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 PDF

Info

Publication number: FI65261C
Authority: FI; Finland
Prior art keywords: pala; ethanol; phosphonoacetyl; disodium; water
Prior art date: 1977-11-14

Application number

FI783467A

Other languages

English (en)

Finnish (fi)

Other versions

FI783467A7 (fi

FI65261B (fi

Inventor

Robert John Schultz

Fred William Starks

Original Assignee

Starks Ass

Priority date (The priority date 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 date listed.)

1977-11-14

Filing date

1978-11-14

Publication date

1984-04-10

1978-11-14 Application filed by Starks Ass filed Critical Starks Ass

1979-05-15 Publication of FI783467A7 publication Critical patent/FI783467A7/fi

1983-12-30 Application granted granted Critical

1983-12-30 Publication of FI65261B publication Critical patent/FI65261B/fi

1984-04-10 Publication of FI65261C publication Critical patent/FI65261C/fi

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)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

FI783467A 1977-11-14 1978-11-14 Foerfarande foer framstaellning av farmakologiskt anvaendbart dinatriumsalt av n-(fosfonoacetyl)-l-asparaginsyra FI65261C (fi)

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)	GB2051070B (de)
GR (1)	GR65247B (de)
NL (1)	NL7811252A (de)
NZ (1)	NZ188909A (de)
SE (1)	SE439774B (de)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
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 AT AT0813278A patent/AT374485B/de active
- 1978-11-14 SE SE7811736A patent/SE439774B/sv not_active IP Right Cessation
- 1978-11-14 CH CH1170578A patent/CH636595A5/fr not_active IP Right Cessation
- 1978-11-14 NZ NZ188909A patent/NZ188909A/xx unknown
- 1978-11-14 DK DK506278A patent/DK149134C/da 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
- 1978-11-14 DE DE19782849396 patent/DE2849396A1/de not_active Withdrawn
- 1978-11-14 JP JP13947278A patent/JPS5492920A/ja active Pending
- 1978-11-14 GB GB8024584A patent/GB2051070B/en not_active Expired
- 1978-11-14 GR GR57650A patent/GR65247B/el unknown
- 1978-11-14 GB GB7844508A patent/GB2008118B/en not_active Expired
- 1978-11-14 CA CA316,224A patent/CA1110266A/en not_active Expired
- 1978-11-14 FI FI783467A patent/FI65261C/fi not_active IP Right Cessation

Also Published As

Publication number	Publication date
DK506278A (da)	1979-05-15
AU520966B2 (en)	1982-03-11
CA1110266A (en)	1981-10-06
DK149134C (da)	1986-07-14
ATA813278A (de)	1983-09-15
AT374485B (de)	1984-04-25
GB2008118A (en)	1979-05-31
AU4152878A (en)	1979-05-24
CH636595A5 (fr)	1983-06-15
FR2408617A1 (fr)	1979-06-08
SE7811736L (sv)	1979-05-15
SE439774B (sv)	1985-07-01
NZ188909A (en)	1980-10-08
JPS5492920A (en)	1979-07-23
FI783467A7 (fi)	1979-05-15
GB2051070A (en)	1981-01-14
GB2008118B (en)	1982-08-04
DE2849396A1 (de)	1979-05-17
NL7811252A (nl)	1979-05-16
FI65261B (fi)	1983-12-30
DK149134B (da)	1986-02-10
GR65247B (en)	1980-07-31
FR2408617B1 (de)	1983-11-18
GB2051070B (en)	1982-08-04

Legal Events

Date	Code	Title	Description
1996-06-24	MM	Patent lapsed
2004-08-31	MM	Patent lapsed	Owner name: STARKS ASSOCIATES INC.

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