Family
ID=49624225
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE13793812A HUE032197T2 (en) | 2012-05-24 | 2013-03-15 | Synthetic and purification methods for phosphaplatin compounds and uses thereof |
| HUE16203851A HUE046327T2 (hu) | 2012-05-24 | 2013-03-15 | Tisztítási eljárás foszfaplatin vegyületekhez |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HUE16203851A HUE046327T2 (hu) | 2012-05-24 | 2013-03-15 | Tisztítási eljárás foszfaplatin vegyületekhez |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US8846964B2 (enExample) |
| EP (2) | EP2855496B1 (enExample) |
| JP (1) | JP5833795B2 (enExample) |
| CN (2) | CN106967124B (enExample) |
| CY (2) | CY1118746T1 (enExample) |
| DK (2) | DK3202769T3 (enExample) |
| ES (2) | ES2619412T3 (enExample) |
| HR (2) | HRP20170416T1 (enExample) |
| HU (2) | HUE032197T2 (enExample) |
| IN (1) | IN2014KN02722A (enExample) |
| LT (2) | LT2855496T (enExample) |
| PL (2) | PL3202769T3 (enExample) |
| PT (2) | PT3202769T (enExample) |
| RS (2) | RS59725B1 (enExample) |
| SI (2) | SI2855496T1 (enExample) |
| SM (2) | SMT201700168T1 (enExample) |
| TW (2) | TWI653237B (enExample) |
| WO (1) | WO2013176764A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT3202769T (pt) * | 2012-05-24 | 2019-10-31 | Phosplatin Therapeutics Llc | Processos de síntese e de purificação para compostos de fosfaplatina e aplicações dos mesmos |
| KR102419247B1 (ko) * | 2016-04-06 | 2022-07-11 | 포스플라틴 테라퓨틱스 인코포레이티드 | 포스파플라틴 액제 제형 |
| CN110381952B (zh) | 2017-01-06 | 2023-10-20 | 弗斯普拉廷治疗有限公司 | 作为治疗剂用于治疗骨癌或血癌的磷铂化合物 |
| 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 |
| KR20080096682A (ko) * | 2006-01-30 | 2008-10-31 | 플라트코 테크놀로지스 (프로프라이어터리) 리미티드 | 백금(ⅱ) 착물의 제조법 |
| NZ582049A (en) * | 2007-05-18 | 2012-12-21 | Tti Ellebeau Inc | Transdermal delivery devices assuring an improved release of an active principle through a biological interface |
| PL2173337T3 (pl) | 2007-08-06 | 2014-11-28 | Univ Ohio | Fosfaplatyny i ich zastosowanie w leczeniu raków opornych na cisplatynę i karboplatynę |
| JP5860872B2 (ja) * | 2010-06-04 | 2016-02-16 | オハイオ ユニバーシティー | ホスファプラチン、及び癌治療のためのそれらの使用 |
| MX357865B (es) * | 2011-10-05 | 2018-07-25 | N Bose Rathindra | Procedimientos eficientes para preparación a gran escala de agentes antitumorales de fosfaplatinos. |
| PT3202769T (pt) * | 2012-05-24 | 2019-10-31 | Phosplatin Therapeutics Llc | Processos de síntese e de purificação para compostos de fosfaplatina e aplicações dos mesmos |
-
2013
- 2013-03-15 PT PT162038517T patent/PT3202769T/pt unknown
- 2013-03-15 EP EP13793812.2A patent/EP2855496B1/en active Active
- 2013-03-15 RS RS20191364A patent/RS59725B1/sr unknown
- 2013-03-15 CN CN201710071127.6A patent/CN106967124B/zh active Active
- 2013-03-15 HR HRP20170416TT patent/HRP20170416T1/hr unknown
- 2013-03-15 PL PL16203851T patent/PL3202769T3/pl unknown
- 2013-03-15 ES ES13793812.2T patent/ES2619412T3/es active Active
- 2013-03-15 WO PCT/US2013/031885 patent/WO2013176764A1/en not_active Ceased
- 2013-03-15 ES ES16203851T patent/ES2751668T3/es active Active
- 2013-03-15 HU HUE13793812A patent/HUE032197T2/en unknown
- 2013-03-15 SI SI201330565A patent/SI2855496T1/sl unknown
- 2013-03-15 DK DK16203851T patent/DK3202769T3/da active
- 2013-03-15 PL PL13793812T patent/PL2855496T3/pl unknown
- 2013-03-15 HU HUE16203851A patent/HUE046327T2/hu unknown
- 2013-03-15 CN CN201380026289.8A patent/CN104540839B/zh active Active
- 2013-03-15 LT LTEP13793812.2T patent/LT2855496T/lt unknown
- 2013-03-15 IN IN2722KON2014 patent/IN2014KN02722A/en unknown
- 2013-03-15 RS RS20170272A patent/RS55806B1/sr unknown
- 2013-03-15 PT PT137938122T patent/PT2855496T/pt unknown
- 2013-03-15 EP EP16203851.7A patent/EP3202769B1/en active Active
- 2013-03-15 SI SI201331598T patent/SI3202769T1/sl unknown
- 2013-03-15 JP JP2015514010A patent/JP5833795B2/ja active Active
- 2013-03-15 SM SM20170168T patent/SMT201700168T1/it unknown
- 2013-03-15 LT LT16203851T patent/LT3202769T/lt unknown
- 2013-03-15 DK DK13793812.2T patent/DK2855496T3/en active
- 2013-03-15 SM SM20190617T patent/SMT201900617T1/it unknown
- 2013-04-01 TW TW106122720A patent/TWI653237B/zh active
- 2013-04-01 TW TW102111669A patent/TWI599361B/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 |
|---|---|---|
| US8859796B1 (en) | Synthetic and purification methods for phosphaplatin compounds and uses thereof | |
| Cini et al. | Mechanistic and stereochemical investigation of imino ethers formed by alcoholysis of coordinated nitriles: X-ray crystal structures of cis-and trans-bis (1-imino-1-methoxyethane) dichloroplatinum (II) | |
| JP2009525273A (ja) | 白金（ｉｉ）錯体の調製 | |
| JP2018505148A (ja) | セニクリビロックの製造方法及び関連類似体 | |
| CN108521780B (zh) | 一锅法制备双二羧酸二氨络铂(ii)衍生物的方法 | |
| CN101402655A (zh) | 一种米铂的制备方法 | |
| CZ297703B6 (cs) | Oxaliplatina s nízkým obsahem doprovodných necistot a zpusob její výroby | |
| US8637669B2 (en) | Production method for adefovir dipivoxil | |
| CN102127119B (zh) | 一种米铂的制备方法 | |
| 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 | |
| CN107118147B (zh) | 联苯乙酮腙-3-乙酰基吲哚西弗碱的制备、结构和用途 | |
| CN119462542B (zh) | 一种三聚氯氰肟酯及其合成方法 | |
| CN110357907B (zh) | 一种4,6-二(吡啶-2-基)嘧啶-2-胺铜配合物的制备方法及用途 | |
| KR20130021476A (ko) | 라미부딘 옥살레이트 및 이의 제조방법 | |
| JP2010275246A (ja) | ルテニウム錯体の製造方法 | |
| CN112694432B (zh) | 一种阿比朵尔关键中间体的制备方法 | |
| Makarov et al. | Highly polarized enamines. 2. Unusual transformation of α, α-diamino-β-cyano-β-nitroethylene derivatives into 4, 6-bisdimethylamino-5-nitropyrimidine | |
| JP2013245210A (ja) | ルテニウム錯体の製造方法 |