CA2851254A1 - Efficient processes for large scale preparation of phophaplatins antitumor agents - Google Patents
Efficient processes for large scale preparation of phophaplatins antitumor agents Download PDFInfo
- Publication number
- CA2851254A1 CA2851254A1 CA2851254A CA2851254A CA2851254A1 CA 2851254 A1 CA2851254 A1 CA 2851254A1 CA 2851254 A CA2851254 A CA 2851254A CA 2851254 A CA2851254 A CA 2851254A CA 2851254 A1 CA2851254 A1 CA 2851254A1
- Authority
- CA
- Canada
- Prior art keywords
- reaction mixture
- phosphaplatins
- approximately
- pyrophosphate
- temperature
- 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.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 57
- 230000008569 process Effects 0.000 title claims abstract description 50
- 239000002246 antineoplastic agent Substances 0.000 title description 6
- 238000002360 preparation method Methods 0.000 title description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 68
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims abstract description 33
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 33
- 235000011180 diphosphates Nutrition 0.000 claims abstract description 29
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 18
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 15
- 238000003756 stirring Methods 0.000 claims abstract description 6
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 6
- 239000003446 ligand Substances 0.000 claims description 31
- 239000011541 reaction mixture Substances 0.000 claims description 30
- 150000001412 amines Chemical class 0.000 claims description 12
- 239000000539 dimer Substances 0.000 claims description 3
- 230000001376 precipitating effect Effects 0.000 claims 4
- 239000006227 byproduct Substances 0.000 claims 2
- 230000035484 reaction time Effects 0.000 abstract description 12
- 239000007858 starting material Substances 0.000 abstract description 6
- 239000000463 material Substances 0.000 abstract description 3
- 238000004064 recycling Methods 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 25
- 229940048084 pyrophosphate Drugs 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 15
- 239000000243 solution Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- 229910017604 nitric acid Inorganic materials 0.000 description 6
- NDBYXKQCPYUOMI-UHFFFAOYSA-N platinum(4+) Chemical class [Pt+4] NDBYXKQCPYUOMI-UHFFFAOYSA-N 0.000 description 6
- SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 5
- 239000012467 final product Substances 0.000 description 5
- 238000001556 precipitation Methods 0.000 description 5
- 239000000376 reactant Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 238000004949 mass spectrometry Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 238000012512 characterization method Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 150000003057 platinum Chemical class 0.000 description 3
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000010192 crystallographic characterization Methods 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 238000001394 phosphorus-31 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 150000003058 platinum compounds Chemical class 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002390 rotary evaporation Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 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 2
- 239000000126 substance Substances 0.000 description 2
- 238000003828 vacuum filtration Methods 0.000 description 2
- 238000004679 31P NMR spectroscopy Methods 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 238000012565 NMR experiment Methods 0.000 description 1
- 229920000388 Polyphosphate Chemical class 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000011365 complex material Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000007862 dimeric product Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000011580 nude mouse model Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 239000001205 polyphosphate Chemical class 0.000 description 1
- 235000011176 polyphosphates Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 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 1
- 241000894007 species Species 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical class OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 239000002699 waste material Substances 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)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161543540P | 2011-10-05 | 2011-10-05 | |
| US61/543,540 | 2011-10-05 | ||
| US201213922917A | 2012-10-05 | 2012-10-05 | |
| PCT/US2012/059016 WO2013052839A1 (en) | 2011-10-05 | 2012-10-05 | Efficient processes for large scale preparation of phosphaplatins antitumor agents |
| US13922917 | 2012-10-05 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2851254A1 true CA2851254A1 (en) | 2013-04-11 |
Family
ID=48044196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2851254A Abandoned CA2851254A1 (en) | 2011-10-05 | 2012-10-05 | Efficient processes for large scale preparation of phophaplatins antitumor agents |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN104010508B (zh) |
| CA (1) | CA2851254A1 (zh) |
| WO (1) | WO2013052839A1 (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201808717QA (en) * | 2016-04-06 | 2018-11-29 | Phosplatin Therapeutics Llc | Phosphaplatin liquid formulations |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2173337B1 (en) | 2007-08-06 | 2014-07-30 | Ohio University | Phosphaplatins and their use in the treatment of cancers resistant to cisplantin and carboplatin |
| EP2493608A1 (en) | 2009-10-26 | 2012-09-05 | Celanese International Corporation | Processes for making ethanol from acetic acid |
| WO2011153365A1 (en) * | 2010-06-04 | 2011-12-08 | Ohio University | Phosphaplatins and their use for treatment of cancers |
-
2012
- 2012-10-05 CA CA2851254A patent/CA2851254A1/en not_active Abandoned
- 2012-10-05 CN CN201280059538.9A patent/CN104010508B/zh not_active Expired - Fee Related
- 2012-10-05 WO PCT/US2012/059016 patent/WO2013052839A1/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| WO2013052839A1 (en) | 2013-04-11 |
| CN104010508B (zh) | 2017-03-15 |
| CN104010508A (zh) | 2014-08-27 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20171004 |
|
| FZDE | Discontinued |
Effective date: 20210831 |
|
| FZDE | Discontinued |
Effective date: 20210831 |