JPH0257523B2 - - Google Patents
Info
- Publication number
- JPH0257523B2 JPH0257523B2 JP62083962A JP8396287A JPH0257523B2 JP H0257523 B2 JPH0257523 B2 JP H0257523B2 JP 62083962 A JP62083962 A JP 62083962A JP 8396287 A JP8396287 A JP 8396287A JP H0257523 B2 JPH0257523 B2 JP H0257523B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- cyan
- aziridine
- methyl
- drug according
- 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 - Lifetime
Links
- -1 tetrahydrofurfuryl group Chemical group 0.000 claims description 23
- 239000003814 drug Chemical group 0.000 claims description 15
- 230000003308 immunostimulating effect Effects 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- OFGUDXIHTSHDIV-UHFFFAOYSA-N 1-methylaziridine-2-carbonitrile Chemical compound CN1CC1C#N OFGUDXIHTSHDIV-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- OHFJFMFONWLZIX-UHFFFAOYSA-N 1-[(2-chlorophenyl)methyl]aziridine-2-carbonitrile Chemical compound ClC1=CC=CC=C1CN1C(C#N)C1 OHFJFMFONWLZIX-UHFFFAOYSA-N 0.000 claims description 2
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 150000002825 nitriles Chemical group 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- VJKHOEXAOMOUAI-UHFFFAOYSA-N 1-(pyrimidin-2-ylmethyl)aziridine-2-carbonitrile Chemical compound N#CC1CN1CC1=NC=CC=N1 VJKHOEXAOMOUAI-UHFFFAOYSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 238000009835 boiling Methods 0.000 description 26
- 150000001875 compounds Chemical class 0.000 description 22
- 239000000126 substance Substances 0.000 description 15
- 238000002844 melting Methods 0.000 description 13
- 230000008018 melting Effects 0.000 description 13
- 229920000609 methyl cellulose Polymers 0.000 description 9
- 239000001923 methylcellulose Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000002246 antineoplastic agent Substances 0.000 description 8
- 229940127089 cytotoxic agent Drugs 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 238000010953 Ames test Methods 0.000 description 6
- 231100000039 Ames test Toxicity 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 5
- 229960005091 chloramphenicol Drugs 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 4
- 229960001438 immunostimulant agent Drugs 0.000 description 4
- 239000003022 immunostimulating agent Substances 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 230000002503 metabolic effect Effects 0.000 description 4
- 231100000299 mutagenicity Toxicity 0.000 description 4
- 230000007886 mutagenicity Effects 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- 230000003385 bacteriostatic effect Effects 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000004698 lymphocyte Anatomy 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- MAYLHGVPMVDUIX-UHFFFAOYSA-N 1-(2-chloroethyl)aziridine-2-carbonitrile Chemical compound ClCCN1CC1C#N MAYLHGVPMVDUIX-UHFFFAOYSA-N 0.000 description 2
- BLBSHRFZHWOWNW-UHFFFAOYSA-N 1-benzylaziridine-2-carbonitrile Chemical compound N#CC1CN1CC1=CC=CC=C1 BLBSHRFZHWOWNW-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PPQNQXQZIWHJRB-UHFFFAOYSA-N Methylcholanthrene Chemical compound C1=CC=C2C3=CC4=CC=C(C)C(CC5)=C4C5=C3C=CC2=C1 PPQNQXQZIWHJRB-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 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 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- PGZUFTROELAOMP-UHFFFAOYSA-N aziridine-2-carbonitrile Chemical class N#CC1CN1 PGZUFTROELAOMP-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- CLENIVYWUANSKB-UHFFFAOYSA-N ethyl 3-(2-cyanoaziridin-1-yl)prop-2-enoate Chemical compound CCOC(=O)C=CN1CC1C#N CLENIVYWUANSKB-UHFFFAOYSA-N 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 206010024378 leukocytosis Diseases 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
- 230000003505 mutagenic effect Effects 0.000 description 2
- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- ZDSLWQTWYUJOJR-UHFFFAOYSA-N 1-(1-adamantyl)aziridine-2-carbonitrile Chemical compound N#CC1CN1C1(C2)CC(C3)CC2CC3C1 ZDSLWQTWYUJOJR-UHFFFAOYSA-N 0.000 description 1
- FLWGCYLFRPRTGF-UHFFFAOYSA-N 1-(2,2-dichloroethyl)aziridine-2-carbonitrile Chemical compound ClC(Cl)CN1CC1C#N FLWGCYLFRPRTGF-UHFFFAOYSA-N 0.000 description 1
- PXRQJBFQKFGYPW-UHFFFAOYSA-N 1-(2-cyano-1-phenylethenyl)aziridine-2-carbonitrile Chemical group C=1C=CC=CC=1C(=CC#N)N1CC1C#N PXRQJBFQKFGYPW-UHFFFAOYSA-N 0.000 description 1
- JJRCJJPDRBCKEL-UHFFFAOYSA-N 1-(2-methylsulfonylethyl)aziridine-2-carbonitrile Chemical compound CS(=O)(=O)CCN1CC1C#N JJRCJJPDRBCKEL-UHFFFAOYSA-N 0.000 description 1
- DXEFILDXSFLEIC-UHFFFAOYSA-N 1-(3-methylsulfanylpropyl)aziridine-2-carbonitrile Chemical compound CSCCCN1CC1C#N DXEFILDXSFLEIC-UHFFFAOYSA-N 0.000 description 1
- RVLVZVMYWUQNIN-UHFFFAOYSA-N 1-(3-oxoprop-1-enyl)aziridine-2-carbonitrile Chemical compound O=CC=CN1CC1C#N RVLVZVMYWUQNIN-UHFFFAOYSA-N 0.000 description 1
- NGYSMPWNVYTSDR-UHFFFAOYSA-N 1-(cyclohexen-1-ylmethyl)aziridine-2-carbonitrile Chemical compound N#CC1CN1CC1=CCCCC1 NGYSMPWNVYTSDR-UHFFFAOYSA-N 0.000 description 1
- KUFHSAOGAVKLAB-UHFFFAOYSA-N 1-(furan-2-ylmethyl)aziridine-2-carbonitrile Chemical compound N#CC1CN1CC1=CC=CO1 KUFHSAOGAVKLAB-UHFFFAOYSA-N 0.000 description 1
- FGPYAOIHADYVRJ-UHFFFAOYSA-N 1-[(2-methylsulfanylphenyl)methyl]aziridine-2-carbonitrile Chemical compound CSC1=CC=CC=C1CN1C(C#N)C1 FGPYAOIHADYVRJ-UHFFFAOYSA-N 0.000 description 1
- UNHFDEBWKDTGOD-UHFFFAOYSA-N 1-[(3,4-dimethoxyphenyl)methyl]aziridine-2-carbonitrile Chemical compound C1=C(OC)C(OC)=CC=C1CN1C(C#N)C1 UNHFDEBWKDTGOD-UHFFFAOYSA-N 0.000 description 1
- QVGUJBCKGUQJIK-UHFFFAOYSA-N 1-[(4-hydroxyphenyl)methyl]aziridine-2-carbonitrile Chemical compound C1=CC(O)=CC=C1CN1C(C#N)C1 QVGUJBCKGUQJIK-UHFFFAOYSA-N 0.000 description 1
- WPDOLUNSZXEAOQ-UHFFFAOYSA-N 1-[(4-methylphenyl)methyl]aziridine-2-carbonitrile Chemical compound C1=CC(C)=CC=C1CN1C(C#N)C1 WPDOLUNSZXEAOQ-UHFFFAOYSA-N 0.000 description 1
- WXPLMDJJWMLWQB-UHFFFAOYSA-N 1-[(5-methyl-2-nitrophenyl)methyl]aziridine-2-carbonitrile Chemical compound CC1=CC=C([N+]([O-])=O)C(CN2C(C2)C#N)=C1 WXPLMDJJWMLWQB-UHFFFAOYSA-N 0.000 description 1
- ILEDCFHTCZGQGD-UHFFFAOYSA-N 1-[[3-(trifluoromethyl)phenyl]methyl]aziridine-2-carbonitrile Chemical compound FC(F)(F)C1=CC=CC(CN2C(C2)C#N)=C1 ILEDCFHTCZGQGD-UHFFFAOYSA-N 0.000 description 1
- OQNAIENCXDWJFB-UHFFFAOYSA-N 1-but-2-ynylaziridine-2-carbonitrile Chemical compound CC#CCN1CC1C#N OQNAIENCXDWJFB-UHFFFAOYSA-N 0.000 description 1
- JZDIDTHPBYSKOD-UHFFFAOYSA-N 1-cyclopropylaziridine-2-carbonitrile Chemical compound N#CC1CN1C1CC1 JZDIDTHPBYSKOD-UHFFFAOYSA-N 0.000 description 1
- WOWAQLYHJYQANU-UHFFFAOYSA-N 1-pentylaziridine-2-carbonitrile Chemical compound CCCCCN1CC1C#N WOWAQLYHJYQANU-UHFFFAOYSA-N 0.000 description 1
- PGGYBMMLXSFYRM-UHFFFAOYSA-N 1-prop-2-ynylaziridine-2-carbonitrile Chemical compound C#CCN1CC1C#N PGGYBMMLXSFYRM-UHFFFAOYSA-N 0.000 description 1
- LWWMXPUFGZOIFI-UHFFFAOYSA-N 1-propan-2-ylaziridine-2-carbonitrile Chemical compound CC(C)N1CC1C#N LWWMXPUFGZOIFI-UHFFFAOYSA-N 0.000 description 1
- MAVDYPIEZAPIEI-UHFFFAOYSA-N 1-propylaziridine-2-carbonitrile Chemical compound CCCN1CC1C#N MAVDYPIEZAPIEI-UHFFFAOYSA-N 0.000 description 1
- BSBUUBUYBRAQMM-UHFFFAOYSA-N 1-tert-butylaziridine-2-carbonitrile Chemical compound CC(C)(C)N1CC1C#N BSBUUBUYBRAQMM-UHFFFAOYSA-N 0.000 description 1
- XGGDPSICSVGWGQ-UHFFFAOYSA-N 1-thiophen-2-ylaziridine-2-carbonitrile Chemical group N#CC1CN1C1=CC=CS1 XGGDPSICSVGWGQ-UHFFFAOYSA-N 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- RMSRKYVNQYEPHO-UHFFFAOYSA-N 2-cyanoaziridine-1-carboxamide Chemical compound NC(=O)N1CC1C#N RMSRKYVNQYEPHO-UHFFFAOYSA-N 0.000 description 1
- FUBFWTUFPGFHOJ-UHFFFAOYSA-N 2-nitrofuran Chemical class [O-][N+](=O)C1=CC=CO1 FUBFWTUFPGFHOJ-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 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 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-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
- 206010028400 Mutagenic effect Diseases 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 238000011785 NMRI mouse Methods 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- LZRVAAYXGFWSDY-UHFFFAOYSA-N aziridine-2-carboxamide Chemical compound NC(=O)C1CN1 LZRVAAYXGFWSDY-UHFFFAOYSA-N 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- NWWQRQNXGXVWJV-CLTKARDFSA-N dimethyl (z)-2-(2-cyanoaziridin-1-yl)but-2-enedioate Chemical compound COC(=O)\C=C(C(=O)OC)/N1CC1C#N NWWQRQNXGXVWJV-CLTKARDFSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- SBSCIUUGENBGCC-UHFFFAOYSA-N ethyl 2-(2-cyanoaziridin-1-yl)acetate Chemical compound CCOC(=O)CN1CC1C#N SBSCIUUGENBGCC-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229920006158 high molecular weight polymer Polymers 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 231100000219 mutagenic Toxicity 0.000 description 1
- 231100000243 mutagenic effect Toxicity 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical group C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002511 phenobarbital sodium Drugs 0.000 description 1
- WRLGYAWRGXKSKG-UHFFFAOYSA-M phenobarbital sodium Chemical compound [Na+].C=1C=CC=CC=1C1(CC)C(=O)NC([O-])=NC1=O WRLGYAWRGXKSKG-UHFFFAOYSA-M 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000003071 polychlorinated biphenyls Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/08—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782833986 DE2833986A1 (de) | 1978-08-03 | 1978-08-03 | Immunstimulierende n-substituierte aziridin-2-carbonsaeurederivate, verfahren zu ihrer herstellung sowie arzneimittel, die diese substanzen enthalten |
| DE2833986.8 | 1978-08-03 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63258415A JPS63258415A (ja) | 1988-10-25 |
| JPH0257523B2 true JPH0257523B2 (h) | 1990-12-05 |
Family
ID=6046078
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9878079A Granted JPS5522694A (en) | 1978-08-03 | 1979-08-03 | N substituted aziridinn22carboxylic acid derivative*its manufacture and immunity stimulant drug containing it |
| JP62083962A Granted JPS63258415A (ja) | 1978-08-03 | 1987-04-07 | Ｎ−置換２−シアンアジリジンを含有する免疫刺戟性薬剤 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9878079A Granted JPS5522694A (en) | 1978-08-03 | 1979-08-03 | N substituted aziridinn22carboxylic acid derivative*its manufacture and immunity stimulant drug containing it |
Country Status (39)
| Country | Link |
|---|---|
| US (3) | US4321194A (h) |
| JP (2) | JPS5522694A (h) |
| KR (1) | KR860000320B1 (h) |
| AR (1) | AR228945A1 (h) |
| AT (1) | AT379382B (h) |
| AU (1) | AU524572B2 (h) |
| BE (1) | BE878020A (h) |
| CA (1) | CA1142530A (h) |
| CH (1) | CH645540A5 (h) |
| CS (1) | CS227301B2 (h) |
| DD (1) | DD145267A5 (h) |
| DE (1) | DE2833986A1 (h) |
| DK (1) | DK156431C (h) |
| EG (1) | EG14369A (h) |
| ES (1) | ES483116A1 (h) |
| FI (1) | FI70570C (h) |
| FR (2) | FR2432317A1 (h) |
| GB (2) | GB2026863B (h) |
| GR (1) | GR74424B (h) |
| HK (1) | HK13285A (h) |
| HU (1) | HU184610B (h) |
| IE (1) | IE48462B1 (h) |
| IL (1) | IL57939A (h) |
| IT (1) | IT1123503B (h) |
| KE (1) | KE3493A (h) |
| LU (1) | LU81563A1 (h) |
| MY (1) | MY8600045A (h) |
| NL (1) | NL187239C (h) |
| NO (1) | NO152413C (h) |
| NZ (1) | NZ191169A (h) |
| OA (1) | OA06310A (h) |
| PH (1) | PH19007A (h) |
| PL (1) | PL126531B1 (h) |
| PT (1) | PT70009A (h) |
| SE (1) | SE445552B (h) |
| SG (1) | SG85784G (h) |
| SU (1) | SU1145927A3 (h) |
| YU (1) | YU41169B (h) |
| ZA (1) | ZA793966B (h) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3446713A1 (de) * | 1984-12-21 | 1986-06-26 | Boehringer Mannheim Gmbh, 6800 Mannheim | N-substituierte aziridin-2-carbonsaeurederivate, verfahren zu deren herstellung sowie diese substanzen enthaltende arzneimittel |
| JPS6287512A (ja) * | 1985-10-11 | 1987-04-22 | ベ−リンガ−・マンハイム・ゲゼルシヤフト・ミツト・ベシユレンクテル・ハフツング | 選択的免疫抑制剤 |
| US4925835A (en) * | 1986-05-01 | 1990-05-15 | Sloan-Kettering Institute For Cancer Research | Aziridinyl putrescine containing compositions and their uses in treating prostate cancer |
| KR19980083844A (ko) * | 1997-05-19 | 1998-12-05 | 이웅열 | 새로운 아지리딘 유도체 및 그 제조방법 |
| FR2776292B1 (fr) * | 1998-03-20 | 2004-09-10 | Oncopharm | Cephalotaxanes porteurs de chaine laterale et leur procede de synthese |
| KR20010000195A (ko) * | 2000-08-10 | 2001-01-05 | 하현준 | (2ｒ)- 및 (2ｓ)-아지리딘-2-카르복실산 에스테르 및(2ｒ)- 및 (2ｓ)-2-히드록시메틸 아지리딘 제조 방법 |
| US20030129222A1 (en) * | 2000-11-21 | 2003-07-10 | Gabriel Lopez-Berestein | Liposomal imexon |
| WO2002041871A2 (en) * | 2000-11-21 | 2002-05-30 | Board Of Regents, The University Of Texas System | Composition comprising an imexon or derivatives thereof and lipids |
| US6982263B2 (en) * | 2001-06-08 | 2006-01-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitriles useful as reversible inhibitors of cysteine proteases |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1470223A1 (de) * | 1962-09-05 | 1969-12-04 | Siegfried Ag | Verfahren zur Herstellung neuer stickstoffhaltiger Heterocyclen |
| DE2528460A1 (de) * | 1975-06-26 | 1977-01-13 | Boehringer Mannheim Gmbh | Verwendung von l-carboxamido-2- cyan-aziridin als immunstimulans |
| DE2530960A1 (de) | 1975-07-11 | 1977-01-27 | Huels Chemische Werke Ag | 2-(n-substituierte)-aziridinyl-delta hoch 2 -oxazoline und verfahren zu ihrer herstellung |
| DE2538672A1 (de) * | 1975-08-30 | 1977-03-10 | Boehringer Mannheim Gmbh | Verwendung von derivaten der propionsaeure |
| DE2656240C2 (de) * | 1976-12-11 | 1983-11-03 | Boehringer Mannheim Gmbh, 6800 Mannheim | Neue Aziridin-Derivate, Verfahren zu deren Herstellung und pharmazeutische Mittel |
| CA1092606A (en) * | 1976-10-05 | 1980-12-30 | Herbert Berger | 1-(n-acylcarbamoyl)-2-cyano-aziridines and the preparation thereof |
| GB1550065A (en) * | 1976-10-29 | 1979-08-08 | Inst Organicheskogo Sinteza Ak | Pharmaceutical composition processing antitumour activity |
| AR218645A1 (es) * | 1976-12-11 | 1980-06-30 | Boehringer Mannheim Gmbh | Procedimiento para preparar derivados de esteres del acido 1-aziridina-carboxilico |
-
1978
- 1978-08-03 DE DE19782833986 patent/DE2833986A1/de active Granted
-
1979
- 1979-07-20 CA CA000332281A patent/CA1142530A/en not_active Expired
- 1979-07-20 KR KR7902440A patent/KR860000320B1/ko not_active Expired
- 1979-07-23 US US06/059,863 patent/US4321194A/en not_active Expired - Lifetime
- 1979-07-27 CS CS795237A patent/CS227301B2/cs unknown
- 1979-07-27 AU AU49308/79A patent/AU524572B2/en not_active Ceased
- 1979-07-27 AR AR277498A patent/AR228945A1/es active
- 1979-07-30 PH PH22826A patent/PH19007A/en unknown
- 1979-07-30 GR GR59726A patent/GR74424B/el unknown
- 1979-07-30 IT IT24769/79A patent/IT1123503B/it active
- 1979-07-30 LU LU81563A patent/LU81563A1/de unknown
- 1979-07-30 DK DK320379A patent/DK156431C/da not_active IP Right Cessation
- 1979-07-30 SE SE7906461A patent/SE445552B/sv not_active IP Right Cessation
- 1979-07-30 NL NLAANVRAGE7905855,A patent/NL187239C/xx not_active IP Right Cessation
- 1979-07-31 IL IL57939A patent/IL57939A/xx unknown
- 1979-07-31 DD DD79214711A patent/DD145267A5/de unknown
- 1979-07-31 PT PT70009A patent/PT70009A/pt unknown
- 1979-07-31 NZ NZ191169A patent/NZ191169A/xx unknown
- 1979-07-31 CH CH707079A patent/CH645540A5/de not_active IP Right Cessation
- 1979-07-31 FI FI792393A patent/FI70570C/fi not_active IP Right Cessation
- 1979-08-01 BE BE0/196560A patent/BE878020A/fr not_active IP Right Cessation
- 1979-08-01 SU SU792791952A patent/SU1145927A3/ru active
- 1979-08-02 ZA ZA00793966A patent/ZA793966B/xx unknown
- 1979-08-02 HU HU79BO1800A patent/HU184610B/hu not_active IP Right Cessation
- 1979-08-02 GB GB7926975A patent/GB2026863B/en not_active Expired
- 1979-08-02 PL PL1979217527A patent/PL126531B1/pl unknown
- 1979-08-02 GB GB08215159A patent/GB2106896B/en not_active Expired
- 1979-08-02 FR FR7919830A patent/FR2432317A1/fr active Granted
- 1979-08-02 AT AT0531479A patent/AT379382B/de active
- 1979-08-02 YU YU1881/79A patent/YU41169B/xx unknown
- 1979-08-02 NO NO792545A patent/NO152413C/no unknown
- 1979-08-03 OA OA56865A patent/OA06310A/xx unknown
- 1979-08-03 ES ES483116A patent/ES483116A1/es not_active Expired
- 1979-08-03 JP JP9878079A patent/JPS5522694A/ja active Granted
- 1979-08-04 EG EG473/79A patent/EG14369A/xx active
- 1979-08-08 IE IE1478/79A patent/IE48462B1/en not_active IP Right Cessation
-
1980
- 1980-02-13 FR FR8003132A patent/FR2445316A1/fr active Granted
-
1981
- 1981-06-01 US US06/268,964 patent/US4409236A/en not_active Expired - Fee Related
- 1981-12-28 US US06/334,614 patent/US4410532A/en not_active Expired - Fee Related
-
1984
- 1984-11-29 SG SG857/84A patent/SG85784G/en unknown
-
1985
- 1985-01-04 KE KE3493A patent/KE3493A/xx unknown
- 1985-02-19 HK HK132/85A patent/HK13285A/xx unknown
-
1986
- 1986-12-30 MY MY45/86A patent/MY8600045A/xx unknown
-
1987
- 1987-04-07 JP JP62083962A patent/JPS63258415A/ja active Granted
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