JPH0215534B2 - - Google Patents
Info
- Publication number
- JPH0215534B2 JPH0215534B2 JP63301133A JP30113388A JPH0215534B2 JP H0215534 B2 JPH0215534 B2 JP H0215534B2 JP 63301133 A JP63301133 A JP 63301133A JP 30113388 A JP30113388 A JP 30113388A JP H0215534 B2 JPH0215534 B2 JP H0215534B2
- Authority
- JP
- Japan
- Prior art keywords
- leuco
- acid
- dihydroxy
- compound
- compounds
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 35
- PYKYMHQGRFAEBM-UHFFFAOYSA-N anthraquinone Natural products CCC(=O)c1c(O)c2C(=O)C3C(C=CC=C3O)C(=O)c2cc1CC(=O)OC PYKYMHQGRFAEBM-UHFFFAOYSA-N 0.000 claims description 4
- 150000004056 anthraquinones Chemical class 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000007787 solid Substances 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 11
- 239000000243 solution Substances 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- QJQPINQAQJTYMH-UHFFFAOYSA-N 5,8,9,10-tetrahydroxy-2,3-dihydroanthracene-1,4-dione Chemical compound O=C1CCC(=O)C2=C1C(O)=C1C(O)=CC=C(O)C1=C2O QJQPINQAQJTYMH-UHFFFAOYSA-N 0.000 description 5
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 239000006185 dispersion Substances 0.000 description 5
- 208000003747 lymphoid leukemia Diseases 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 208000032839 leukemia Diseases 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia 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
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 229910021645 metal ion Inorganic materials 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- PKZCRWFNSBIBEW-UHFFFAOYSA-N 2-n,2-n,2-trimethylpropane-1,2-diamine Chemical compound CN(C)C(C)(C)CN PKZCRWFNSBIBEW-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000005587 bubbling Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- -1 for example Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011081 inoculation Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000000116 mitigating effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000003352 sequestering agent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- VKGQPUZNCZPZKI-UHFFFAOYSA-N (diaminomethylideneamino)azanium;sulfate Chemical compound NN=C(N)N.NN=C(N)N.OS(O)(=O)=O VKGQPUZNCZPZKI-UHFFFAOYSA-N 0.000 description 1
- SOGCSKLTQHBFLP-UHFFFAOYSA-N 1,4,5,8-tetrahydroxyanthraquinone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(O)=CC=C2O SOGCSKLTQHBFLP-UHFFFAOYSA-N 0.000 description 1
- 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 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- USVHXCUDFIVGGM-UHFFFAOYSA-N 2-amino-1,1-dimethylguanidine;hydroiodide Chemical compound I.CN(C)C(\N)=N\N USVHXCUDFIVGGM-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FRDAATYAJDYRNW-UHFFFAOYSA-N 3-methyl-3-pentanol Chemical compound CCC(C)(O)CC FRDAATYAJDYRNW-UHFFFAOYSA-N 0.000 description 1
- ORDLJERQKZRBRZ-UHFFFAOYSA-N 4,5-dihydro-1h-imidazol-2-ylhydrazine;hydrochloride Chemical compound Cl.NNC1=NCCN1 ORDLJERQKZRBRZ-UHFFFAOYSA-N 0.000 description 1
- CROBLTRUKGNQGK-UHFFFAOYSA-N 4,5-dihydro-1h-imidazole;hydroiodide Chemical compound I.C1CN=CN1 CROBLTRUKGNQGK-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 238000011765 DBA/2 mouse Methods 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000003567 ascitic fluid Anatomy 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000004108 freeze drying Methods 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
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229910001428 transition metal ion Inorganic materials 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/44—Nitrogen atoms not forming part of a nitro radical
- C07D233/52—Nitrogen atoms not forming part of a nitro radical with hetero atoms directly attached to said nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/04—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (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)
- Lubricants (AREA)
Description
æ¬çºæã¯ãäžèšäžè¬åŒïŒ
åŒäžã§ïŒ²ïŒRâ²ããã³Râ³ã¯æ°ŽçŽ ããã³çŽéãŸã
ã¯æåãéäœçŽã¢ã«ãã«ïŒC1ãC4ïŒåºããæã
ã°ã«ãŒãããéžæãããããã¯Râ²ããã³Râ³ã¯å ±
åããŠã¢ã«ãã¬ã³ïŒâCH2âïŒïœã§ãããããã§ïœã¯
ïŒãïŒã®æŽæ°ã§ããã ã§è¡šããããïŒïŒïŒâãã¹âïŒã°ã¢ããžãã«ã¢ã
ã³ïŒâïŒïŒïŒâãžããããã·ã¢ã³ãã©ããã³é¡ã®
åé§äœããäžèšäžè¬åŒïŒ åŒäžã§ïŒ²ïŒRâ²ïŒRâ³åã³ïœã¯åèšã®æå³ãæã
ãã ã«ãã€ãŠè¡šããããšãã§ããæ°èŠãã€ã³å¡©åºé¡ã
ãã³ãããã®äºå€ç°æ§åœ¢æ ã䞊ã³ã«è£œè¬åŠçã«å
容ããããšãã§ãããããã®é žä»å å¡©ã«é¢ããã
ã®ã§ããã æ¬çºæã®æ°èŠååç©ã¯ãç¹åŸŽçãªèç¹ãšåžåã¹
ãã¯ãã«ãæããèµ€è€è²ä¹è³éè²ã®çµæ¶æ§ç©è³ªãš
ããŠååŸããããšãã§ãäžã€ãããã¯ãéé¢å¡©åº
ã®å€§éšåãæ°Žã«äžæº¶æ§ã§ããäžã€ãããã®äžéšã¯
倧éšåã®ææ©æº¶å€äžã«äžæº¶ã§ããããã«ãäœçŽã¢
ã«ã«ããŒã«ã§æŽæµããããšã«ãã€ãŠç²Ÿè£œããããš
ãã§ãããæ¬çºæã®ææ©å¡©åºïŒããã³ïŒã¯ã
çš®ã ã®è¬çåŠçã«èš±å®¹ãããææ©ããã³ç¡æ©ã®å¡©
圢æè©Šå€ãšå ±ã«ãé žä»å å¡©ã圢æãããããã
ãŠãé©åã«ã¯äžæ§æº¶å€äžã§ãææ©éé¢å¡©åºãé žãš
æ··åããããšã«ãã€ãŠåœ¢æããããé žä»å å¡©ã¯ã
ããšãã°ç¡«é žãçé žãå¡©é žãèåæ°ŽçŽ é žãã¹ã«ã
ã¢ãã³é žãã¯ãšã³é žãä¹³é žããªã³ãŽé žãã³ãã¯
é žãé ç³é žãé ¢é žãå®æ¯éŠé žãã°ã«ã³ã³é žãã¢ã¹
ã³ã«ãã³é žãªã©ã®ãããªé žãçšããŠåœ¢æããã
ããæ¬çºæã®ç®çã«å¯ŸããŠã¯ãéé¢å¡©åºã¯ããã
ãã®é žä»å å¡©ãšåçã§ãããæ¬çºæã®ææ©å¡©åºã®
é žä»å å¡©ã¯ãäžè¬ã«ãæ°Žãã¡ã¿ããŒã«ããã³ãšã¿
ããŒã«äžã«ã¯æ¯èŒçå¯æº¶ã§ããããããšãã°ãžãš
ãã«ãšãŒãã«ããã³ãŒã³ããã«ãšã³ãªã©ã®ãããª
é極æ§ã®ææ©æº¶å€ã«ã¯æ¯èŒçäžæº¶æ§ã®ãçµæ¶æ§åº
äœã§ããã æ¬çºæã®æ°èŠååç©ïŒïŒã¯ãäžèšåå¿åŒã«åŸ
ã€ãŠå®¹éã«è£œé ããããšãã§ãäžã€å®¹æã«ååç©
ïŒïŒã«è»¢åããããšãã§ããïŒ åŒäžã§ïŒ²ïŒRâ²ïŒRâ³ããã³ïœã¯åèšãšåæ§ã§ããã
ãã®åå¿åŒã«åŸã€ãŠããã€ã³ïŒïŒïŒïŒïŒïŒïŒâã
ãã©ããããã·ã¢ã³ãã©ããã³ïŒïŒããããšã
ã°ïŒ®ïŒïŒ®ïŒNâ²ïŒNâ²âããã©ã¡ãã«ãšãã¬ã³ãžã¢
ãã³ãïŒâã¡ããã·ãšã¿ããŒã«ãã¡ã¿ããŒã«ããš
ã¿ããŒã«ãæ°Žããžã¡ãã«ãã«ã ã¢ãããŸãã¯ãã
ãã®æ··åç©äžã§ãçªçŽ ã®é°å²æ°äžã«ãçŽ40ä¹è³çŽ
60âã«ãããŠãé©åœãªã¢ããã°ã¢ããžã³ïŒïŒãš
ïŒæé以äžãããŠçž®åãããŠãçžåœãããã€ã³å¡©
åºïŒïŒãšããããã€ã³å¡©åºïŒïŒã¯ãããšãã°
空æ°é žåãŸãã¯ã¯ãã©ãã«ãéé žåæ°ŽçŽ ãããã¯
éããŠé žãããªãŠã ã«ããåŠçã®ãããªçš®ã ã®æ¹
æ³ã«ãã€ãŠã容æã«è³éŠæèªå°äœïŒïŒãžãšå®å š
ã«é žåããããšãã§ããã æ¬æ现æžäžã«èšãæ°èŠååç©ã¯ãã¬ãŒãå€ãé¯
åå€ãŸãã¯éå±ã€ãªã³å°éå€ãšããŠæçšã§ããã
å€äŸ¡éå±ã€ãªã³ãšå ±ã«åœ¢æããé¯äœã¯ãç¹ã«å®å®
ã§äžã€éåžžã¯åçš®ã®ææ©æº¶å€äžã«å¯æº¶ã§ãããã
ããã®æ§è³ªã¯ããããŸã§ããªããéå±ã€ãªã³ã«ã
ãæ±æãåé¡ãããããçš®ã ã®ç®çã«å¯ŸããŠãã
ãšãã°ãé·ç§»éå±ã€ãªã³ã«ããæ±æãé žåå£åãš
çè²ãä¿é²ããã飜åããã³äžé£œå最æ»æ²¹äžŠã³ã«
çåæ°ŽçŽ ãèèªé žããã³ã¯ãã¯ã¹ã®ãããªåçš®ã®
ææ©ç³»äžã®å®å®å€ãšããŠãæ¬çºæã®ååç©ãæçš
ãªãããããæ¬çºæã®æ°èŠååç©ã¯æŽã«ãããã
ã®ç©è³ªã«ãã€ãŠé¯äœã圢æããŸãã¯æœåºãããå€
䟡éå±ã€ãªã³ã®åæã«ãããŠãããã³éå±æ äœãš
ããŠãæçšã§ãããéå±ã€ãªã³å°éå€ã«å ±éãªã
ã®ä»ã®çšéã¯ããããã®ååç©ã«å¯ŸããŠãæçœã§
ãããå ããã«ãå®å šã«è³éŠæã®èªå°äœïŒïŒã®
補é ã«ãããäžéäœãšããŠæçšã§ããã æ¬çºæã®æ°èŠååç©ã¯ãäžèšã®è©Šéšã«ãã€ãŠç¢º
èªãããããã«ãããŠã¹ã«ç§»æ€ããè «çã®çé·ã
æå¶ããæ§è³ªããæããŠããã ãªã³ãççœè¡ç P388è©Šéš äœ¿çšããåç©ã¯ãæäœ17ïœã§ãã¹ãŠã±ïŒïœã®
ç¯å²ã®äœéãæããŠããããã¹ãŠåäžã®æ§ã®
DBAïŒïŒããŠã¹ã§ãããïŒè©Šéšã°ã«ãŒãåœãïŒ
ãŸãã¯ïŒå¹ã®åç©ãçšãããè «çã®ç§»æ€ã¯ããªã³
ãççœè¡ç P388ã®106ã®çŽ°èãå«æãããåžéã
ã0.1mlã®è ¹æ°Žæ¶²ã®è ¹è å 泚å°ã«ãããã®ã§ããã
è©Šéšååç©ãè ¹è å ã«ïŒæ¥ã«ïŒåãïŒåããã³ïŒ
åïŒè «çã®æ¥çš®ã«é¢é£ããŠïŒçš®ã ã®æäžéã§æäž
ãããåç©ã®ééãèšãäžã€çåæ°ãæ£èŠãªåºæº
ã§30æ¥éèšé²ãããçåæéäžå€®å€ããã³åŠçœ®ã
ãåç©ïŒïŒŽïŒïŒå¯Ÿç §åç©ïŒïŒ£ïŒãšããŠã®çåæé
ã®æ¯ãèšç®ãããéœæ§ã®å¯Ÿç §ååç©ã¯60mgïŒKgã®
泚å°ãšããŠäžããïŒâãã«ãªããŠã©ã·ã«ã§ããã
æ¬çºæã®ä»£è¡šçãªååç©ããã³åèååç©ã«ãã
ãã®è©Šéšã®çµæã第ïŒè¡šã«ç€ºããå¹æã®åºæºã¯
ïŒïŒ£Ã100125ïŒ ã§ããã
ã¯æåãéäœçŽã¢ã«ãã«ïŒC1ãC4ïŒåºããæã
ã°ã«ãŒãããéžæãããããã¯Râ²ããã³Râ³ã¯å ±
åããŠã¢ã«ãã¬ã³ïŒâCH2âïŒïœã§ãããããã§ïœã¯
ïŒãïŒã®æŽæ°ã§ããã ã§è¡šããããïŒïŒïŒâãã¹âïŒã°ã¢ããžãã«ã¢ã
ã³ïŒâïŒïŒïŒâãžããããã·ã¢ã³ãã©ããã³é¡ã®
åé§äœããäžèšäžè¬åŒïŒ åŒäžã§ïŒ²ïŒRâ²ïŒRâ³åã³ïœã¯åèšã®æå³ãæã
ãã ã«ãã€ãŠè¡šããããšãã§ããæ°èŠãã€ã³å¡©åºé¡ã
ãã³ãããã®äºå€ç°æ§åœ¢æ ã䞊ã³ã«è£œè¬åŠçã«å
容ããããšãã§ãããããã®é žä»å å¡©ã«é¢ããã
ã®ã§ããã æ¬çºæã®æ°èŠååç©ã¯ãç¹åŸŽçãªèç¹ãšåžåã¹
ãã¯ãã«ãæããèµ€è€è²ä¹è³éè²ã®çµæ¶æ§ç©è³ªãš
ããŠååŸããããšãã§ãäžã€ãããã¯ãéé¢å¡©åº
ã®å€§éšåãæ°Žã«äžæº¶æ§ã§ããäžã€ãããã®äžéšã¯
倧éšåã®ææ©æº¶å€äžã«äžæº¶ã§ããããã«ãäœçŽã¢
ã«ã«ããŒã«ã§æŽæµããããšã«ãã€ãŠç²Ÿè£œããããš
ãã§ãããæ¬çºæã®ææ©å¡©åºïŒããã³ïŒã¯ã
çš®ã ã®è¬çåŠçã«èš±å®¹ãããææ©ããã³ç¡æ©ã®å¡©
圢æè©Šå€ãšå ±ã«ãé žä»å å¡©ã圢æãããããã
ãŠãé©åã«ã¯äžæ§æº¶å€äžã§ãææ©éé¢å¡©åºãé žãš
æ··åããããšã«ãã€ãŠåœ¢æããããé žä»å å¡©ã¯ã
ããšãã°ç¡«é žãçé žãå¡©é žãèåæ°ŽçŽ é žãã¹ã«ã
ã¢ãã³é žãã¯ãšã³é žãä¹³é žããªã³ãŽé žãã³ãã¯
é žãé ç³é žãé ¢é žãå®æ¯éŠé žãã°ã«ã³ã³é žãã¢ã¹
ã³ã«ãã³é žãªã©ã®ãããªé žãçšããŠåœ¢æããã
ããæ¬çºæã®ç®çã«å¯ŸããŠã¯ãéé¢å¡©åºã¯ããã
ãã®é žä»å å¡©ãšåçã§ãããæ¬çºæã®ææ©å¡©åºã®
é žä»å å¡©ã¯ãäžè¬ã«ãæ°Žãã¡ã¿ããŒã«ããã³ãšã¿
ããŒã«äžã«ã¯æ¯èŒçå¯æº¶ã§ããããããšãã°ãžãš
ãã«ãšãŒãã«ããã³ãŒã³ããã«ãšã³ãªã©ã®ãããª
é極æ§ã®ææ©æº¶å€ã«ã¯æ¯èŒçäžæº¶æ§ã®ãçµæ¶æ§åº
äœã§ããã æ¬çºæã®æ°èŠååç©ïŒïŒã¯ãäžèšåå¿åŒã«åŸ
ã€ãŠå®¹éã«è£œé ããããšãã§ãäžã€å®¹æã«ååç©
ïŒïŒã«è»¢åããããšãã§ããïŒ åŒäžã§ïŒ²ïŒRâ²ïŒRâ³ããã³ïœã¯åèšãšåæ§ã§ããã
ãã®åå¿åŒã«åŸã€ãŠããã€ã³ïŒïŒïŒïŒïŒïŒïŒâã
ãã©ããããã·ã¢ã³ãã©ããã³ïŒïŒããããšã
ã°ïŒ®ïŒïŒ®ïŒNâ²ïŒNâ²âããã©ã¡ãã«ãšãã¬ã³ãžã¢
ãã³ãïŒâã¡ããã·ãšã¿ããŒã«ãã¡ã¿ããŒã«ããš
ã¿ããŒã«ãæ°Žããžã¡ãã«ãã«ã ã¢ãããŸãã¯ãã
ãã®æ··åç©äžã§ãçªçŽ ã®é°å²æ°äžã«ãçŽ40ä¹è³çŽ
60âã«ãããŠãé©åœãªã¢ããã°ã¢ããžã³ïŒïŒãš
ïŒæé以äžãããŠçž®åãããŠãçžåœãããã€ã³å¡©
åºïŒïŒãšããããã€ã³å¡©åºïŒïŒã¯ãããšãã°
空æ°é žåãŸãã¯ã¯ãã©ãã«ãéé žåæ°ŽçŽ ãããã¯
éããŠé žãããªãŠã ã«ããåŠçã®ãããªçš®ã ã®æ¹
æ³ã«ãã€ãŠã容æã«è³éŠæèªå°äœïŒïŒãžãšå®å š
ã«é žåããããšãã§ããã æ¬æ现æžäžã«èšãæ°èŠååç©ã¯ãã¬ãŒãå€ãé¯
åå€ãŸãã¯éå±ã€ãªã³å°éå€ãšããŠæçšã§ããã
å€äŸ¡éå±ã€ãªã³ãšå ±ã«åœ¢æããé¯äœã¯ãç¹ã«å®å®
ã§äžã€éåžžã¯åçš®ã®ææ©æº¶å€äžã«å¯æº¶ã§ãããã
ããã®æ§è³ªã¯ããããŸã§ããªããéå±ã€ãªã³ã«ã
ãæ±æãåé¡ãããããçš®ã ã®ç®çã«å¯ŸããŠãã
ãšãã°ãé·ç§»éå±ã€ãªã³ã«ããæ±æãé žåå£åãš
çè²ãä¿é²ããã飜åããã³äžé£œå最æ»æ²¹äžŠã³ã«
çåæ°ŽçŽ ãèèªé žããã³ã¯ãã¯ã¹ã®ãããªåçš®ã®
ææ©ç³»äžã®å®å®å€ãšããŠãæ¬çºæã®ååç©ãæçš
ãªãããããæ¬çºæã®æ°èŠååç©ã¯æŽã«ãããã
ã®ç©è³ªã«ãã€ãŠé¯äœã圢æããŸãã¯æœåºãããå€
䟡éå±ã€ãªã³ã®åæã«ãããŠãããã³éå±æ äœãš
ããŠãæçšã§ãããéå±ã€ãªã³å°éå€ã«å ±éãªã
ã®ä»ã®çšéã¯ããããã®ååç©ã«å¯ŸããŠãæçœã§
ãããå ããã«ãå®å šã«è³éŠæã®èªå°äœïŒïŒã®
補é ã«ãããäžéäœãšããŠæçšã§ããã æ¬çºæã®æ°èŠååç©ã¯ãäžèšã®è©Šéšã«ãã€ãŠç¢º
èªãããããã«ãããŠã¹ã«ç§»æ€ããè «çã®çé·ã
æå¶ããæ§è³ªããæããŠããã ãªã³ãççœè¡ç P388è©Šéš äœ¿çšããåç©ã¯ãæäœ17ïœã§ãã¹ãŠã±ïŒïœã®
ç¯å²ã®äœéãæããŠããããã¹ãŠåäžã®æ§ã®
DBAïŒïŒããŠã¹ã§ãããïŒè©Šéšã°ã«ãŒãåœãïŒ
ãŸãã¯ïŒå¹ã®åç©ãçšãããè «çã®ç§»æ€ã¯ããªã³
ãççœè¡ç P388ã®106ã®çŽ°èãå«æãããåžéã
ã0.1mlã®è ¹æ°Žæ¶²ã®è ¹è å 泚å°ã«ãããã®ã§ããã
è©Šéšååç©ãè ¹è å ã«ïŒæ¥ã«ïŒåãïŒåããã³ïŒ
åïŒè «çã®æ¥çš®ã«é¢é£ããŠïŒçš®ã ã®æäžéã§æäž
ãããåç©ã®ééãèšãäžã€çåæ°ãæ£èŠãªåºæº
ã§30æ¥éèšé²ãããçåæéäžå€®å€ããã³åŠçœ®ã
ãåç©ïŒïŒŽïŒïŒå¯Ÿç §åç©ïŒïŒ£ïŒãšããŠã®çåæé
ã®æ¯ãèšç®ãããéœæ§ã®å¯Ÿç §ååç©ã¯60mgïŒKgã®
泚å°ãšããŠäžããïŒâãã«ãªããŠã©ã·ã«ã§ããã
æ¬çºæã®ä»£è¡šçãªååç©ããã³åèååç©ã«ãã
ãã®è©Šéšã®çµæã第ïŒè¡šã«ç€ºããå¹æã®åºæºã¯
ïŒïŒ£Ã100125ïŒ ã§ããã
ãè¡šã
é»ç®æ§é»è²è
«B16
䜿çšããåç©ã¯ããã¹ãŠåäžã®æ§ã®ãæäœ17ïœ
ã§Â±ïŒïœã®ç¯å²å ã®äœéãæããC57BCïŒïŒã
ãŠã¹ã§ãããïŒè©Šéšã°ã«ãŒãåœãéåžžã¯10å¹ã®å
ç©ãçšãããé»ç®æ§é»è²è «B16è «çã®ïŒïœã®éšå
ããå·åŽãã平衡塩溶液10mläžã§å質åããå質
åç©ã®0.5mlã®éšåè©Šæãåè©Šéšåç©ã®è ¹è å ã«
移æ€ãããè©Šéšååç©ã¯çš®ã ã®æäžéã§ïŒæ¥ã«ïŒ
åä¹è³ïŒåïŒè «çã®æ¥çš®ã«é¢é£ããŠïŒè ¹è å ã«æ
äžãããåç©ã®äœéãèšãäžã€çåæ°ãæ£èŠèŠæº
ã§60æ¥éèšé²ãããçåæéäžå€®å€ããã³åŠçœ®å
ç©ïŒïŒŽïŒïŒå¯Ÿç §åç©ïŒïŒ£ïŒãšããŠã®çåæéã®æ¯
ãèšç®ãããéœæ§ã®å¯Ÿç §ååç©ã¯20mgïŒKgã®æ³šå°
ããŠæäžããïŒâãã«ãªããŠã©ã·ã«ã§ãããæ¬çº
æã®ä»£è¡šçãªååç©ããã³åèååç©ã«ãããã®
è©Šéšã®çµæã第ïŒè¡šã«ç€ºããå¹æã«å¯Ÿããåºæºã¯
ïŒïŒ£Ã100125ïŒ ã§ããã
ã§Â±ïŒïœã®ç¯å²å ã®äœéãæããC57BCïŒïŒã
ãŠã¹ã§ãããïŒè©Šéšã°ã«ãŒãåœãéåžžã¯10å¹ã®å
ç©ãçšãããé»ç®æ§é»è²è «B16è «çã®ïŒïœã®éšå
ããå·åŽãã平衡塩溶液10mläžã§å質åããå質
åç©ã®0.5mlã®éšåè©Šæãåè©Šéšåç©ã®è ¹è å ã«
移æ€ãããè©Šéšååç©ã¯çš®ã ã®æäžéã§ïŒæ¥ã«ïŒ
åä¹è³ïŒåïŒè «çã®æ¥çš®ã«é¢é£ããŠïŒè ¹è å ã«æ
äžãããåç©ã®äœéãèšãäžã€çåæ°ãæ£èŠèŠæº
ã§60æ¥éèšé²ãããçåæéäžå€®å€ããã³åŠçœ®å
ç©ïŒïŒŽïŒïŒå¯Ÿç §åç©ïŒïŒ£ïŒãšããŠã®çåæéã®æ¯
ãèšç®ãããéœæ§ã®å¯Ÿç §ååç©ã¯20mgïŒKgã®æ³šå°
ããŠæäžããïŒâãã«ãªããŠã©ã·ã«ã§ãããæ¬çº
æã®ä»£è¡šçãªååç©ããã³åèååç©ã«ãããã®
è©Šéšã®çµæã第ïŒè¡šã«ç€ºããå¹æã«å¯Ÿããåºæºã¯
ïŒïŒ£Ã100125ïŒ ã§ããã
ãè¡šã
ãªã³ãççœè¡ç
L1210è©Šéš
æé ã¯ãè
«çã®ç§»æ€ããçåæéäžå€®å€ãèšç®
ããããŠã¹ã«å¯ŸããŠ105现èïŒããŠã¹ã®æ¿åºŠã§ãª
ã³ãççœè¡ç L1210ãæ¥çš®ããããšããæããäž
ã€è©Šéšååç©ãïŒæ¥ã«ïŒåã ãæäžããã»ãã¯ã
ãªã³ãççœè¡ç P388è©Šéšã«å¯Ÿãããã®ãšåæ§ã§
ãããåèååç©ã«ãããã®è©Šéšã®çµæããäžèš
第ïŒè¡šã«ç€ºããå¹æã«å¯Ÿããåºæºã¯ïŒŽïŒïŒ£Ã100
125ïŒ ã§ããã
ããããŠã¹ã«å¯ŸããŠ105现èïŒããŠã¹ã®æ¿åºŠã§ãª
ã³ãççœè¡ç L1210ãæ¥çš®ããããšããæããäž
ã€è©Šéšååç©ãïŒæ¥ã«ïŒåã ãæäžããã»ãã¯ã
ãªã³ãççœè¡ç P388è©Šéšã«å¯Ÿãããã®ãšåæ§ã§
ãããåèååç©ã«ãããã®è©Šéšã®çµæããäžèš
第ïŒè¡šã«ç€ºããå¹æã«å¯Ÿããåºæºã¯ïŒŽïŒïŒ£Ã100
125ïŒ ã§ããã
ãè¡šã
æ¬çºæã®æ°èŠååç©ãããªãã¡ãäžèšæ§é åŒïŒ
åŒäžã§ïŒ²ïŒRâ²ããã³Râ³ã¯ãæ°ŽçŽ ããã³çŽéãŸ
ãã¯æåãéäœçŽã¢ã«ãã«ïŒC1ãC4ïŒåºããæ
ãã°ã«ãŒãããéžæããããšãã§ããRâ²ããã³
Râ³ã¯ã¢ã«ãã¬ã³ïŒâCH2âïŒïœã§ãã€ãŠããããã
ãã§ïœã¯ïŒãïŒã®æŽæ°ã§ããã ã«ãã€ãŠè¡šããããšãã§ããïŒïŒïŒâãã¹ïŒã°ã¢
ããžãã«ã¢ããïŒâïŒïŒïŒâãžããããã·ã¢ã³ã
ã©ããã³é¡ã®ãã€ã³å¡©åºããã³ç¡æ¯ã®é žä»å å¡©ã
å«æãã補è¬çµæç©ã¯ãåºä¹³åç©ã«ãããçæ§ã®
ç æ°ã軜æžããããã«æçšã§ãããæ¬çºæã®ãã®
å±é¢ã¯ãæ°èŠçµæç©ããã³ãããçšããŠåºä¹³é¡ã«
ãããçœè¡ç 䞊ã³ã«é¢é£ããæªæ§è «çã®éè¡ãã
ã³ïŒãŸãã¯ç·©åãèªçºãããããã®æ¹æ³ãå å«ã
ãã æ¬çºæã®è£œè¬çµæç©ããã³æ°èŠååç©ã¯ãïŒæ¥
åœãäœéïŒKgã«ã€ããŠçŽïŒmgä¹è³çŽ1.0ïœã®éã§
æäžãããšãã¯ã移æ€ããããŠã¹ã®è «çã®å¢æ®ã
æå¶ãäžã€åºä¹³åç©ã«ãããçœè¡ç ããã³é¢é£ã
ãæªæ§è «çã®éè¡ããã³ïŒãŸãã¯ç·©åãèªçºã
ããæé©ã®çµæã®ããã®å¥œé©ãªæäžéç¯å²ã¯ãïŒ
æ¥åœãã«äœéïŒKgã«ã€ããŠçŽïŒmgä¹è³çŽ100mgã§
ããããã®ãããªé©éåäœã䜿çšããŠãäœéçŽ70
Kgã®æ£è ã«å¯ŸããŠå šéã§çŽ850mgä¹è³çŽ7.0ïœã®æŽ»
æ§ç©è³ªãšãªãããã«ã24æéå ã«æäžããããã®
ããã«é©éç¯å²ã¯ãæé©ã®æ²»çå¹æãäžãããã
ã«èª¿ç¯ããããšãã§ãããããšãã°ãïŒæ¥ã«ãã
ã€ãã«åããé©éãæäžããŠããããããããã¯
æ²»çæ æ³ã®æ¥è¿«ã«ããæ瀺ã«æ¯äŸããŠæäžéãäœ
äžãããããšãã§ããã ããšãã°éèå ãçèå ãŸãã¯ç®äžãžã®æ³šå°ãš
ãããããªã䟿å®ã®æ¹æ³ã§æŽ»æ§ååç©ãæäžãã
ããšãå®éçã«æå©ã§ããããšã¯ãããŸã§ããª
ãã 掻æ§ååç©ã¯ãéçµå£çã«ãŸãã¯è ¹è å ã«æäž
ããããšãã§ãããéé¢å¡©åºãŸãã¯è£œè¬åŠçã«èš±
容ãããå¡©ãšããŠã®æŽ»æ§ååç©ã®æº¶æ¶²ã¯ãããšã
ã°ããããã·ãããã«ã»ã«ããŒã¹ã®ãããªçé¢æŽ»
æ§å€ãšæ··åããããšãé©åœãªæ°Žäžã§ã調補ããã
ãšãã§ãããåæ£æ¶²ã¯ãã°ãªã»ãªã³ã液ç¶ããªã¡
ãã¬ã³ã°ãªã³ãŒã«ããã³ãããã®æ··åç©äžã§ãäž
ã€æ²¹äžã§èª¿è£œããããšãã§ããã貯èµãšäœ¿çšã®é
åžžã®æ¡ä»¶äžã§ããããã®è£œå€ã¯åŸ®çç©ã®çé·ãé²
ãããã®é²è å€ãå«æããã 泚å°çšãšããŠé©ãã補è¬åœ¢æ ã¯ãç¡èã®æ°Žæº¶æ¶²
ãŸãã¯åæ£æ¶²ãããã³ç¡èã®æ³šå°æ¶²ãŸãã¯åæ£æ¶²
ã®å³åžèª¿è£œã®ããã®ç¡èã®ç²æ«ãå å«ãããäœã
ã®å Žåã«ãããŠãã補å€åœ¢æ ã¯ç¡èã§ããäžã€å®¹
æã«æ³šå°åšã§æ³šå°ã§ããçšåºŠã«æµåæ§ã§ããããš
ãå¿ èŠã§ããããŸãã補é ããã³è²¯èµã®æ¡ä»¶äžã«
å®å®ã§ãªããã°ãªããäžã€ããšãã°çŽ°èããã³ç
èé¡ã®ãããªåŸ®çç©ã®æ±æäœçšã«å¯ŸããŠä¿å šãã
ãªããã°ãªããªããæ äœã¯ãããšãã°æ°Žããšã¿ã
ãŒã«ãããªãªãŒã«ïŒããšãã°ãã°ãªã»ãªã³ããã
ãã¬ã³ã°ãªã³ãŒã«ãããã³æ¶²ç¶ããªãšãã¬ã³ã°ãª
ã³ãŒã«ãªã©ïŒãé©åœãªãããã®æ··åç©ããã³æ€ç©
æ²¹ã¯å«æãã溶å€ãŸãã¯åæ£åªäœãšããããšãã§
ãããé©åœãªæµåæ§ã¯ãããšãã°ã¬ã·ãã³ã®ãã
ãªè¢«èŠã®äœ¿çšã«ãã€ãŠãåæ£æ¶²ã®å Žåã«ãããŠ
ã¯ãå¿ èŠãªç²åºŠã®ä¿æã«ãã€ãŠãäžã€çé¢æŽ»æ§å€
ã®äœ¿çšã«ãã€ãŠãä¿ã€ããšãã§ããã埮çç©ã®äœ
çšã®é²æ¢ã¯ãåçš®ã®æ现èããã³æçèå€ãããš
ãã°ããã©ãã³é¡ãã¯ãããã¿ããŒã«ãããšããŒ
ã«ããœã«ãã³é žããã¡ããŒã¶ã«ãªã©ã«ãã€ãŠãé
æããããšãã§ãããå€ãã®å Žåã«ãç匵å€ãã
ãšãã°ç³ãŸãã¯å¡©åãããªãŠã ããå«æãããã
ãšã奜ãŸããã泚å°çšçµæç©ã®å»¶é·ãããåžå
ã¯ãåžåãé 延ãããè¬å€ãããšãã°ã¢ãã¹ãã¢
ãªã³é žã¢ã«ãããŠã ããã³ãŒã©ãã³ãçµæç©äžã§
䜿çšããããšã«ãã€ãŠãéæããããšãã§ããã ç¡èã®æ³šå°æ¶²ã¯ãå¿ èŠéã®æŽ»æ§ååç©ããå¿ èŠ
ã«å¿ããå ã«æããåçš®ã®ãã®ä»ã®æåãšå ±ã«é©
åœãªæº¶å€äžã«å°å ¥ããæ» èæ¿Ÿéããããšã«ãã€
ãŠã調補ãããäžè¬ã«ãåæ£æ¶²ã¯ãçš®ã ã®ç¡èã®
掻æ§æåããåºæ¬çãªåæ£åªäœããã³å ã«æãã
ãã®ããã®ãã®ä»ã®å¿ èŠãªæåãå«æããç¡èã®
賊圢è¬äžã«å°å ¥ããããšã«ãã€ãŠã調補ãããç¡
èã®æ³šå°æ¶²ã®èª¿è£œã®ããã®ç¡èã®ç²æ«ã®å Žåã«
ã¯ã奜é©ãªèª¿è£œæ¹æ³ã¯ãç空也ç¥ããã³åçµä¹Ÿç¥
æ¹æ³ã§ãã€ãŠããããã®æ¹æ³ã¯ãäºãæ» èæ¿Ÿéã
ã掻æ§æåãšãã®ä»ã®å¿ èŠãªæåã®æº¶æ¶²ãããã
ããã®æ··åç©ã®ç²æ«ãäžããã æ¬æ现æžäžã§äœ¿çšããå Žåã®â補è¬åŠçã«èš±å®¹
ãããæ äœâã¯ãä»»æã®æº¶å€ãåæ£åªäœã被èŠã
æ现èå€ããã³æçèå€ãç匵å€äžŠã³ã«åžåé 延
å€ãªã©ã®ãã¹ãŠãå å«ããã補è¬åŠçã«æŽ»æ§ãªç©
質ã«å¯Ÿãããããã®åªäœããã³é åå€ã®äœ¿çšã¯ã
ãã®åéã«ãããŠå ¬ç¥ã§ãããæ £çšãããåªäœã
ãã³é åå€ã®äœãããããã掻æ§æåãšäž¡ç«ããª
ãå Žåãé€ãã°ã補è¬çµæç©äžã«ããã䜿çšãæ
å³ããããšãã§ãããè£å ã®æŽ»æ§æåãçµæç©äž
ã«é åããããšãã§ããã æäžã®å®¹æãããã³æäžéã®åäžæ§ã®ããã«é©
éåäœåœ¢æ ã«ããéçµå£çµæç©ãåŠæ¹ããããšã
ç¹ã«æå©ã§ãããæ¬çºæã«ãããŠäœ¿çšããå Žåã®
é©éåäœåœ¢æ ãšã¯ãæ²»çãã¹ãåºä¹³é¡å¯Ÿç §ãžã®å
äœæäžéãšããŠé©ããç©ççã«åé¢ããåäœãæ
å³ããååäœã¯å¿ èŠãªè£œè¬æ äœãšçµåããããæ
ãŸããæ²»çå¹æãäžããããã«èšç®ãããäºå®ã
ãéã®æŽ»æ§ç©è³ªãå«æããŠãããæ¬çºæã®æ°èŠé©
éåäœåœ¢æ ã«å¯Ÿãã詳现ã¯(a)掻æ§ç©è³ªã®ç¬ç¹ãªæ§
質ãšéæãã¹ãç¹å®ã®æ²»çå¹æãããã³(b)æ¬æ现
æžäžã«è©³çŽ°ã«èšããããã«èäœçã«å¥åº·ãæãªã€
ãŠãããç çãªç¶æ ã«ããæ£è ã®ç æ°ã®æ²»çã®ã
ãã®ããã掻æ§ç©è³ªã®åŠæ¹ã®æè¡ã«ãããŠåºæã®
å¶éã«ãã€ãŠèŠå®ããäžã€ããã«çŽæ¥ã«äŸåã
ãã 䟿å®çäžã€å¹æçãªæäžã®ããã«ã¯ã䞻掻æ§æ
åãåèšã®åŠãé©éåäœåœ¢æ äžã§æå¹ãªéã§é©åœ
ãªè£œè¬åŠçã«èš±å®¹ãããæ äœãšå ±ã«é åãããå
äœé©é圢æ ã¯ã䞻掻æ§ååç©ããããšãã°ãçŽ
0.1ä¹è³çŽ500mgã®ç¯å²ã®éã§ã奜ãŸããã¯çŽïŒä¹
è³çŽ500mgã®éã§ãå«æãããå²åãšããŠè¡šãã
ãšã掻æ§ååç©ã¯äžè¬ã«ãæ äœïŒmlåœãã«çŽïŒä¹
è³çŽ500mgã®éã§ååšãããããè£è¶³çãªæŽ»æ§æ
åãå«æããçµæç©ã®å Žåã«ã¯ãé©éã¯ã該æå
ã®éåžžã®æäžéããã³æäžã®æ¹åŒãåèã«ããŠã
決å®ããããšãã§ããã çã®éè¡ããã³ç·©åã¯ãããšãã°ãè ¹è å æäž
ãçšããŠéæããããšãã§ãããïŒåã®éèå é©
éãŸãã¯ç¹°è¿ãã®æ¯æ¥ã®é©éãæäžããããšãã§
ãããå€ãã®å ŽåãçŽïŒãŸãã¯10æ¥ã«è³ããŸã§ã®
æ¯æ¥ã®æäžã§å åã§ãããïŒæ¥çœ®ããŸãã¯ãã以
äžã®ééã§ãïŒæ¥åé©éãŸãã¯ïŒæäžéãåäžã
ãããšãå¯èœã§ãããé©éåºæºããæãããªãã
ã«ãæäžãã䞻掻æ§æåã®éã¯ãçãä¿æãã宿
äž»ã«å¯Ÿãã现èæ¯æ§ã«ããé床ã®æ害ãªå¯äœçšã®
ååšãªãã«ãçœè¡ç ãªã©ã®éè¡ããã³ç·©åãä¿ã
ããã«ååãªéã§ãããæ¬æ现æžã«ãããŠçšãã
å Žåã®çæ§ã®ç æ°ã¯ãããšãã°çœè¡ç ã®ãããªè¡
液ã®æªæ§è «çã䞊ã³ã«ããšãã°é»è²è «ãèºçãã
ã³ä¹³çã®ãããªããã®ä»ã®ç¢ºå®ãªããã³äžç¢ºå®ãª
æªæ§è «çãæå³ãããéè¡ããã³ç·©åãšã¯ãè «ç
ã®å¢æ®ãŸãã¯ãã®ä»ã®ç æ°ã®è¡šç€ºããæ²»çããªã
å Žåã®ç æ°ã®çµéãšæ¯èŒããŠãé»æ¢ãŸãã¯é 延ã
ããããšãæå³ããã æ¬çºæã以äžã®ç¹å®çãªå®æœäŸãšé¢é£ãããŠæŽ
ã«è©³çŽ°ã«èª¬æããã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâãžã°ã¢ããžã³ã»
ïŒå¡©é žå¡© 19.70ïœã®ç¡«é žã¢ããã°ã¢ããžã³ãš16.0mlã®10N
æ°Žé žåãããªãŠã 氎溶液ã®æ··åç©ãæ¹æãäžã€ã
ããŸããå šéšãªããªããŸã§ããç ãããã®æ··åç©
ã75mlã®ãšã¿ããŒã«ã§åžéãã氷济äžã§å·åŽãäž
ã€90.0ïœã®3AååãµãããçšããŠïŒæé也ç¥ã
ããæ¿Ÿéã«ãã€ãŠåºäœãé€å»ãã35mlãã€ã®ãšã¿
ããŒã«ãçšããŠïŒåæŽæµããã濟液ãšæŽæ¶²ãåã
ãäžã€15åéçªçŽ ãå¹èŸŒãããšã«ãã€ãŠè±æ°ãã
ã®ã¡ã10.97ïœã®ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâãã
ã©ããããã·ã¢ã³ãã©ããã³ãçªçŽ äžã«å ããã
ãã®æ··åç©ãæ¹æãäžã€çªçŽ äžã«50ã51âã®æ²¹æµŽ
äžã§ïŒæéå ç±ãã次ãã§16æéæŸå·ããããã®
æ··åç©ãå·åŽããæ¿Ÿéã«ãã€ãŠåºäœãéããå·ãš
ã¿ããŒã«ã§æŽæµããŠãéŠé¡ã®ååç©ã®ïŒïŒïŒâãž
ãããèªå°äœã§ããé»è²ã®åºäœ13.87ïœãååŸã
ãã 11.60ïœã®ãã®ïŒïŒïŒâãžãããååç©ã®æ¹æ
æžæ¿æ¶²ã200mlã®ïŒâã¡ããã·ãšã¿ããŒã«äžã®
7.50ïœã®ã¯ãã©ãã«ã«å ãã次ãã§æ°·æµŽã§å·åŽã
ãªãã15.0mlã®ãšã¿ããŒã«äžã®8Nå¡©é žã滎å ã
ãããšã«ãã€ãŠé žåããããã®æ··åç©ã宀枩ã§16
æéæ¹æããã®ã¡ããžãšãã«ãšã¿ããŒã«ã§åžéã
ããåºäœãéããããã©ããããã©ã³ã§æŽæµã
ãŠã12.53ïœã®æ玫è²ã®åºäœãååŸããããã®çŽ«
è²ã®åºäœã®10.0ïœã®éšåãç²æ«ç¶ãšãã23âã®
300mlã®æ°Žäžã§ïŒæéæ¹æããã®ã¡ãé å¿åé¢ã
ããäžæŸæ¶²ãåŸçãäžã€æ¿Ÿéããã濟液ãåçµä¹Ÿ
ç¥ããèµ€è€è²ã®åºäœãšããŠæ¬å®æœäŸã®çæç©ãå
åŸãããNMRã·ã°ãã«ïŒÎŽ8.00ã7.74åã³7.60ã
ã€ã¯ãããªã¡ãŒã¿ãŒãIRïŒ5.97â8.33ã å®æœäŸ ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹
ïŒâïŒïŒâã€ãããŸãªã³âïŒâã€ã«ïŒâããã©
ãžãã¢ã³ãã©ããã³ 50mlã®ã¡ã¿ããŒã«äžã®3.94ïœã®ïŒâããã©ãžã
âïŒâã€ãããŸãªã³ã»å¡©é žå¡©ïŒã¢ã¡ãªã«åè¡åœç¹
èš±3931152å·ïŒã®æº¶æ¶²ããäºãã¡ã¿ããŒã«ã§æŽæµ
ããŠãã15ïœã®ããªã¹ãã¬ã³åçŽæ°Žé žåã¢ã³ã¢ã
ãŠã æš¹èãå«æããã«ã©ã äžã«éããããšã«ãã€
ãŠãéé¢å¡©åºãšãããè©Šæãã«ã©ã äžã§äœåã®ã¡
ã¿ããŒã«ã§æŽæµããã溶é¢æ¶²ãšæŽæµæ¶²ã®èžçºã¯ã
3.3ïœã®é»è€è²ã®æ²¹ãäžããã40mlã®ïŒ®ïŒNâ²ïŒ
Nâ²âããã©ã¡ãã«ãšãã¬ã³ãžã¢ãã³ïŒãšã¿ããŒ
ã«ïŒïŒïŒïŒïŒäžã®ãã®æ²¹ã®æ¿Ÿé溶液ãããã®äžã«
çªçŽ ã15åéå¹èŸŒãããšã«ãã€ãŠè±æ°ãã次ãã§
2.02ïœã®ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâããã©ããã
ãã·ã¢ã³ãã©ããã³ãçªçŽ äžã«å ãããçæãã
æ··åç©ãçªçŽ äžã«æ¹æãäžã€50ã52âã®æ²¹æº¶äžã§
ïŒæéå ç±ããããã®æ··åç©ãçªçŽ äžã«48æéæŸ
眮ããçæããåºäœãæ¿Ÿéã«ãã€ãŠéããïŒ
ïŒNâ²ïŒNâ²âããã©ã¡ãã«ãšãã¬ã³ãžã¢ãã³ã§
ïŒåããšã¿ããŒã«ã§ïŒåæŽæµããŠãèµ€è€è²åºäœãš
ããŠ0.03ïœã®æ¬å®æœäŸã®çæç©ãååŸããã
NMRã·ã°ãã«ïŒÎŽ7.22åã³8.33ãã€ã¯ãããªã¡ãŒ
ã¿ãŒãIRïŒ6.20â8.15ã å®æœäŸ ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹
ïŒâïŒïŒâã€ãããŸãªã³âïŒâã€ã«ïŒâïŒâã¡
ãã«ããã©ãžãã¢ã³ãã©ããã³ 200mlã®ãšã¿ããŒã«äžã®48.8ïœã®ïŒâã¡ãã«ã
ãªâïŒâã€ãããŸãªã³ã»æ²åæ°ŽçŽ å¡©ãš10.0ïœã®ã¡
ãã«ããã©ãžã³ã®æº¶æ¶²ãéæµæž©åºŠã§æ°æéå ç±
ããæž æŸåããã®ã¡ãâ10âã«å·åŽãããæ²æŸ±ã
éãããžãšãã«ãšãŒãã«ã§æŽæµããã®ã¡ã也ç¥ã
ãŠïŒâïŒïŒâã¡ãã«ããã©ãžã³ïŒã€ãããŸãªã³ã»
æ²åæ°ŽçŽ å¡©ãååŸããã ãã®æ²åæ°ŽçŽ å¡©ãéé¢å¡©åºã«å€ããã®ã¡ãå®æœ
äŸïŒãšåæ§ã«ããŠã¢ã«çã«ååã®éã®ãã€ã³â
ïŒïŒïŒïŒïŒïŒïŒâããã©ããããã·ã¢ã³ãã©ãã
ã³ãšåå¿ãããŠãæ·¡é»è²ã®åºäœãšããŠéŠé¡ã®åå
ç©ãååŸããã å®æœäŸ ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹
ïŒâïŒïŒïŒïŒïŒïŒïŒïŒâããã©ãããâ1Hâ
ïŒïŒïŒâãžã¢ãŒãã³âïŒâã€ã«ïŒããã©ãžã³ïŒœ
ã¢ã³ãã©ããã³ 6.41ïœã®éã®ïŒâããã©ãžã³âïŒïŒïŒïŒïŒïŒïŒ
âããã©ãããâ1HâïŒïŒïŒâãžã¢ãŒãã³æ²å
æ°ŽçŽ å¡©ïŒã¢ã¡ãªã«åè¡åœç¹èš±3931152å·ïŒãéé¢
å¡©åºã«å€ããå®æœäŸïŒã«ããããšåæ§ã«2.02ïœã®
ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâããã©ããããã·ã¢ã³
ãã©ããã³ãšåå¿ãããŠãæ·¡é»è²ã®åºäœãšããŠéŠ
é¡ã®ååç©ãååŸããã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâïŒïŒïŒïŒ3â²âã
ãã©ã¡ãã«ãžã°ã¢ããžã³ã»ïŒå¡©é žå¡© 9.2ïœã®ïŒâã¢ããâïŒïŒïŒâãžã¡ãã«ã°ã¢ã
ãžã³ã»æ²åæ°ŽçŽ å¡©ïŒ»FinneganããJ.Org.Chem.
18ã779ïŒ1953ïŒïŒœã4.0mlã®10Næ°Žé žåãããªãŠã
氎溶液ã«ãã€ãŠã¢ã«ã«ãªæ§åãããã®åŸã«5.48ïœ
ã®ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâããã©ããããã·ã¢
ã³ãã©ããã³ãšåå¿ããäžã€åèäŸïŒã«ããããš
åæ§ã«ã¯ãã©ãã«ã«ãã€ãŠé žåããããšã«ãã€
ãŠãæ·¡é»è²ã®åºäœãšããŠãææã®çæç©ãååŸã
ãã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâïŒïŒ3â²âãžã¡ã
ã«ãžã°ã¢ããžã³ã»ïŒå¡©é žå¡© åèäŸïŒã«ããããšåæ§ãªïŒâã¢ããâïŒâã¡
ãã«ã°ã¢ããžã³æ²åæ°ŽçŽ å¡©ã®åŠçã¯ãéŠé¡ã®åå
ç©ãäžããã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâïŒïŒ3â²âãžïŒïŒ
âããã«ïŒãžã°ã¢ããžã³ã»ïŒå¡©é žå¡© åèäŸïŒã®æé ã«ãã€ãŠãïŒâã¢ããâïŒâ
ïŒïŒâããã«ïŒã°ã¢ããžã³ã»æ²åæ°ŽçŽ å¡©ïŒ»Short
ããMed.Chem.ïŒïŒã275ïŒ1963ïŒïŒœãããéŠé¡ã®
ååç©ãååŸããã
ãã¯æåãéäœçŽã¢ã«ãã«ïŒC1ãC4ïŒåºããæ
ãã°ã«ãŒãããéžæããããšãã§ããRâ²ããã³
Râ³ã¯ã¢ã«ãã¬ã³ïŒâCH2âïŒïœã§ãã€ãŠããããã
ãã§ïœã¯ïŒãïŒã®æŽæ°ã§ããã ã«ãã€ãŠè¡šããããšãã§ããïŒïŒïŒâãã¹ïŒã°ã¢
ããžãã«ã¢ããïŒâïŒïŒïŒâãžããããã·ã¢ã³ã
ã©ããã³é¡ã®ãã€ã³å¡©åºããã³ç¡æ¯ã®é žä»å å¡©ã
å«æãã補è¬çµæç©ã¯ãåºä¹³åç©ã«ãããçæ§ã®
ç æ°ã軜æžããããã«æçšã§ãããæ¬çºæã®ãã®
å±é¢ã¯ãæ°èŠçµæç©ããã³ãããçšããŠåºä¹³é¡ã«
ãããçœè¡ç 䞊ã³ã«é¢é£ããæªæ§è «çã®éè¡ãã
ã³ïŒãŸãã¯ç·©åãèªçºãããããã®æ¹æ³ãå å«ã
ãã æ¬çºæã®è£œè¬çµæç©ããã³æ°èŠååç©ã¯ãïŒæ¥
åœãäœéïŒKgã«ã€ããŠçŽïŒmgä¹è³çŽ1.0ïœã®éã§
æäžãããšãã¯ã移æ€ããããŠã¹ã®è «çã®å¢æ®ã
æå¶ãäžã€åºä¹³åç©ã«ãããçœè¡ç ããã³é¢é£ã
ãæªæ§è «çã®éè¡ããã³ïŒãŸãã¯ç·©åãèªçºã
ããæé©ã®çµæã®ããã®å¥œé©ãªæäžéç¯å²ã¯ãïŒ
æ¥åœãã«äœéïŒKgã«ã€ããŠçŽïŒmgä¹è³çŽ100mgã§
ããããã®ãããªé©éåäœã䜿çšããŠãäœéçŽ70
Kgã®æ£è ã«å¯ŸããŠå šéã§çŽ850mgä¹è³çŽ7.0ïœã®æŽ»
æ§ç©è³ªãšãªãããã«ã24æéå ã«æäžããããã®
ããã«é©éç¯å²ã¯ãæé©ã®æ²»çå¹æãäžãããã
ã«èª¿ç¯ããããšãã§ãããããšãã°ãïŒæ¥ã«ãã
ã€ãã«åããé©éãæäžããŠããããããããã¯
æ²»çæ æ³ã®æ¥è¿«ã«ããæ瀺ã«æ¯äŸããŠæäžéãäœ
äžãããããšãã§ããã ããšãã°éèå ãçèå ãŸãã¯ç®äžãžã®æ³šå°ãš
ãããããªã䟿å®ã®æ¹æ³ã§æŽ»æ§ååç©ãæäžãã
ããšãå®éçã«æå©ã§ããããšã¯ãããŸã§ããª
ãã 掻æ§ååç©ã¯ãéçµå£çã«ãŸãã¯è ¹è å ã«æäž
ããããšãã§ãããéé¢å¡©åºãŸãã¯è£œè¬åŠçã«èš±
容ãããå¡©ãšããŠã®æŽ»æ§ååç©ã®æº¶æ¶²ã¯ãããšã
ã°ããããã·ãããã«ã»ã«ããŒã¹ã®ãããªçé¢æŽ»
æ§å€ãšæ··åããããšãé©åœãªæ°Žäžã§ã調補ããã
ãšãã§ãããåæ£æ¶²ã¯ãã°ãªã»ãªã³ã液ç¶ããªã¡
ãã¬ã³ã°ãªã³ãŒã«ããã³ãããã®æ··åç©äžã§ãäž
ã€æ²¹äžã§èª¿è£œããããšãã§ããã貯èµãšäœ¿çšã®é
åžžã®æ¡ä»¶äžã§ããããã®è£œå€ã¯åŸ®çç©ã®çé·ãé²
ãããã®é²è å€ãå«æããã 泚å°çšãšããŠé©ãã補è¬åœ¢æ ã¯ãç¡èã®æ°Žæº¶æ¶²
ãŸãã¯åæ£æ¶²ãããã³ç¡èã®æ³šå°æ¶²ãŸãã¯åæ£æ¶²
ã®å³åžèª¿è£œã®ããã®ç¡èã®ç²æ«ãå å«ãããäœã
ã®å Žåã«ãããŠãã補å€åœ¢æ ã¯ç¡èã§ããäžã€å®¹
æã«æ³šå°åšã§æ³šå°ã§ããçšåºŠã«æµåæ§ã§ããããš
ãå¿ èŠã§ããããŸãã補é ããã³è²¯èµã®æ¡ä»¶äžã«
å®å®ã§ãªããã°ãªããäžã€ããšãã°çŽ°èããã³ç
èé¡ã®ãããªåŸ®çç©ã®æ±æäœçšã«å¯ŸããŠä¿å šãã
ãªããã°ãªããªããæ äœã¯ãããšãã°æ°Žããšã¿ã
ãŒã«ãããªãªãŒã«ïŒããšãã°ãã°ãªã»ãªã³ããã
ãã¬ã³ã°ãªã³ãŒã«ãããã³æ¶²ç¶ããªãšãã¬ã³ã°ãª
ã³ãŒã«ãªã©ïŒãé©åœãªãããã®æ··åç©ããã³æ€ç©
æ²¹ã¯å«æãã溶å€ãŸãã¯åæ£åªäœãšããããšãã§
ãããé©åœãªæµåæ§ã¯ãããšãã°ã¬ã·ãã³ã®ãã
ãªè¢«èŠã®äœ¿çšã«ãã€ãŠãåæ£æ¶²ã®å Žåã«ãããŠ
ã¯ãå¿ èŠãªç²åºŠã®ä¿æã«ãã€ãŠãäžã€çé¢æŽ»æ§å€
ã®äœ¿çšã«ãã€ãŠãä¿ã€ããšãã§ããã埮çç©ã®äœ
çšã®é²æ¢ã¯ãåçš®ã®æ现èããã³æçèå€ãããš
ãã°ããã©ãã³é¡ãã¯ãããã¿ããŒã«ãããšããŒ
ã«ããœã«ãã³é žããã¡ããŒã¶ã«ãªã©ã«ãã€ãŠãé
æããããšãã§ãããå€ãã®å Žåã«ãç匵å€ãã
ãšãã°ç³ãŸãã¯å¡©åãããªãŠã ããå«æãããã
ãšã奜ãŸããã泚å°çšçµæç©ã®å»¶é·ãããåžå
ã¯ãåžåãé 延ãããè¬å€ãããšãã°ã¢ãã¹ãã¢
ãªã³é žã¢ã«ãããŠã ããã³ãŒã©ãã³ãçµæç©äžã§
䜿çšããããšã«ãã€ãŠãéæããããšãã§ããã ç¡èã®æ³šå°æ¶²ã¯ãå¿ èŠéã®æŽ»æ§ååç©ããå¿ èŠ
ã«å¿ããå ã«æããåçš®ã®ãã®ä»ã®æåãšå ±ã«é©
åœãªæº¶å€äžã«å°å ¥ããæ» èæ¿Ÿéããããšã«ãã€
ãŠã調補ãããäžè¬ã«ãåæ£æ¶²ã¯ãçš®ã ã®ç¡èã®
掻æ§æåããåºæ¬çãªåæ£åªäœããã³å ã«æãã
ãã®ããã®ãã®ä»ã®å¿ èŠãªæåãå«æããç¡èã®
賊圢è¬äžã«å°å ¥ããããšã«ãã€ãŠã調補ãããç¡
èã®æ³šå°æ¶²ã®èª¿è£œã®ããã®ç¡èã®ç²æ«ã®å Žåã«
ã¯ã奜é©ãªèª¿è£œæ¹æ³ã¯ãç空也ç¥ããã³åçµä¹Ÿç¥
æ¹æ³ã§ãã€ãŠããããã®æ¹æ³ã¯ãäºãæ» èæ¿Ÿéã
ã掻æ§æåãšãã®ä»ã®å¿ èŠãªæåã®æº¶æ¶²ãããã
ããã®æ··åç©ã®ç²æ«ãäžããã æ¬æ现æžäžã§äœ¿çšããå Žåã®â補è¬åŠçã«èš±å®¹
ãããæ äœâã¯ãä»»æã®æº¶å€ãåæ£åªäœã被èŠã
æ现èå€ããã³æçèå€ãç匵å€äžŠã³ã«åžåé 延
å€ãªã©ã®ãã¹ãŠãå å«ããã補è¬åŠçã«æŽ»æ§ãªç©
質ã«å¯Ÿãããããã®åªäœããã³é åå€ã®äœ¿çšã¯ã
ãã®åéã«ãããŠå ¬ç¥ã§ãããæ £çšãããåªäœã
ãã³é åå€ã®äœãããããã掻æ§æåãšäž¡ç«ããª
ãå Žåãé€ãã°ã補è¬çµæç©äžã«ããã䜿çšãæ
å³ããããšãã§ãããè£å ã®æŽ»æ§æåãçµæç©äž
ã«é åããããšãã§ããã æäžã®å®¹æãããã³æäžéã®åäžæ§ã®ããã«é©
éåäœåœ¢æ ã«ããéçµå£çµæç©ãåŠæ¹ããããšã
ç¹ã«æå©ã§ãããæ¬çºæã«ãããŠäœ¿çšããå Žåã®
é©éåäœåœ¢æ ãšã¯ãæ²»çãã¹ãåºä¹³é¡å¯Ÿç §ãžã®å
äœæäžéãšããŠé©ããç©ççã«åé¢ããåäœãæ
å³ããååäœã¯å¿ èŠãªè£œè¬æ äœãšçµåããããæ
ãŸããæ²»çå¹æãäžããããã«èšç®ãããäºå®ã
ãéã®æŽ»æ§ç©è³ªãå«æããŠãããæ¬çºæã®æ°èŠé©
éåäœåœ¢æ ã«å¯Ÿãã詳现ã¯(a)掻æ§ç©è³ªã®ç¬ç¹ãªæ§
質ãšéæãã¹ãç¹å®ã®æ²»çå¹æãããã³(b)æ¬æ现
æžäžã«è©³çŽ°ã«èšããããã«èäœçã«å¥åº·ãæãªã€
ãŠãããç çãªç¶æ ã«ããæ£è ã®ç æ°ã®æ²»çã®ã
ãã®ããã掻æ§ç©è³ªã®åŠæ¹ã®æè¡ã«ãããŠåºæã®
å¶éã«ãã€ãŠèŠå®ããäžã€ããã«çŽæ¥ã«äŸåã
ãã 䟿å®çäžã€å¹æçãªæäžã®ããã«ã¯ã䞻掻æ§æ
åãåèšã®åŠãé©éåäœåœ¢æ äžã§æå¹ãªéã§é©åœ
ãªè£œè¬åŠçã«èš±å®¹ãããæ äœãšå ±ã«é åãããå
äœé©é圢æ ã¯ã䞻掻æ§ååç©ããããšãã°ãçŽ
0.1ä¹è³çŽ500mgã®ç¯å²ã®éã§ã奜ãŸããã¯çŽïŒä¹
è³çŽ500mgã®éã§ãå«æãããå²åãšããŠè¡šãã
ãšã掻æ§ååç©ã¯äžè¬ã«ãæ äœïŒmlåœãã«çŽïŒä¹
è³çŽ500mgã®éã§ååšãããããè£è¶³çãªæŽ»æ§æ
åãå«æããçµæç©ã®å Žåã«ã¯ãé©éã¯ã該æå
ã®éåžžã®æäžéããã³æäžã®æ¹åŒãåèã«ããŠã
決å®ããããšãã§ããã çã®éè¡ããã³ç·©åã¯ãããšãã°ãè ¹è å æäž
ãçšããŠéæããããšãã§ãããïŒåã®éèå é©
éãŸãã¯ç¹°è¿ãã®æ¯æ¥ã®é©éãæäžããããšãã§
ãããå€ãã®å ŽåãçŽïŒãŸãã¯10æ¥ã«è³ããŸã§ã®
æ¯æ¥ã®æäžã§å åã§ãããïŒæ¥çœ®ããŸãã¯ãã以
äžã®ééã§ãïŒæ¥åé©éãŸãã¯ïŒæäžéãåäžã
ãããšãå¯èœã§ãããé©éåºæºããæãããªãã
ã«ãæäžãã䞻掻æ§æåã®éã¯ãçãä¿æãã宿
äž»ã«å¯Ÿãã现èæ¯æ§ã«ããé床ã®æ害ãªå¯äœçšã®
ååšãªãã«ãçœè¡ç ãªã©ã®éè¡ããã³ç·©åãä¿ã
ããã«ååãªéã§ãããæ¬æ现æžã«ãããŠçšãã
å Žåã®çæ§ã®ç æ°ã¯ãããšãã°çœè¡ç ã®ãããªè¡
液ã®æªæ§è «çã䞊ã³ã«ããšãã°é»è²è «ãèºçãã
ã³ä¹³çã®ãããªããã®ä»ã®ç¢ºå®ãªããã³äžç¢ºå®ãª
æªæ§è «çãæå³ãããéè¡ããã³ç·©åãšã¯ãè «ç
ã®å¢æ®ãŸãã¯ãã®ä»ã®ç æ°ã®è¡šç€ºããæ²»çããªã
å Žåã®ç æ°ã®çµéãšæ¯èŒããŠãé»æ¢ãŸãã¯é 延ã
ããããšãæå³ããã æ¬çºæã以äžã®ç¹å®çãªå®æœäŸãšé¢é£ãããŠæŽ
ã«è©³çŽ°ã«èª¬æããã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâãžã°ã¢ããžã³ã»
ïŒå¡©é žå¡© 19.70ïœã®ç¡«é žã¢ããã°ã¢ããžã³ãš16.0mlã®10N
æ°Žé žåãããªãŠã 氎溶液ã®æ··åç©ãæ¹æãäžã€ã
ããŸããå šéšãªããªããŸã§ããç ãããã®æ··åç©
ã75mlã®ãšã¿ããŒã«ã§åžéãã氷济äžã§å·åŽãäž
ã€90.0ïœã®3AååãµãããçšããŠïŒæé也ç¥ã
ããæ¿Ÿéã«ãã€ãŠåºäœãé€å»ãã35mlãã€ã®ãšã¿
ããŒã«ãçšããŠïŒåæŽæµããã濟液ãšæŽæ¶²ãåã
ãäžã€15åéçªçŽ ãå¹èŸŒãããšã«ãã€ãŠè±æ°ãã
ã®ã¡ã10.97ïœã®ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâãã
ã©ããããã·ã¢ã³ãã©ããã³ãçªçŽ äžã«å ããã
ãã®æ··åç©ãæ¹æãäžã€çªçŽ äžã«50ã51âã®æ²¹æµŽ
äžã§ïŒæéå ç±ãã次ãã§16æéæŸå·ããããã®
æ··åç©ãå·åŽããæ¿Ÿéã«ãã€ãŠåºäœãéããå·ãš
ã¿ããŒã«ã§æŽæµããŠãéŠé¡ã®ååç©ã®ïŒïŒïŒâãž
ãããèªå°äœã§ããé»è²ã®åºäœ13.87ïœãååŸã
ãã 11.60ïœã®ãã®ïŒïŒïŒâãžãããååç©ã®æ¹æ
æžæ¿æ¶²ã200mlã®ïŒâã¡ããã·ãšã¿ããŒã«äžã®
7.50ïœã®ã¯ãã©ãã«ã«å ãã次ãã§æ°·æµŽã§å·åŽã
ãªãã15.0mlã®ãšã¿ããŒã«äžã®8Nå¡©é žã滎å ã
ãããšã«ãã€ãŠé žåããããã®æ··åç©ã宀枩ã§16
æéæ¹æããã®ã¡ããžãšãã«ãšã¿ããŒã«ã§åžéã
ããåºäœãéããããã©ããããã©ã³ã§æŽæµã
ãŠã12.53ïœã®æ玫è²ã®åºäœãååŸããããã®çŽ«
è²ã®åºäœã®10.0ïœã®éšåãç²æ«ç¶ãšãã23âã®
300mlã®æ°Žäžã§ïŒæéæ¹æããã®ã¡ãé å¿åé¢ã
ããäžæŸæ¶²ãåŸçãäžã€æ¿Ÿéããã濟液ãåçµä¹Ÿ
ç¥ããèµ€è€è²ã®åºäœãšããŠæ¬å®æœäŸã®çæç©ãå
åŸãããNMRã·ã°ãã«ïŒÎŽ8.00ã7.74åã³7.60ã
ã€ã¯ãããªã¡ãŒã¿ãŒãIRïŒ5.97â8.33ã å®æœäŸ ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹
ïŒâïŒïŒâã€ãããŸãªã³âïŒâã€ã«ïŒâããã©
ãžãã¢ã³ãã©ããã³ 50mlã®ã¡ã¿ããŒã«äžã®3.94ïœã®ïŒâããã©ãžã
âïŒâã€ãããŸãªã³ã»å¡©é žå¡©ïŒã¢ã¡ãªã«åè¡åœç¹
èš±3931152å·ïŒã®æº¶æ¶²ããäºãã¡ã¿ããŒã«ã§æŽæµ
ããŠãã15ïœã®ããªã¹ãã¬ã³åçŽæ°Žé žåã¢ã³ã¢ã
ãŠã æš¹èãå«æããã«ã©ã äžã«éããããšã«ãã€
ãŠãéé¢å¡©åºãšãããè©Šæãã«ã©ã äžã§äœåã®ã¡
ã¿ããŒã«ã§æŽæµããã溶é¢æ¶²ãšæŽæµæ¶²ã®èžçºã¯ã
3.3ïœã®é»è€è²ã®æ²¹ãäžããã40mlã®ïŒ®ïŒNâ²ïŒ
Nâ²âããã©ã¡ãã«ãšãã¬ã³ãžã¢ãã³ïŒãšã¿ããŒ
ã«ïŒïŒïŒïŒïŒäžã®ãã®æ²¹ã®æ¿Ÿé溶液ãããã®äžã«
çªçŽ ã15åéå¹èŸŒãããšã«ãã€ãŠè±æ°ãã次ãã§
2.02ïœã®ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâããã©ããã
ãã·ã¢ã³ãã©ããã³ãçªçŽ äžã«å ãããçæãã
æ··åç©ãçªçŽ äžã«æ¹æãäžã€50ã52âã®æ²¹æº¶äžã§
ïŒæéå ç±ããããã®æ··åç©ãçªçŽ äžã«48æéæŸ
眮ããçæããåºäœãæ¿Ÿéã«ãã€ãŠéããïŒ
ïŒNâ²ïŒNâ²âããã©ã¡ãã«ãšãã¬ã³ãžã¢ãã³ã§
ïŒåããšã¿ããŒã«ã§ïŒåæŽæµããŠãèµ€è€è²åºäœãš
ããŠ0.03ïœã®æ¬å®æœäŸã®çæç©ãååŸããã
NMRã·ã°ãã«ïŒÎŽ7.22åã³8.33ãã€ã¯ãããªã¡ãŒ
ã¿ãŒãIRïŒ6.20â8.15ã å®æœäŸ ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹
ïŒâïŒïŒâã€ãããŸãªã³âïŒâã€ã«ïŒâïŒâã¡
ãã«ããã©ãžãã¢ã³ãã©ããã³ 200mlã®ãšã¿ããŒã«äžã®48.8ïœã®ïŒâã¡ãã«ã
ãªâïŒâã€ãããŸãªã³ã»æ²åæ°ŽçŽ å¡©ãš10.0ïœã®ã¡
ãã«ããã©ãžã³ã®æº¶æ¶²ãéæµæž©åºŠã§æ°æéå ç±
ããæž æŸåããã®ã¡ãâ10âã«å·åŽãããæ²æŸ±ã
éãããžãšãã«ãšãŒãã«ã§æŽæµããã®ã¡ã也ç¥ã
ãŠïŒâïŒïŒâã¡ãã«ããã©ãžã³ïŒã€ãããŸãªã³ã»
æ²åæ°ŽçŽ å¡©ãååŸããã ãã®æ²åæ°ŽçŽ å¡©ãéé¢å¡©åºã«å€ããã®ã¡ãå®æœ
äŸïŒãšåæ§ã«ããŠã¢ã«çã«ååã®éã®ãã€ã³â
ïŒïŒïŒïŒïŒïŒïŒâããã©ããããã·ã¢ã³ãã©ãã
ã³ãšåå¿ãããŠãæ·¡é»è²ã®åºäœãšããŠéŠé¡ã®åå
ç©ãååŸããã å®æœäŸ ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹
ïŒâïŒïŒïŒïŒïŒïŒïŒïŒâããã©ãããâ1Hâ
ïŒïŒïŒâãžã¢ãŒãã³âïŒâã€ã«ïŒããã©ãžã³ïŒœ
ã¢ã³ãã©ããã³ 6.41ïœã®éã®ïŒâããã©ãžã³âïŒïŒïŒïŒïŒïŒïŒ
âããã©ãããâ1HâïŒïŒïŒâãžã¢ãŒãã³æ²å
æ°ŽçŽ å¡©ïŒã¢ã¡ãªã«åè¡åœç¹èš±3931152å·ïŒãéé¢
å¡©åºã«å€ããå®æœäŸïŒã«ããããšåæ§ã«2.02ïœã®
ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâããã©ããããã·ã¢ã³
ãã©ããã³ãšåå¿ãããŠãæ·¡é»è²ã®åºäœãšããŠéŠ
é¡ã®ååç©ãååŸããã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâïŒïŒïŒïŒ3â²âã
ãã©ã¡ãã«ãžã°ã¢ããžã³ã»ïŒå¡©é žå¡© 9.2ïœã®ïŒâã¢ããâïŒïŒïŒâãžã¡ãã«ã°ã¢ã
ãžã³ã»æ²åæ°ŽçŽ å¡©ïŒ»FinneganããJ.Org.Chem.
18ã779ïŒ1953ïŒïŒœã4.0mlã®10Næ°Žé žåãããªãŠã
氎溶液ã«ãã€ãŠã¢ã«ã«ãªæ§åãããã®åŸã«5.48ïœ
ã®ãã€ã³âïŒïŒïŒïŒïŒïŒïŒâããã©ããããã·ã¢
ã³ãã©ããã³ãšåå¿ããäžã€åèäŸïŒã«ããããš
åæ§ã«ã¯ãã©ãã«ã«ãã€ãŠé žåããããšã«ãã€
ãŠãæ·¡é»è²ã®åºäœãšããŠãææã®çæç©ãååŸã
ãã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâïŒïŒ3â²âãžã¡ã
ã«ãžã°ã¢ããžã³ã»ïŒå¡©é žå¡© åèäŸïŒã«ããããšåæ§ãªïŒâã¢ããâïŒâã¡
ãã«ã°ã¢ããžã³æ²åæ°ŽçŽ å¡©ã®åŠçã¯ãéŠé¡ã®åå
ç©ãäžããã åèäŸ ïŒ ïŒïŒ1â²âïŒïŒïŒïŒâãžããããã·âïŒïŒïŒâã¢
ã³ãã©ãããã¬ã³ãžã€ããïŒâïŒïŒ3â²âãžïŒïŒ
âããã«ïŒãžã°ã¢ããžã³ã»ïŒå¡©é žå¡© åèäŸïŒã®æé ã«ãã€ãŠãïŒâã¢ããâïŒâ
ïŒïŒâããã«ïŒã°ã¢ããžã³ã»æ²åæ°ŽçŽ å¡©ïŒ»Short
ããMed.Chem.ïŒïŒã275ïŒ1963ïŒïŒœãããéŠé¡ã®
ååç©ãååŸããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ åŒïŒ åŒäžã§ ïŒRâ²ããã³Râ³ã¯ãæ°ŽçŽ ããã³çŽéãŸãã¯æ
åãéäœçŽã¢ã«ãã«ïŒC1ãC4ïŒåºããæãã°ã«
ãŒãããéžæãããããã¯Râ²ããã³Râ³ã¯å ±åã
ãŠã¢ã«ãã¬ã³ïŒâCH2âïŒïœã§ãããããã§ïœã¯ïŒã
ïŒã®æŽæ°ã§ããã ãæããååç©ããæãã°ã«ãŒãããéžæããå
åç©ã ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâã
ã¹ïŒ»ïŒâïŒïŒâã€ãããŸãªã³âïŒâã€ã«ïŒããã©
ãžãã¢ã³ãã©ããã³ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒ
é èšèŒã®ååç©ã ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâã
ã¹ïŒ»ïŒâïŒïŒâã€ãããŸãªã³âïŒâã€ã«ïŒâïŒâã¡
ãã«ããã©ãžãâã¢ã³ãã©ããã³ã§ããç¹èš±è«
æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâã
ã¹ïŒ»ïŒâïŒïŒïŒïŒïŒïŒïŒïŒâããã©ãããâ1Hâ
ïŒïŒïŒâãžã¢ãŒãã³âïŒâã€ã«ïŒâïŒâããã©ãž
ãã¢ã³ãã©ããã³ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé
èšèŒã®ååç©ã
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87,908 | 1979-10-24 | ||
| US06/087,908 US4275010A (en) | 1979-10-24 | 1979-10-24 | 5,8-Dihydroxy-1,4-bis(guanidinylamino)anthraquinones |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14639480A Division JPS5681554A (en) | 1979-10-24 | 1980-10-21 | 5*88dihydroxyy1*44bis*guanidylamino** anthraquinones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02157A JPH02157A (ja) | 1990-01-05 |
| JPH0215534B2 true JPH0215534B2 (ja) | 1990-04-12 |
Family
ID=22207978
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14639480A Granted JPS5681554A (en) | 1979-10-24 | 1980-10-21 | 5*88dihydroxyy1*44bis*guanidylamino** anthraquinones |
| JP63301133A Granted JPH02157A (ja) | 1979-10-24 | 1988-11-30 | ãã€ã³âïŒïŒïŒâãžããããã·âïŒïŒïŒâãã¹ïŒã°ã¢ããžãã«ã¢ããïŒâã¢ã³ãã©ããã³é¡ |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP14639480A Granted JPS5681554A (en) | 1979-10-24 | 1980-10-21 | 5*88dihydroxyy1*44bis*guanidylamino** anthraquinones |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US4275010A (ja) |
| EP (1) | EP0027877B1 (ja) |
| JP (2) | JPS5681554A (ja) |
| CA (1) | CA1152506A (ja) |
| DE (1) | DE3064138D1 (ja) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0550813U (ja) * | 1991-12-06 | 1993-07-02 | ã³ã¡ããæ ªåŒäŒç€Ÿ | èªåè»çšã¢ã³ããã®åä»è£ 眮 |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4333875A (en) * | 1979-10-24 | 1982-06-08 | American Cyanamid Company | 5,8-Dihydroxy-1,4-bis(guanidinylamino)anthraquinones |
| US4526788A (en) * | 1983-03-18 | 1985-07-02 | American Cyanamid Company | Polymeric[[(oxazolidinyl)alkyl]amino]anthraquinones |
| GB8923075D0 (en) * | 1989-10-13 | 1989-11-29 | Patterson Laurence H | Anti-cancer compounds |
| US20070117784A1 (en) * | 2005-03-04 | 2007-05-24 | Novacea, Inc. | Treatment of hyperproliferative diseases with anthraquinones |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3364220A (en) * | 1963-11-13 | 1968-01-16 | Colgate Palmolive Co | Heterocyclicaminoalkylguanidines |
| SE445996B (sv) * | 1977-08-15 | 1986-08-04 | American Cyanamid Co | Nya atrakinonderivat |
| GB2009171B (en) * | 1977-11-28 | 1982-08-18 | American Cyanamid Co | Anthracene bis-carbonyl hydrazones and derivatives |
-
1979
- 1979-10-24 US US06/087,908 patent/US4275010A/en not_active Expired - Lifetime
-
1980
- 1980-09-02 DE DE8080105206T patent/DE3064138D1/de not_active Expired
- 1980-09-02 EP EP80105206A patent/EP0027877B1/en not_active Expired
- 1980-09-04 CA CA000359561A patent/CA1152506A/en not_active Expired
- 1980-10-21 JP JP14639480A patent/JPS5681554A/ja active Granted
-
1988
- 1988-11-30 JP JP63301133A patent/JPH02157A/ja active Granted
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0550813U (ja) * | 1991-12-06 | 1993-07-02 | ã³ã¡ããæ ªåŒäŒç€Ÿ | èªåè»çšã¢ã³ããã®åä»è£ 眮 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP0027877B1 (en) | 1983-07-13 |
| CA1152506A (en) | 1983-08-23 |
| JPH0121142B2 (ja) | 1989-04-19 |
| JPH02157A (ja) | 1990-01-05 |
| EP0027877A1 (en) | 1981-05-06 |
| JPS5681554A (en) | 1981-07-03 |
| DE3064138D1 (de) | 1983-08-18 |
| US4275010A (en) | 1981-06-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0037486B1 (en) | Metal chelates of 1,4-bis(substituted-amino)-5,8-dihydroxy-anthraquinones | |
| KR840001965B1 (ko) | ìížëŒìŒ-9,10-ë¹ì€-칎륎볎ë-íëëŒì¡Ž ì ë첎 ì ì¡°ë°©ë² | |
| US4544759A (en) | Platinum complexes of antitumor agents | |
| US3892799A (en) | Phenoxyalkylamines and their salts | |
| JPH0215534B2 (ja) | ||
| US4389399A (en) | Thiocarbamoyl heterocycle-anthraquinone derivatives | |
| US4278689A (en) | 1,4-Bis(substituted-amino)-5,8-dihydroxy-anthraquinones and leuco bases thereof | |
| US4540788A (en) | Schiff bases of [(aminoalkyl or substituted aminoalkyl)amino]-9,10-anthracenediones | |
| US4278605A (en) | Heteroalkylenebisanthraquinones | |
| US4410524A (en) | Novel 1,4-bis(substituted-amino)-5,8-dihydroxyanthraquinones and leuco bases thereof | |
| US4888137A (en) | Novel 1,4-bis(substituted-amino(-5,8-dihydroxyanthraquinones and leuco bases thereof | |
| JPS6361937B2 (ja) | ||
| JPS63264580A (ja) | ïŒâïŒïŒâããã¢ã«ãã«ïŒâïŒïŒïŒâãªããµãã€ã³ããã³ïŒâïŒïŒâããã¢ã«ãã«ïŒâïŒïŒïŒâãžãã€ã³ | |
| US4456552A (en) | 1,4-Bis(substituted-amino)-5,8-dihydroxyanthraquinones and leuco bases thereof | |
| US4900838A (en) | Acylation products of bis(2-imidazolin-2-ylhydrazones) of 9,10-anthracenedicarboxaldehyde | |
| CA1178203A (en) | Method of treating tumors in warm-blooded animals with novel compositions of matter | |
| DE2008693A1 (de) | Neue 'Pyrazoline | |
| US4187373A (en) | Novel dihydrobenzanthracene derivatives | |
| US4375469A (en) | Oxaza heterocycle-anthraquinones, pharmaceutical compositions thereof and method of use thereof | |
| DE1620466C3 (de) | 2,3,5,6-Tetrahydroindolderivate und Verfahren zu ihrer Herstellung | |
| EP0210291A1 (en) | Platinum complexes of antitumor agents | |
| JPS61122254A (ja) | æ°èŠãªãã¹âïŒçœ®æã¢ããïŒã¢ã³ãã©ãã³é¡ | |
| US4235996A (en) | Bis(2-imidazolin-2-ylhydrazone)-9,10-dihydro-9,10-anthracenedicarboxaldehydes | |
| CA1321204C (en) | Acylation products of bis(2-imidazolin-2- ylhydrazones) of 9,10-anthracenedicarboxaldehyde | |
| EP0085760A2 (en) | Novel 1-4-bis(substituted-amino)-5,8-dihydroxyanthraquinones and leuco bases thereof |