FI65261C - Foerfarande foer framstaellning av farmakologiskt anvaendbart dinatriumsalt av n-(fosfonoacetyl)-l-asparaginsyra - Google Patents
Foerfarande foer framstaellning av farmakologiskt anvaendbart dinatriumsalt av n-(fosfonoacetyl)-l-asparaginsyra Download PDFInfo
- Publication number
- FI65261C FI65261C FI783467A FI783467A FI65261C FI 65261 C FI65261 C FI 65261C FI 783467 A FI783467 A FI 783467A FI 783467 A FI783467 A FI 783467A FI 65261 C FI65261 C FI 65261C
- Authority
- FI
- Finland
- Prior art keywords
- pala
- ethanol
- phosphonoacetyl
- disodium
- water
- Prior art date
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 106
- ZZKNRXZVGOYGJT-VKHMYHEASA-N (2s)-2-[(2-phosphonoacetyl)amino]butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)CP(O)(O)=O ZZKNRXZVGOYGJT-VKHMYHEASA-N 0.000 claims description 86
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 73
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 47
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 34
- 229960000583 acetic acid Drugs 0.000 claims description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- PEOGKOTVGUTAEM-UHFFFAOYSA-N (2-chloro-2-oxoethyl)phosphonic acid Chemical compound OP(O)(=O)CC(Cl)=O PEOGKOTVGUTAEM-UHFFFAOYSA-N 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 12
- 239000012362 glacial acetic acid Substances 0.000 claims description 11
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 8
- 150000003946 cyclohexylamines Chemical class 0.000 claims description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 8
- 229960005261 aspartic acid Drugs 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 6
- 239000001632 sodium acetate Substances 0.000 claims description 6
- 235000017281 sodium acetate Nutrition 0.000 claims description 6
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 claims description 5
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 claims description 5
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 4
- 239000012535 impurity Substances 0.000 claims description 4
- WZCWSQWJAAXHCP-QVTWQEFQSA-J tetrasodium;(2s)-2-[(2-phosphonatoacetyl)amino]butanedioate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)C[C@@H](C([O-])=O)NC(=O)CP([O-])([O-])=O WZCWSQWJAAXHCP-QVTWQEFQSA-J 0.000 claims description 4
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 claims description 3
- 229950011008 tetrachloroethylene Drugs 0.000 claims description 3
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 2
- 230000000144 pharmacologic effect Effects 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims 1
- 239000000243 solution Substances 0.000 description 47
- 239000000203 mixture Substances 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 26
- 239000007787 solid Substances 0.000 description 25
- -1 phosphonoacetyl Chemical group 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 22
- 150000001875 compounds Chemical class 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- 150000003839 salts Chemical class 0.000 description 21
- 239000000463 material Substances 0.000 description 18
- 239000000706 filtrate Substances 0.000 description 16
- 239000003921 oil Substances 0.000 description 16
- 235000019198 oils Nutrition 0.000 description 16
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000011521 glass Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- MHLMRBVCMNDOCW-UHFFFAOYSA-N acetic acid;butan-1-ol;hydrate Chemical compound O.CC(O)=O.CCCCO MHLMRBVCMNDOCW-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 239000001913 cellulose Substances 0.000 description 7
- 229920002678 cellulose Polymers 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 7
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 7
- 230000003287 optical effect Effects 0.000 description 7
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 7
- 230000003595 spectral effect Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 230000009466 transformation Effects 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- JDWFOTLBRARKLZ-UHFFFAOYSA-N azanium;ethanol;hydroxide;hydrate Chemical compound [NH4+].O.[OH-].CCO JDWFOTLBRARKLZ-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 229910052698 phosphorus Inorganic materials 0.000 description 6
- 239000011574 phosphorus Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000007912 intraperitoneal administration Methods 0.000 description 4
- 239000012299 nitrogen atmosphere Substances 0.000 description 4
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- HLMUYZYLPUHSNV-NTISSMGPSA-N [(2s)-1,4-dioxo-1,4-bis(phenylmethoxy)butan-2-yl]azanium;4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C([C@H](N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 HLMUYZYLPUHSNV-NTISSMGPSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 3
- 239000012258 stirred mixture Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 235000019502 Orange oil Nutrition 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- BQAMWLOABQRMAO-INIZCTEOSA-N dibenzyl (2s)-2-aminobutanedioate Chemical compound C([C@H](N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 BQAMWLOABQRMAO-INIZCTEOSA-N 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000010502 orange oil Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- GTLWADFFABIGAE-UHFFFAOYSA-N 1-chloroethylbenzene Chemical compound CC(Cl)C1=CC=CC=C1 GTLWADFFABIGAE-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000001382 Experimental Melanoma Diseases 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
- 241000124008 Mammalia Species 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000003637 basic solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003729 cation exchange resin Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 238000010549 co-Evaporation Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000013058 crude material Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000694 effects 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
- 239000000839 emulsion Substances 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 201000003866 lung sarcoma Diseases 0.000 description 1
- NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 150000004685 tetrahydrates Chemical class 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85138277A | 1977-11-14 | 1977-11-14 | |
| US85138277 | 1977-11-14 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI783467A7 FI783467A7 (fi) | 1979-05-15 |
| FI65261B FI65261B (fi) | 1983-12-30 |
| FI65261C true FI65261C (fi) | 1984-04-10 |
Family
ID=25310650
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI783467A FI65261C (fi) | 1977-11-14 | 1978-11-14 | Foerfarande foer framstaellning av farmakologiskt anvaendbart dinatriumsalt av n-(fosfonoacetyl)-l-asparaginsyra |
Country Status (14)
| Country | Link |
|---|---|
| JP (1) | JPS5492920A (de) |
| AT (1) | AT374485B (de) |
| AU (1) | AU520966B2 (de) |
| CA (1) | CA1110266A (de) |
| CH (1) | CH636595A5 (de) |
| DE (1) | DE2849396A1 (de) |
| DK (1) | DK149134C (de) |
| FI (1) | FI65261C (de) |
| FR (1) | FR2408617A1 (de) |
| GB (2) | GB2008118B (de) |
| GR (1) | GR65247B (de) |
| NL (1) | NL7811252A (de) |
| NZ (1) | NZ188909A (de) |
| SE (1) | SE439774B (de) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4284579A (en) * | 1979-07-17 | 1981-08-18 | The United States Of America As Represented By The Of The Department Of Health & Human Services | (N-Phosphonacetyl-L-aspartato)(1,2-diaminocyclchexane)platinum(II) or alkali metal salt |
-
1978
- 1978-11-13 AU AU41528/78A patent/AU520966B2/en not_active Expired
- 1978-11-14 FI FI783467A patent/FI65261C/fi not_active IP Right Cessation
- 1978-11-14 GB GB7844508A patent/GB2008118B/en not_active Expired
- 1978-11-14 JP JP13947278A patent/JPS5492920A/ja active Pending
- 1978-11-14 DE DE19782849396 patent/DE2849396A1/de not_active Withdrawn
- 1978-11-14 SE SE7811736A patent/SE439774B/sv not_active IP Right Cessation
- 1978-11-14 DK DK506278A patent/DK149134C/da not_active IP Right Cessation
- 1978-11-14 AT AT0813278A patent/AT374485B/de active
- 1978-11-14 GB GB8024584A patent/GB2051070B/en not_active Expired
- 1978-11-14 GR GR57650A patent/GR65247B/el unknown
- 1978-11-14 NZ NZ188909A patent/NZ188909A/xx unknown
- 1978-11-14 CA CA316,224A patent/CA1110266A/en not_active Expired
- 1978-11-14 CH CH1170578A patent/CH636595A5/fr not_active IP Right Cessation
- 1978-11-14 NL NL7811252A patent/NL7811252A/xx not_active Application Discontinuation
- 1978-11-14 FR FR7832098A patent/FR2408617A1/fr active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| SE7811736L (sv) | 1979-05-15 |
| JPS5492920A (en) | 1979-07-23 |
| DK149134B (da) | 1986-02-10 |
| NZ188909A (en) | 1980-10-08 |
| SE439774B (sv) | 1985-07-01 |
| FR2408617B1 (de) | 1983-11-18 |
| FR2408617A1 (fr) | 1979-06-08 |
| GB2008118A (en) | 1979-05-31 |
| FI65261B (fi) | 1983-12-30 |
| GR65247B (en) | 1980-07-31 |
| AU520966B2 (en) | 1982-03-11 |
| AT374485B (de) | 1984-04-25 |
| AU4152878A (en) | 1979-05-24 |
| NL7811252A (nl) | 1979-05-16 |
| GB2008118B (en) | 1982-08-04 |
| DK506278A (da) | 1979-05-15 |
| DK149134C (da) | 1986-07-14 |
| ATA813278A (de) | 1983-09-15 |
| CH636595A5 (fr) | 1983-06-15 |
| GB2051070B (en) | 1982-08-04 |
| DE2849396A1 (de) | 1979-05-17 |
| FI783467A7 (fi) | 1979-05-15 |
| CA1110266A (en) | 1981-10-06 |
| GB2051070A (en) | 1981-01-14 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: STARKS ASSOCIATES INC. |