FI69849C - Foerfarande foer framstaellning av nya oxazafosforin-4-tio-alkansulfonsyror och deras neutrala salter - Google Patents
Foerfarande foer framstaellning av nya oxazafosforin-4-tio-alkansulfonsyror och deras neutrala salter Download PDFInfo
- Publication number
- FI69849C FI69849C FI821021A FI821021A FI69849C FI 69849 C FI69849 C FI 69849C FI 821021 A FI821021 A FI 821021A FI 821021 A FI821021 A FI 821021A FI 69849 C FI69849 C FI 69849C
- Authority
- FI
- Finland
- Prior art keywords
- cation
- hydrogen
- formula
- chloroethyl
- oxazaphosphorin
- Prior art date
Links
- 241000277284 Salvelinus fontinalis Species 0.000 title 1
- 150000001768 cations Chemical class 0.000 claims description 38
- 150000001875 compounds Chemical class 0.000 claims description 28
- -1 2-methanesulfonyloxyethyl Chemical group 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 15
- 239000002585 base Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 12
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 9
- 230000007935 neutral effect Effects 0.000 claims description 8
- 150000007513 acids Chemical class 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 3
- ZRALSGWEFCBTJO-UHFFFAOYSA-O guanidinium Chemical compound NC(N)=[NH2+] ZRALSGWEFCBTJO-UHFFFAOYSA-O 0.000 claims description 3
- YNAVUWVOSKDBBP-UHFFFAOYSA-O morpholinium Chemical compound [H+].C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-O 0.000 claims description 3
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical compound [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 238000006386 neutralization reaction Methods 0.000 claims 4
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 1
- 150000002500 ions Chemical class 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 18
- RANONBLIHMVXAJ-UHFFFAOYSA-N 4-hydroxycyclophosphamide Chemical compound OC1CCOP(=O)(N(CCCl)CCCl)N1 RANONBLIHMVXAJ-UHFFFAOYSA-N 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical class ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 7
- 239000013078 crystal Substances 0.000 description 6
- 229960004397 cyclophosphamide Drugs 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 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 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 150000003863 ammonium salts Chemical class 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- AJEODFLNPFNMOH-UHFFFAOYSA-N cyclohexanamine;2-sulfanylethanesulfonic acid Chemical compound NC1CCCCC1.OS(=O)(=O)CCS AJEODFLNPFNMOH-UHFFFAOYSA-N 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 4
- 230000001472 cytotoxic effect Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 239000003456 ion exchange resin Substances 0.000 description 4
- 229920003303 ion-exchange polymer Polymers 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 159000000000 sodium salts Chemical class 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- PBUUPFTVAPUWDE-UHFFFAOYSA-N 2-[[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid Chemical compound OS(=O)(=O)CCSC1CCOP(=O)(N(CCCl)CCCl)N1 PBUUPFTVAPUWDE-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000005341 cation exchange Methods 0.000 description 3
- QJYQSFRDJBQMCT-UHFFFAOYSA-N cyclohexanamine;ethanesulfonic acid Chemical compound CCS(O)(=O)=O.NC1CCCCC1 QJYQSFRDJBQMCT-UHFFFAOYSA-N 0.000 description 3
- PAFZNILMFXTMIY-UHFFFAOYSA-O cyclohexylammonium Chemical compound [NH3+]C1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-O 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 3
- 206010003445 Ascites Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-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
- XOGTZOOQQBDUSI-UHFFFAOYSA-M Mesna Chemical compound [Na+].[O-]S(=O)(=O)CCS XOGTZOOQQBDUSI-UHFFFAOYSA-M 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
- FLCMCTKYSHCVAJ-UHFFFAOYSA-N OC1=PNOC=C1 Chemical class OC1=PNOC=C1 FLCMCTKYSHCVAJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- MNZWMOYKIOLZMQ-UHFFFAOYSA-N azanium;2-sulfanylethanesulfonate Chemical compound [NH4+].[O-]S(=O)(=O)CCS MNZWMOYKIOLZMQ-UHFFFAOYSA-N 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 231100000636 lethal dose Toxicity 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 2
- QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- 150000003573 thiols Chemical class 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
- ALBLDSJUMDVBBN-UHFFFAOYSA-N 2,3-bis(sulfanyl)propane-1-sulfonic acid;cyclohexanamine Chemical compound NC1CCCCC1.OS(=O)(=O)CC(S)CS ALBLDSJUMDVBBN-UHFFFAOYSA-N 0.000 description 1
- MIJDSYMOBYNHOT-UHFFFAOYSA-N 2-(ethylamino)ethanol Chemical compound CCNCCO MIJDSYMOBYNHOT-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- QVJCZZWOXQCCNO-UHFFFAOYSA-N 2-[[2-[bis(2-chloroethyl)amino]-6-methyl-2-oxo-1,3,2lambda5-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid cyclohexanamine Chemical compound NC1CCCCC1.CC1CC(SCCS(O)(=O)=O)NP(=O)(N(CCCl)CCCl)O1 QVJCZZWOXQCCNO-UHFFFAOYSA-N 0.000 description 1
- FSUAEOOVKQFXOQ-UHFFFAOYSA-N 2-[[3-(2-chloroethyl)-2-(2-chloroethylamino)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid;cyclohexanamine Chemical compound NC1CCCCC1.OS(=O)(=O)CCSC1CCOP(=O)(NCCCl)N1CCCl FSUAEOOVKQFXOQ-UHFFFAOYSA-N 0.000 description 1
- RAXABQCFPAWRSY-UHFFFAOYSA-N 2-[bis(2-chloroethyl)amino]-3-(2-chloroethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-ol Chemical compound OC1CCOP(=O)(N(CCCl)CCCl)N1CCCl RAXABQCFPAWRSY-UHFFFAOYSA-N 0.000 description 1
- AUZWMQVFGIPVSC-UHFFFAOYSA-N 2-[bis(2-chloroethyl)amino]-6-methyl-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-ol Chemical compound CC1CC(O)NP(=O)(N(CCCl)CCCl)O1 AUZWMQVFGIPVSC-UHFFFAOYSA-N 0.000 description 1
- UWKDZWSATBBGBN-UHFFFAOYSA-N 2-[ethyl(methyl)amino]ethanol Chemical compound CCN(C)CCO UWKDZWSATBBGBN-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 description 1
- 229940006193 2-mercaptoethanesulfonic acid Drugs 0.000 description 1
- ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical class N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 description 1
- OBDVFOBWBHMJDG-UHFFFAOYSA-N 3-mercapto-1-propanesulfonic acid Chemical compound OS(=O)(=O)CCCS OBDVFOBWBHMJDG-UHFFFAOYSA-N 0.000 description 1
- JHUJMHKRHQPBRG-UHFFFAOYSA-N 4-Hydroxyifosfamide Chemical compound OC1CCOP(=O)(NCCCl)N1CCCl JHUJMHKRHQPBRG-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 241001132374 Asta Species 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- ZELBJASDQBDWNO-UHFFFAOYSA-N CCS.NC1CCCCC1 Chemical compound CCS.NC1CCCCC1 ZELBJASDQBDWNO-UHFFFAOYSA-N 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 201000000274 Carcinosarcoma Diseases 0.000 description 1
- 102100035861 Cytosolic 5'-nucleotidase 1A Human genes 0.000 description 1
- 101000802744 Homo sapiens Cytosolic 5'-nucleotidase 1A Proteins 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 1
- AKNUHUCEWALCOI-UHFFFAOYSA-N N-ethyldiethanolamine Chemical compound OCCN(CC)CCO AKNUHUCEWALCOI-UHFFFAOYSA-N 0.000 description 1
- RJKVRVNBAOYSNA-UHFFFAOYSA-N NC(N)=N.CCCS(O)(=O)=O Chemical compound NC(N)=N.CCCS(O)(=O)=O RJKVRVNBAOYSNA-UHFFFAOYSA-N 0.000 description 1
- QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
- RRLLQBBEKWMSKH-UHFFFAOYSA-M SCC(CS(=O)(=O)[O-])C.[Na+] Chemical compound SCC(CS(=O)(=O)[O-])C.[Na+] RRLLQBBEKWMSKH-UHFFFAOYSA-M 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- 241001279009 Strychnos toxifera Species 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 238000007171 acid catalysis Methods 0.000 description 1
- 239000003377 acid catalyst Substances 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
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 1
- KMPWYEUPVWOPIM-LSOMNZGLSA-N cinchonine Chemical compound C1=CC=C2C([C@@H]([C@H]3N4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-LSOMNZGLSA-N 0.000 description 1
- ZNEWHQLOPFWXOF-UHFFFAOYSA-N coenzyme M Chemical compound OS(=O)(=O)CCS ZNEWHQLOPFWXOF-UHFFFAOYSA-N 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
- LRIMZGPWMZRRNL-UHFFFAOYSA-N cyclohexanamine;3-sulfanylpropane-1-sulfonic acid Chemical compound [NH3+]C1CCCCC1.[O-]S(=O)(=O)CCCS LRIMZGPWMZRRNL-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 150000002019 disulfides Chemical class 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- FYAQQULBLMNGAH-UHFFFAOYSA-N hexane-1-sulfonic acid Chemical compound CCCCCCS(O)(=O)=O FYAQQULBLMNGAH-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- MFFFLTFYDPAEMX-UHFFFAOYSA-M lithium;2-sulfanylethanesulfonate Chemical compound [Li+].[O-]S(=O)(=O)CCS MFFFLTFYDPAEMX-UHFFFAOYSA-M 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- ODCRXSAVEXGPAA-UHFFFAOYSA-L magnesium;2-[[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonate Chemical compound [Mg+2].[O-]S(=O)(=O)CCSC1CCOP(=O)(N(CCCl)CCCl)N1.[O-]S(=O)(=O)CCSC1CCOP(=O)(N(CCCl)CCCl)N1 ODCRXSAVEXGPAA-UHFFFAOYSA-L 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- CRVGTESFCCXCTH-UHFFFAOYSA-N methyl diethanolamine Chemical compound OCCN(C)CCO CRVGTESFCCXCTH-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- HHWSNFZZGOJQCT-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-4-(2-hydroxysulfonothioylethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-amine Chemical compound OS(=O)(=S)CCC1CCOP(=O)(N(CCCl)CCCl)N1 HHWSNFZZGOJQCT-UHFFFAOYSA-N 0.000 description 1
- WBVDYFWHGAIKCG-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-4-ethoxy-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-amine Chemical compound CCOC1CCOP(=O)(N(CCCl)CCCl)N1 WBVDYFWHGAIKCG-UHFFFAOYSA-N 0.000 description 1
- SYTRPFOIUVLVTB-UHFFFAOYSA-N n,n-bis(2-chloroethyl)-4-methoxy-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-amine Chemical compound COC1CCOP(=O)(N(CCCl)CCCl)N1 SYTRPFOIUVLVTB-UHFFFAOYSA-N 0.000 description 1
- DAZXVJBJRMWXJP-UHFFFAOYSA-N n,n-dimethylethylamine Chemical compound CCN(C)C DAZXVJBJRMWXJP-UHFFFAOYSA-N 0.000 description 1
- GNVRJGIVDSQCOP-UHFFFAOYSA-N n-ethyl-n-methylethanamine Chemical compound CCN(C)CC GNVRJGIVDSQCOP-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 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
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229930010796 primary metabolite Natural products 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- VSOPDDIBJHHIBT-UHFFFAOYSA-M sodium;3-[[2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2$l^{5}-oxazaphosphinan-4-yl]sulfanyl]propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CCCSC1CCOP(=O)(N(CCCl)CCCl)N1 VSOPDDIBJHHIBT-UHFFFAOYSA-M 0.000 description 1
- PXRGAUOLIWDZSW-UHFFFAOYSA-M sodium;6-sulfanylhexane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CCCCCCS PXRGAUOLIWDZSW-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 229960005453 strychnine Drugs 0.000 description 1
- XHJZXCYPSJOWPV-UHFFFAOYSA-N sulfanyl ethanesulfonate Chemical compound CCS(=O)(=O)OS XHJZXCYPSJOWPV-UHFFFAOYSA-N 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000005406 washing Methods 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)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3111428 | 1981-03-24 | ||
| DE19813111428 DE3111428A1 (de) | 1981-03-24 | 1981-03-24 | Oxazaphosphorin-4-thio-alkansulfonsaeuren und deren neutrale salze, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI821021A0 FI821021A0 (fi) | 1982-03-23 |
| FI821021L FI821021L (fi) | 1982-09-25 |
| FI69849B FI69849B (fi) | 1985-12-31 |
| FI69849C true FI69849C (fi) | 1986-05-26 |
Family
ID=6128090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI821021A FI69849C (fi) | 1981-03-24 | 1982-03-23 | Foerfarande foer framstaellning av nya oxazafosforin-4-tio-alkansulfonsyror och deras neutrala salter |
Country Status (31)
| Country | Link |
|---|---|
| US (2) | US4623742A (da) |
| JP (1) | JPS57169496A (da) |
| AT (1) | AT381317B (da) |
| AU (1) | AU544493B2 (da) |
| BE (1) | BE892589A (da) |
| BG (1) | BG38489A3 (da) |
| CA (1) | CA1194479A (da) |
| CH (1) | CH648852A5 (da) |
| DD (1) | DD201799A5 (da) |
| DE (1) | DE3111428A1 (da) |
| DK (1) | DK171843B1 (da) |
| EG (1) | EG15703A (da) |
| ES (1) | ES8303440A1 (da) |
| FI (1) | FI69849C (da) |
| FR (1) | FR2502626B1 (da) |
| GB (1) | GB2095256B (da) |
| GR (1) | GR75533B (da) |
| HU (1) | HU186915B (da) |
| IE (1) | IE53054B1 (da) |
| IL (1) | IL65255A (da) |
| IT (1) | IT1150499B (da) |
| LU (1) | LU84032A1 (da) |
| NL (1) | NL192741C (da) |
| NO (1) | NO163692C (da) |
| PL (1) | PL129426B1 (da) |
| PT (1) | PT74641B (da) |
| RO (1) | RO84661B (da) |
| SE (1) | SE452159B (da) |
| SU (1) | SU1318167A3 (da) |
| YU (1) | YU61582A (da) |
| ZA (1) | ZA821637B (da) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3111428A1 (de) * | 1981-03-24 | 1982-10-07 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Oxazaphosphorin-4-thio-alkansulfonsaeuren und deren neutrale salze, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen |
| DE3279834D1 (en) * | 1981-12-31 | 1989-08-31 | Asta Pharma Ag | 4-sulfido-oxaza phosphorines and their use in the treatment of cancer, and in immunosuppression |
| ZA851062B (en) * | 1984-03-01 | 1985-11-27 | Asta Werke Ag Chem Fab | Salts of oxazaphosphorine derivatives and process for their production |
| DE3569737D1 (en) * | 1984-03-01 | 1989-06-01 | Asta Pharma Ag | Salts of oxazaphosphorine derivatives |
| DE3415726A1 (de) * | 1984-04-27 | 1985-10-31 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Verfahren zur herstellung von in 4-stellung substituierten oxazaphosphorin-derivaten |
| FR2567129B1 (fr) * | 1984-07-06 | 1986-12-05 | Adir | Nouveaux derives de l'oxaazaphosphorine, leur procede de preparation et les compositions pharmaceutiques les renfermant |
| US5204335A (en) * | 1986-10-31 | 1993-04-20 | Asta Pharma Aktiengesellschaft | Ifosfamide lyophilisate and process for its preparation |
| ES2040394T3 (es) * | 1988-03-19 | 1993-10-16 | Asta Medica Aktiengesellschaft | Procedimiento para preparar un material liofilizado de ifosfamida y mesna. |
| US5190929A (en) * | 1988-05-25 | 1993-03-02 | Research Corporation Technologies, Inc. | Cyclophosphamide analogs useful as anti-tumor agents |
| RO113611B1 (ro) * | 1990-08-03 | 1998-09-30 | Asta Pharma Ag | Preparate solide de ifosfamida, administrate oral si procedeu de obtinere |
| US5661188A (en) * | 1995-06-07 | 1997-08-26 | Medical Research Foundation and Infrastructure Development for Health Services--Nahariya Hospital Branch | Therapeutic uses for sodium 2-mercaptoethanesulphonate (mesna) |
| US20080223826A1 (en) * | 2007-03-13 | 2008-09-18 | Stephen Mazur | Reagent Delivery using a Membrane-Mediated Process |
| FR2968662B1 (fr) | 2010-12-10 | 2013-11-22 | Roussy Inst Gustave | Nouveaux derives d'oxazaphosphorines pre-activees, utilisation et methode de preparation |
| GB2626789A (en) * | 2023-02-03 | 2024-08-07 | Exactmer Ltd | Deprotection processes and cation scavengers for use in the same |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2107936C3 (de) * | 1971-02-19 | 1978-06-08 | Asta-Werke Ag Chemische Fabrik, 4800 Bielefeld | Alkylsulfonsäureester von 2-Oxo-13,2-oxazaphosphorinanen und diese enthaltende pharmazeutische Präparate |
| DE1645921C3 (de) * | 1966-07-11 | 1978-10-12 | Asta-Werke Ag Chemische Fabrik, 4800 Bielefeld | 2-Oxo-13,2-osazaphosphorinane, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Präparate |
| DE2201675A1 (de) * | 1972-01-14 | 1973-07-19 | Asta Werke Ag Chem Fab | Alkylsulfonsaeureester 1,3,2-oxazaphospha-cyclischer verbindungen, verfahren zu ihrer herstellung und pharmazeutische praeparate |
| JPS5159886A (da) * | 1974-11-20 | 1976-05-25 | Shionogi Seiyaku Kk | |
| JPS54157580A (en) | 1978-05-29 | 1979-12-12 | Otsuka Pharmaceut Co Ltd | Optically active oxazaphosphorine derivative |
| JPS5826919B2 (ja) | 1978-11-07 | 1983-06-06 | 大塚製薬株式会社 | シクロ↓−１，３，２↓−オキサアザホスホル誘導体の製造法 |
| JPS55154984A (en) * | 1979-05-24 | 1980-12-02 | Shionogi & Co Ltd | Novel 4-substituted-2h-1,3,2-oxaazaphospholine-2-oxide derivative |
| DE3220672A1 (de) | 1981-03-24 | 1983-12-08 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Cis-oxazaphosphorin-4-thio-alkansulfonsaeuren, ihre neutralen salze, verfahren zur herstellung derselben und diese enthaltenden pharmazeutischen praeparate |
| DE3111428A1 (de) | 1981-03-24 | 1982-10-07 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Oxazaphosphorin-4-thio-alkansulfonsaeuren und deren neutrale salze, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische zubereitungen |
| DE3220432A1 (de) | 1981-03-24 | 1983-12-01 | Asta-Werke Ag, Chemische Fabrik, 4800 Bielefeld | Oxazaphosphorin-4-thio-alkansulfonsaeure, ihre neutralen salze, verfahren zur herstellung derselben und diese enthaltenden pharmazeutischen praeparate |
-
1981
- 1981-03-24 DE DE19813111428 patent/DE3111428A1/de active Granted
-
1982
- 1982-03-08 CH CH1390/82A patent/CH648852A5/de not_active IP Right Cessation
- 1982-03-09 IE IE531/82A patent/IE53054B1/en unknown
- 1982-03-11 ZA ZA821637A patent/ZA821637B/xx unknown
- 1982-03-12 AU AU81344/82A patent/AU544493B2/en not_active Ceased
- 1982-03-12 GB GB8207375A patent/GB2095256B/en not_active Expired
- 1982-03-15 IL IL65255A patent/IL65255A/xx unknown
- 1982-03-17 AT AT0106382A patent/AT381317B/de not_active IP Right Cessation
- 1982-03-17 GR GR67621A patent/GR75533B/el unknown
- 1982-03-22 FR FR8204823A patent/FR2502626B1/fr not_active Expired
- 1982-03-22 RO RO106989A patent/RO84661B/ro unknown
- 1982-03-22 SE SE8201807A patent/SE452159B/sv not_active IP Right Cessation
- 1982-03-22 YU YU00615/82A patent/YU61582A/xx unknown
- 1982-03-23 CA CA000399098A patent/CA1194479A/en not_active Expired
- 1982-03-23 ES ES510677A patent/ES8303440A1/es not_active Expired
- 1982-03-23 SU SU823414100A patent/SU1318167A3/ru active
- 1982-03-23 IT IT20351/82A patent/IT1150499B/it active
- 1982-03-23 JP JP57044779A patent/JPS57169496A/ja active Granted
- 1982-03-23 PT PT74641A patent/PT74641B/pt unknown
- 1982-03-23 NO NO820957A patent/NO163692C/no not_active IP Right Cessation
- 1982-03-23 DD DD82238374A patent/DD201799A5/de unknown
- 1982-03-23 EG EG82156A patent/EG15703A/xx active
- 1982-03-23 HU HU82879A patent/HU186915B/hu unknown
- 1982-03-23 BE BE2/59642A patent/BE892589A/fr not_active IP Right Cessation
- 1982-03-23 FI FI821021A patent/FI69849C/fi not_active IP Right Cessation
- 1982-03-23 DK DK129882A patent/DK171843B1/da not_active IP Right Cessation
- 1982-03-24 NL NL8201227A patent/NL192741C/nl not_active IP Right Cessation
- 1982-03-24 LU LU84032A patent/LU84032A1/de unknown
- 1982-03-24 BG BG055941A patent/BG38489A3/xx unknown
- 1982-08-24 PL PL1982235606A patent/PL129426B1/pl unknown
-
1984
- 1984-12-19 US US06/683,374 patent/US4623742A/en not_active Expired - Lifetime
-
1988
- 1988-02-02 US US07/149,954 patent/US4929607A/en not_active Expired - Lifetime
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI69849C (fi) | Foerfarande foer framstaellning av nya oxazafosforin-4-tio-alkansulfonsyror och deras neutrala salter | |
| US3074992A (en) | Novel cyclic phosphoric acid ester amides, and the production thereof | |
| EP0280741B1 (en) | Mitomycin derivatives | |
| BR112012007869B1 (pt) | Processo de síntese de ergotioneína e seus derivados | |
| EP0313874B1 (en) | Disulfur analogs of LL-E33288 antitumor agents | |
| JPH041759B2 (da) | ||
| HU208830B (en) | Process for producing anti-virus pharmaceutical preparatives containing phospholididic derivatives | |
| US4716242A (en) | Salts of oxazaphosphorine derivatives | |
| CH644613A5 (it) | Mono(2-ammonio-2-idrossimetil-1,3-propandiolo) (2r-cis)-(3-metilossiranil)fosfonato, sua preparazione e composizioni farmaceutiche che lo contengono. | |
| FI78705B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara bassalter av cyklofosfamidderivat. | |
| FI68402C (fi) | Foerfarande foer framstaellning av ett terapeutiskt anvaendbart 9-(2-hydroxietoximetyl)guaninmonofosfatderivat | |
| FI80700B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara mitomycinanaloger. | |
| FI60869B (fi) | Foerfarande foer framstaellning av nya terapeutiskt anvaendbara cefalosporiner | |
| JPS59205382A (ja) | アミノ２硫化物 | |
| FI72313C (fi) | Foerfarande foer foerdelning av racematet s-(karboxi-metyl)-(r,s)-cystein i isomerer (b). | |
| Sosnovsky et al. | In the Search for New Anticancer Drugs. 27. Synthesis and Comparison of Anticancer Activity in Vivo of Amino Acids, Carbohydrates, and Carbohydrate-Amino Acid Conjugates Containing the [N′‐(2‐chloroethyl)‐N′‐nitrosoamino] carbonyl group | |
| US4467103A (en) | Processes for the preparation of spectinomycin analogs, products and intermediates therein | |
| FI95382C (fi) | 6,7-dihydro-5H-pyratsolo/1,2-a//1,2,4/triatsolium-6-yylidisulfidi, menetelmä sen valmistamiseksi käyttäen pyratsolidiini-4-yylidisulfidia ja pyratsoliini-4-yylidisulfidi | |
| WO2023155006A1 (en) | Total syntheses of selenoneine, iso-selenoneine, and isomers | |
| IL107141A (en) | History of phospholipids containing high elements from the main group V, their preparation and pharmaceutical preparations containing them | |
| JPS61194095A (ja) | （１，２‐ジフエニル‐エチレンジアミン）‐白金（２）錯体、その製法及び該化合物を含有する抗腫瘍剤 | |
| Palacios et al. | An efficient synthesis of functionalized α-amino-phosphine oxides and-phosphonates by addition of aminoalcohols to 4-phosphorylated-1, 2-diaza-1, 3-butadienes | |
| FI93962C (fi) | 6,7-dihydro-6-merkapto-5H-pyratsolo/1,2-a//1,2,4/triatsolium-välituotteet ja menetelmä niiden valmistamiseksi | |
| SU289597A1 (ru) | Способ разделения рацемической смеси (цис-1,2- | |
| EP0060028A1 (en) | Cephalosporin derivatives and process for their preparation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MA | Patent expired |
Owner name: ASTA-WERKE AKTIENGESELLSCHAFT CHEMISCHE |