SE452006B - N-/4(3-aminopropyl)aminobutyl/-2-(omega-guanidinofettsyraamido)-2-substituerad etanamid, salt derav och forfarande for framstellning derav - Google Patents
N-/4(3-aminopropyl)aminobutyl/-2-(omega-guanidinofettsyraamido)-2-substituerad etanamid, salt derav och forfarande for framstellning deravInfo
- Publication number
- SE452006B SE452006B SE8205698A SE8205698A SE452006B SE 452006 B SE452006 B SE 452006B SE 8205698 A SE8205698 A SE 8205698A SE 8205698 A SE8205698 A SE 8205698A SE 452006 B SE452006 B SE 452006B
- Authority
- SE
- Sweden
- Prior art keywords
- aminopropyl
- aminobutyl
- mixture
- mmol
- guanidino
- Prior art date
Links
- -1 (3-AMINOPROPYL) AMINOBUTYL Chemical class 0.000 title claims description 32
- 239000002253 acid Substances 0.000 title claims description 17
- 238000000034 method Methods 0.000 title claims description 15
- 150000003839 salts Chemical class 0.000 title claims description 13
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical class CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 title claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 79
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 34
- 239000000194 fatty acid Substances 0.000 claims description 22
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 15
- 229930195729 fatty acid Natural products 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 229910052727 yttrium Inorganic materials 0.000 claims description 5
- 125000003368 amide group Chemical group 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 150000004665 fatty acids Chemical class 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 2
- HFNDGMJKLKYYRZ-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-methoxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical group NC(N)=NCCCCCCC(=O)NC(OC)C(=O)NCCCCNCCCN HFNDGMJKLKYYRZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- GSAGCSXLLNPRMG-UHFFFAOYSA-N 6-amino-2,2-dihydroxyhexanamide Chemical compound NCCCCC(C(=O)N)(O)O GSAGCSXLLNPRMG-UHFFFAOYSA-N 0.000 claims 1
- IACGVEDRAQXQRI-UHFFFAOYSA-N COC(CCCCN)(C(=O)N)NC(=O)C=CCCCCN=C(N)N Chemical compound COC(CCCCN)(C(=O)N)NC(=O)C=CCCCCN=C(N)N IACGVEDRAQXQRI-UHFFFAOYSA-N 0.000 claims 1
- OTBHHUPVCYLGQO-UHFFFAOYSA-N bis(3-aminopropyl)amine Chemical group NCCCNCCCN OTBHHUPVCYLGQO-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- 239000000203 mixture Substances 0.000 description 98
- 239000000243 solution Substances 0.000 description 83
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- 239000000843 powder Substances 0.000 description 57
- 238000003786 synthesis reaction Methods 0.000 description 56
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 54
- 230000015572 biosynthetic process Effects 0.000 description 53
- 239000011541 reaction mixture Substances 0.000 description 45
- 238000006243 chemical reaction Methods 0.000 description 36
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 34
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- 239000011734 sodium Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 229920005654 Sephadex Polymers 0.000 description 22
- 239000012507 Sephadex™ Substances 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000010410 layer Substances 0.000 description 20
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 230000002829 reductive effect Effects 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 15
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 15
- 239000000126 substance Substances 0.000 description 15
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 14
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 14
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 14
- JBVZQDJNGFOSNX-UHFFFAOYSA-N Spergualin Natural products NCCCNCCCCNC(=O)C(O)NC(=O)CC(O)CCCCNC(=CN)N JBVZQDJNGFOSNX-UHFFFAOYSA-N 0.000 description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- GDVNLLJNADMLLR-BBRMVZONSA-N Spergualin Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)C[C@@H](O)CCCCN=C(N)N GDVNLLJNADMLLR-BBRMVZONSA-N 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 11
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 8
- OKKJLVBELUTLKV-MICDWDOJSA-N deuteriomethanol Chemical compound [2H]CO OKKJLVBELUTLKV-MICDWDOJSA-N 0.000 description 8
- HAXKLTHULHEENJ-UHFFFAOYSA-N n-[4-(3-aminopropylamino)butyl]-2,2-dihydroxyacetamide;dihydrochloride Chemical compound Cl.Cl.NCCCNCCCCNC(=O)C(O)O HAXKLTHULHEENJ-UHFFFAOYSA-N 0.000 description 8
- 230000035484 reaction time Effects 0.000 description 8
- TZGPACAKMCUCKX-UHFFFAOYSA-N 2-hydroxyacetamide Chemical compound NC(=O)CO TZGPACAKMCUCKX-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 238000000862 absorption spectrum Methods 0.000 description 7
- 230000029936 alkylation Effects 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- ROBLTDOHDSGGDT-UHFFFAOYSA-M sodium;pentane-1-sulfonate Chemical compound [Na+].CCCCCS([O-])(=O)=O ROBLTDOHDSGGDT-UHFFFAOYSA-M 0.000 description 7
- 208000005156 Dehydration Diseases 0.000 description 6
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- 101100298295 Drosophila melanogaster flfl gene Proteins 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000018044 dehydration Effects 0.000 description 6
- 238000006297 dehydration reaction Methods 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- YZMBJIBYULJNRB-HOCLYGCPSA-N (3s)-n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxyethyl]-7-(diaminomethylideneamino)-3-hydroxyheptanamide Chemical compound NCCCNCCCCNC[C@H](O)NC(=O)C[C@@H](O)CCCCNC(N)=N YZMBJIBYULJNRB-HOCLYGCPSA-N 0.000 description 5
- 101100283604 Caenorhabditis elegans pigk-1 gene Proteins 0.000 description 5
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- PJDINCOFOROBQW-LURJTMIESA-N (3S)-3,7-diaminoheptanoic acid Chemical compound NCCCC[C@H](N)CC(O)=O PJDINCOFOROBQW-LURJTMIESA-N 0.000 description 4
- MUBPBZMXUDIFIC-UHFFFAOYSA-N 7-(diaminomethylideneamino)hept-2-enamide Chemical compound NC(=N)NCCCCC=CC(N)=O MUBPBZMXUDIFIC-UHFFFAOYSA-N 0.000 description 4
- HCGIZHOBCPEDCE-UHFFFAOYSA-N 8-(diaminomethylideneamino)-3-hydroxyoctanamide Chemical compound NC(=N)NCCCCCC(O)CC(N)=O HCGIZHOBCPEDCE-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000003377 acid catalyst Substances 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000010531 catalytic reduction reaction Methods 0.000 description 4
- 229920001429 chelating resin Polymers 0.000 description 4
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 4
- 238000005194 fractionation Methods 0.000 description 4
- 230000009036 growth inhibition Effects 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- KLKKIENVIGQBAG-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCNC(=O)OC(C)(C)C)C=C1 KLKKIENVIGQBAG-UHFFFAOYSA-N 0.000 description 3
- HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 3
- RWWIIOHLSYTJOO-UHFFFAOYSA-N 7-(diaminomethylideneamino)hept-2-enamide;hydrochloride Chemical compound Cl.NC(=N)NCCCCC=CC(N)=O RWWIIOHLSYTJOO-UHFFFAOYSA-N 0.000 description 3
- FTUSVSFXDXMXGE-UHFFFAOYSA-N 7-(diaminomethylideneamino)heptanamide;hydrochloride Chemical compound Cl.NC(=N)NCCCCCCC(N)=O FTUSVSFXDXMXGE-UHFFFAOYSA-N 0.000 description 3
- CAAJHSPSOKKTHO-UHFFFAOYSA-N 8-(diaminomethylideneamino)-3-hydroxyoctanamide;hydrochloride Chemical compound Cl.NC(=O)CC(O)CCCCCNC(N)=N CAAJHSPSOKKTHO-UHFFFAOYSA-N 0.000 description 3
- YNGHJNDCGMVSOI-UHFFFAOYSA-N 9-(diaminomethylideneamino)-3-hydroxynonanamide;hydrochloride Chemical compound Cl.NC(=O)CC(O)CCCCCCNC(N)=N YNGHJNDCGMVSOI-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 231100000111 LD50 Toxicity 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- IZGKHHFFYLRBPL-UHFFFAOYSA-N benzyl n-(4-aminobutyl)carbamate Chemical compound NCCCCNC(=O)OCC1=CC=CC=C1 IZGKHHFFYLRBPL-UHFFFAOYSA-N 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
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- 150000007524 organic acids Chemical class 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 239000012279 sodium borohydride Substances 0.000 description 3
- 229910000033 sodium borohydride Inorganic materials 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- FADMHTYRZPLWIG-ZDUSSCGKSA-N (3s)-3-hydroxy-7-(phenylmethoxycarbonylamino)heptanoic acid Chemical compound OC(=O)C[C@@H](O)CCCCNC(=O)OCC1=CC=CC=C1 FADMHTYRZPLWIG-ZDUSSCGKSA-N 0.000 description 2
- YATBDEUMIYUAFJ-LURJTMIESA-N (3s)-7-(diaminomethylideneamino)-3-hydroxyheptanamide Chemical compound NC(=N)NCCCC[C@H](O)CC(N)=O YATBDEUMIYUAFJ-LURJTMIESA-N 0.000 description 2
- JPBYXYFQKIDRAL-RGMNGODLSA-N (3s)-7-(diaminomethylideneamino)-3-hydroxyheptanamide;hydrochloride Chemical compound Cl.NC(=O)C[C@@H](O)CCCCNC(N)=N JPBYXYFQKIDRAL-RGMNGODLSA-N 0.000 description 2
- JZCFXGYSVUKZCC-LURJTMIESA-N (3s)-7-amino-3-hydroxyheptanamide Chemical compound NCCCC[C@H](O)CC(N)=O JZCFXGYSVUKZCC-LURJTMIESA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- KPBNTQKMZNZGFX-UHFFFAOYSA-N 2,2-dihydroxyacetamide Chemical compound NC(=O)C(O)O KPBNTQKMZNZGFX-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- RXQDBVWDABAAHL-UHFFFAOYSA-N 6-(phenylmethoxycarbonylamino)hexanoic acid Chemical compound OC(=O)CCCCCNC(=O)OCC1=CC=CC=C1 RXQDBVWDABAAHL-UHFFFAOYSA-N 0.000 description 2
- JENQBROIBNPWKL-UHFFFAOYSA-N 8-(diaminomethylideneamino)oct-2-enamide Chemical compound NC(=N)NCCCCCC=CC(N)=O JENQBROIBNPWKL-UHFFFAOYSA-N 0.000 description 2
- MDGHRKWWAWEERV-UHFFFAOYSA-N 8-(diaminomethylideneamino)oct-2-enamide;hydrochloride Chemical compound Cl.NC(=N)NCCCCCC=CC(N)=O MDGHRKWWAWEERV-UHFFFAOYSA-N 0.000 description 2
- CWZQGDYUKRPZPO-UHFFFAOYSA-N 8-amino-3-hydroxyoctanamide;hydrochloride Chemical compound Cl.NCCCCCC(O)CC(N)=O CWZQGDYUKRPZPO-UHFFFAOYSA-N 0.000 description 2
- ONHVUBFFNZEONS-UHFFFAOYSA-N 9-(diaminomethylideneamino)non-2-enamide Chemical compound NC(=N)NCCCCCCC=CC(N)=O ONHVUBFFNZEONS-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000193830 Bacillus <bacterium> Species 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 229910021592 Copper(II) chloride Inorganic materials 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- AXSPHUWXYSZPBG-UHFFFAOYSA-N Gusperimus hydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N AXSPHUWXYSZPBG-UHFFFAOYSA-N 0.000 description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
- 208000007093 Leukemia L1210 Diseases 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
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- 150000002334 glycols Chemical class 0.000 description 1
- IDINUJSAMVOPCM-UHFFFAOYSA-N gusperimus Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000011968 lewis acid catalyst Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002032 methanolic fraction Substances 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- YTQGHFCRGPJUNX-UHFFFAOYSA-N n,n-diethylethanamine;pyridine;hydrate Chemical compound O.C1=CC=NC=C1.CCN(CC)CC YTQGHFCRGPJUNX-UHFFFAOYSA-N 0.000 description 1
- DKDPMDVAVZRGTP-UHFFFAOYSA-N n-(4,7-diaminoheptyl)-2,2-dihydroxyacetamide Chemical compound NCCCC(N)CCCNC(=O)C(O)O DKDPMDVAVZRGTP-UHFFFAOYSA-N 0.000 description 1
- DTJWFFNXTUXVEG-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-ethoxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NC(=N)NCCCCCCC(=O)NC(OCC)C(=O)NCCCCNCCCN DTJWFFNXTUXVEG-UHFFFAOYSA-N 0.000 description 1
- IMYNTLHWOBLDHO-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-ethoxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NC(N)=NCCCCCCC(=O)NC(OCC)C(=O)NCCCCNCCCN IMYNTLHWOBLDHO-UHFFFAOYSA-N 0.000 description 1
- LKGGVBDNKYMYTE-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-4-(diaminomethylideneamino)butanamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCN=C(N)N LKGGVBDNKYMYTE-UHFFFAOYSA-N 0.000 description 1
- KLZFDZFZFKYDDS-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-4-(diaminomethylideneamino)butanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CCCN=C(N)N KLZFDZFZFKYDDS-UHFFFAOYSA-N 0.000 description 1
- YTDLXOSFYJTHPB-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-5-(diaminomethylideneamino)pentanamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCNC(N)=N YTDLXOSFYJTHPB-UHFFFAOYSA-N 0.000 description 1
- DQPZVSKDNASILC-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-5-(diaminomethylideneamino)pentanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CCCCN=C(N)N DQPZVSKDNASILC-UHFFFAOYSA-N 0.000 description 1
- NZTVYLZBUPAXIL-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-6-(diaminomethylideneamino)hexanamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCNC(N)=N NZTVYLZBUPAXIL-UHFFFAOYSA-N 0.000 description 1
- CLLZTTNXKJPGJS-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-6-(diaminomethylideneamino)hexanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCN=C(N)N CLLZTTNXKJPGJS-UHFFFAOYSA-N 0.000 description 1
- MKUGGUKWGIYTLW-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)hept-2-enamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)C=CCCCCNC(N)=N MKUGGUKWGIYTLW-UHFFFAOYSA-N 0.000 description 1
- MMINUXOXDGGRTG-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-8-(diaminomethylideneamino)-3-hydroxyoctanamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CC(O)CCCCCNC(N)=N MMINUXOXDGGRTG-UHFFFAOYSA-N 0.000 description 1
- MGUIVRUJJINNAA-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-8-(diaminomethylideneamino)-3-hydroxyoctanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CC(O)CCCCCNC(N)=N MGUIVRUJJINNAA-UHFFFAOYSA-N 0.000 description 1
- WVTDVZFRENFLCN-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-9-(diaminomethylideneamino)-3-hydroxynonanamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CC(O)CCCCCCNC(N)=N WVTDVZFRENFLCN-UHFFFAOYSA-N 0.000 description 1
- GWMVBHPBRXYELC-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-9-(diaminomethylideneamino)-3-hydroxynonanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CC(O)CCCCCCNC(N)=N GWMVBHPBRXYELC-UHFFFAOYSA-N 0.000 description 1
- RUBRRBVSGJKUET-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-9-(diaminomethylideneamino)non-2-enamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)C=CCCCCCCNC(N)=N RUBRRBVSGJKUET-UHFFFAOYSA-N 0.000 description 1
- YWLJUVZANPCCSU-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-9-(diaminomethylideneamino)nonanamide Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCCCNC(N)=N YWLJUVZANPCCSU-UHFFFAOYSA-N 0.000 description 1
- AYDBRGAZXHIOFZ-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-9-(diaminomethylideneamino)nonanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCCCN=C(N)N AYDBRGAZXHIOFZ-UHFFFAOYSA-N 0.000 description 1
- DVDYAPWXDJAFEU-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-methoxy-2-oxoethyl]-4-(diaminomethylideneamino)butanamide Chemical compound NC(=N)NCCCC(=O)NC(OC)C(=O)NCCCCNCCCN DVDYAPWXDJAFEU-UHFFFAOYSA-N 0.000 description 1
- LWJUGNSPFPXXJZ-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-methoxy-2-oxoethyl]-6-(diaminomethylideneamino)hexanamide;trihydrochloride Chemical compound Cl.Cl.Cl.NC(N)=NCCCCCC(=O)NC(OC)C(=O)NCCCCNCCCN LWJUGNSPFPXXJZ-UHFFFAOYSA-N 0.000 description 1
- BSCRJZGTAMSJCS-UHFFFAOYSA-N n-[2-[4-(3-aminopropylamino)butylamino]-1-methoxy-2-oxoethyl]-9-(diaminomethylideneamino)nonanamide Chemical compound NCCCNCCCCNC(=O)C(OC)NC(=O)CCCCCCCCNC(N)=N BSCRJZGTAMSJCS-UHFFFAOYSA-N 0.000 description 1
- PYIZVKUBZVSTJN-UHFFFAOYSA-N n-[4-(3-aminopropylamino)butyl]-2,2-dihydroxyacetamide Chemical compound NCCCNCCCCNC(=O)C(O)O PYIZVKUBZVSTJN-UHFFFAOYSA-N 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 231100001160 nonlethal Toxicity 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 1
- 229960004583 pranlukast Drugs 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IGJAYGNJQNIACJ-UHFFFAOYSA-N tert-butyl n-[3-[4-[(2-methylpropan-2-yl)oxycarbonylamino]butylamino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCNCCCNC(=O)OC(C)(C)C IGJAYGNJQNIACJ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003623 transition metal compounds Chemical class 0.000 description 1
- LEMQFBIYMVUIIG-UHFFFAOYSA-N trifluoroborane;hydrofluoride Chemical compound F.FB(F)F LEMQFBIYMVUIIG-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C07D209/48—Iso-indoles; Hydrogenated iso-indoles with oxygen atoms in positions 1 and 3, e.g. phthalimide
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/12—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/04—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton
- C07C279/14—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of guanidine groups bound to acyclic carbon atoms of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P13/00—Preparation of nitrogen-containing organic compounds
- C12P13/02—Amides, e.g. chloramphenicol or polyamides; Imides or polyimides; Urethanes, i.e. compounds comprising N-C=O structural element or polyurethanes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP56159503A JPS5862152A (ja) | 1981-10-08 | 1981-10-08 | Ｎ−〔４−（３−アミノプロピル）アミノブチル〕−２−（ω−グアニジノ脂肪酸アミド）−２−ヒドロキシエタンアミドおよびその誘導体ならびにその製造法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| SE8205698D0 SE8205698D0 (sv) | 1982-10-06 |
| SE8205698L SE8205698L (sv) | 1983-04-09 |
| SE452006B true SE452006B (sv) | 1987-11-09 |
Family
ID=15695187
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE8205698A SE452006B (sv) | 1981-10-08 | 1982-10-06 | N-/4(3-aminopropyl)aminobutyl/-2-(omega-guanidinofettsyraamido)-2-substituerad etanamid, salt derav och forfarande for framstellning derav |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US4518532A (cs) |
| JP (1) | JPS5862152A (cs) |
| KR (1) | KR870000656B1 (cs) |
| AT (1) | AT393680B (cs) |
| AU (1) | AU554489B2 (cs) |
| BE (1) | BE894651A (cs) |
| CA (1) | CA1187513A (cs) |
| CH (1) | CH653015A5 (cs) |
| CS (1) | CS268654B2 (cs) |
| DE (1) | DE3236725A1 (cs) |
| DK (1) | DK166080C (cs) |
| ES (2) | ES8402558A1 (cs) |
| FR (1) | FR2514350B1 (cs) |
| GB (1) | GB2111480B (cs) |
| HU (1) | HU187417B (cs) |
| IT (1) | IT1189373B (cs) |
| NL (1) | NL193107C (cs) |
| SE (1) | SE452006B (cs) |
| YU (1) | YU44678B (cs) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5862152A (ja) * | 1981-10-08 | 1983-04-13 | Microbial Chem Res Found | Ｎ−〔４−（３−アミノプロピル）アミノブチル〕−２−（ω−グアニジノ脂肪酸アミド）−２−ヒドロキシエタンアミドおよびその誘導体ならびにその製造法 |
| JPS60181056A (ja) * | 1984-02-29 | 1985-09-14 | Takara Shuzo Co Ltd | Ν−〔４−（３−アミノプロピル）アミノブチル〕−２，２−ジヒドロキシエタンアミドの製造法 |
| JPS60185758A (ja) * | 1984-03-02 | 1985-09-21 | Microbial Chem Res Found | フエニレン基を有するスパガリン関連化合物およびその製造法 |
| JPS61129119A (ja) * | 1984-11-13 | 1986-06-17 | Microbial Chem Res Found | 新規免疫抑制剤 |
| JPS61165322A (ja) * | 1985-01-14 | 1986-07-26 | Microbial Chem Res Found | スパガリン類の注射用凍結乾燥製剤 |
| JPH0742268B2 (ja) * | 1985-08-27 | 1995-05-10 | 財団法人微生物化学研究会 | フエニレン基を有するスパガリン類縁化合物及びその製造法 |
| EP0241797B1 (en) * | 1986-04-04 | 1991-06-12 | Microbial Chemistry Research Foundation | Novel spergualin-related compounds and process for producing the same |
| JP2605762B2 (ja) * | 1986-12-10 | 1997-04-30 | 武田薬品工業株式会社 | δ−ハイドロキシ−β−リジン誘導体およびその製造法 |
| US5061787A (en) * | 1988-06-24 | 1991-10-29 | Nippon Kayaku Kabushiki Kaisha | Novel spergualin-related compounds and compositions |
| JPH0776204B2 (ja) * | 1988-07-01 | 1995-08-16 | 寳酒造株式会社 | スパガリン類の精製法 |
| US4990536A (en) * | 1989-04-03 | 1991-02-05 | Nippon Kayaku Kabushiki Kaisha | Immunopotentiator and spergualin-related compound therefor |
| RU2171811C2 (ru) * | 1989-05-29 | 2001-08-10 | Такара Сузо Ко., Лтд., (Jp), Ниппон Каяку Кабусики Кайся | КРИСТАЛЛИЧЕСКИЙ ТРИГИДРОХЛОРИД ДЕОКСИСПЕРГУАЛИНА В β-ФОРМЕ, ОБЛАДАЮЩИЙ ПРОТИВООПУХОЛЕВОЙ АКТИВНОСТЬЮ И СПОСОБ ЕГО ПОЛУЧЕНИЯ |
| US5162581A (en) * | 1989-05-29 | 1992-11-10 | Takaru Shuzo Co., Ltd. | Crystalline deoxyspergualin, process for its preparation and suppository containing the same |
| US5196453A (en) * | 1989-05-29 | 1993-03-23 | Takara Shuzo Co., Ltd. | Crystalline deoxyspergualin, process for its preparation and suppository containing the same |
| YU48230B (sh) * | 1989-05-29 | 1997-08-22 | Takara Shuzo Co.Ltd. | Kristalni deoksispergvalin i postupak za njegovo pripremanje |
| DE69104291T2 (de) * | 1990-07-20 | 1995-05-18 | Nippon Kayaku Kk | Spergulinähnliche Verbindungen und ihre Verwendung. |
| WO1994004140A1 (fr) * | 1992-08-19 | 1994-03-03 | Nippon Kayaku Kabushiki Kaisha | Medicament anti-protozoose |
| CA2183917A1 (en) * | 1995-09-26 | 1997-03-27 | Xuebao Wang | Preparation of optically active (s)-(-) and (r)-(+)- deoxyspergualin and novel intermediates thereof |
| CN1203846C (zh) | 1998-03-19 | 2005-06-01 | 布里斯托尔-迈尔斯斯奎布公司 | 高溶解性药物的双相控释递送系统和方法 |
| US20020142000A1 (en) * | 1999-01-15 | 2002-10-03 | Digan Mary Ellen | Anti-CD3 immunotoxins and therapeutic uses therefor |
| US6656917B1 (en) * | 1999-06-30 | 2003-12-02 | Marker Gene Technologies, Inc. | Compositions and methods for targeted enzymatic release of cell regulatory compounds |
| US8716558B2 (en) | 1999-06-30 | 2014-05-06 | Marker Gene Technologies, Inc. | Method of altering glycosylation of proteins in response to nojirimycin glucuronide in a plant cell expressing glucuronidase |
| AU2003280437A1 (en) * | 2002-06-27 | 2004-01-19 | Microport Medical (Shanghai) Co., Ltd. | Drug eluting stent |
| US7635773B2 (en) | 2008-04-28 | 2009-12-22 | Cydex Pharmaceuticals, Inc. | Sulfoalkyl ether cyclodextrin compositions |
| CN107080846A (zh) | 2010-07-09 | 2017-08-22 | 詹姆斯.特林卡.格林 | 用于包括瑞格列净的短半衰期药物的组合立即/延迟释放递送系统 |
| HUE058834T2 (hu) | 2012-02-15 | 2022-09-28 | Cydex Pharmaceuticals Inc | Elõállítási eljárás ciklodextrin-származékokhoz |
| MX353603B (es) | 2012-02-28 | 2018-01-19 | Cydex Pharmaceuticals Inc | Composiciones de ciclodextrina alquilada y procesos para preparar y utilizar las mismas. |
| KR102112119B1 (ko) | 2012-10-22 | 2020-05-19 | 사이덱스 파마슈티칼스, 인크. | 알킬화된 시클로덱스트린 조성물 및 이의 제조 및 사용 방법 |
| HUE063851T2 (hu) | 2014-08-22 | 2024-02-28 | Cydex Pharmaceuticals Inc | Frakcionált alkilezett ciklodextrin készítmények és eljárás ezek elõállítására és alkalmazására |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3799988A (en) * | 1969-04-02 | 1974-03-26 | Taiho Pharmaceutical Co Ltd | {107 -guanidino acid diamide derivatives and manufacturing the same |
| JPS5748957A (en) * | 1980-09-08 | 1982-03-20 | Microbial Chem Res Found | Novel antibiotic bmg 162-af2, its preparation and carcinostatic agent comprising it as active ingredient |
| JPS57185254A (en) * | 1981-05-11 | 1982-11-15 | Microbial Chem Res Found | Novel carcinostatic substances and their preparation |
| JPS57192347A (en) * | 1981-05-18 | 1982-11-26 | Microbial Chem Res Found | N-(4-(3-aminopropyl)aminobutyl)-2,2-dihydroxyethanamide and its synthesis |
| JPS5862152A (ja) * | 1981-10-08 | 1983-04-13 | Microbial Chem Res Found | Ｎ−〔４−（３−アミノプロピル）アミノブチル〕−２−（ω−グアニジノ脂肪酸アミド）−２−ヒドロキシエタンアミドおよびその誘導体ならびにその製造法 |
| JPS5942356A (ja) * | 1982-09-02 | 1984-03-08 | Microbial Chem Res Found | スパガリン関連化合物およびその製造法 |
| US4525299A (en) * | 1983-05-10 | 1985-06-25 | Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai | (-)-15-Deoxyspergualin, process for the preparation thereof, and intermediate of the same |
-
1981
- 1981-10-08 JP JP56159503A patent/JPS5862152A/ja active Granted
-
1982
- 1982-09-29 US US06/426,372 patent/US4518532A/en not_active Expired - Lifetime
- 1982-10-04 DE DE19823236725 patent/DE3236725A1/de active Granted
- 1982-10-05 AU AU89121/82A patent/AU554489B2/en not_active Expired
- 1982-10-06 ES ES516258A patent/ES8402558A1/es not_active Expired
- 1982-10-06 AT AT0369682A patent/AT393680B/de not_active IP Right Cessation
- 1982-10-06 NL NL8203874A patent/NL193107C/nl not_active IP Right Cessation
- 1982-10-06 CA CA000412980A patent/CA1187513A/en not_active Expired
- 1982-10-06 SE SE8205698A patent/SE452006B/sv not_active IP Right Cessation
- 1982-10-07 HU HU823215A patent/HU187417B/hu unknown
- 1982-10-07 CS CS827179A patent/CS268654B2/cs unknown
- 1982-10-07 CH CH5895/82A patent/CH653015A5/de not_active IP Right Cessation
- 1982-10-07 GB GB08228636A patent/GB2111480B/en not_active Expired
- 1982-10-07 IT IT49228/82A patent/IT1189373B/it active
- 1982-10-07 KR KR8204571A patent/KR870000656B1/ko not_active Expired
- 1982-10-07 DK DK445182A patent/DK166080C/da active
- 1982-10-08 YU YU2276/82A patent/YU44678B/xx unknown
- 1982-10-08 FR FR8216894A patent/FR2514350B1/fr not_active Expired
- 1982-10-08 BE BE0/209206A patent/BE894651A/fr unknown
-
1983
- 1983-10-14 ES ES526501A patent/ES526501A0/es active Granted
-
1985
- 1985-04-15 US US06/723,169 patent/US4658058A/en not_active Expired - Lifetime
-
1988
- 1988-03-15 US US07/170,611 patent/US4983328A/en not_active Expired - Lifetime
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