CS208798B2 - Method of making the new derivatives of the n-substituted aziridin-2-carboxyl acid - Google Patents
Method of making the new derivatives of the n-substituted aziridin-2-carboxyl acid Download PDFInfo
- Publication number
- CS208798B2 CS208798B2 CS801134A CS113480A CS208798B2 CS 208798 B2 CS208798 B2 CS 208798B2 CS 801134 A CS801134 A CS 801134A CS 113480 A CS113480 A CS 113480A CS 208798 B2 CS208798 B2 CS 208798B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- cyano
- group
- aziridine
- formula
- hal
- Prior art date
Links
- 239000002253 acid Substances 0.000 title description 7
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 44
- -1 N-substituted aziridine-2-carboxylic acid Chemical class 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000002560 nitrile group Chemical group 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000126 substance Substances 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- 238000009835 boiling Methods 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 11
- 239000013543 active substance Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- BRLOYEZITUGJIQ-UHFFFAOYSA-N 1-ethoxyaziridine-2-carbonitrile Chemical compound CCON1CC1C#N BRLOYEZITUGJIQ-UHFFFAOYSA-N 0.000 description 6
- GDSNWDNQYWSZQR-UHFFFAOYSA-N 1-methoxyaziridine-2-carbonitrile Chemical compound CON1CC1C#N GDSNWDNQYWSZQR-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- 229940127089 cytotoxic agent Drugs 0.000 description 6
- 230000003308 immunostimulating effect Effects 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 6
- 235000012239 silicon dioxide Nutrition 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 210000000265 leukocyte Anatomy 0.000 description 5
- 230000007935 neutral effect Effects 0.000 description 5
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 238000007127 saponification reaction Methods 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- OYMQRTSYDQVPGI-UHFFFAOYSA-N 1-[(3-fluorophenyl)methoxy]aziridine-2-carbonitrile Chemical compound FC1=CC=CC(CON2C(C2)C#N)=C1 OYMQRTSYDQVPGI-UHFFFAOYSA-N 0.000 description 3
- SJFDGCBOMIAMIW-UHFFFAOYSA-N 1-butan-2-yloxyaziridine-2-carbonitrile Chemical compound CCC(C)ON1CC1C#N SJFDGCBOMIAMIW-UHFFFAOYSA-N 0.000 description 3
- ARRIEYYNOLTVTE-UHFFFAOYSA-N 2,3-dibromopropanenitrile Chemical compound BrCC(Br)C#N ARRIEYYNOLTVTE-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 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 3
- 229960005091 chloramphenicol Drugs 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000008298 dragée Substances 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000001900 immune effect Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 3
- 230000003313 weakening effect Effects 0.000 description 3
- RFDXBINFEIBBHC-UHFFFAOYSA-N 1-(2-hydroxyethoxy)aziridine-2-carbonitrile Chemical compound OCCON1CC1C#N RFDXBINFEIBBHC-UHFFFAOYSA-N 0.000 description 2
- NOXPFQDJOJMZMD-UHFFFAOYSA-N 1-(2-phenoxyethoxy)aziridine-2-carbonitrile Chemical compound N#CC1CN1OCCOC1=CC=CC=C1 NOXPFQDJOJMZMD-UHFFFAOYSA-N 0.000 description 2
- VOCGFLKQAQIZPC-UHFFFAOYSA-N 1-(pyridin-2-ylmethoxy)aziridine-2-carbonitrile Chemical compound N#CC1CN1OCC1=CC=CC=N1 VOCGFLKQAQIZPC-UHFFFAOYSA-N 0.000 description 2
- VIJHSZAOZSRXFK-UHFFFAOYSA-N 1-(pyrimidin-2-ylmethoxy)aziridine-2-carbonitrile Chemical compound N#CC1CN1OCC1=NC=CC=N1 VIJHSZAOZSRXFK-UHFFFAOYSA-N 0.000 description 2
- RIDRDPSNXQMLRE-UHFFFAOYSA-N 1-[(4-chlorophenyl)methoxy]aziridine-2-carbonitrile Chemical compound C1=CC(Cl)=CC=C1CON1C(C#N)C1 RIDRDPSNXQMLRE-UHFFFAOYSA-N 0.000 description 2
- BENWBQSVIMMBAD-UHFFFAOYSA-N 1-[(4-cyanophenyl)methoxy]aziridine-2-carbonitrile Chemical compound N#CC1CN1OCC1=CC=C(C#N)C=C1 BENWBQSVIMMBAD-UHFFFAOYSA-N 0.000 description 2
- JTOPVFPJNGCHBH-UHFFFAOYSA-N 1-ethoxyaziridine-2-carboxamide Chemical compound CCON1CC1C(N)=O JTOPVFPJNGCHBH-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- QLJCWRYCVUCMJR-UHFFFAOYSA-N 1-phenylmethoxyaziridine-2-carbonitrile Chemical compound N#CC1CN1OCC1=CC=CC=C1 QLJCWRYCVUCMJR-UHFFFAOYSA-N 0.000 description 2
- UHXFUMWAJADCOU-UHFFFAOYSA-N 1-propan-2-yloxyaziridine-2-carbonitrile Chemical compound CC(C)ON1CC1C#N UHXFUMWAJADCOU-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-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
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- WBGBOXYJYPVLQJ-UHFFFAOYSA-N aziridine-2-carboxylic acid Chemical class OC(=O)C1CN1 WBGBOXYJYPVLQJ-UHFFFAOYSA-N 0.000 description 2
- 229950005499 carbon tetrachloride Drugs 0.000 description 2
- 230000000973 chemotherapeutic effect Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 230000032050 esterification Effects 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- RCGNSUSAMLATNI-UHFFFAOYSA-N ethyl 2-(2-cyanoaziridin-1-yl)oxyacetate Chemical compound CCOC(=O)CON1CC1C#N RCGNSUSAMLATNI-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
- 238000011049 filling Methods 0.000 description 2
- 229920006158 high molecular weight polymer Polymers 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- YLGXILFCIXHCMC-JHGZEJCSSA-N methyl cellulose Chemical compound COC1C(OC)C(OC)C(COC)O[C@H]1O[C@H]1C(OC)C(OC)C(OC)OC1COC YLGXILFCIXHCMC-JHGZEJCSSA-N 0.000 description 2
- 150000002825 nitriles Chemical group 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- AQFWNELGMODZGC-UHFFFAOYSA-N o-ethylhydroxylamine Chemical compound CCON AQFWNELGMODZGC-UHFFFAOYSA-N 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- HVEMVEPLKBVVII-UHFFFAOYSA-N 1-(2,2,2-trichloroethoxy)aziridine-2-carbonitrile Chemical compound ClC(Cl)(Cl)CON1CC1C#N HVEMVEPLKBVVII-UHFFFAOYSA-N 0.000 description 1
- DRZJVKFVJROTKA-UHFFFAOYSA-N 1-(2,3-dihydroxypropoxy)aziridine-2-carbonitrile Chemical compound OCC(O)CON1CC1C#N DRZJVKFVJROTKA-UHFFFAOYSA-N 0.000 description 1
- CNKVCMCFWYEQTP-UHFFFAOYSA-N 1-(2-bromoethoxy)aziridine-2-carbonitrile Chemical compound BrCCON1CC1C#N CNKVCMCFWYEQTP-UHFFFAOYSA-N 0.000 description 1
- DPICRNDUHONRRE-UHFFFAOYSA-N 1-(2-fluoroethoxy)aziridine-2-carbonitrile Chemical compound FCCON1CC1C#N DPICRNDUHONRRE-UHFFFAOYSA-N 0.000 description 1
- BWGGPKPFHIZRBK-UHFFFAOYSA-N 1-(2-methylprop-2-enoxy)aziridine-2-carbonitrile Chemical compound CC(=C)CON1CC1C#N BWGGPKPFHIZRBK-UHFFFAOYSA-N 0.000 description 1
- LHIWUILBUDGKIO-UHFFFAOYSA-N 1-(2-phenylethoxy)aziridine-2-carbonitrile Chemical compound N#CC1CN1OCCC1=CC=CC=C1 LHIWUILBUDGKIO-UHFFFAOYSA-N 0.000 description 1
- PCXJFVCLABSWID-UHFFFAOYSA-N 1-(3-chloropropoxy)aziridine-2-carbonitrile Chemical compound ClCCCON1CC1C#N PCXJFVCLABSWID-UHFFFAOYSA-N 0.000 description 1
- AKCQEWYNXLMTBJ-UHFFFAOYSA-N 1-(oxan-2-yloxy)aziridine-2-carbonitrile Chemical compound N#CC1CN1OC1OCCCC1 AKCQEWYNXLMTBJ-UHFFFAOYSA-N 0.000 description 1
- ZECLPFVNKPHSTL-UHFFFAOYSA-N 1-(pyrimidin-4-ylmethoxy)aziridine-2-carbonitrile Chemical compound N#CC1CN1OCC1=CC=NC=N1 ZECLPFVNKPHSTL-UHFFFAOYSA-N 0.000 description 1
- NEGXJJOQVLQKLK-UHFFFAOYSA-N 1-[(2,4-dichlorophenyl)methoxy]aziridine-2-carbonitrile Chemical compound ClC1=CC(Cl)=CC=C1CON1C(C#N)C1 NEGXJJOQVLQKLK-UHFFFAOYSA-N 0.000 description 1
- GXIGOUKMEUMZPH-UHFFFAOYSA-N 1-[(2-methylphenyl)methoxy]aziridine-2-carbonitrile;o-[(2-methylphenyl)methyl]hydroxylamine Chemical compound CC1=CC=CC=C1CON.CC1=CC=CC=C1CON1C(C#N)C1 GXIGOUKMEUMZPH-UHFFFAOYSA-N 0.000 description 1
- QCWRAYVYRMPPHS-UHFFFAOYSA-N 1-[(2-methylpropan-2-yl)oxy]aziridine-2-carbonitrile Chemical compound CC(C)(C)ON1CC1C#N QCWRAYVYRMPPHS-UHFFFAOYSA-N 0.000 description 1
- ROORJSYHNQLLPE-UHFFFAOYSA-N 1-[(3,4-dichlorophenyl)methoxy]aziridine-2-carbonitrile Chemical compound C1=C(Cl)C(Cl)=CC=C1CON1C(C#N)C1 ROORJSYHNQLLPE-UHFFFAOYSA-N 0.000 description 1
- ZCQGZPCEEFLUBP-UHFFFAOYSA-N 1-[(4-methoxyphenyl)methoxy]aziridine-2-carbonitrile Chemical compound C1=CC(OC)=CC=C1CON1C(C#N)C1 ZCQGZPCEEFLUBP-UHFFFAOYSA-N 0.000 description 1
- MHFLYTBHTPDEMW-UHFFFAOYSA-N 1-[(5-chloro-2-methoxyphenyl)methoxy]aziridine-2-carbonitrile Chemical compound COC1=CC=C(Cl)C=C1CON1C(C#N)C1 MHFLYTBHTPDEMW-UHFFFAOYSA-N 0.000 description 1
- WKWVENMQOPQDKT-UHFFFAOYSA-N 1-[2-(2-cyanoaziridin-1-yl)oxyethoxy]aziridine-2-carbonitrile Chemical compound N#CC1CN1OCCON1C(C#N)C1 WKWVENMQOPQDKT-UHFFFAOYSA-N 0.000 description 1
- VXHWYNDVNDLONP-UHFFFAOYSA-N 1-[[3-(trifluoromethyl)phenyl]methoxy]aziridine-2-carbonitrile Chemical compound FC(F)(F)C1=CC=CC(CON2C(C2)C#N)=C1 VXHWYNDVNDLONP-UHFFFAOYSA-N 0.000 description 1
- UOMXSAFFKWLANI-UHFFFAOYSA-N 1-but-2-enoxyaziridine-2-carbonitrile Chemical compound CC=CCON1CC1C#N UOMXSAFFKWLANI-UHFFFAOYSA-N 0.000 description 1
- QMEZXLOAIMFYGM-UHFFFAOYSA-N 1-but-3-en-2-yloxyaziridine-2-carbonitrile Chemical compound C=CC(C)ON1CC1C#N QMEZXLOAIMFYGM-UHFFFAOYSA-N 0.000 description 1
- COZVEHXKOVVOES-UHFFFAOYSA-N 1-butoxyaziridine-2-carbonitrile Chemical compound CCCCON1CC1C#N COZVEHXKOVVOES-UHFFFAOYSA-N 0.000 description 1
- RYPDKDRELPPGQB-UHFFFAOYSA-N 1-butoxyaziridine-2-carboxamide Chemical compound CCCCON1CC1C(N)=O RYPDKDRELPPGQB-UHFFFAOYSA-N 0.000 description 1
- SQQQNWQUZZRQPH-UHFFFAOYSA-N 1-cyclohexyloxyaziridine-2-carbonitrile Chemical compound N#CC1CN1OC1CCCCC1 SQQQNWQUZZRQPH-UHFFFAOYSA-N 0.000 description 1
- REUAVJSWWRCZKU-UHFFFAOYSA-N 1-hexoxyaziridine-2-carbonitrile Chemical compound CCCCCCON1CC1C#N REUAVJSWWRCZKU-UHFFFAOYSA-N 0.000 description 1
- ZKNSXSCILQBZDL-UHFFFAOYSA-N 1-hydroxyaziridine-2-carbonitrile Chemical compound ON1CC1C#N ZKNSXSCILQBZDL-UHFFFAOYSA-N 0.000 description 1
- GTGFSWQGAWZNCH-UHFFFAOYSA-N 1-hydroxyaziridine-2-carboxylic acid Chemical class ON1CC1C(O)=O GTGFSWQGAWZNCH-UHFFFAOYSA-N 0.000 description 1
- HSTVLAGVLFMZSU-UHFFFAOYSA-N 1-methoxy-3-phenylaziridine-2-carbonitrile Chemical compound CON1C(C#N)C1C1=CC=CC=C1 HSTVLAGVLFMZSU-UHFFFAOYSA-N 0.000 description 1
- GUDAPRGEJOYFBQ-UHFFFAOYSA-N 1-methoxyaziridine-2-carboxamide Chemical compound CON1CC1C(N)=O GUDAPRGEJOYFBQ-UHFFFAOYSA-N 0.000 description 1
- CCCRYBADWAPXJV-UHFFFAOYSA-N 1-pentoxyaziridine-2-carbonitrile Chemical compound CCCCCON1CC1C#N CCCRYBADWAPXJV-UHFFFAOYSA-N 0.000 description 1
- HJUIYUKFMGRRKB-UHFFFAOYSA-N 1-phenylmethoxyaziridine-2-carboxamide Chemical compound NC(=O)C1CN1OCC1=CC=CC=C1 HJUIYUKFMGRRKB-UHFFFAOYSA-N 0.000 description 1
- VEQHGEDGUCJHFJ-UHFFFAOYSA-N 1-prop-2-ynoxyaziridine-2-carbonitrile Chemical compound C#CCON1CC1C#N VEQHGEDGUCJHFJ-UHFFFAOYSA-N 0.000 description 1
- ITNDGLYKTQAGFT-UHFFFAOYSA-N 1-propan-2-yloxyaziridine-2-carboxamide Chemical compound CC(C)ON1CC1C(N)=O ITNDGLYKTQAGFT-UHFFFAOYSA-N 0.000 description 1
- LXAAHIQLUNWJOX-UHFFFAOYSA-N 1-propoxyaziridine-2-carbonitrile Chemical compound CCCON1CC1C#N LXAAHIQLUNWJOX-UHFFFAOYSA-N 0.000 description 1
- NRLLTKQLGNTDJH-UHFFFAOYSA-N 2-(2-cyanoaziridin-1-yl)oxyacetic acid Chemical compound OC(=O)CON1CC1C#N NRLLTKQLGNTDJH-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- WWWTWPXKLJTKPM-UHFFFAOYSA-N 2-aminooxyethanol Chemical compound NOCCO WWWTWPXKLJTKPM-UHFFFAOYSA-N 0.000 description 1
- MWYKQBAMQAPYDK-UHFFFAOYSA-N 2-bromo-3-(ethoxyamino)propanenitrile Chemical compound CCONCC(Br)C#N MWYKQBAMQAPYDK-UHFFFAOYSA-N 0.000 description 1
- WADSJYLPJPTMLN-UHFFFAOYSA-N 3-(cycloundecen-1-yl)-1,2-diazacycloundec-2-ene Chemical compound C1CCCCCCCCC=C1C1=NNCCCCCCCC1 WADSJYLPJPTMLN-UHFFFAOYSA-N 0.000 description 1
- FSNGIQIKJSUZLR-UHFFFAOYSA-N 3-methyl-1-[(2-methylphenyl)methoxy]aziridine-2-carbonitrile Chemical compound CC1C(C#N)N1OCC1=CC=CC=C1C FSNGIQIKJSUZLR-UHFFFAOYSA-N 0.000 description 1
- ATBANLOLDZIUOW-UHFFFAOYSA-N 4-(aminooxymethyl)benzonitrile Chemical compound NOCC1=CC=C(C#N)C=C1 ATBANLOLDZIUOW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920000945 Amylopectin Polymers 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
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 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 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
- 240000005702 Galium aparine Species 0.000 description 1
- 235000014820 Galium aparine Nutrition 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 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
- 241000700159 Rattus Species 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229920006318 anionic polymer Polymers 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000001185 bone marrow Anatomy 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
- 238000002619 cancer immunotherapy Methods 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000003857 carboxamides Chemical class 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
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical compound CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- DASRSRJUJQHXPM-UHFFFAOYSA-N ethyl 1-ethoxyaziridine-2-carboxylate Chemical compound CCON1CC1C(=O)OCC DASRSRJUJQHXPM-UHFFFAOYSA-N 0.000 description 1
- YZFMNJQGUHSTEZ-UHFFFAOYSA-N ethyl 1-methoxyaziridine-2-carboxylate Chemical compound CCOC(=O)C1CN1OC YZFMNJQGUHSTEZ-UHFFFAOYSA-N 0.000 description 1
- OENICUBCLXKLJQ-UHFFFAOYSA-N ethyl 2,3-dibromopropanoate Chemical compound CCOC(=O)C(Br)CBr OENICUBCLXKLJQ-UHFFFAOYSA-N 0.000 description 1
- VNUUSOJDAJMVLQ-UHFFFAOYSA-N ethyl 2-aminooxyacetate Chemical compound CCOC(=O)CON VNUUSOJDAJMVLQ-UHFFFAOYSA-N 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 239000008173 hydrogenated soybean oil Substances 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 150000004767 nitrides Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- UQVFAWQNJLTMMF-UHFFFAOYSA-N o-(2-aminooxyethyl)hydroxylamine Chemical compound NOCCON UQVFAWQNJLTMMF-UHFFFAOYSA-N 0.000 description 1
- VNRCHSPQYNKHIQ-UHFFFAOYSA-N o-(2-bromoethyl)hydroxylamine Chemical compound NOCCBr VNRCHSPQYNKHIQ-UHFFFAOYSA-N 0.000 description 1
- HWKGEDJHAMSGKI-UHFFFAOYSA-N o-(2-phenoxyethyl)hydroxylamine Chemical compound NOCCOC1=CC=CC=C1 HWKGEDJHAMSGKI-UHFFFAOYSA-N 0.000 description 1
- NLXXVSKHVGDQAT-UHFFFAOYSA-N o-(oxan-2-yl)hydroxylamine Chemical compound NOC1CCCCO1 NLXXVSKHVGDQAT-UHFFFAOYSA-N 0.000 description 1
- PMPPBLLDPIXDRE-UHFFFAOYSA-N o-(pyridin-2-ylmethyl)hydroxylamine Chemical compound NOCC1=CC=CC=N1 PMPPBLLDPIXDRE-UHFFFAOYSA-N 0.000 description 1
- VFRQBXCZQQMVMI-UHFFFAOYSA-N o-(pyrimidin-2-ylmethyl)hydroxylamine Chemical compound NOCC1=NC=CC=N1 VFRQBXCZQQMVMI-UHFFFAOYSA-N 0.000 description 1
- OQLOZQGGZZHUDX-UHFFFAOYSA-N o-(pyrimidin-4-ylmethyl)hydroxylamine Chemical compound NOCC1=CC=NC=N1 OQLOZQGGZZHUDX-UHFFFAOYSA-N 0.000 description 1
- RWUMUUIIAOFEFC-UHFFFAOYSA-N o-[(2,4-dichlorophenyl)methyl]hydroxylamine Chemical compound NOCC1=CC=C(Cl)C=C1Cl RWUMUUIIAOFEFC-UHFFFAOYSA-N 0.000 description 1
- SBFMICWCOXGUSR-UHFFFAOYSA-N o-[(2-methylphenyl)methyl]hydroxylamine;hydrochloride Chemical compound Cl.CC1=CC=CC=C1CON SBFMICWCOXGUSR-UHFFFAOYSA-N 0.000 description 1
- OVMBDDNTFJQHST-UHFFFAOYSA-N o-[(3,4-dichlorophenyl)methyl]hydroxylamine Chemical compound NOCC1=CC=C(Cl)C(Cl)=C1 OVMBDDNTFJQHST-UHFFFAOYSA-N 0.000 description 1
- SUZMAAZWMHDSHJ-UHFFFAOYSA-N o-[(3,4-dimethoxyphenyl)methyl]hydroxylamine Chemical compound COC1=CC=C(CON)C=C1OC SUZMAAZWMHDSHJ-UHFFFAOYSA-N 0.000 description 1
- INUFRNDIHFACLU-UHFFFAOYSA-N o-[(3-fluorophenyl)methyl]hydroxylamine Chemical compound NOCC1=CC=CC(F)=C1 INUFRNDIHFACLU-UHFFFAOYSA-N 0.000 description 1
- MVSMBIBGGPSEHQ-UHFFFAOYSA-N o-[(4-methoxyphenyl)methyl]hydroxylamine Chemical compound COC1=CC=C(CON)C=C1 MVSMBIBGGPSEHQ-UHFFFAOYSA-N 0.000 description 1
- MLWXTMVARHZBPA-UHFFFAOYSA-N o-[(4-methylphenyl)methyl]hydroxylamine Chemical compound CC1=CC=C(CON)C=C1 MLWXTMVARHZBPA-UHFFFAOYSA-N 0.000 description 1
- GFGYMCCYOCCAON-UHFFFAOYSA-N o-[(5-chloro-2-methoxyphenyl)methyl]hydroxylamine Chemical compound COC1=CC=C(Cl)C=C1CON GFGYMCCYOCCAON-UHFFFAOYSA-N 0.000 description 1
- XYEOALKITRFCJJ-UHFFFAOYSA-N o-benzylhydroxylamine Chemical compound NOCC1=CC=CC=C1 XYEOALKITRFCJJ-UHFFFAOYSA-N 0.000 description 1
- KPTCZURLWZSRKB-UHFFFAOYSA-N o-prop-2-enylhydroxylamine Chemical compound NOCC=C KPTCZURLWZSRKB-UHFFFAOYSA-N 0.000 description 1
- HLYVNXRHROOICH-UHFFFAOYSA-N o-propan-2-ylhydroxylamine Chemical compound CC(C)ON HLYVNXRHROOICH-UHFFFAOYSA-N 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
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- ORTFAQDWJHRMNX-UHFFFAOYSA-M oxidooxomethyl Chemical compound [O-][C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-M 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000008194 pharmaceutical composition Substances 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
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- XYKIUTSFQGXHOW-UHFFFAOYSA-N propan-2-one;toluene Chemical compound CC(C)=O.CC1=CC=CC=C1 XYKIUTSFQGXHOW-UHFFFAOYSA-N 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 150000004671 saturated fatty acids Chemical class 0.000 description 1
- 125000005624 silicic acid group Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- IUTYMHORIFSPCU-UHFFFAOYSA-M sodium;1-ethoxyaziridine-2-carboxylate Chemical compound [Na+].CCON1CC1C([O-])=O IUTYMHORIFSPCU-UHFFFAOYSA-M 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation 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
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000001993 wax Substances 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
- C07D203/22—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 hetero atoms directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
-
- 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
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Transplantation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19792906603 DE2906603A1 (de) | 1979-02-21 | 1979-02-21 | N-substituierte aziridin-2-carbonsaeurederivate, verfahren zu deren herstellung sowie diese substanzen enthaltende arzneimittel |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS208798B2 true CS208798B2 (en) | 1981-09-15 |
Family
ID=6063481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS801134A CS208798B2 (en) | 1979-02-21 | 1980-02-19 | Method of making the new derivatives of the n-substituted aziridin-2-carboxyl acid |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US4397848A (enEXAMPLES) |
| EP (1) | EP0014976B1 (enEXAMPLES) |
| JP (1) | JPS55113760A (enEXAMPLES) |
| AR (1) | AR223863A1 (enEXAMPLES) |
| AT (1) | ATE818T1 (enEXAMPLES) |
| AU (1) | AU529982B2 (enEXAMPLES) |
| CA (1) | CA1148962A (enEXAMPLES) |
| CS (1) | CS208798B2 (enEXAMPLES) |
| DD (1) | DD148772A5 (enEXAMPLES) |
| DE (2) | DE2906603A1 (enEXAMPLES) |
| ES (1) | ES488656A1 (enEXAMPLES) |
| FI (1) | FI70702C (enEXAMPLES) |
| HU (1) | HU182801B (enEXAMPLES) |
| IE (1) | IE49267B1 (enEXAMPLES) |
| IL (1) | IL59425A (enEXAMPLES) |
| PL (1) | PL129707B1 (enEXAMPLES) |
| PT (1) | PT70847A (enEXAMPLES) |
| SU (1) | SU1181541A3 (enEXAMPLES) |
| ZA (1) | ZA80902B (enEXAMPLES) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JPH07301287A (ja) * | 1995-03-23 | 1995-11-14 | Sumitomo Heavy Ind Ltd | 制御装置に用いられる内接噛合遊星歯車機構 |
| CA2294243C (en) | 1997-06-27 | 2008-12-30 | Arizona Board Of Regents, University Of Arizona | Novel cyanoaziridines for treating cancer |
| 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 |
| EP1455763B1 (en) * | 2001-12-21 | 2007-10-03 | Supernus Pharmaceuticals, Inc. | Oral capsule formulation with increased physical stability |
| US20040005339A1 (en) * | 2002-06-28 | 2004-01-08 | Shojaei Amir H. | Formulations of fenofibrate and/or fenofibrate derivatives with improved oral bioavailability |
| RS20050532A (en) | 2003-01-14 | 2007-12-31 | Arena Pharmaceuticals Inc., | 1,2,3-trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prpphylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| US20070066590A1 (en) * | 2003-02-24 | 2007-03-22 | Jones Robert M | Phenyl-and pyridylpiperidine-derivatives as modulators of glucose metabolism |
| AR045047A1 (es) | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| ATE415397T1 (de) * | 2004-06-04 | 2008-12-15 | Arena Pharm Inc | Substituierte aryl- und heteroarylderivate als modulatoren des stoffwechsels und für die prophylaxe und behandlung von damit in zusammenhang stehenden erkrankungen |
| MY148521A (en) * | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| DOP2006000010A (es) | 2005-01-10 | 2006-07-31 | Arena Pharm Inc | Procedimiento para preparar eteres aromáticos |
| EA013084B1 (ru) * | 2005-09-16 | 2010-02-26 | Арена Фармасьютикалз, Инк. | Модуляторы метаболизма и лечение связанных с ним нарушений |
| TW200811140A (en) * | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
| TW200811147A (en) * | 2006-07-06 | 2008-03-01 | Arena Pharm Inc | Modulators of metabolism and the treatment of disorders related thereto |
| SG10201500639TA (en) | 2010-01-27 | 2015-03-30 | Arena Pharm Inc | Processes for the preparation of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3-yl)acetic acid and salts thereof |
| CA2812061A1 (en) | 2010-09-22 | 2012-03-29 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| UA126268C2 (uk) | 2015-01-06 | 2022-09-14 | Арена Фармасьютікалз, Інк. | СПОСОБИ ЛІКУВАННЯ СТАНІВ, ПОВ'ЯЗАНИХ З РЕЦЕПТОРОМ S1P<sub>1 </sub> |
| DK3310760T3 (da) | 2015-06-22 | 2022-10-24 | Arena Pharm Inc | Krystallinsk L-argininsalt af (R)-2-(7-(4-cyclopentyl-3-(trifluormethyl)benzyloxy)-1,2,3,4-tetrahydrocyclopenta[b]indol-3- yl)eddikesyre til anvendelse ved S1P1-receptor-associerede lidelser |
| US11534424B2 (en) | 2017-02-16 | 2022-12-27 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| MX2020013157A (es) | 2018-06-06 | 2021-04-29 | Arena Pharm Inc | Métodos de tratamiento de afecciones relacionadas con el receptor s1p1. |
| CN113816887A (zh) * | 2021-08-31 | 2021-12-21 | 华中科技大学 | 一种氮杂环丙烷类化合物及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2644820A1 (de) * | 1976-10-05 | 1978-04-06 | Boehringer Mannheim Gmbh | Cancerostatisch und immunstimulierend wirkende 1-(n-acyl-carbamoyl)-2-cyanaziridine sowie verfahren zur herstellung derselben |
| DE2731264A1 (de) | 1977-07-11 | 1979-02-01 | Boehringer Mannheim Gmbh | Neue 1-acyl-2-cyanaziridine, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische zubereitungen |
-
1979
- 1979-02-21 DE DE19792906603 patent/DE2906603A1/de not_active Withdrawn
-
1980
- 1980-02-15 ES ES488656A patent/ES488656A1/es not_active Expired
- 1980-02-16 DE DE8080100792T patent/DE3060268D1/de not_active Expired
- 1980-02-16 EP EP80100792A patent/EP0014976B1/de not_active Expired
- 1980-02-16 AT AT80100792T patent/ATE818T1/de not_active IP Right Cessation
- 1980-02-18 PL PL1980222088A patent/PL129707B1/pl unknown
- 1980-02-18 AU AU55649/80A patent/AU529982B2/en not_active Ceased
- 1980-02-18 SU SU802882348A patent/SU1181541A3/ru active
- 1980-02-18 CA CA000345886A patent/CA1148962A/en not_active Expired
- 1980-02-18 ZA ZA00800902A patent/ZA80902B/xx unknown
- 1980-02-19 IL IL59425A patent/IL59425A/xx unknown
- 1980-02-19 HU HU80383A patent/HU182801B/hu not_active IP Right Cessation
- 1980-02-19 CS CS801134A patent/CS208798B2/cs unknown
- 1980-02-19 DD DD80219137A patent/DD148772A5/de not_active IP Right Cessation
- 1980-02-20 FI FI800510A patent/FI70702C/fi not_active IP Right Cessation
- 1980-02-20 IE IE327/80A patent/IE49267B1/en unknown
- 1980-02-20 PT PT70847A patent/PT70847A/pt unknown
- 1980-02-21 JP JP1977580A patent/JPS55113760A/ja active Granted
-
1981
- 1981-02-15 AR AR279976A patent/AR223863A1/es active
- 1981-02-20 US US06/236,375 patent/US4397848A/en not_active Expired - Fee Related
-
1983
- 1983-05-17 US US06/495,548 patent/US4517183A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US4397848A (en) | 1983-08-09 |
| IL59425A0 (en) | 1980-05-30 |
| EP0014976B1 (de) | 1982-04-07 |
| HU182801B (en) | 1984-03-28 |
| AU529982B2 (en) | 1983-06-30 |
| PL129707B1 (en) | 1984-06-30 |
| ATE818T1 (de) | 1982-04-15 |
| JPH0150700B2 (enEXAMPLES) | 1989-10-31 |
| IL59425A (en) | 1984-05-31 |
| FI800510A7 (fi) | 1980-08-22 |
| EP0014976A1 (de) | 1980-09-03 |
| AR223863A1 (es) | 1981-09-30 |
| CA1148962A (en) | 1983-06-28 |
| US4517183A (en) | 1985-05-14 |
| SU1181541A3 (ru) | 1985-09-23 |
| DE2906603A1 (de) | 1980-09-04 |
| PL222088A1 (enEXAMPLES) | 1980-12-01 |
| JPS55113760A (en) | 1980-09-02 |
| PT70847A (de) | 1980-03-01 |
| ZA80902B (en) | 1981-03-25 |
| FI70702B (fi) | 1986-06-26 |
| DD148772A5 (de) | 1981-06-10 |
| DE3060268D1 (en) | 1982-05-19 |
| IE49267B1 (en) | 1985-09-04 |
| FI70702C (fi) | 1986-10-06 |
| AU5564980A (en) | 1980-08-28 |
| IE800327L (en) | 1980-08-21 |
| ES488656A1 (es) | 1980-09-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS208798B2 (en) | Method of making the new derivatives of the n-substituted aziridin-2-carboxyl acid | |
| TWI791511B (zh) | 細胞凋亡誘導劑 | |
| US4217359A (en) | Carbamate derivatives of mercaptoacyl hydroxy prolines | |
| US4048306A (en) | Aldehyde-erythromycylamine condensation products | |
| JPH06510041A (ja) | 抗ｈｉｖ（ａｉｄｓ）薬剤 | |
| US5786383A (en) | Pharmaceutical preparation | |
| US3639477A (en) | Novel propoxyguanidine compounds and means of producing the same | |
| GB2243832A (en) | 2-substituted 4-acetamido-5-chloro-n-[2-(diethylamino)ethyl]-benzamide derivative | |
| GB2073752A (en) | 2,6-diaminobularines | |
| US4410532A (en) | N-Substituted aziridine-2-carboxylic acid derivatives and their immuno-stimulation compositions and methods | |
| KR0178956B1 (ko) | 항균성 페넴 에스테르 유도체 | |
| EP0103320A2 (en) | Acetylsalicylic acid thioesters, a process for their preparation and pharmaceutical compositions containing them | |
| GB2046091A (en) | Pharmaceutical compositions containing beta-diketones for promoting the enteric absorption of pharmacologically active substances | |
| KR0178957B1 (ko) | 페넴 화합물 | |
| EP0211157B1 (de) | Isoxazolderivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutischen Präparate | |
| US3911010A (en) | Aminophenylamidines, their production and their pharmaceutical use | |
| US4252943A (en) | Carbamate derivatives of mercaptoacyl hydroxy prolines | |
| FR2516510A1 (fr) | Derives de la (trimethoxy-3,4,5-cinnamoyl)-1-aminocarbonylethyl-4-piperazine substituee utilisables en pharmacie et procede pour leur preparation | |
| GB2170200A (en) | Acylaminoalkanoyl compounds | |
| EP0047358B1 (en) | Indol acetic derivatives, process for producing the same and pharmaceutical compositions comprising the same | |
| FI80440C (fi) | Analogifoerfarande foer framstaellning av terapeutiskt anvaendbara afidkolanderivat. | |
| FI66856C (fi) | Foerfarande foer framstaellning av nya hjaertstimulerande alkanolaminderivat | |
| US4454327A (en) | 5-Oxo-2,2-pyrrolidinedipropanoic acid and ester derivatives thereof | |
| CZ20012482A3 (cs) | Deriváty ((aminoiminomethyl)amino)alkankarboxamidu a jejich pouľití v terapii | |
| US3993761A (en) | Antibacterial compositions |