DE2831094C2 - - Google Patents
Info
- Publication number
- DE2831094C2 DE2831094C2 DE2831094A DE2831094A DE2831094C2 DE 2831094 C2 DE2831094 C2 DE 2831094C2 DE 2831094 A DE2831094 A DE 2831094A DE 2831094 A DE2831094 A DE 2831094A DE 2831094 C2 DE2831094 C2 DE 2831094C2
- Authority
- DE
- Germany
- Prior art keywords
- chloroethyl
- bis
- dideoxy
- nitrosoureido
- mixture
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired
Links
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 claims description 39
- 150000001875 compounds Chemical class 0.000 claims description 35
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 16
- 239000004386 Erythritol Substances 0.000 claims description 15
- 229940009714 erythritol Drugs 0.000 claims description 15
- 229920005862 polyol Polymers 0.000 claims description 15
- 235000019414 erythritol Nutrition 0.000 claims description 13
- 150000003077 polyols Chemical class 0.000 claims description 13
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- UNXHWFMMPAWVPI-QWWZWVQMSA-N D-threitol Chemical compound OC[C@@H](O)[C@H](O)CO UNXHWFMMPAWVPI-QWWZWVQMSA-N 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- FBPFZTCFMRRESA-GUCUJZIJSA-N galactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-GUCUJZIJSA-N 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 229940126601 medicinal product Drugs 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 36
- 239000000243 solution Substances 0.000 description 35
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 206010028980 Neoplasm Diseases 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000000126 substance Substances 0.000 description 17
- 238000004809 thin layer chromatography Methods 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000003463 adsorbent Substances 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000013078 crystal Substances 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 229940125904 compound 1 Drugs 0.000 description 9
- 208000032839 leukemia Diseases 0.000 description 9
- 206010003445 Ascites Diseases 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- LZDSILRDTDCIQT-UHFFFAOYSA-N dinitrogen trioxide Chemical compound [O-][N+](=O)N=O LZDSILRDTDCIQT-UHFFFAOYSA-N 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000005457 ice water Substances 0.000 description 7
- 239000013558 reference substance Substances 0.000 description 7
- 235000010288 sodium nitrite Nutrition 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- BCMYXYHEMGPZJN-UHFFFAOYSA-N 1-chloro-2-isocyanatoethane Chemical compound ClCCN=C=O BCMYXYHEMGPZJN-UHFFFAOYSA-N 0.000 description 6
- VJQMZEJRWWLMAQ-UHFFFAOYSA-N 3-(2-chloroethyl)-1-[4-[2-chloroethylcarbamoyl(nitroso)amino]-2,3-dihydroxybutyl]-1-nitrosourea Chemical compound ClCCNC(=O)N(N=O)CC(O)C(O)CN(N=O)C(=O)NCCCl VJQMZEJRWWLMAQ-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 231100001274 therapeutic index Toxicity 0.000 description 6
- 241000699670 Mus sp. Species 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- -1 1,3-disubstituted cyclic polyols Chemical class 0.000 description 4
- JSBOOJIFKJXLAF-OCAPTIKFSA-N 1-(2-chloroethyl)-3-[(2s,3r)-4-(2-chloroethylcarbamoylamino)-2,3-dihydroxybutyl]urea Chemical compound ClCCNC(=O)NC[C@H](O)[C@H](O)CNC(=O)NCCCl JSBOOJIFKJXLAF-OCAPTIKFSA-N 0.000 description 4
- QELOJZNVHQXTMT-ZYUZMQFOSA-N 3-(2-chloroethyl)-1-[(2r,3r,4r,5r)-6-[2-chloroethylcarbamoyl(nitroso)amino]-2,3,4,5-tetrahydroxyhexyl]-1-nitrosourea Chemical compound ClCCNC(=O)N(N=O)C[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CN(N=O)C(=O)NCCCl QELOJZNVHQXTMT-ZYUZMQFOSA-N 0.000 description 4
- 201000009030 Carcinoma Diseases 0.000 description 4
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 208000009916 Yoshida Sarcoma Diseases 0.000 description 4
- ANJXCDGVELYPJR-UHFFFAOYSA-N acetic acid;ethyl acetate;hydrate Chemical compound O.CC(O)=O.CCOC(C)=O ANJXCDGVELYPJR-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 4
- 230000035876 healing Effects 0.000 description 4
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 229940104230 thymidine Drugs 0.000 description 4
- LLMKXBFBKPFYMX-ZYUZMQFOSA-N 1-(2-chloroethyl)-3-[(2r,3r,4r,5r)-6-(2-chloroethylcarbamoylamino)-2,3,4,5-tetrahydroxyhexyl]urea Chemical compound ClCCNC(=O)NC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CNC(=O)NCCCl LLMKXBFBKPFYMX-ZYUZMQFOSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 102000053602 DNA Human genes 0.000 description 3
- 108020004414 DNA Proteins 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 208000001382 Experimental Melanoma Diseases 0.000 description 3
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 230000001085 cytostatic effect Effects 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000002349 favourable effect Effects 0.000 description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- HHAVHBDPWSUKHZ-UHFFFAOYSA-N propan-2-ol;propan-2-one Chemical compound CC(C)O.CC(C)=O HHAVHBDPWSUKHZ-UHFFFAOYSA-N 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- PDHWCVRAWIIKPC-ZXZARUISSA-N (2s,3r)-1,4-diazidobutane-2,3-diol Chemical compound [N-]=[N+]=NC[C@H](O)[C@H](O)CN=[N+]=[N-] PDHWCVRAWIIKPC-ZXZARUISSA-N 0.000 description 2
- DGHOCXJONPLHGT-OCAPTIKFSA-N 1-(2-chloroethyl)-3-[(2s,3r)-4-[[2-chloroethyl(nitroso)carbamoyl]amino]-2,3-dihydroxybutyl]-1-nitrosourea Chemical compound ClCCN(N=O)C(=O)NC[C@H](O)[C@H](O)CNC(=O)N(CCCl)N=O DGHOCXJONPLHGT-OCAPTIKFSA-N 0.000 description 2
- JSBOOJIFKJXLAF-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[4-(2-chloroethylcarbamoylamino)-2,3-dihydroxybutyl]urea Chemical compound ClCCNC(=O)NCC(O)C(O)CNC(=O)NCCCl JSBOOJIFKJXLAF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 101000835998 Homo sapiens SRA stem-loop-interacting RNA-binding protein, mitochondrial Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 208000007093 Leukemia L1210 Diseases 0.000 description 2
- 208000008342 Leukemia P388 Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 102100025491 SRA stem-loop-interacting RNA-binding protein, mitochondrial Human genes 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000007059 acute toxicity Effects 0.000 description 2
- 231100000403 acute toxicity Toxicity 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 231100000682 maximum tolerated dose Toxicity 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 239000001272 nitrous oxide Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000011833 salt mixture Substances 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- XDPGXUIEXVDTAK-KVTDHHQDSA-N (2r,3r,4r,5r)-1,6-diaminohexane-2,3,4,5-tetrol Chemical compound NC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CN XDPGXUIEXVDTAK-KVTDHHQDSA-N 0.000 description 1
- NVKGVBZZSJFQLM-UHFFFAOYSA-N 1-(2-chloroethyl)-1-nitrosourea Chemical class NC(=O)N(N=O)CCCl NVKGVBZZSJFQLM-UHFFFAOYSA-N 0.000 description 1
- DGHOCXJONPLHGT-UHFFFAOYSA-N 1-(2-chloroethyl)-3-[4-[[2-chloroethyl(nitroso)carbamoyl]amino]-2,3-dihydroxybutyl]-1-nitrosourea Chemical compound ClCCN(N=O)C(=O)NCC(O)C(O)CNC(=O)N(CCCl)N=O DGHOCXJONPLHGT-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- OHQDSQLEWIOXQT-UHFFFAOYSA-N CO.C(C)(=O)[O-].[NH4+].C(Cl)(Cl)Cl Chemical compound CO.C(C)(=O)[O-].[NH4+].C(Cl)(Cl)Cl OHQDSQLEWIOXQT-UHFFFAOYSA-N 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- UNXHWFMMPAWVPI-IMJSIDKUSA-N L-threitol Chemical compound OC[C@H](O)[C@@H](O)CO UNXHWFMMPAWVPI-IMJSIDKUSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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- 206010027458 Metastases to lung Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
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- 238000010171 animal model Methods 0.000 description 1
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- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002603 chloroethyl group Chemical group [H]C([*])([H])C([H])([H])Cl 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
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- 210000001072 colon Anatomy 0.000 description 1
- 201000010989 colorectal carcinoma Diseases 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- SYZWSSNHPZXGML-UHFFFAOYSA-N dichloromethane;oxolane Chemical compound ClCCl.C1CCOC1 SYZWSSNHPZXGML-UHFFFAOYSA-N 0.000 description 1
- BLEBFDYUDVZRFG-UHFFFAOYSA-N dichloromethane;propan-2-ol Chemical compound ClCCl.CC(C)O BLEBFDYUDVZRFG-UHFFFAOYSA-N 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- HQVFCQRVQFYGRJ-UHFFFAOYSA-N formic acid;hydrate Chemical compound O.OC=O HQVFCQRVQFYGRJ-UHFFFAOYSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
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- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000009935 nitrosation Effects 0.000 description 1
- 238000007034 nitrosation reaction Methods 0.000 description 1
- VPCDQGACGWYTMC-UHFFFAOYSA-N nitrosyl chloride Chemical compound ClN=O VPCDQGACGWYTMC-UHFFFAOYSA-N 0.000 description 1
- 235000019392 nitrosyl chloride Nutrition 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- 229940074439 potassium sodium tartrate Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/66—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to halogen atoms or to nitro or nitroso groups
- C07C275/68—N-nitroso ureas
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/14—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D317/28—Radicals substituted by nitrogen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Polyurethanes Or Polyureas (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU77GO1386A HU176101B (en) | 1977-12-29 | 1977-12-29 | Process for producing bis-bracket-nitrozo-ureido-bracket closed-polyol derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2831094A1 DE2831094A1 (de) | 1979-07-12 |
| DE2831094C2 true DE2831094C2 (en, 2012) | 1988-12-15 |
Family
ID=10996842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19782831094 Granted DE2831094A1 (de) | 1977-12-29 | 1978-07-14 | Bis-(nitrosoureido)-polyolderivate, solche enthaltende arzneimittel und verfahren zur herstellung derselben sowie di-(ureido)-polyolderivate |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US4237273A (en, 2012) |
| JP (1) | JPS5495517A (en, 2012) |
| AT (1) | AT360045B (en, 2012) |
| AU (1) | AU523845B2 (en, 2012) |
| BE (1) | BE868988A (en, 2012) |
| BG (1) | BG30016A3 (en, 2012) |
| CA (1) | CA1108182A (en, 2012) |
| CH (1) | CH639363A5 (en, 2012) |
| CS (1) | CS201010B2 (en, 2012) |
| DD (1) | DD137224A5 (en, 2012) |
| DE (1) | DE2831094A1 (en, 2012) |
| DK (1) | DK155047C (en, 2012) |
| ES (1) | ES471778A1 (en, 2012) |
| FI (1) | FI69058C (en, 2012) |
| FR (1) | FR2415096A1 (en, 2012) |
| GB (1) | GB2011382B (en, 2012) |
| GR (1) | GR64891B (en, 2012) |
| HU (1) | HU176101B (en, 2012) |
| IL (1) | IL55138A (en, 2012) |
| IT (1) | IT1097647B (en, 2012) |
| NL (1) | NL7807587A (en, 2012) |
| NO (1) | NO149960C (en, 2012) |
| PL (1) | PL112198B1 (en, 2012) |
| PT (1) | PT68301A (en, 2012) |
| RO (1) | RO77027A (en, 2012) |
| SE (1) | SE446529B (en, 2012) |
| YU (1) | YU41314B (en, 2012) |
| ZA (1) | ZA783980B (en, 2012) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2459231A1 (fr) | 1979-06-19 | 1981-01-09 | Anvar | Nouveaux derives de la cystamine utiles comme medicaments |
| JPS5775993A (en) * | 1980-10-30 | 1982-05-12 | Tetsuo Suami | Novel nitrosourea derivative and its preparation |
| EP0428849A3 (en) * | 1989-09-28 | 1991-07-31 | Hoechst Aktiengesellschaft | Retroviral protease inhibitors |
| AU8320691A (en) * | 1990-07-06 | 1992-02-04 | Smithkline Beecham Corporation | Inhibitors of retroviral proteases |
| DE10026698A1 (de) | 2000-05-30 | 2001-12-06 | Basf Ag | Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung |
| US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
| US8377952B2 (en) | 2003-08-28 | 2013-02-19 | Abbott Laboratories | Solid pharmaceutical dosage formulation |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH518270A (de) * | 1969-03-07 | 1972-01-31 | Hoffmann La Roche | Verfahren zur Herstellung von Nitrosoharnstoffverbindungen |
| JPS5135382B2 (en, 2012) * | 1972-08-04 | 1976-10-01 | ||
| JPS50128266A (en, 2012) * | 1974-03-26 | 1975-10-09 | ||
| JPS5126876A (en) * | 1974-08-08 | 1976-03-05 | Suami T | Shinkina nitorosonyosojudotaino seizohoho |
| US4066750A (en) * | 1976-08-02 | 1978-01-03 | Astra Chemical Products Ab | Lactosyl substituted ureides in ruminant feedstuff |
| JPS5331664A (en) * | 1976-09-02 | 1978-03-25 | Suami T | Production of novel nitroso urea derivatives |
| JPS5395917A (en) * | 1977-02-03 | 1978-08-22 | Tokyo Tanabe Co | Process for preparing nitrosourea derivative of glucopyranose |
| US4148921A (en) * | 1977-07-13 | 1979-04-10 | Suami T | Antitumor agents |
-
1977
- 1977-12-29 HU HU77GO1386A patent/HU176101B/hu unknown
-
1978
- 1978-07-11 AT AT500178A patent/AT360045B/de not_active IP Right Cessation
- 1978-07-12 ZA ZA00783980A patent/ZA783980B/xx unknown
- 1978-07-12 GR GR56762A patent/GR64891B/el unknown
- 1978-07-13 SE SE7807804A patent/SE446529B/xx not_active IP Right Cessation
- 1978-07-13 CS CS784690A patent/CS201010B2/cs unknown
- 1978-07-13 AU AU38027/78A patent/AU523845B2/en not_active Expired
- 1978-07-13 GB GB7829687A patent/GB2011382B/en not_active Expired
- 1978-07-13 FR FR7820939A patent/FR2415096A1/fr active Granted
- 1978-07-13 FI FI782238A patent/FI69058C/fi not_active IP Right Cessation
- 1978-07-13 IL IL55138A patent/IL55138A/xx unknown
- 1978-07-14 DK DK317878A patent/DK155047C/da not_active IP Right Cessation
- 1978-07-14 BG BG040404A patent/BG30016A3/xx unknown
- 1978-07-14 NO NO782447A patent/NO149960C/no unknown
- 1978-07-14 PT PT68301A patent/PT68301A/pt unknown
- 1978-07-14 DE DE19782831094 patent/DE2831094A1/de active Granted
- 1978-07-14 NL NL7807587A patent/NL7807587A/xx not_active Application Discontinuation
- 1978-07-14 CH CH764278A patent/CH639363A5/de not_active IP Right Cessation
- 1978-07-14 IT IT25682/78A patent/IT1097647B/it active
- 1978-07-14 YU YU1699/78A patent/YU41314B/xx unknown
- 1978-07-14 BE BE189274A patent/BE868988A/xx not_active IP Right Cessation
- 1978-07-14 DD DD78206731A patent/DD137224A5/xx not_active IP Right Cessation
- 1978-07-15 JP JP8569978A patent/JPS5495517A/ja active Granted
- 1978-07-15 ES ES471778A patent/ES471778A1/es not_active Expired
- 1978-07-15 RO RO7894680A patent/RO77027A/ro unknown
- 1978-07-15 PL PL1978208436A patent/PL112198B1/pl unknown
- 1978-07-17 US US05/925,822 patent/US4237273A/en not_active Expired - Lifetime
- 1978-07-17 CA CA307,574A patent/CA1108182A/en not_active Expired
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Legal Events
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| 8110 | Request for examination paragraph 44 | ||
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |