CH636595A5 - Procede de preparation de derives de l'acide n-(phosphonoacetyl)-l-aspartique et derives nouveaux ainsi obtenus. - Google Patents

Procede de preparation de derives de l'acide n-(phosphonoacetyl)-l-aspartique et derives nouveaux ainsi obtenus. Download PDF

Info

Publication number: CH636595A5
Authority: CH; Switzerland
Prior art keywords: ethanol; pala; water; acid; phosphonoacetyl
Prior art date: 1977-11-14

Application number

CH1170578A

Other languages

English (en)

French (fr)

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

1983-06-15

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

1983-06-15 Publication of CH636595A5 publication Critical patent/CH636595A5/fr

Links

239000002253 acid Substances 0.000 title description 19
238000002360 preparation method Methods 0.000 title description 18
-1 phosphonoacetyl Chemical group 0.000 title description 16
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 215
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 description 154
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 109
229910001868 water Inorganic materials 0.000 description 107
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 104
239000000243 solution Substances 0.000 description 87
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 72
239000000047 product Substances 0.000 description 71
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 64
239000000203 mixture Substances 0.000 description 64
150000003839 salts Chemical class 0.000 description 55
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 53
MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 45
229960000583 acetic acid Drugs 0.000 description 41
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
239000007787 solid Substances 0.000 description 33
XUYJLQHKOGNDPB-UHFFFAOYSA-N phosphonoacetic acid Chemical compound OC(=O)CP(O)(O)=O XUYJLQHKOGNDPB-UHFFFAOYSA-N 0.000 description 31
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
239000000706 filtrate Substances 0.000 description 30
238000001914 filtration Methods 0.000 description 30
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 27
150000001875 compounds Chemical class 0.000 description 25
238000000034 method Methods 0.000 description 24
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 23
229960005261 aspartic acid Drugs 0.000 description 23
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 22
239000003921 oil Substances 0.000 description 22
235000019198 oils Nutrition 0.000 description 22
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 21
CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 21
CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 21
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 21
239000011734 sodium Substances 0.000 description 21
229910052698 phosphorus Inorganic materials 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
238000004458 analytical method Methods 0.000 description 18
150000003946 cyclohexylamines Chemical class 0.000 description 17
238000003756 stirring Methods 0.000 description 17
PEOGKOTVGUTAEM-UHFFFAOYSA-N (2-chloro-2-oxoethyl)phosphonic acid Chemical compound OP(O)(=O)CC(Cl)=O PEOGKOTVGUTAEM-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
239000000725 suspension Substances 0.000 description 16
238000004809 thin layer chromatography Methods 0.000 description 16
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 15
238000005481 NMR spectroscopy Methods 0.000 description 15
239000000908 ammonium hydroxide Substances 0.000 description 15
230000008569 process Effects 0.000 description 15
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
150000002148 esters Chemical class 0.000 description 14
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 14
230000003595 spectral effect Effects 0.000 description 14
239000007864 aqueous solution Substances 0.000 description 13
238000006243 chemical reaction Methods 0.000 description 13
238000001514 detection method Methods 0.000 description 13
239000002904 solvent Substances 0.000 description 13
239000001913 cellulose Substances 0.000 description 12
229920002678 cellulose Polymers 0.000 description 12
239000012362 glacial acetic acid Substances 0.000 description 12
239000011521 glass Substances 0.000 description 12
238000012545 processing Methods 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
238000001816 cooling Methods 0.000 description 11
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 11
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 11
230000003287 optical effect Effects 0.000 description 10
239000000843 powder Substances 0.000 description 10
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 9
238000009835 boiling Methods 0.000 description 9
159000000007 calcium salts Chemical class 0.000 description 9
239000003153 chemical reaction reagent Substances 0.000 description 9
239000012043 crude product Substances 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
238000011084 recovery Methods 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 8
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
238000001556 precipitation Methods 0.000 description 8
238000010992 reflux Methods 0.000 description 8
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 7
235000019445 benzyl alcohol Nutrition 0.000 description 7
230000007062 hydrolysis Effects 0.000 description 7
238000006460 hydrolysis reaction Methods 0.000 description 7
239000011574 phosphorus Substances 0.000 description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
239000002246 antineoplastic agent Substances 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
238000012800 visualization Methods 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
230000008030 elimination Effects 0.000 description 5
238000003379 elimination reaction Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
OLAPPGSPBNVTRF-UHFFFAOYSA-N naphthalene-1,4,5,8-tetracarboxylic acid Chemical compound C1=CC(C(O)=O)=C2C(C(=O)O)=CC=C(C(O)=O)C2=C1C(O)=O OLAPPGSPBNVTRF-UHFFFAOYSA-N 0.000 description 5
239000001632 sodium acetate Substances 0.000 description 5
235000017281 sodium acetate Nutrition 0.000 description 5
239000012265 solid product Substances 0.000 description 5
QWUWMCYKGHVNAV-UHFFFAOYSA-N 1,2-dihydrostilbene Chemical group C=1C=CC=CC=1CCC1=CC=CC=C1 QWUWMCYKGHVNAV-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
229940009098 aspartate Drugs 0.000 description 4
239000011575 calcium Substances 0.000 description 4
229910052739 hydrogen Inorganic materials 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
239000012535 impurity Substances 0.000 description 4
238000007912 intraperitoneal administration Methods 0.000 description 4
238000005342 ion exchange Methods 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
239000011347 resin Substances 0.000 description 4
229920005989 resin Polymers 0.000 description 4
238000012360 testing method Methods 0.000 description 4
238000005406 washing Methods 0.000 description 4
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 3
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
206010028980 Neoplasm Diseases 0.000 description 3
235000019502 Orange oil Nutrition 0.000 description 3
CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
230000001464 adherent effect Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
125000002091 cationic group Chemical group 0.000 description 3
238000012512 characterization method Methods 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 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
239000010502 orange oil Substances 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
229950011008 tetrachloroethylene Drugs 0.000 description 3
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 3
IGQGXIVCGKMRAM-UHFFFAOYSA-N 4-amino-3-methylbenzenesulfonamide Chemical compound CC1=CC(S(N)(=O)=O)=CC=C1N IGQGXIVCGKMRAM-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
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 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
241000209140 Triticum Species 0.000 description 2
235000021307 Triticum Nutrition 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
229910052791 calcium Inorganic materials 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
238000010908 decantation Methods 0.000 description 2
238000000921 elemental analysis Methods 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000004108 freeze drying Methods 0.000 description 2
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
239000011630 iodine Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
238000002156 mixing Methods 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
150000004885 piperazines Chemical class 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 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
GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 2
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
SVMQGCLBYPUIFB-WNQIDUERSA-N (2s)-2-aminobutanedioic acid;4-methylbenzenesulfonic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O.CC1=CC=C(S(O)(=O)=O)C=C1 SVMQGCLBYPUIFB-WNQIDUERSA-N 0.000 description 1
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
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
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BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
WMYAVEAHGFUHFE-WNQIDUERSA-N N1CCNCC1.N[C@@H](CC(=O)O)C(=O)O Chemical compound N1CCNCC1.N[C@@H](CC(=O)O)C(=O)O WMYAVEAHGFUHFE-WNQIDUERSA-N 0.000 description 1
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KXSLJPFXTIACAG-UHFFFAOYSA-N [Na].[Na].[Na].[Na].[Na] Chemical compound [Na].[Na].[Na].[Na].[Na] KXSLJPFXTIACAG-UHFFFAOYSA-N 0.000 description 1
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VHUUQVKOLVNVRT-UHFFFAOYSA-O azanium;hydron;hydroxide Chemical compound [NH4+].O VHUUQVKOLVNVRT-UHFFFAOYSA-O 0.000 description 1
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238000005660 chlorination reaction Methods 0.000 description 1
238000013461 design Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
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 1
ILBZEWOOBCRRAP-NTISSMGPSA-N dibenzyl (2s)-2-aminobutanedioate;hydrochloride Chemical compound Cl.C([C@H](N)C(=O)OCC=1C=CC=CC=1)C(=O)OCC1=CC=CC=C1 ILBZEWOOBCRRAP-NTISSMGPSA-N 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
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XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
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238000010253 intravenous injection Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
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208000032839 leukemia Diseases 0.000 description 1
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150000004682 monohydrates Chemical class 0.000 description 1
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ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
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125000004193 piperazinyl group Chemical group 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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239000012264 purified product Substances 0.000 description 1
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239000010935 stainless steel Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
230000004083 survival effect Effects 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
230000009466 transformation Effects 0.000 description 1
238000000844 transformation Methods 0.000 description 1
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 1
239000003039 volatile agent Substances 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
- 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)

CH1170578A 1977-11-14 1978-11-14 Procede de preparation de derives de l'acide n-(phosphonoacetyl)-l-aspartique et derives nouveaux ainsi obtenus. CH636595A5 (fr)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US85138277A	1977-11-14	1977-11-14

Publications (1)

Publication Number	Publication Date
CH636595A5 true CH636595A5 (fr)	1983-06-15

Family

ID=25310650

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH1170578A CH636595A5 (fr)	1977-11-14	1978-11-14	Procede de preparation de derives de l'acide n-(phosphonoacetyl)-l-aspartique et derives nouveaux ainsi obtenus.

Country Status (14)

Country	Link
JP (1)	JPS5492920A (da)
AT (1)	AT374485B (da)
AU (1)	AU520966B2 (da)
CA (1)	CA1110266A (da)
CH (1)	CH636595A5 (da)
DE (1)	DE2849396A1 (da)
DK (1)	DK149134C (da)
FI (1)	FI65261C (da)
FR (1)	FR2408617A1 (da)
GB (2)	GB2008118B (da)
GR (1)	GR65247B (da)
NL (1)	NL7811252A (da)
NZ (1)	NZ188909A (da)
SE (1)	SE439774B (da)

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 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 (da)	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
GB2051070B (en)	1982-08-04
DE2849396A1 (de)	1979-05-17
FI783467A7 (fi)	1979-05-15
CA1110266A (en)	1981-10-06
FI65261C (fi)	1984-04-10
GB2051070A (en)	1981-01-14

Legal Events

Date	Code	Title	Description
1996-07-15	PL	Patent ceased

Publication	Publication Date	Title
EP0318377B1 (fr)	1993-08-25	Nouveaux composés énantiomères dérivés d'amino-acides, leur procédé de préparation et leurs applications thérapeutiques
LU87290A1 (fr)	1990-02-07	Derives de 4'-phosphates de glucosides d'epipodophyllotoxine
JPH02202896A (ja)	1990-08-10	リン脂質ヌクレオシド類
MC1618A1 (fr)	1985-07-18	Steroides
JPS58146560A (ja)	1983-09-01	Ｎ―アセチルシステインのサリチル誘導体及びその製造方法並びにこの誘導体を用いた薬剤
EP0787135A1 (fr)	1997-08-06	Derives hydrosolubles d'epipodophyllotoxine, leur procede de preparation, leur utilisation a titre de medicament, et leur utilisation destinee aux traitements anticancereux
US4348522A (en)	1982-09-07	N-(phosphonacetyl)-L-aspartic acid salts with piperazine, cyclohexylamine and calcium
FR2516924A1 (fr)	1983-05-27	Acides phosphinylalcanoyl- amines a action therapeutique
MC1182A1 (fr)	1978-12-22	Procede de preparation de derives de la guanine
US4215070A (en)	1980-07-29	N-(Phosphonoacetyl)-L-aspartic acid compounds and methods for their preparation
FI65261C (fi)	1984-04-10	Foerfarande foer framstaellning av farmakologiskt anvaendbart dinatriumsalt av n-(fosfonoacetyl)-l-asparaginsyra
US4179464A (en)	1979-12-18	Preparation of N-(phosphonoacetyl)-L-aspartic acid
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EP0121635A1 (fr)	1984-10-17	3',5'-Diarabinosides, leur préparation et leur application en thérapeutique
US4267126A (en)	1981-05-12	N-(Phosphonoacetyl)-L-aspartic acid compounds
EP0311521B1 (fr)	1992-04-08	Dérivés des céphalosphorines à pharmacocinétique améliorée, procédé pour leur préparation, compositions pharmaceutiques les contenant et intermédiaire de synthèse
EP0269512B1 (fr)	1991-09-11	Dérivés des céphalosporines à pharmacocinétique améliorée, procédé pour leur préparation et compositions pharmaceutiques les contenant
WO2009098369A1 (fr)	2009-08-13	Composes antimitotiques derives d'alcaloïdes de vinca, leur preparation et leur application en therapeutique
US3992543A (en)	1976-11-16	(Pyridyl-3)-methyl 2-(p-chlorophenoxy-phenoxy) propionate and use as a hypolipemising drug
MC1242A1 (fr)	1979-10-26	Derives peptidiques,procede pour leur preparation et leur application dans des preparations pharmaceutiques
JPH09505813A (ja)	1997-06-10	ビフェニル沃素化誘導体及びその診断用途
IL37224A (en)	1974-12-31	Pharmaceutical preparations containing 3 - acyloxypropyl - 2 - trimethyl ammonium (noble phosphates
CA2038976C (fr)	1995-09-26	Procede industriel de preparation du n-(desacetyl-0-4 vinblastinoyl-23)amino-1 methyl-2 propylphosphonate de diethyle (1s) et de ses sels
EP0143399A2 (en)	1985-06-05	Cysteine derivatives, a process for their preparation, and pharmaceutical compostions which contain them
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