SE458203B - Foerfarande foer framstaellning av 4-karbamoyloxiazafosforiner samt farmaceutiska beredningar foer behandling av maligna tumoerer och liknande maligna sjukdomar - Google Patents
Foerfarande foer framstaellning av 4-karbamoyloxiazafosforiner samt farmaceutiska beredningar foer behandling av maligna tumoerer och liknande maligna sjukdomarInfo
- Publication number
- SE458203B SE458203B SE8105340A SE8105340A SE458203B SE 458203 B SE458203 B SE 458203B SE 8105340 A SE8105340 A SE 8105340A SE 8105340 A SE8105340 A SE 8105340A SE 458203 B SE458203 B SE 458203B
- Authority
- SE
- Sweden
- Prior art keywords
- alkyl
- hydrogen
- mmol
- chloroethyl
- hydroxy
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 7
- 206010028980 Neoplasm Diseases 0.000 title claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 title claims description 3
- 238000002360 preparation method Methods 0.000 title claims description 3
- 238000011282 treatment Methods 0.000 title claims description 3
- 201000010099 disease Diseases 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title 1
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 150000002431 hydrogen Chemical group 0.000 claims description 8
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- VZZWPFPWQGVAHK-UHFFFAOYSA-N 2h-oxazaphosphinin-4-yl carbamate Chemical class NC(=O)OC1=PNOC=C1 VZZWPFPWQGVAHK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012442 inert solvent Substances 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003377 acid catalyst Substances 0.000 claims description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 230000036210 malignancy Effects 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 238000002844 melting Methods 0.000 description 19
- 230000008018 melting Effects 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- -1 alkyl ketones Chemical class 0.000 description 11
- 239000013078 crystal Substances 0.000 description 10
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- RANONBLIHMVXAJ-UHFFFAOYSA-N 4-hydroxycyclophosphamide Chemical compound OC1CCOP(=O)(N(CCCl)CCCl)N1 RANONBLIHMVXAJ-UHFFFAOYSA-N 0.000 description 9
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 229960001330 hydroxycarbamide Drugs 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- GHTXIUJUEVFYHW-NYYWCZLTSA-N (ne)-n-[3-[amino-[bis(2-chloroethyl)amino]phosphoryl]oxypropylidene]hydroxylamine Chemical compound ClCCN(CCCl)P(=O)(N)OCC\C=N\O GHTXIUJUEVFYHW-NYYWCZLTSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical class NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000004202 carbamide Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 4
- DRAJWRKLRBNJRQ-UHFFFAOYSA-N Hydroxycarbamic acid Chemical class ONC(O)=O DRAJWRKLRBNJRQ-UHFFFAOYSA-N 0.000 description 4
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 229960004397 cyclophosphamide Drugs 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- KMUZEPMBBDHYBC-UHFFFAOYSA-N 2-(hydroxycarbamoylamino)acetic acid Chemical compound ONC(=O)NCC(O)=O KMUZEPMBBDHYBC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 235000021395 porridge Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- IZJCEZHCNFRDKR-UHFFFAOYSA-N 4-ethoxy-2h-oxazaphosphinine Chemical compound CCOC1=PNOC=C1 IZJCEZHCNFRDKR-UHFFFAOYSA-N 0.000 description 2
- QTALEJBFHUYLPY-UHFFFAOYSA-N C(C)(=O)O.C(C1=CC=CC=C1)N=C=O Chemical compound C(C)(=O)O.C(C1=CC=CC=C1)N=C=O QTALEJBFHUYLPY-UHFFFAOYSA-N 0.000 description 2
- 101100298295 Drosophila melanogaster flfl gene Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- FLCMCTKYSHCVAJ-UHFFFAOYSA-N OC1=PNOC=C1 Chemical class OC1=PNOC=C1 FLCMCTKYSHCVAJ-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 239000004133 Sodium thiosulphate Substances 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- BJCVXPUCICIZQC-UHFFFAOYSA-N benzyl 2-(hydroxycarbamoylamino)acetate Chemical compound ONC(=O)NCC(=O)OCC1=CC=CC=C1 BJCVXPUCICIZQC-UHFFFAOYSA-N 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229910052717 sulfur Chemical group 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- NEHSQHPPBUJKKZ-UHFFFAOYSA-N 1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-1-hydroxyurea Chemical compound NC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 NEHSQHPPBUJKKZ-UHFFFAOYSA-N 0.000 description 1
- AKGCYKHMRWIWJQ-UHFFFAOYSA-N 1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-3-(2-bromophenyl)-1-hydroxyurea Chemical compound C=1C=CC=C(Br)C=1NC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 AKGCYKHMRWIWJQ-UHFFFAOYSA-N 0.000 description 1
- QFZCQXSJDLVPCY-UHFFFAOYSA-N 1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-3-(4-bromophenyl)-1-hydroxyurea Chemical compound C=1C=C(Br)C=CC=1NC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 QFZCQXSJDLVPCY-UHFFFAOYSA-N 0.000 description 1
- DPSSZJQTMCEKNL-UHFFFAOYSA-N 1-[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]-3-cyclohexyl-1-hydroxyurea Chemical compound C1CCCCC1NC(=O)N(O)C1CCOP(=O)(N(CCCl)CCCl)N1 DPSSZJQTMCEKNL-UHFFFAOYSA-N 0.000 description 1
- CZQIJQFTRGDODI-UHFFFAOYSA-N 1-bromo-4-isocyanatobenzene Chemical compound BrC1=CC=C(N=C=O)C=C1 CZQIJQFTRGDODI-UHFFFAOYSA-N 0.000 description 1
- SXJYSIBLFGQAND-UHFFFAOYSA-N 1-isocyanato-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(N=C=O)=C1 SXJYSIBLFGQAND-UHFFFAOYSA-N 0.000 description 1
- GFNKTLQTQSALEJ-UHFFFAOYSA-N 1-isocyanato-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(N=C=O)C=C1 GFNKTLQTQSALEJ-UHFFFAOYSA-N 0.000 description 1
- RAXABQCFPAWRSY-UHFFFAOYSA-N 2-[bis(2-chloroethyl)amino]-3-(2-chloroethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-ol Chemical compound OC1CCOP(=O)(N(CCCl)CCCl)N1CCCl RAXABQCFPAWRSY-UHFFFAOYSA-N 0.000 description 1
- ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 description 1
- 241000428352 Amma Species 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- BCSPUHMNKHYRRO-UHFFFAOYSA-N ONC(=O)OCC.ONC(OCC)=O Chemical compound ONC(=O)OCC.ONC(OCC)=O BCSPUHMNKHYRRO-UHFFFAOYSA-N 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- 241000220317 Rosa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- VYWQTJWGWLKBQA-UHFFFAOYSA-N [amino(hydroxy)methylidene]azanium;chloride Chemical class Cl.NC(N)=O VYWQTJWGWLKBQA-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- LURYMYITPCOQAU-UHFFFAOYSA-N benzoyl isocyanate Chemical compound O=C=NC(=O)C1=CC=CC=C1 LURYMYITPCOQAU-UHFFFAOYSA-N 0.000 description 1
- VLQHNAMRWPQWNK-UHFFFAOYSA-N benzyl 2-aminoacetate;hydron;chloride Chemical compound Cl.NCC(=O)OCC1=CC=CC=C1 VLQHNAMRWPQWNK-UHFFFAOYSA-N 0.000 description 1
- PQBSPTAPCMSZAA-UHFFFAOYSA-N benzyl n-hydroxycarbamate Chemical compound ONC(=O)OCC1=CC=CC=C1 PQBSPTAPCMSZAA-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000000973 chemotherapeutic effect Effects 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- KQWGXHWJMSMDJJ-UHFFFAOYSA-N cyclohexyl isocyanate Chemical compound O=C=NC1CCCCC1 KQWGXHWJMSMDJJ-UHFFFAOYSA-N 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- VFKUVJKBMUOOQX-UHFFFAOYSA-N n-hydroxymorpholine-4-carboxamide Chemical compound ONC(=O)N1CCOCC1 VFKUVJKBMUOOQX-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000927 organotoxic Toxicity 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000012958 reprocessing Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system
-
- 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 Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8029222 | 1980-09-10 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SE8105340L SE8105340L (sv) | 1982-03-11 |
| SE458203B true SE458203B (sv) | 1989-03-06 |
Family
ID=10515985
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8105340A SE458203B (sv) | 1980-09-10 | 1981-09-08 | Foerfarande foer framstaellning av 4-karbamoyloxiazafosforiner samt farmaceutiska beredningar foer behandling av maligna tumoerer och liknande maligna sjukdomar |
Country Status (29)
| Country | Link |
|---|---|
| JP (1) | JPS5785396A (fi) |
| AR (1) | AR231989A1 (fi) |
| AT (1) | AT386210B (fi) |
| AU (1) | AU538275B2 (fi) |
| BE (1) | BE890276A (fi) |
| CA (2) | CA1161453A (fi) |
| CH (1) | CH650787A5 (fi) |
| CS (1) | CS227680B2 (fi) |
| DD (1) | DD202166A5 (fi) |
| DE (1) | DE3133309A1 (fi) |
| DK (1) | DK400481A (fi) |
| EG (1) | EG15392A (fi) |
| ES (1) | ES8206544A1 (fi) |
| FI (1) | FI70026C (fi) |
| FR (1) | FR2489825A1 (fi) |
| GR (1) | GR75300B (fi) |
| HU (1) | HU185953B (fi) |
| IE (1) | IE51784B1 (fi) |
| IL (1) | IL63661A (fi) |
| IT (2) | IT1198350B (fi) |
| LU (1) | LU83613A1 (fi) |
| NL (1) | NL8104093A (fi) |
| NO (1) | NO161261C (fi) |
| PL (1) | PL128627B1 (fi) |
| PT (1) | PT73645B (fi) |
| RO (1) | RO83972B (fi) |
| SE (1) | SE458203B (fi) |
| YU (1) | YU42584B (fi) |
| ZA (1) | ZA815922B (fi) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0158057B1 (de) * | 1984-03-01 | 1989-04-26 | ASTA Pharma AG | Neue Salze von Oxazaphosphorin-Derivaten |
| ZA851062B (en) * | 1984-03-01 | 1985-11-27 | Asta Werke Ag Chem Fab | Salts of oxazaphosphorine derivatives and process for their production |
| WO2016089208A2 (en) | 2014-12-04 | 2016-06-09 | Stichting Maastricht Radiation Oncology "Maastro-Clinic" | Sulfonamide, sulfamate and sulfamide derivatives of anti-cancer agents |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA955937A (en) * | 1971-06-28 | 1974-10-08 | Shionogi And Co. Ltd. | Cyclic phosphamide derivatives |
| US3911005A (en) * | 1974-09-12 | 1975-10-07 | Monsanto Co | 1,3,2-Diazaphospholidine compounds |
| JPS5159886A (fi) * | 1974-11-20 | 1976-05-25 | Shionogi Seiyaku Kk |
-
1981
- 1981-08-22 DE DE19813133309 patent/DE3133309A1/de active Granted
- 1981-08-25 IE IE1951/81A patent/IE51784B1/en unknown
- 1981-08-26 IL IL63661A patent/IL63661A/xx not_active IP Right Cessation
- 1981-08-26 AU AU74657/81A patent/AU538275B2/en not_active Ceased
- 1981-08-26 ZA ZA815922A patent/ZA815922B/xx unknown
- 1981-08-31 CH CH5584/81A patent/CH650787A5/de not_active IP Right Cessation
- 1981-08-31 GR GR65896A patent/GR75300B/el unknown
- 1981-09-03 NL NL8104093A patent/NL8104093A/xx not_active Application Discontinuation
- 1981-09-04 CS CS816537A patent/CS227680B2/cs unknown
- 1981-09-07 AT AT0386481A patent/AT386210B/de not_active IP Right Cessation
- 1981-09-07 LU LU83613A patent/LU83613A1/de unknown
- 1981-09-08 EG EG508/81A patent/EG15392A/xx active
- 1981-09-08 HU HU812580A patent/HU185953B/hu unknown
- 1981-09-08 FR FR8116999A patent/FR2489825A1/fr active Granted
- 1981-09-08 DD DD81233132A patent/DD202166A5/de unknown
- 1981-09-08 RO RO105257A patent/RO83972B/ro unknown
- 1981-09-08 SE SE8105340A patent/SE458203B/sv not_active IP Right Cessation
- 1981-09-09 PT PT73645A patent/PT73645B/pt unknown
- 1981-09-09 DK DK400481A patent/DK400481A/da not_active Application Discontinuation
- 1981-09-09 CA CA000385516A patent/CA1161453A/en not_active Expired
- 1981-09-09 ES ES505324A patent/ES8206544A1/es not_active Expired
- 1981-09-09 FI FI812798A patent/FI70026C/fi not_active IP Right Cessation
- 1981-09-09 IT IT23860/81A patent/IT1198350B/it active
- 1981-09-09 JP JP56141108A patent/JPS5785396A/ja active Granted
- 1981-09-09 PL PL1981232960A patent/PL128627B1/pl unknown
- 1981-09-09 BE BE2/59345A patent/BE890276A/fr not_active IP Right Cessation
- 1981-09-09 NO NO813063A patent/NO161261C/no unknown
- 1981-09-10 YU YU2179/81A patent/YU42584B/xx unknown
- 1981-09-10 AR AR286736A patent/AR231989A1/es active
-
1984
- 1984-05-30 CA CA000455507A patent/CA1184563B/en not_active Expired
- 1984-06-12 IT IT21372/84A patent/IT1220985B/it active
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CZ412898A3 (cs) | Substituované cyklopentanové sloučeniny, použitelné jako inhibitory neuraminidázy | |
| US3867396A (en) | Triazolyl phosphorus compounds | |
| SE446267B (sv) | Nya kinolylguanidinderivat, forfaranden for framstellning derav samt farmaceutiska kompositioner innehallande nemnda derivat | |
| US4283541A (en) | Pyridylacyl-hydroxamates | |
| SE458203B (sv) | Foerfarande foer framstaellning av 4-karbamoyloxiazafosforiner samt farmaceutiska beredningar foer behandling av maligna tumoerer och liknande maligna sjukdomar | |
| CS195677B2 (en) | Method of producing new derivatives of alkyl-n-acyl-6,7-aziridino-6-deamino-7-deoxy-alfa-thiolincosaminide | |
| CS271476B2 (en) | Method of pyrimidine's new derivatives production | |
| US3956500A (en) | Carbamate pesticidal compositions | |
| US3040046A (en) | Quinoxalines and processes for their production | |
| CA2122960A1 (en) | Polycyclic compounds and processes for the preparation thereof | |
| KR910016689A (ko) | 우레아 유도체 및 이의 염, 이를 함유하는 약제학적 조성물 및 이의 제조방법 | |
| Sullivan et al. | Studies in. beta.-lactams. Synthesis of. beta.-lactams via cycloaddition of iminodithiocarbonate esters with azidoketene | |
| US4118389A (en) | Ketoxime carbamates | |
| GB2106896A (en) | N-substituted aziridine-2-carboxylic acid derivatives | |
| US4215075A (en) | Ketoxime carbamates | |
| Rufer et al. | Chemotherapeutic Nitroheterocycles. 6. Substituted 5-aminomethyl-3-(5-nitro-2-imidazolylmethyleneamino)-2-oxazolidinones | |
| US3803145A (en) | Quinoxaline-di-n-oxides | |
| CA1043334A (en) | Carbamate pesticidal compositions | |
| US3980796A (en) | Substituted 2-alkoxycarbonylamine-5-(6)-phenylmercapto-benzimidazoles | |
| US3969511A (en) | Insecticidal, miticidal and lepidoptericidal active isothiuronium complex acids and free bases | |
| US3767808A (en) | Oximecarbamate pesticidal compositions and their use | |
| DE69113338T2 (de) | Pyranobenzoxadiazolderivate. | |
| US2728765A (en) | Penicillin salts of bis-aralkylalkenylenediamines | |
| KR840001670B1 (ko) | 옥탄데센산 아미드의 제조방법 | |
| US4154732A (en) | Ketoxime carbamates |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| NUG | Patent has lapsed |
Ref document number: 8105340-7 Effective date: 19920408 Format of ref document f/p: F |