JPS64951B2 - - Google Patents
Info
- Publication number
- JPS64951B2 JPS64951B2 JP54169489A JP16948979A JPS64951B2 JP S64951 B2 JPS64951 B2 JP S64951B2 JP 54169489 A JP54169489 A JP 54169489A JP 16948979 A JP16948979 A JP 16948979A JP S64951 B2 JPS64951 B2 JP S64951B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- dihydro
- bis
- quinolyloxy
- carboxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- XOQQVKDBGLYPGH-UHFFFAOYSA-N 2-oxo-1h-quinoline-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=CC2=C1 XOQQVKDBGLYPGH-UHFFFAOYSA-N 0.000 claims abstract description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 15
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical group C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 150000001768 cations Chemical class 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- -1 alkali metal cation Chemical class 0.000 claims description 23
- 239000002585 base Substances 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- RMAIJGKQCPYNQI-UHFFFAOYSA-N 7-[3-(3-carboxy-1-ethyl-4-oxoquinolin-7-yl)oxy-2-hydroxypropoxy]-1-ethyl-4-oxoquinoline-3-carboxylic acid Chemical compound CCN1C=C(C(O)=O)C(=O)C=2C1=CC(OCC(O)COC1=CC=C3C(=O)C(C(O)=O)=CN(C3=C1)CC)=CC=2 RMAIJGKQCPYNQI-UHFFFAOYSA-N 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 5
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 4
- JEBJIWLJHQOTIA-UHFFFAOYSA-N 2-hydroxy-4-quinolone-3-carboxylic acid Chemical class C1=CC=C2NC(=O)C(C(=O)O)=C(O)C2=C1 JEBJIWLJHQOTIA-UHFFFAOYSA-N 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 150000004985 diamines Chemical class 0.000 claims description 3
- 150000002690 malonic acid derivatives Chemical class 0.000 claims description 3
- NZLLPESLBKZUOL-UHFFFAOYSA-N 1-butyl-7-[3-(1-butyl-3-carboxy-4-oxoquinolin-7-yl)oxy-2-hydroxypropoxy]-4-oxoquinoline-3-carboxylic acid Chemical compound CCCCN1C=C(C(O)=O)C(=O)C=2C1=CC(OCC(O)COC1=CC=C3C(=O)C(C(O)=O)=CN(C3=C1)CCCC)=CC=2 NZLLPESLBKZUOL-UHFFFAOYSA-N 0.000 claims description 2
- QQMDZTLDFGFVRM-UHFFFAOYSA-N 6-[3-(3-carboxy-1-ethyl-4-oxoquinolin-6-yl)oxy-2-hydroxypropoxy]-1-ethyl-4-oxoquinoline-3-carboxylic acid Chemical compound CCN1C=C(C(O)=O)C(=O)C2=CC(OCC(O)COC=3C=C4C(=O)C(C(O)=O)=CN(C4=CC=3)CC)=CC=C21 QQMDZTLDFGFVRM-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- HXPDOMFVTRELQL-UHFFFAOYSA-N 8-[3-(3-carboxy-1-ethyl-4-oxoquinolin-8-yl)oxy-2-hydroxypropoxy]-1-ethyl-4-oxoquinoline-3-carboxylic acid Chemical compound CCN1C=C(C(O)=O)C(=O)C2=C1C(OCC(O)COC=1C=CC=C3C(=O)C(C(O)=O)=CN(C=13)CC)=CC=C2 HXPDOMFVTRELQL-UHFFFAOYSA-N 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims description 2
- 125000005490 tosylate group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract description 2
- 125000001589 carboacyl group Chemical group 0.000 abstract description 2
- 229910052739 hydrogen Inorganic materials 0.000 abstract 2
- 239000001257 hydrogen Substances 0.000 abstract 2
- 230000000144 pharmacologic effect Effects 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 13
- 229960004592 isopropanol Drugs 0.000 description 13
- 238000010992 reflux Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
- 239000013543 active substance Substances 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 235000011121 sodium hydroxide Nutrition 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 235000011118 potassium hydroxide Nutrition 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000012265 solid product Substances 0.000 description 6
- 239000000654 additive Substances 0.000 description 5
- 229960000265 cromoglicic acid Drugs 0.000 description 5
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- HQARDVLSJLCFBA-UHFFFAOYSA-N 4-[(4-aminophenyl)carbamoyl]-1h-imidazole-5-carboxylic acid Chemical compound C1=CC(N)=CC=C1NC(=O)C1=C(C(O)=O)NC=N1 HQARDVLSJLCFBA-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 229940124630 bronchodilator Drugs 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000032050 esterification Effects 0.000 description 3
- 238000005886 esterification reaction Methods 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000003380 propellant Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
- AOISKVKPUJRRBF-UHFFFAOYSA-N 1-butyl-7-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(OC)C=C2N(CCCC)C=C(C(O)=O)C(=O)C2=C1 AOISKVKPUJRRBF-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 238000007126 N-alkylation reaction Methods 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 235000011181 potassium carbonates Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical compound C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 description 1
- KVSUFKFZLZCWDJ-UHFFFAOYSA-N 1,3-bis(3-aminophenoxy)propan-2-ol Chemical compound NC1=CC=CC(OCC(O)COC=2C=C(N)C=CC=2)=C1 KVSUFKFZLZCWDJ-UHFFFAOYSA-N 0.000 description 1
- GUAIZUNCNLCGFT-UHFFFAOYSA-N 1,3-bis(3-nitrophenoxy)propan-2-ol Chemical compound C=1C=CC([N+]([O-])=O)=CC=1OCC(O)COC1=CC=CC([N+]([O-])=O)=C1 GUAIZUNCNLCGFT-UHFFFAOYSA-N 0.000 description 1
- FTQYNLXPSONGSQ-UHFFFAOYSA-N 1,3-bis(4-aminophenoxy)propan-2-ol Chemical compound C1=CC(N)=CC=C1OCC(O)COC1=CC=C(N)C=C1 FTQYNLXPSONGSQ-UHFFFAOYSA-N 0.000 description 1
- KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical group CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- TZUQEMMNWWBEMO-UHFFFAOYSA-N 1-butyl-7-hydroxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(O)C=C2N(CCCC)C=C(C(O)=O)C(=O)C2=C1 TZUQEMMNWWBEMO-UHFFFAOYSA-N 0.000 description 1
- SKKHQZCXXSAJCP-UHFFFAOYSA-N 1-ethyl-6-hydroxy-4-oxoquinoline-3-carboxylic acid Chemical compound OC1=CC=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 SKKHQZCXXSAJCP-UHFFFAOYSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- RTZZCYNQPHTPPL-UHFFFAOYSA-N 3-nitrophenol Chemical compound OC1=CC=CC([N+]([O-])=O)=C1 RTZZCYNQPHTPPL-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-UHFFFAOYSA-N 6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNCC(O)C(O)C(O)C(O)CO MBBZMMPHUWSWHV-UHFFFAOYSA-N 0.000 description 1
- NLHTVFMVBOSSGD-UHFFFAOYSA-N 7-[2-acetyloxy-3-(3-carboxy-1-ethyl-4-oxoquinolin-7-yl)oxypropoxy]-1-ethyl-4-oxoquinoline-3-carboxylic acid Chemical compound CCN1C=C(C(O)=O)C(=O)C=2C1=CC(OCC(COC1=CC=C3C(=O)C(C(O)=O)=CN(C3=C1)CC)OC(C)=O)=CC=2 NLHTVFMVBOSSGD-UHFFFAOYSA-N 0.000 description 1
- KHPRZDGNEDKXPI-UHFFFAOYSA-N 7-[3-[(3-carboxy-4-oxo-1h-quinolin-7-yl)oxy]-2-hydroxypropoxy]-4-oxo-1h-quinoline-3-carboxylic acid Chemical compound N1C=C(C(O)=O)C(=O)C=2C1=CC(OCC(COC=1C=C3C(C(C(C(O)=O)=CN3)=O)=CC=1)O)=CC=2 KHPRZDGNEDKXPI-UHFFFAOYSA-N 0.000 description 1
- OVHSUIUJTJYRDO-UHFFFAOYSA-N 7-hydroxy-1-methyl-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(O)C=C2N(C)C=C(C(O)=O)C(=O)C2=C1 OVHSUIUJTJYRDO-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000018569 Respiratory Tract disease Diseases 0.000 description 1
- 229930189077 Rifamycin Natural products 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000013566 allergen Substances 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000000889 atomisation Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006267 biphenyl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000015115 caffÚ latte Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- GYYUHQIQWWNEOR-UHFFFAOYSA-N ethyl 1-[3-(3-ethoxycarbonyl-4-oxoquinolin-1-yl)oxy-2-hydroxypropoxy]-4-oxoquinoline-3-carboxylate Chemical compound C(C)OC(=O)C1=CN(C2=CC=CC=C2C1=O)OCC(CON1C=C(C(C2=CC=CC=C12)=O)C(=O)OCC)O GYYUHQIQWWNEOR-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 125000001183 hydrocarbyl group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960001317 isoprenaline Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 description 1
- 229960005287 lincomycin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229960002657 orciprenaline Drugs 0.000 description 1
- 229940092253 ovalbumin Drugs 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229960003292 rifamycin Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- YVOFSHPIJOYKSH-NLYBMVFSSA-M sodium rifomycin sv Chemical compound [Na+].OC1=C(C(O)=C2C)C3=C([O-])C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O YVOFSHPIJOYKSH-NLYBMVFSSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 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
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 239000004552 water soluble powder Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Pulmonology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Communicable Diseases (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Description
æ¬çºæã¯æ°èŠãããã³ã«ã«ãã³é
žèªå°äœåã³ã
ã®è£œæ³ã«é¢ããã äœçšç©è³ªãšããŠã¯ãã¢ã°ãªã·ã³é žãå«æãã補
å€ããæ°ç®¡æ¯ççªãèªçºããä»åšç©è³ªãäŸãã°ã
ã¹ã¿ãã³åã³SRSâã®èºã®è¥æºçŽ°èããã®éé¢
ãåžå ¥ã«ããæå¶ãããããã€ãŠäºé²çã«äœ¿çšã
ãéã«ã¢ã¬ã«ã®ãŒæ§ããããã®æ²»çã«ããããŠå¥œ
é©ã§ããããšã¯å ¬ç¥ã§ãããâãžã€ãŒãã«ã»ãª
ãã»ã¡ãã€ã·ãã«ã»ã±ãã¹ããªãŒïŒJ.Med.
ChemïŒâã第15å·»ã583é 1972幎ãã äžè¬åŒïŒ ãåŒäžåºïŒ
ã®è£œæ³ã«é¢ããã äœçšç©è³ªãšããŠã¯ãã¢ã°ãªã·ã³é žãå«æãã補
å€ããæ°ç®¡æ¯ççªãèªçºããä»åšç©è³ªãäŸãã°ã
ã¹ã¿ãã³åã³SRSâã®èºã®è¥æºçŽ°èããã®éé¢
ãåžå ¥ã«ããæå¶ãããããã€ãŠäºé²çã«äœ¿çšã
ãéã«ã¢ã¬ã«ã®ãŒæ§ããããã®æ²»çã«ããããŠå¥œ
é©ã§ããããšã¯å ¬ç¥ã§ãããâãžã€ãŒãã«ã»ãª
ãã»ã¡ãã€ã·ãã«ã»ã±ãã¹ããªãŒïŒJ.Med.
ChemïŒâã第15å·»ã583é 1972幎ãã äžè¬åŒïŒ ãåŒäžåºïŒ
ãåŒãã¯
ïŒã€ã®ãããã³åºã®ïŒäœãïŒäœãåã¯ïŒäœã«ååš
ãããã€ïœåã³ïœã¯ïŒãïŒã®æ°ãè¡šãããR1ã¯
æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢ã«ãã«åºãè¡š
ãããR2ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢
ã·ã«åºãè¡šããããã€ïŒžã¯æ°ŽçŽ ååãççåŠçã«
å®å šãªå¡©åºã®ã«ããªã³åã¯ïŒ£âååæ°ïŒãïŒã®ã¢
ã«ãã«åºãè¡šãããã®æ°èŠãããã³ã«ã«ãã³é žèª
å°äœãåºïŒ
ãããã€ïœåã³ïœã¯ïŒãïŒã®æ°ãè¡šãããR1ã¯
æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢ã«ãã«åºãè¡š
ãããR2ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢
ã·ã«åºãè¡šããããã€ïŒžã¯æ°ŽçŽ ååãççåŠçã«
å®å šãªå¡©åºã®ã«ããªã³åã¯ïŒ£âååæ°ïŒãïŒã®ã¢
ã«ãã«åºãè¡šãããã®æ°èŠãããã³ã«ã«ãã³é žèª
å°äœãåºïŒ
ãåŒããïŒã€
ã®ãããã³åºã®ããããïŒäœãããããïŒäœåã¯
ããããïŒäœã«ååšãããããã³ã«ã«ãã³é žèªå°
äœãïœåã³ïœãããããïŒãè¡šãããããã³ã«ã«
ãã³é žèªå°äœãR2ã¯æ°ŽçŽ ååãè¡šãããããã³
ã«ã«ãã³é žèªå°äœããæ°ŽçŽ ååãã¢ã«ã«ãªéå±
ã«ããªã³ãã¢ã«ã«ãªåé¡éå±ã«ããªã³ãã¢ã³ã¢ã
ãŠã ã«ããªã³ãããã©ãžãã«ã«ããªã³åã¯ïŒ®âã¡
ãã«ã°ã«ã«ãã³ã«ããªã³ã§ãããããã³ã«ã«ãã³
é žèªå°äœã詳现ã«ã¯ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâããã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâã¡ãã«âïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâïŒ
âãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâïŒ
âãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒâã¢ã»ããã·âïŒïŒïŒâãã¹âïŒïŒâãšãã«
âïŒâã«ã«ããã·âïŒïŒïŒâãžãããâïŒâãªã
ãœâïŒâãããªã«ãªãã·ïŒâãããã³ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã å¡©ã¯
ã¯ãã¢ã°ãªã·ã³é žã®ãããªãŠã å¡©ãšåæ§ã®æ§è³ªã
æãããã該ååç©ã«å¯ŸããŠãã®ä»ã«ããããæ²»
çã«æå©ãªæ¶çåã³æèæ§äœçšãæããå©ç¹ãæ
ã€ã äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœã¯çœ®æå
R1ãšããŠïŒ£âååæ°ïŒãïŒã®ãæå©ã«ïŒãïŒã®
ã¢ã«ãã«åºãäŸãã°ã¡ãã«ããšãã«ããããã«ã
ã€ãœãããã«ãããã«ãã€ãœããã«ãïœâãã
ã«ããã³ãã«åã¯ããã·ã«åºãæããŠããŠããã 眮æåR2ãšããŠãããã³ã«ã«ãã³é žèªå°äœã¯
âååïŒãïŒåãåã¯ç¹ã«ïŒãïŒåãå«æãã
ã¢ã·ã«åºãæå©ã«ã¢ã«ã«ãã€ã«åºåã¯ãã³ãŸã€ã«
åºãæããŠããŠããã奜é©ãªã¢ã«ã«ãã€ã«åºã¯äŸ
ãã°ãã«ãã«åºãã¢ã»ãã«åºãããããªãã«åºã
ãããªã«åºãåã¯ãªã¯ã¿ãã«åºã§ããã 氎溶æ§ãé«ããããã«ããæ°ŽçŽ ååãè¡šãã
äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœãççåŠç
ã«å®å šãªå¡©åºãçšããŠå¡©ã«å€ããããšãã§ããã
奜é©ãªå¡©ã¯äŸãã°ã¢ã«ã«ãªéå±å¡©ïŒæå©ã«ãªããŠ
ã å¡©ããããªãŠã å¡©åã¯ã«ãªãŠã å¡©ïŒãã¢ã«ã«ãª
åé¡éå±å¡©ïŒæå©ã«ãã°ãã·ãŠã å¡©åã¯ã«ã«ã·ãŠ
ã å¡©ïŒãé ïŒïŒâå¡©ãã¢ã³ã¢ããŠã å¡©åã¯ææ©
ã¢ãã³ïŒäŸãã°ããªãšã¿ããŒã«ã¢ãã³ãããã©ãž
ã³ãâã¡ãã«ã°ãªã«ãã³çïŒã®å¡©ã§ããã æ¢ã«äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœãæ
ã¢ã¬ã«ã®ãŒæ§ãæ¶çæ§åã³æèæ§äœçšã«åªããŠã
ãããšã¯èšèŒããã æã¢ã¬ã«ã®ãŒæ§äœçšã®æž¬å®ã§ã¯ãã©ããã®åå
ç®èã¢ããã€ã©ãã·âïŒPCAïŒã®ã¢ãã«ã§ã®ä»
åšç©è³ªéé¢ã®é»æ¢ã枬å®ããããšãã§ããããªã
ãªãŒïŒZ.OvaryïŒèïŒã€ã ãããžã«ã«ã»ã¡ãœããº
ïŒImmnological MethodsïŒãã¢ã¯ãã€ãïŒJ.F.
AckroydïŒç·šããã©ãã¯ãŠãšã«ã»ãµã€ãšã³ãã€
ãã€ãã¯åºçïŒBlackwell Scientific Publ.ïŒããª
ã¯ã¹ããªãŒãã1964幎ã269é ãããã®ããã«ã©ã
ããæšæºåIgEâå«æè¶ å ç«è¡æž ã®çš®ã ã®åžéç©
ïŒïŒïŒïŒåã³ïŒïŒ16ïŒã®ç®èå 泚å°ã«ããååæ
äœããã48æéåŸè©Šéšãã¹ãååç©ããããªãŠã
å¡©ãšããŠççåŠçé£å¡©æº¶æ¶²äžã«æº¶ãããŠããã€ã¢
ã©ãŒã²ã³ãšããŠãªãã«ããã³ãå±æçã¢ã¬ã«ã®ãŒ
åå¿ãè¯å¥œã«æž¬å®ããããã«è²çŽ ãšçµåãããŠé
èå æäžãè¡ãªãã è©Šéšååç©ã®ååšã§ã®ã¢ã¬ã«ã®ãŒåå¿ã®æå¶ã
æå¶å€ãçšããªãéã®ã¢ã¬ã«ã®ãŒåå¿ãšæ¯èŒããŠ
枬å®ãããåŸãããå€ãè¡šïŒã«èšèŒããã è¡šããåãããã«æ¬çºæã«ããååç©ãšã¯ãã¢
ã°ãªã·ã³é žãšã¯çããå€ãæããã
ããããïŒäœã«ååšãããããã³ã«ã«ãã³é žèªå°
äœãïœåã³ïœãããããïŒãè¡šãããããã³ã«ã«
ãã³é žèªå°äœãR2ã¯æ°ŽçŽ ååãè¡šãããããã³
ã«ã«ãã³é žèªå°äœããæ°ŽçŽ ååãã¢ã«ã«ãªéå±
ã«ããªã³ãã¢ã«ã«ãªåé¡éå±ã«ããªã³ãã¢ã³ã¢ã
ãŠã ã«ããªã³ãããã©ãžãã«ã«ããªã³åã¯ïŒ®âã¡
ãã«ã°ã«ã«ãã³ã«ããªã³ã§ãããããã³ã«ã«ãã³
é žèªå°äœã詳现ã«ã¯ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâããã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâã¡ãã«âïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâïŒ
âãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâïŒ
âãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒâã¢ã»ããã·âïŒïŒïŒâãã¹âïŒïŒâãšãã«
âïŒâã«ã«ããã·âïŒïŒïŒâãžãããâïŒâãªã
ãœâïŒâãããªã«ãªãã·ïŒâãããã³ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã å¡©ã¯
ã¯ãã¢ã°ãªã·ã³é žã®ãããªãŠã å¡©ãšåæ§ã®æ§è³ªã
æãããã該ååç©ã«å¯ŸããŠãã®ä»ã«ããããæ²»
çã«æå©ãªæ¶çåã³æèæ§äœçšãæããå©ç¹ãæ
ã€ã äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœã¯çœ®æå
R1ãšããŠïŒ£âååæ°ïŒãïŒã®ãæå©ã«ïŒãïŒã®
ã¢ã«ãã«åºãäŸãã°ã¡ãã«ããšãã«ããããã«ã
ã€ãœãããã«ãããã«ãã€ãœããã«ãïœâãã
ã«ããã³ãã«åã¯ããã·ã«åºãæããŠããŠããã 眮æåR2ãšããŠãããã³ã«ã«ãã³é žèªå°äœã¯
âååïŒãïŒåãåã¯ç¹ã«ïŒãïŒåãå«æãã
ã¢ã·ã«åºãæå©ã«ã¢ã«ã«ãã€ã«åºåã¯ãã³ãŸã€ã«
åºãæããŠããŠããã奜é©ãªã¢ã«ã«ãã€ã«åºã¯äŸ
ãã°ãã«ãã«åºãã¢ã»ãã«åºãããããªãã«åºã
ãããªã«åºãåã¯ãªã¯ã¿ãã«åºã§ããã 氎溶æ§ãé«ããããã«ããæ°ŽçŽ ååãè¡šãã
äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœãççåŠç
ã«å®å šãªå¡©åºãçšããŠå¡©ã«å€ããããšãã§ããã
奜é©ãªå¡©ã¯äŸãã°ã¢ã«ã«ãªéå±å¡©ïŒæå©ã«ãªããŠ
ã å¡©ããããªãŠã å¡©åã¯ã«ãªãŠã å¡©ïŒãã¢ã«ã«ãª
åé¡éå±å¡©ïŒæå©ã«ãã°ãã·ãŠã å¡©åã¯ã«ã«ã·ãŠ
ã å¡©ïŒãé ïŒïŒâå¡©ãã¢ã³ã¢ããŠã å¡©åã¯ææ©
ã¢ãã³ïŒäŸãã°ããªãšã¿ããŒã«ã¢ãã³ãããã©ãž
ã³ãâã¡ãã«ã°ãªã«ãã³çïŒã®å¡©ã§ããã æ¢ã«äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœãæ
ã¢ã¬ã«ã®ãŒæ§ãæ¶çæ§åã³æèæ§äœçšã«åªããŠã
ãããšã¯èšèŒããã æã¢ã¬ã«ã®ãŒæ§äœçšã®æž¬å®ã§ã¯ãã©ããã®åå
ç®èã¢ããã€ã©ãã·âïŒPCAïŒã®ã¢ãã«ã§ã®ä»
åšç©è³ªéé¢ã®é»æ¢ã枬å®ããããšãã§ããããªã
ãªãŒïŒZ.OvaryïŒèïŒã€ã ãããžã«ã«ã»ã¡ãœããº
ïŒImmnological MethodsïŒãã¢ã¯ãã€ãïŒJ.F.
AckroydïŒç·šããã©ãã¯ãŠãšã«ã»ãµã€ãšã³ãã€
ãã€ãã¯åºçïŒBlackwell Scientific Publ.ïŒããª
ã¯ã¹ããªãŒãã1964幎ã269é ãããã®ããã«ã©ã
ããæšæºåIgEâå«æè¶ å ç«è¡æž ã®çš®ã ã®åžéç©
ïŒïŒïŒïŒåã³ïŒïŒ16ïŒã®ç®èå 泚å°ã«ããååæ
äœããã48æéåŸè©Šéšãã¹ãååç©ããããªãŠã
å¡©ãšããŠççåŠçé£å¡©æº¶æ¶²äžã«æº¶ãããŠããã€ã¢
ã©ãŒã²ã³ãšããŠãªãã«ããã³ãå±æçã¢ã¬ã«ã®ãŒ
åå¿ãè¯å¥œã«æž¬å®ããããã«è²çŽ ãšçµåãããŠé
èå æäžãè¡ãªãã è©Šéšååç©ã®ååšã§ã®ã¢ã¬ã«ã®ãŒåå¿ã®æå¶ã
æå¶å€ãçšããªãéã®ã¢ã¬ã«ã®ãŒåå¿ãšæ¯èŒããŠ
枬å®ãããåŸãããå€ãè¡šïŒã«èšèŒããã è¡šããåãããã«æ¬çºæã«ããååç©ãšã¯ãã¢
ã°ãªã·ã³é žãšã¯çããå€ãæããã
ãè¡šã
æ¶çæ§äœçšã¯ã«ã©ã²ãšãã³è©Šéšã§æž¬å®ããããŠ
ã€ã³ã¿ãŒïŒC.A.WinterïŒããªãºãªãŒïŒE.A.
RisleyïŒåã³ãã¹ïŒG.W.NussïŒå ±èïŒâããã·â
ãã€ã³ã°ã»ãªãã»ã¶ã»ãœãµã€ãã€ã»ããªãŒã»ãšã¯
ã¹ããªã¡ã³ã¿ã«ã»ããªããžâã»ã¢ã³ãã»ã¡ãã€ã·
ã³ïŒProc.Soc.exp.Biol.Med.ïŒâã第111å·»ã544ã
547é ã1962幎ããçµæãè¡šïŒã«ãŸãšãããè¡šãã
æ¬çºæã«ããååç©ã¯æçœãªæ¶çäœçšãæããã
ããšã¯ç°ãªãã¯ãã¢ã°ãªã·ã³é žã¯ããããŠåŒ±ãäœ
çšã瀺ãã«ãããªãããåã¯å šã該äœçšã瀺ããª
ãããšãåãã
ã€ã³ã¿ãŒïŒC.A.WinterïŒããªãºãªãŒïŒE.A.
RisleyïŒåã³ãã¹ïŒG.W.NussïŒå ±èïŒâããã·â
ãã€ã³ã°ã»ãªãã»ã¶ã»ãœãµã€ãã€ã»ããªãŒã»ãšã¯
ã¹ããªã¡ã³ã¿ã«ã»ããªããžâã»ã¢ã³ãã»ã¡ãã€ã·
ã³ïŒProc.Soc.exp.Biol.Med.ïŒâã第111å·»ã544ã
547é ã1962幎ããçµæãè¡šïŒã«ãŸãšãããè¡šãã
æ¬çºæã«ããååç©ã¯æçœãªæ¶çäœçšãæããã
ããšã¯ç°ãªãã¯ãã¢ã°ãªã·ã³é žã¯ããããŠåŒ±ãäœ
çšã瀺ãã«ãããªãããåã¯å šã該äœçšã瀺ããª
ãããšãåãã
ãè¡šã
æèäœçšã¯è©Šéšç®¡å
ã«ãããéæžåžéè©Šéšã§æž¬
å®ãããçµæãè¡šïŒã«ãŸãšãããè¡šããæ¬çºæã
ãååç©ããžããã¯ã¹ã»ãããŠã¢ãã¢ãš
ïŒDiplococcus PneumoniaeïŒåã³äžé£ã®ã¹ã¿ã
ãã³ã¯ã¹ã»ã¢ãŠã¬ãŠã¹ïŒStaphylococcus
aureusïŒã®èæ ªã«å¯Ÿããæèäœçšãæãããã
ã¯ãã¢ã°ãªã·ã³é žãå šãŠã®æ€äœçŽ°èã«å¯ŸããŠäœçš
ãæããªãããšãæçœã§ããã
å®ãããçµæãè¡šïŒã«ãŸãšãããè¡šããæ¬çºæã
ãååç©ããžããã¯ã¹ã»ãããŠã¢ãã¢ãš
ïŒDiplococcus PneumoniaeïŒåã³äžé£ã®ã¹ã¿ã
ãã³ã¯ã¹ã»ã¢ãŠã¬ãŠã¹ïŒStaphylococcus
aureusïŒã®èæ ªã«å¯Ÿããæèäœçšãæãããã
ã¯ãã¢ã°ãªã·ã³é žãå šãŠã®æ€äœçŽ°èã«å¯ŸããŠäœçš
ãæããªãããšãæçœã§ããã
ãè¡šã
äžè¬åŒïŒ©ã®ãããã³ã«ã«ãã³é
žèªå°äœã¯ãã®è£œ
è¬åŠçæ§è³ªã«åºã¥ãã¬ã¬ãŒãã¹è£œè¬åŠã§åžžçšã®è³Š
圢å€ãšå©å€ãšçµåããŠæå©ã«åŒåžè·¯ã®ççåã³ã¢
ã¬ã«ã®ãŒæ§çŸæ£ãäŸãã°æ°ç®¡æ¯ããããåã¯éŒ»ç
ã®æ²»çã«å¥œé©ã§ããã å»è¬ã®è£œé ã¯åžžæ³ã§ãäœçšç©è³ªã奜é©ãªæ·»å
å€ã賊圢å€åã³ç¯å³å€ãšå ±ã«ææã®æäžåœ¢ãäŸã
ã°é å€ãç³è¡£é ãã«ãã»ã«ã溶液åã¯æå©ã«åžå ¥
å€ã«ããããšã«ããè¡ãªãã åžå ¥å€ã®è£œé ã«ã¯ããããã³ã«ã«ãã³é žèªå°äœ
ãèªäœå ¬ç¥ã®æ¹æ³ã§ç²æ«ã«ãããåã¯å¥œé©ãªæº¶å€
äžã«æº¶ãããåã¯æžæ¿ããããã€å Žåã«ãã奜é©
ãªæ·»å ç©ãäŸãã°åžéå€ãå¢ç²å€ãæžæ¿å©å€ãåŽ
å°ã¬ã¹ãç¯å³å€ãå ãããåžå ¥å€ã®ããã®äœçšç©
質ãšããŠã¯äžè¬ã«ãããã³ã«ã«ãã³é žèªå°äœïŒçš®
åã¯ãããã³ã«ã«ãã³é žèªå°äœïŒçš®ã®æ··åç©ã䜿
çšãããããããã³ã«ã«ãã³é žèªå°äœã®ä»ã«ä»å
çã«æŽã«ä»ã®äœçšç©è³ªãäŸãã°æçç©è³ªãäŸãã°
ã¯ãã©ã ããšãã³ãŒã«ãããã©ã·ã¯ãªã³ãããã·
ãªã³ãã»ãã¢ãã¹ããªã³ããªã³ã³ãã€ã·ã³ããšãª
ãããã€ã·ã³åã¯ãªãã¢ãã€ã·ã³ãåã¯æå©ã«ä»
ã®æ°ç®¡æ¯æ¡åŒµå€ãäŸãã°ãªã«ã·ãã¬ããªã³ãã€ãœ
ãšã¿ãªã³åã¯ç¹ã«ã€ãœãã¬ããªã³ïŒå¡©ãæå©ã«ç¡«
é žå¡©ãšããŠïŒãå«æããåžå ¥å€ã調補ããããšã
å¯èœã§ããã æŽã«äœçšç©è³ªãççåŠçã«èªå®¹æ§ã®æº¶å€ãäŸã
ã°æ°Žåã¯ã¢ã«ã³ãŒã«äžã«æº¶ãããåã¯æžæ¿ããã
次ãã§å Žåã«ããåžžçšã®æ·»å ç©ãå ããããšãå¯
èœã§ããã æå©ã«äœçšç©è³ª0.01ã10ïŒ ãå«æãããåŸãã
ã溶液åã¯æžæ¿æ¶²ãåžžçšã®åžå ¥åšãçšããŠé©çšã
ãããšãã§ããã ä»æ¹äœçšç©è³ªãå Žåã«ããåžžçšã®æ·»å ç©ãšäžç·
ã«ççåŠçã«èªå®¹æ§ã®åŽå°ã¬ã¹ãäŸãã°ããªã²ã³
ïŒFrigenïŒ äžã«æžæ¿ãããåã¯æº¶è§£ããããã€
åŸãããæžæ¿æ¶²åã¯æº¶æ¶²ãæå©ã«ã¯æçšåŒã®èšã
ãããŠããã¹ãã¬ãŒã¬ã³äžã«å å¡«ãããæå©ã«äœ
çšç©è³ª0.01ã10ïŒ ãå«æãããåŸãããåžå ¥å€ã
åžžæ³ã§é©çšããã åŽé§ä¹Ÿç¥ã«ã¯ç¹ã«äœçšç©è³ªã埮ç²ååã¯æ²æŸ±ã«
ããå¹³åç²åºŠ0.01ã10ÎŒã«ããã®ãæå©ã§ããã ä¿åæ§ãé«ããã€ãšãŒããŸã«åœ¢æã容æã«ãã
ããã«ãããã®ã³ã«ãã³ã€ãç²æ«ã«æå©ã«æŽã«ä»
å çã«åºäœã®ãè¬åŠçã«ã¯äœçšã®ãªãã氎溶æ§ç²
æ«ç¶è³Šåœ¢å€ïŒå¹³åç²åºŠ20ã400ÎŒïŒãæ·»å ããã
賊圢å€ãšããŠäŸãã°ããã¹ãã©ã³ããã³ãããã
ã°ã«ã³ãŒã¹åã¯ã©ã¯ããŒã¹ã奜é©ã§ãããããã
ã®ç²æ«ç¶åžå ¥å€ã«ã¯ãä»å çã«æŽã«æ·»å ç©ãäŸã
ã°ç¯å³å€ïŒäŸãã°ãµãã«ãªã³ïŒåã¯æ°ç®¡æ¯æ¡åŒµå€
ïŒäŸãã°ã€ãœãã¬ããªã³ã¹ã«ããšãŒãïŒãæ·»å ã
ãŠããããäžè¬ã«äœçšç©è³ª0.1ã30ïŒ ãå«æããã
ç²æ«ç¶åžå ¥å€ã®è£œé åã³äœ¿çšã¯äŸãã°è±åœç¹èš±ç¬¬
1144906å·æ现æžã«èšèŒãããŠããã æ¬çºæã«ããã°åžå ¥å€ã¯æ¢ã«è¿°ã¹ãããã«ãæ
å©ã«åŒåžåšã®ã¢ã¬ã«ã®ãŒæ§çŸæ£ãäŸãã°éŒ»çãæ¯
èç±åã¯æ°ç®¡æ¯ããããã®æ²»çã«äœ¿çšãããã åžå ¥ã®éã«é©çšãããåžå ¥å€ã®éã¯ç æ°ã®çšåºŠ
åã³æ²»çè ã®äœè³ªã«å¿ããŠå€åãããäžè¬ã«ïŒåºŠ
ã®åžå ¥ã«ã€ããããã³ã«ã«ãã³é žèªå°äœçŽ0.1ã
100mgãæå©ã«ïŒã50mgãå Žåã«ããæ°ç®¡æ¯æ¡åŒµ
å€0.01ã10mgãšçµåããŠæäžããã äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœã¯ã (a) äžè¬åŒïŒ ãåŒäžïœïŒïœåã³R2ã¯åèšã®ãã®ãè¡šããã
ã®ãžã¢ãã³ãšäžè¬åŒïŒ ãåŒäžR3åã³R4ã¯ããããâååæ°ïŒã
ïŒã®ã¢ã«ãã«åºãè¡šãããã®ããã³é žèªå°äœã
çž®åããåŸãããäžè¬åŒïŒ ãåŒäžïœïŒïœïŒR2åã³R3ã¯åèšã®ãã®ãè¡š
ãããã®ååç©ãå ç±ãããã€ææã«ããåŸã
ãããããã³ã«ã«ãã³é žèªå°äœã鹞åãããšã¹
ãã«åããâã¢ã«ãã«åããåã¯ççåŠçã«
å®å šãªå¡©åºãçšããŠå¡©ã«å€ãããå㯠(b) äžè¬åŒïŒ ãåŒäžïŒžåã³R1ã¯åèšã®ãã®ãè¡šãããHO
åºã¯ãããã³æ žã®ïŒäœãïŒäœåã¯ïŒäœã«äœçœ®ã
ããã®ããããã·ãããã³ã«ã«ãã³é žèªå°äœã
äžè¬åŒïŒ ãåŒäžïœïŒïœåã³R2ã¯åèšã®ãã®ãè¡šããã
ã¯å¡©çŽ ååãèçŽ ååãæ²çŽ ååãã¡ã·ã©ã
åºåã¯ãã·ã©ãåºãè¡šããããåã¯äžè¬åŒïŒ ãåŒäžïœåã³ïŒ¹ã¯åèšã®ãã®ãè¡šãããã®å
åç©ãšçž®åãããã€ææã«ããåŸãããããã
ã³ã«ã«ãã³é žèªå°äœã鹞åãããšã¹ãã«åãã
âã¢ã«ãã«åããåã¯ççåŠçã«å®å šãªå¡©åº
ãçšããŠå¡©ã«å€ããããšã«ãã補é ãããã æ¹æ³(a)ã«ããæ¹æ³ã¯èªäœå ¬ç¥ã®æ¹æ³ã§å®æœãã
ããŠãã«ãŒïŒJuckerïŒïŒEdïŒèãâãã«ãã·ãŠãªã
ãã»ã¢ã«ããã€ãããã«ãã«ã·ãŠã³ã°
ïŒFortschritte ArzneimittelforschungïŒâã第21
å·»ã1fé ã1977幎ããããªãã¡äŸãã°äžè¬åŒã®
ãžã¢ãã³ãåŒã®ããã³é žèªå°äœãšåå¿ãããã
ã€äžè¬åŒã®ååç©ãåŸãããã®åå¿ã«ã¯è§Šåªå
ã¯æº¶å€ã®ååšã¯å¿ èŠããªããããã¡ãã該åå¿ã
ä»å çãªæº¶å€ãäŸãã°ã¯ãã«çåæ°ŽçŽ ïŒå¡©åã¡ã
ã¬ã³ããžããã«ãšãŒãã«ããžãªããµã³ãããã©ã
ãããã©ã³çïŒããšãŒãã«ïŒãžã€ãœãããã«ãšãŒ
ãã«ããžããã«ãšãŒãã«ããžãªããµã³ãããã©ã
ãããã©ã³çïŒåã¯å極æ§äžæ§æº¶å€ïŒãžã¡ãã«ã
ã«ã ã¢ããããããµããã«çé žããªã¢ããçïŒã®
ååšã§å®æœããããšãå¯èœã§ããããã®åå¿å·¥çš
ã¯æå©ã«åå¿æž©åºŠ20âã150âã§å®æœããã åèšã®å·¥çšã«ç¶ãäžè¬åŒã®ååç©ã®å ç±ã¯æ
å©ã«é«æ²žç¹æº¶å€ïŒäŸãã°é±æ²¹ããžããšãã«ããžã
ãšãã«ãšãŒãã«åã¯ããŠãã«ã ïŒDawthermïŒ
ïŒã®ååšã§200âã350âã§è¡ãªãã該åå¿ã§ã¯
åå¿æž©åºŠã¯ãåå¿æ··åç©ã«è§ŠåªãšããŠä»å çã«ã«
ã€ã¹é žïŒé ¢é žãç¡«é žãããªçé žãããªåŒåç¡ŒçŽ ã
ãªãã·å¡©åçãäžå¡©åçãäºå¡©åçãå¡©åã¢ã«ã
ããŠã ãå¡©åäºéçïŒãæ·»å ãããšãçŽ50âã
200âã«äœäžããã æ¹æ³(b)ã«ããæ¬çºæã®æ¹æ³ã§ã¯äžè¬åŒã®ãã
ããã·ãããã³ã«ã«ãã³é žèªå°äœãäžæŽ»æ§æº¶å€äž
ã§ãã€å¡©åºæ§è§Šåªã®ååšã§äžè¬åŒåã¯ã®åå
ç©ãšçž®åãããããã®åå¿ã¯æå©ã«çœ®æåR1ã
ã¢ã«ãã«åºãè¡šããäžè¬åŒã®ããããã·ããã
ã³ã«ã«ãã³é žèªå°äœãçšããŠå®æœãããã該åå¿
ã«ã€ããŠå¡©åºæ§è§ŠåªãšããŠäŸãã°ã¢ã«ã«ãªéå±æ°Ž
çŽ çé žå¡©ïŒçé žæ°ŽçŽ ãããªãŠã ãçé žæ°ŽçŽ ã«ãªãŠ
ã ïŒãã¢ã«ã«ãªçé žå¡©ïŒçé žãããªãŠã ãçé žã«
ãªãŠã ïŒãã¢ã«ã«ãªéå±æ°Žé žåç©ïŒæ°Žé žåãããª
ãŠã ãæ°Žé žåã«ãªãŠã ïŒåã¯ã¢ã«ã«ãªéå±ã¢ã«ã³
ã¬ãŒãïŒãããªãŠã ã¡ãã©ãŒãããããªãŠã ãšã
ã©ãŒããã«ãªãŠã ã¡ãã©ãŒããã«ãªãŠã ïœâãã
ã©ãŒãçïŒã䜿çšããŠããã奜é©ãªæº¶å€ã¯äŸãã°
äœçŽã¢ã«ã³ãŒã«ïŒç¹ã«ïŒ£âååæ°ïŒãïŒã®ãã®ã
äŸãã°ã¡ã¿ããŒã«ããšã¿ããŒã«ããããããŒã«ã
ã€ãœãããããŒã«åã¯ïœâãã¿ããŒã«ïŒã極æ§ãš
ãŒãã«ïŒãžãªããµã³ãããã©ããããã©ã³ãã°ãª
ã³ãŒã«ãžã¡ãã«ãšãŒãã«ãã°ãªã³ãŒã«ã¢ãã¡ãã«
ãšãŒãã«çïŒåã¯å極æ§äžæ§æº¶å€ïŒäŸãã°ãžã¡ã
ã«ãã«ã ã¢ãããâã¡ãã«ã¢ã»ãã¢ããããžã¡
ãã«ã¹ã«ããã·ãåã¯ãããµã¡ãã«çé žããªã¢ã
ãïŒã§ããã ææã«ããåŒç¶ãå®æœããããšã¹ãã«ã®é¹žåã¯
èªäœå ¬ç¥ã®æäœæ¹æ³ã§å®æœããããäŸãã°æ°Žåã¯
æ°Žæ§ã¢ã«ã³ãŒã«äžã§é žæ§è§ŠåªãäŸãã°å¡©é žãç¡«
é žãïœâãã«ãšã³ã¹ã«ãã³é žåã¯å¡©åºæ§è§ŠåªãäŸ
ãã°çé žæ°ŽçŽ ã«ãªãŠã ãçé žã«ãªãŠã ãæ°Žé žåã
ããªãŠã åã¯æ°Žé žåã«ãªãŠã ã®ååšã§ã®ãšã¹ãã«
ã®é¹žåãæããããã ææã«ããåŒç¶ãå®æœããããå Žåã«ããååš
ããäºçŽã¢ããåºã®ã¢ã«ãã«åã¯åæ§ã«ãããªã³
èªå°äœã®ïŒ®âã¢ã«ãã«åã§äžè¬ã«äœ¿çšãããå ¬ç¥
æ¹æ³ã«ããè¡ãªãã äŸãã°ååç©ã®çªçŽ ååãéå±æ°ŽçŽ åç©åã¯é
å±ã¢ãããäŸãã°æ°ŽçŽ åãããªãŠã åã¯ãããªãŠ
ã ã¢ãããšã®åå¿ã«ããéå±ã«ãããã€ããããŠ
åŸãããåå¿æ§ååç©ã«ãæçµçã«ææã®çåæ°Ž
çŽ åºã®ç¡«é žå¡©åã¯ããã²ã³åç©ïŒå¡©åç©ãèåç©
åã¯æ²åç©ïŒãäœçšãããã該åå¿ã§ã¯åå¿æž©åºŠ
çŽïŒâã120âã§å®æœãããæå©ã«æ¥µæ§äžæ§æº¶å€ã
äŸãã°ãžã¡ãã«ãã«ã ã¢ãããâã¡ãã«ãããª
ãã³åã¯ãããµã¡ãã«çé žããªã¢ããã䜿çšã
ãã ææã«ããå®æœãããæ¹æ³ãšããŠåŒç¶ãè¡ãªã
ããéé¢ã®ããããã·ã¡ãã«åºã®ãšã¹ãã«åã¯å
æ§ã«ããã«å ¬ç¥ã®æ¹æ³ã«ããå®æœããããå¯èœãª
ãšã¹ãã«åæ³ãšããŠäŸãã°ããããã·ååç©ãç¡
æ°Žé žåã¯é žå¡©åç©ã§è³éŠæâè€çŽ ç°åŒååç©ã
äŸãã°ããªãžã³ãã³ãªãžã³åã¯ã«ããžã³ã®ååš
ã§ãåã¯å¡©åºæ§ã¢ã«ã«ãªéå±çé žå¡©ãéçé žãã
ãªãŠã ãéçé žã«ãªãŠã ãçé žãããªãŠã ãæ°Žé ž
åãããªãŠã åã¯æ°Žé žåã«ãªãŠã ã®ååšã§ãšã¹ã
ã«åããããšãæããããã ææã®æ¹æ³ãšããŠåŒç¶ãè¡ãªããããããã³ã«
ã«ãã³é žèªå°äœã®å¡©ãžã®å€æã¯åæ§ã«åœæ¥è ã«å ¬
ç¥ã®æ¡ä»¶äžã§ãååç©ãççåŠçã«å®å šãªå¡©åºã§
äžåããããšã«ããè¡ãªãããã æ¬çºæã«ããæ¹æ³ã®ããã®åºçºç©è³ªã¯å ¬ç¥ã§ãª
ããåã¯èªäœå ¬ç¥ã®æ¹æ³ã§è£œé ã§ããã次ã«è©²åº
çºç©è³ªã®è£œé æ¹æ³ãæ°çš®ã®ä»£è¡šçãªååç©ã«ã€ã
ãŠèšèŒããã  ïŒâããã«âïŒïŒïŒâãžãããâïŒâã¡ãã
ã·âïŒâãããã³âïŒâã«ã«ãã³é ž ïŒâããããã·âïŒâã¡ããã·âãããªã³âïŒ
âã«ã«ãã³é ž11.0ïœïŒ50ããªã¢ã«ïŒããžã¡ãã«ã¹
ã«ããã·ã200mläžã®ç²æ«åæ°Žé žåãããªãŠã
14.0ïœïŒ351ããªã¢ã«ïŒã®æžæ¿æ¶²äžã«å ¥ããã宀
æž©ã§10åæ¹æãã次ãã§èåããã«16.1mlïŒ150
ããªã¢ã«ïŒã滎äžãããã®çµæ枩床ã¯25âãè¶ã
ãªããåŒç¶ã宀枩ã§ïŒæéæ¹æããæ°Žäžã«æ³šãã
ãã€å¡©é žã§é žæ§ã«ãããæ²æŸ±ããçæç©ãæ¿Ÿå
ããæ°Žã§æŽãã也ç¥ããã€ãžã¡ãã«ãã«ã ã¢ãã
ããåçµæ¶ãããã èç¹ïŒ160ã162âãåéïŒ9.18ïœã  ïŒâããã«âïŒïŒïŒâãžãããâïŒâããã
ãã·âïŒâãããã³âïŒâã«ã«ãã³é ž ïŒâããã«âïŒïŒïŒâãžãããâïŒâã¡ããã·
âïŒâãããã³âïŒâã«ã«ãã³é ž5.0ïœïŒ18ããª
ã¢ã«ïŒãèåæ°ŽçŽ é žïŒ48ïŒ ïŒ65mläžã§éæµäžã«ïŒ
æéç ®æ²žãããåŒç¶ãæ°Žäžã«æ³šããåºäœçæç©ã
æ¿Ÿåãããã€ãžã¡ãã«ãã«ã ã¢ããããåçµæ¶ã
ããã èç¹ïŒ228ã240âãåéïŒ3.5ïœ ïŒ£ ïŒïŒïŒâãžãããâïŒâããããã·âïŒâã¡
ãã«âïŒâãããã³âïŒâã«ã«ãã³é ž ïŒïŒïŒâãžãããâïŒâã¡ããã·âïŒâã¡ãã«
âïŒâãããã³âïŒâã«ã«ãã³é ž5.83ïœïŒ25ããª
ã¢ã«ïŒãèåæ°ŽçŽ é ž65mlãšãšãã«éæµäžã«ïŒæé
ç ®æ²žãããæ°Žäžã«æ³šããåºäœçæç©ãæ¿Ÿåããã
ã€é ¢é žããåçµæ¶ãããã èç¹ïŒ285ã293âãåéïŒ5.6ïœ ïŒ€ ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªã
ã·ïŒâïŒâãããããŒã« ïŒâãããããšããŒã«44.3ïœïŒ0.32ã¢ã«ïŒãã€
ãœãããããŒã«1.2äžã«æº¶ããããšãã¯ãã«ã
ããªã³13.7mlãæ·»å ããåŒç¶ãã€ãœãããããŒã«
250mläžã®æ°Žé žåã«ãªãŠã 17.5ïœã®æº¶æ¶²äžŠã³ã«æ°Ž
10mlãæ·»å ãããæ··åç©ãéæµäžã«48æéç ®æ²ž
ãã1/2ã®å®¹éã«æ¿åºŠããæ°Ž250mlãå ãããæ²æŸ±
ããçæç©ãæ¿Ÿåããæ°Žã§æŽãããã€ä¹Ÿç¥ããã èç¹ïŒ110âãåéïŒ24ïœ ïŒ¥ ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªã
ã·ïŒâïŒâãããããŒã« ïŒâãããããšããŒã«8.86ïœïŒ63.7ããªã¢ã«ïŒ
ãã€ãœãããããŒã«250mläžã«æº¶ããããšãã¯ã
ã«ãããªã³2.75mlïŒ35.1ããªã¢ã«ïŒãæ·»å ããåŒ
ç¶ãã€ãœãããããŒã«25mläžã®æ°Žé žåã«ãªãŠã
1.98ïœïŒ35.3ããªã¢ã«ïŒã®æº¶æ¶²äžŠã³ã«æ°ŽïŒmlãæ·»
å ãããæ··åç©ãéæµäžã«48æéç ®æ²žãã1/2ã®
容éã«æ¿çž®ããæ°Ž250mlãå ãããæ²æŸ±ããçæ
ç©ãæ¿Ÿåããã€ãœãããããŒã«ïŒãšã¿ããŒã«
ïŒïŒïŒïŒïŒããåçµæ¶ãããã èç¹ïŒ144ã145âãåéïŒ6.4ïœã 次ã«å®æœäŸã«ã€ãæ¬çºæã詳説ããã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ïœ ãããªãŠã 0.46ïœïŒ20ããªã¢ã«ïŒããšã¿ããŒ
ã«20mläžã«å ¥ãããåå¿çµçµåŸåŸããããããª
ãŠã ãšãã©ãŒã溶液ã«ïŒâãšãã«âïŒïŒïŒâãž
ãããâïŒâããããã·âïŒâãããã³âïŒâ
ã«ã«ãã³é ž2.33ïœïŒ10ããªã¢ã«ïŒã溶ãããåŒ
ç¶ããšãã¯ãã«ãããªã³0.91mlïŒ11.7ããªã¢
ã«ïŒåã³æ²åã«ãªãŠã çè·¡éãæ·»å ãããæ··å
ç©ãïŒæééæµäžã«ç ®æ²žããèžçºæ¿çž®ããã€æ®
枣ãæ°Žäžã«æº¶ããã溶液ãã¯ãããã«ã ãšé ¢é ž
ãšã¹ãã«ãšå ±ã«æ¯çªãããã€å¡©é žã§PHïŒãŸã§ã®
é žæ§ã«ãããæ²æŸ±ããçæç©ãæ¿Ÿåããæ°Žã§æŽ
æµãã也ç¥ãããã€ç±ããžã¡ãã«ãã«ã ã¢ãã
äžã«æº¶ãããçµæ¶åã®ããã«ã€ãœãããã«ãšãŒ
ãã«ãå ãããåŸãããç©è³ªã100âã§ç空äž
ã§ä¹Ÿç¥ããã èç¹ïŒ305ã310âãåéïŒ1.26ïœã ïœ ç²æ«åããæ°Žé žåã«ãªãŠã 0.17ïœïŒ3.0ããª
ã¢ã«ïŒããžã¡ãã«ã¹ã«ããã·ãïŒmläžã«æžæ¿ã
ãããã€ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·â
ïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«0.10ïœïŒ0.22ããª
ã¢ã«ïŒãè£ å ¥ããã宀枩ã§10åæ¹æãã次ãã§
ãžãšãã«ã¹ã«ããšãŒã0.17mlã滎äžããã宀枩
ã§ïŒæéæ¹æãã次ãã§æ°Žäžã«å ¥ãããã€é žæ§
ã«ãããåŸãããåºäœçæç©ãæ¿Ÿåããæ°Žã§æŽ
ããé ¢é žãšå ±ã«ç ®æ²žãããã€ãžã¡ãã«ãã«ã ã¢
ããïŒã€ãœãããã«ãšãŒãã«ããåçµæ¶ãã
ãã èç¹ïŒ305ã310âãåéïŒ0.05ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâããã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ãããªãŠã 0.0096ïœïŒ4.2ããªã¢ã«ïŒããšã¿ã
ãŒã«ïŒmläžã«å ¥ããåŒç¶ãïŒâããã«âïŒïŒïŒâ
ãžãããâïŒâããããã·âïŒâãããã³âïŒâ
ã«ã«ãã³é ž0.56ïœïŒ2.1ããªã¢ã«ïŒããšãã¯ãã«ã
ããªã³0.19mlåã³æ²åã«ãªãŠã çè·¡éãå ããã
ïŒæééæµäžã«ç ®æ²žããåŒç¶ãåå¿æ··åç©ã2N
âNaOHã§å®å šã«æº¶æ¶²ã«ãã次ãã§å¡©é žã§é žæ§
ã«ãããæ²æŸ±ããçæç©ãæ¿Ÿåããæ°Žã§æŽããã
ã€ä¹Ÿç¥ããã èç¹ïŒ255ã260âãåéïŒ0.45ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâã¡ãã«âïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ãããªãŠã 0.46ïœïŒ20ããªã¢ã«ïŒãã¡ã¿ããŒã«
20mläžã«å ¥ããåŒç¶ãïŒïŒïŒâãžããããŒïŒâã
ãããã·âïŒâã¡ãã«âïŒâãããã³âïŒâã«ã«
ãã³é ž2.00ïœïŒ9.1ããªã¢ã«ïŒããšãã¯ãã«ãããª
ã³1.21mlïŒ15.5ããªã¢ã«ïŒåã³æ²åã«ãªãŠã çè·¡
éãå ¥ãããïŒæééæµäžã«ç ®æ²žããèžçºæ¿çž®
ãããã€æ®æž£ãæ°Žäžã«æº¶ããã溶液ãã¯ãããã«
ã ãšå ±ã«æ¯çªãããã€å¡©é žã§é žæ§ã«ãããæ²æŸ±ã
ãçæç©ãæ¿Ÿåããæ°Žã§æŽãããã€ä¹Ÿç¥ããã èç¹ïŒ310âïŒå解ïŒãåéïŒ0.82ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâ
ïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªãã·ïŒ
âïŒâãããããŒã«10ïœïŒ30ããªã¢ã«ïŒãã¡ã¿ã
ãŒã«250mläžã«æº¶ããããã€PdâæšçïŒ10ïŒ ïŒïŒ
ïœã®ååšã§æ°ŽçŽ åããã觊åªãæ¿Ÿå¥ãããã€æº¶æ¶²
ãèžçºãããšãç²è£œïŒïŒïŒâãã¹ïŒïŒâã¢ããã
ãšãã«ãªãã·ïŒâïŒâãããããŒã«8.2ïœãæ®ãã
ããããšããã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ã
ã«100mlãšå ±ã«ïŒæé300âã«å ç±ããåŒç¶ãæ°Žæµ
ãã³ãã«ããç空äžã§100âã§ïŒæéå ç±ããã
éå°ã®ãšããã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ã
ã«ãç空äžã§æºå»ããæ®æž£ãããŠãã«ã
ïŒDowthermïŒïŒ¡ 100mläžã§éæµäžã«30åç ®æ²žã
ããå·åŽåŸã€ãœãããã«ãšãŒãã«ãå ãããæåº
ããç²è£œã®ïŒïŒïŒâãã¹âïŒïŒâãšããã·ã«ã«ã
ãã«âïŒïŒïŒâãžãããâïŒâãªããœâãããªã«
ãªãã·ïŒâïŒâãããããŒã«ãåé¢ãã2Nâ
NaOH150mläžã«æžæ¿ããããã€ïŒæééæµäžã«
ç ®æ²žãããå·åŽåŸæº¶æ¶²ãé ¢é žãšã¹ãã«ãšå ±ã«æ¯çª
ããå¡©é žã§é žæ§ã«ãããã€å°éã®ã¡ã¿ããŒã«ãå
ãããåŸãããçµæ¶è³ªç©è³ªãæ¿Ÿåããæ°Žã§æŽãã
ãã€ä¹Ÿç¥ããã èç¹ïŒïŒ300âãåéïŒ3.2ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâãããªã«ãªãã·ïŒâïŒâ
ãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªãã·ïŒ
âïŒâãããããŒã«10ïœïŒ30ããªã¢ã«ïŒãã¡ã¿ã
ãŒã«äžã§PdïŒæšçïŒ10ïŒ ïŒ1.6ïœã®ååšã§æ°ŽçŽ å
ããã觊åªãæ¿Ÿå¥ãããã€æ¿Ÿæ¶²ãèžçºãããç²è£œ
ã®æ²¹ç¶ïŒïŒïŒâãã¹âïŒïŒâã¢ããããšãã«ãªã
ã·ïŒâïŒâãããããŒã«13ïœãæ®çããããããš
ããã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ãã«100ml
ãšå ±ã«ïŒæé100âã«ãåŒç¶ãæ°Žæµãã³ãã«ãã
ç空äžã§100âã«ïŒæéå ç±ãããéå°ã®ãšãã
ã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ãã«ãç空äžã§
æºå»ããæ®æž£ãããŠãã«ã  150mläžã§30åé
æµäžã«ç ®æ²žãããå·åŽåŸæº¶æ¶²ã«ã€ãœãããã«ãšãŒ
ãã«ãå ãããã€æåºããåºäœçæç©ãæ¿Ÿåã
ããç²è£œïŒïŒïŒâãã¹âïŒïŒâã«ã«ããšããã·â
ïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«ãª
ãã·ïŒâïŒâãããããŒã«ïŒïœãåŸãããããã
2NâNaOH100mläžã§ïŒæééæµäžã«ç ®æ²žããã
æ²æŸ±ããæ²¹ç¶çæç©ãåé¢ãããã€åºäœã«ãªããŸ
ã§ãšãŒãã«ãšå ±ã«æ¹æãããåºäœçæç©ãæ¿Ÿå
ãããžã¡ãã«ãã«ã ã¢ããããåçµæ¶ããããã€
100âã§ç空äžã§ä¹Ÿç¥ããã èç¹ïŒïŒ300âãåé1.4ïœ äŸ ïŒ ïŒïŒïŒâãã¹ïŒïŒâãšãã«âïŒâã«ã«ããã·â
ïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒâãšãã«âïŒïŒïŒâãžãããâïŒâãããã
ã·âïŒâãããã³âïŒâã«ã«ãã³é ž1.5ïœïŒ6.4ã
ãªã¢ã«ïŒããšã¿ããŒã«15mläžã®ãããªãŠã 0.29ïœ
ïŒ12.6ããªã¢ã«ïŒã®æº¶æ¶²äžã«å ¥ããåŒç¶ããšãã¯
ãã«ãããªã³0.58mlïŒ7.5ããªã¢ã«ïŒåã³æ²åã«
ãªãŠã 20mgãæ·»å ãããæ··åç©ãïŒæééæµäžã«
ç ®æ²žããæŸæãªæº¶æ¶²ã«ãªããŸã§2NâNaOHãå
ãã次ãã§2NâHClã§é žæ§ã«ãããæ²æŸ±ããç
æç©ãæ¿Ÿåããé ¢é žããåçµæ¶ããããã€120â
ã§ç空äžã§ä¹Ÿç¥ããã èç¹ïŒïŒ300âãåéïŒ1.3ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ïŒâãšãã«âïŒïŒïŒâãžãããâïŒâãããã
ã·âïŒâãããã³âïŒâã«ã«ãã³é ž0.466ïœïŒïŒ
ããªã¢ã«ïŒãã€ãœãããããŒã«10mläžã«æžæ¿ã
ãããšãã¯ãã«ãããªã³0.086mlïŒ1.1ããªã¢ã«ïŒã
åŒç¶ãã€ãœãããããŒã«ïŒmlåã³æ°ŽïŒæ»Žäžã®æ°Žé ž
åã«ãªãŠã 0.224ïœïŒ4.0ããªã¢ã«ïŒã®æº¶æ¶²ãæ·»å
ãããæ··åç©ã48æééæµäžã«ç ®æ²žãã2Nâ
NaOHãæŸæãªæº¶æ¶²ã«ãªããŸã§å ãã次ãã§2N
âHClã§äžåãããæ²æŸ±ããç©è³ªãæ¿Ÿåããæ°Žã§
æŽãããã€ç空äžã§ä¹Ÿç¥ããã èç¹ïŒ250âïŒå解ïŒãåéïŒ0.2ïœã äŸ ïŒ ïŒâã¢ã»ããã·âïŒïŒïŒâãã¹âïŒïŒâãšãã«
âïŒâã«ã«ããã·âïŒïŒïŒâãžãããâïŒâãª
ããœâïŒâãããªã«ãªãã·ïŒâãããã³ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«1.0ïœïŒ4.3ããªã¢
ã«ïŒãç¡æ°Žé ¢é ž7.5mlãšé ¢é ž7.5mlã®æ··åç©äžã§ïŒ
æé100âã«å ç±ãããåŒç¶ãæ°Žäžã«æ³šããæ²æŸ±
ããåºäœçæç©ãæ¿Ÿåããæ°Žã§æŽãããã€ç空äž
ã§100âã§ä¹Ÿç¥ããã èç¹ïŒ144ã147âãåéïŒ1.0ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒïŒâãããããŒã«ã®äºãããªãŠã å¡© ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«0.52ïœïŒ1.0ããªã¢
ã«ïŒã1NâNaOHâ溶液ïŒmlãšã¡ã¿ãâã«20ml
ã®æ··åç©äžã§å®€æž©ã§æº¶è§£ãããåŒç¶ãç空äžã§èž
çºãããã€æ®æž£ã掻æ§çã§è±è²äžã«æ°Žããåçµæ¶
ãããã èç¹ïŒ315âïŒå解ïŒãåéïŒ0.39ïœã äŸ 10 ãšãŒããŸã«ã®çµæ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã
å¡© 2.00ïŒ ã€ãœãã¬ããªã³ã¹ã«ããšãŒã 0.10ïŒ åŽå°è¬ãããã©ã³ãïŒPropellantïŒ12åã³ãã
ãã©ã³ã14ã®æ··åç©ïŒ60ïŒ40ïŒ å šé100.00ïŒ äŸ 11 ç²æ«èª¿å€ã®çµæ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã
å¡©ã埮现åïŒã8ÎŒ 20mg ã€ãœãã¬ããªã³ã¹ã«ããšãŒãã埮现åïŒã8ÎŒ
0.1mg ã©ã¯ããŒã¹ãç²æ«å80ã120ÎŒ 15mg 衚瀺ã¯æçšåäœã«é¢ããã
è¬åŠçæ§è³ªã«åºã¥ãã¬ã¬ãŒãã¹è£œè¬åŠã§åžžçšã®è³Š
圢å€ãšå©å€ãšçµåããŠæå©ã«åŒåžè·¯ã®ççåã³ã¢
ã¬ã«ã®ãŒæ§çŸæ£ãäŸãã°æ°ç®¡æ¯ããããåã¯éŒ»ç
ã®æ²»çã«å¥œé©ã§ããã å»è¬ã®è£œé ã¯åžžæ³ã§ãäœçšç©è³ªã奜é©ãªæ·»å
å€ã賊圢å€åã³ç¯å³å€ãšå ±ã«ææã®æäžåœ¢ãäŸã
ã°é å€ãç³è¡£é ãã«ãã»ã«ã溶液åã¯æå©ã«åžå ¥
å€ã«ããããšã«ããè¡ãªãã åžå ¥å€ã®è£œé ã«ã¯ããããã³ã«ã«ãã³é žèªå°äœ
ãèªäœå ¬ç¥ã®æ¹æ³ã§ç²æ«ã«ãããåã¯å¥œé©ãªæº¶å€
äžã«æº¶ãããåã¯æžæ¿ããããã€å Žåã«ãã奜é©
ãªæ·»å ç©ãäŸãã°åžéå€ãå¢ç²å€ãæžæ¿å©å€ãåŽ
å°ã¬ã¹ãç¯å³å€ãå ãããåžå ¥å€ã®ããã®äœçšç©
質ãšããŠã¯äžè¬ã«ãããã³ã«ã«ãã³é žèªå°äœïŒçš®
åã¯ãããã³ã«ã«ãã³é žèªå°äœïŒçš®ã®æ··åç©ã䜿
çšãããããããã³ã«ã«ãã³é žèªå°äœã®ä»ã«ä»å
çã«æŽã«ä»ã®äœçšç©è³ªãäŸãã°æçç©è³ªãäŸãã°
ã¯ãã©ã ããšãã³ãŒã«ãããã©ã·ã¯ãªã³ãããã·
ãªã³ãã»ãã¢ãã¹ããªã³ããªã³ã³ãã€ã·ã³ããšãª
ãããã€ã·ã³åã¯ãªãã¢ãã€ã·ã³ãåã¯æå©ã«ä»
ã®æ°ç®¡æ¯æ¡åŒµå€ãäŸãã°ãªã«ã·ãã¬ããªã³ãã€ãœ
ãšã¿ãªã³åã¯ç¹ã«ã€ãœãã¬ããªã³ïŒå¡©ãæå©ã«ç¡«
é žå¡©ãšããŠïŒãå«æããåžå ¥å€ã調補ããããšã
å¯èœã§ããã æŽã«äœçšç©è³ªãççåŠçã«èªå®¹æ§ã®æº¶å€ãäŸã
ã°æ°Žåã¯ã¢ã«ã³ãŒã«äžã«æº¶ãããåã¯æžæ¿ããã
次ãã§å Žåã«ããåžžçšã®æ·»å ç©ãå ããããšãå¯
èœã§ããã æå©ã«äœçšç©è³ª0.01ã10ïŒ ãå«æãããåŸãã
ã溶液åã¯æžæ¿æ¶²ãåžžçšã®åžå ¥åšãçšããŠé©çšã
ãããšãã§ããã ä»æ¹äœçšç©è³ªãå Žåã«ããåžžçšã®æ·»å ç©ãšäžç·
ã«ççåŠçã«èªå®¹æ§ã®åŽå°ã¬ã¹ãäŸãã°ããªã²ã³
ïŒFrigenïŒ äžã«æžæ¿ãããåã¯æº¶è§£ããããã€
åŸãããæžæ¿æ¶²åã¯æº¶æ¶²ãæå©ã«ã¯æçšåŒã®èšã
ãããŠããã¹ãã¬ãŒã¬ã³äžã«å å¡«ãããæå©ã«äœ
çšç©è³ª0.01ã10ïŒ ãå«æãããåŸãããåžå ¥å€ã
åžžæ³ã§é©çšããã åŽé§ä¹Ÿç¥ã«ã¯ç¹ã«äœçšç©è³ªã埮ç²ååã¯æ²æŸ±ã«
ããå¹³åç²åºŠ0.01ã10ÎŒã«ããã®ãæå©ã§ããã ä¿åæ§ãé«ããã€ãšãŒããŸã«åœ¢æã容æã«ãã
ããã«ãããã®ã³ã«ãã³ã€ãç²æ«ã«æå©ã«æŽã«ä»
å çã«åºäœã®ãè¬åŠçã«ã¯äœçšã®ãªãã氎溶æ§ç²
æ«ç¶è³Šåœ¢å€ïŒå¹³åç²åºŠ20ã400ÎŒïŒãæ·»å ããã
賊圢å€ãšããŠäŸãã°ããã¹ãã©ã³ããã³ãããã
ã°ã«ã³ãŒã¹åã¯ã©ã¯ããŒã¹ã奜é©ã§ãããããã
ã®ç²æ«ç¶åžå ¥å€ã«ã¯ãä»å çã«æŽã«æ·»å ç©ãäŸã
ã°ç¯å³å€ïŒäŸãã°ãµãã«ãªã³ïŒåã¯æ°ç®¡æ¯æ¡åŒµå€
ïŒäŸãã°ã€ãœãã¬ããªã³ã¹ã«ããšãŒãïŒãæ·»å ã
ãŠããããäžè¬ã«äœçšç©è³ª0.1ã30ïŒ ãå«æããã
ç²æ«ç¶åžå ¥å€ã®è£œé åã³äœ¿çšã¯äŸãã°è±åœç¹èš±ç¬¬
1144906å·æ现æžã«èšèŒãããŠããã æ¬çºæã«ããã°åžå ¥å€ã¯æ¢ã«è¿°ã¹ãããã«ãæ
å©ã«åŒåžåšã®ã¢ã¬ã«ã®ãŒæ§çŸæ£ãäŸãã°éŒ»çãæ¯
èç±åã¯æ°ç®¡æ¯ããããã®æ²»çã«äœ¿çšãããã åžå ¥ã®éã«é©çšãããåžå ¥å€ã®éã¯ç æ°ã®çšåºŠ
åã³æ²»çè ã®äœè³ªã«å¿ããŠå€åãããäžè¬ã«ïŒåºŠ
ã®åžå ¥ã«ã€ããããã³ã«ã«ãã³é žèªå°äœçŽ0.1ã
100mgãæå©ã«ïŒã50mgãå Žåã«ããæ°ç®¡æ¯æ¡åŒµ
å€0.01ã10mgãšçµåããŠæäžããã äžè¬åŒã®ãããã³ã«ã«ãã³é žèªå°äœã¯ã (a) äžè¬åŒïŒ ãåŒäžïœïŒïœåã³R2ã¯åèšã®ãã®ãè¡šããã
ã®ãžã¢ãã³ãšäžè¬åŒïŒ ãåŒäžR3åã³R4ã¯ããããâååæ°ïŒã
ïŒã®ã¢ã«ãã«åºãè¡šãããã®ããã³é žèªå°äœã
çž®åããåŸãããäžè¬åŒïŒ ãåŒäžïœïŒïœïŒR2åã³R3ã¯åèšã®ãã®ãè¡š
ãããã®ååç©ãå ç±ãããã€ææã«ããåŸã
ãããããã³ã«ã«ãã³é žèªå°äœã鹞åãããšã¹
ãã«åããâã¢ã«ãã«åããåã¯ççåŠçã«
å®å šãªå¡©åºãçšããŠå¡©ã«å€ãããå㯠(b) äžè¬åŒïŒ ãåŒäžïŒžåã³R1ã¯åèšã®ãã®ãè¡šãããHO
åºã¯ãããã³æ žã®ïŒäœãïŒäœåã¯ïŒäœã«äœçœ®ã
ããã®ããããã·ãããã³ã«ã«ãã³é žèªå°äœã
äžè¬åŒïŒ ãåŒäžïœïŒïœåã³R2ã¯åèšã®ãã®ãè¡šããã
ã¯å¡©çŽ ååãèçŽ ååãæ²çŽ ååãã¡ã·ã©ã
åºåã¯ãã·ã©ãåºãè¡šããããåã¯äžè¬åŒïŒ ãåŒäžïœåã³ïŒ¹ã¯åèšã®ãã®ãè¡šãããã®å
åç©ãšçž®åãããã€ææã«ããåŸãããããã
ã³ã«ã«ãã³é žèªå°äœã鹞åãããšã¹ãã«åãã
âã¢ã«ãã«åããåã¯ççåŠçã«å®å šãªå¡©åº
ãçšããŠå¡©ã«å€ããããšã«ãã補é ãããã æ¹æ³(a)ã«ããæ¹æ³ã¯èªäœå ¬ç¥ã®æ¹æ³ã§å®æœãã
ããŠãã«ãŒïŒJuckerïŒïŒEdïŒèãâãã«ãã·ãŠãªã
ãã»ã¢ã«ããã€ãããã«ãã«ã·ãŠã³ã°
ïŒFortschritte ArzneimittelforschungïŒâã第21
å·»ã1fé ã1977幎ããããªãã¡äŸãã°äžè¬åŒã®
ãžã¢ãã³ãåŒã®ããã³é žèªå°äœãšåå¿ãããã
ã€äžè¬åŒã®ååç©ãåŸãããã®åå¿ã«ã¯è§Šåªå
ã¯æº¶å€ã®ååšã¯å¿ èŠããªããããã¡ãã該åå¿ã
ä»å çãªæº¶å€ãäŸãã°ã¯ãã«çåæ°ŽçŽ ïŒå¡©åã¡ã
ã¬ã³ããžããã«ãšãŒãã«ããžãªããµã³ãããã©ã
ãããã©ã³çïŒããšãŒãã«ïŒãžã€ãœãããã«ãšãŒ
ãã«ããžããã«ãšãŒãã«ããžãªããµã³ãããã©ã
ãããã©ã³çïŒåã¯å極æ§äžæ§æº¶å€ïŒãžã¡ãã«ã
ã«ã ã¢ããããããµããã«çé žããªã¢ããçïŒã®
ååšã§å®æœããããšãå¯èœã§ããããã®åå¿å·¥çš
ã¯æå©ã«åå¿æž©åºŠ20âã150âã§å®æœããã åèšã®å·¥çšã«ç¶ãäžè¬åŒã®ååç©ã®å ç±ã¯æ
å©ã«é«æ²žç¹æº¶å€ïŒäŸãã°é±æ²¹ããžããšãã«ããžã
ãšãã«ãšãŒãã«åã¯ããŠãã«ã ïŒDawthermïŒ
ïŒã®ååšã§200âã350âã§è¡ãªãã該åå¿ã§ã¯
åå¿æž©åºŠã¯ãåå¿æ··åç©ã«è§ŠåªãšããŠä»å çã«ã«
ã€ã¹é žïŒé ¢é žãç¡«é žãããªçé žãããªåŒåç¡ŒçŽ ã
ãªãã·å¡©åçãäžå¡©åçãäºå¡©åçãå¡©åã¢ã«ã
ããŠã ãå¡©åäºéçïŒãæ·»å ãããšãçŽ50âã
200âã«äœäžããã æ¹æ³(b)ã«ããæ¬çºæã®æ¹æ³ã§ã¯äžè¬åŒã®ãã
ããã·ãããã³ã«ã«ãã³é žèªå°äœãäžæŽ»æ§æº¶å€äž
ã§ãã€å¡©åºæ§è§Šåªã®ååšã§äžè¬åŒåã¯ã®åå
ç©ãšçž®åãããããã®åå¿ã¯æå©ã«çœ®æåR1ã
ã¢ã«ãã«åºãè¡šããäžè¬åŒã®ããããã·ããã
ã³ã«ã«ãã³é žèªå°äœãçšããŠå®æœãããã該åå¿
ã«ã€ããŠå¡©åºæ§è§ŠåªãšããŠäŸãã°ã¢ã«ã«ãªéå±æ°Ž
çŽ çé žå¡©ïŒçé žæ°ŽçŽ ãããªãŠã ãçé žæ°ŽçŽ ã«ãªãŠ
ã ïŒãã¢ã«ã«ãªçé žå¡©ïŒçé žãããªãŠã ãçé žã«
ãªãŠã ïŒãã¢ã«ã«ãªéå±æ°Žé žåç©ïŒæ°Žé žåãããª
ãŠã ãæ°Žé žåã«ãªãŠã ïŒåã¯ã¢ã«ã«ãªéå±ã¢ã«ã³
ã¬ãŒãïŒãããªãŠã ã¡ãã©ãŒãããããªãŠã ãšã
ã©ãŒããã«ãªãŠã ã¡ãã©ãŒããã«ãªãŠã ïœâãã
ã©ãŒãçïŒã䜿çšããŠããã奜é©ãªæº¶å€ã¯äŸãã°
äœçŽã¢ã«ã³ãŒã«ïŒç¹ã«ïŒ£âååæ°ïŒãïŒã®ãã®ã
äŸãã°ã¡ã¿ããŒã«ããšã¿ããŒã«ããããããŒã«ã
ã€ãœãããããŒã«åã¯ïœâãã¿ããŒã«ïŒã極æ§ãš
ãŒãã«ïŒãžãªããµã³ãããã©ããããã©ã³ãã°ãª
ã³ãŒã«ãžã¡ãã«ãšãŒãã«ãã°ãªã³ãŒã«ã¢ãã¡ãã«
ãšãŒãã«çïŒåã¯å極æ§äžæ§æº¶å€ïŒäŸãã°ãžã¡ã
ã«ãã«ã ã¢ãããâã¡ãã«ã¢ã»ãã¢ããããžã¡
ãã«ã¹ã«ããã·ãåã¯ãããµã¡ãã«çé žããªã¢ã
ãïŒã§ããã ææã«ããåŒç¶ãå®æœããããšã¹ãã«ã®é¹žåã¯
èªäœå ¬ç¥ã®æäœæ¹æ³ã§å®æœããããäŸãã°æ°Žåã¯
æ°Žæ§ã¢ã«ã³ãŒã«äžã§é žæ§è§ŠåªãäŸãã°å¡©é žãç¡«
é žãïœâãã«ãšã³ã¹ã«ãã³é žåã¯å¡©åºæ§è§ŠåªãäŸ
ãã°çé žæ°ŽçŽ ã«ãªãŠã ãçé žã«ãªãŠã ãæ°Žé žåã
ããªãŠã åã¯æ°Žé žåã«ãªãŠã ã®ååšã§ã®ãšã¹ãã«
ã®é¹žåãæããããã ææã«ããåŒç¶ãå®æœããããå Žåã«ããååš
ããäºçŽã¢ããåºã®ã¢ã«ãã«åã¯åæ§ã«ãããªã³
èªå°äœã®ïŒ®âã¢ã«ãã«åã§äžè¬ã«äœ¿çšãããå ¬ç¥
æ¹æ³ã«ããè¡ãªãã äŸãã°ååç©ã®çªçŽ ååãéå±æ°ŽçŽ åç©åã¯é
å±ã¢ãããäŸãã°æ°ŽçŽ åãããªãŠã åã¯ãããªãŠ
ã ã¢ãããšã®åå¿ã«ããéå±ã«ãããã€ããããŠ
åŸãããåå¿æ§ååç©ã«ãæçµçã«ææã®çåæ°Ž
çŽ åºã®ç¡«é žå¡©åã¯ããã²ã³åç©ïŒå¡©åç©ãèåç©
åã¯æ²åç©ïŒãäœçšãããã該åå¿ã§ã¯åå¿æž©åºŠ
çŽïŒâã120âã§å®æœãããæå©ã«æ¥µæ§äžæ§æº¶å€ã
äŸãã°ãžã¡ãã«ãã«ã ã¢ãããâã¡ãã«ãããª
ãã³åã¯ãããµã¡ãã«çé žããªã¢ããã䜿çšã
ãã ææã«ããå®æœãããæ¹æ³ãšããŠåŒç¶ãè¡ãªã
ããéé¢ã®ããããã·ã¡ãã«åºã®ãšã¹ãã«åã¯å
æ§ã«ããã«å ¬ç¥ã®æ¹æ³ã«ããå®æœããããå¯èœãª
ãšã¹ãã«åæ³ãšããŠäŸãã°ããããã·ååç©ãç¡
æ°Žé žåã¯é žå¡©åç©ã§è³éŠæâè€çŽ ç°åŒååç©ã
äŸãã°ããªãžã³ãã³ãªãžã³åã¯ã«ããžã³ã®ååš
ã§ãåã¯å¡©åºæ§ã¢ã«ã«ãªéå±çé žå¡©ãéçé žãã
ãªãŠã ãéçé žã«ãªãŠã ãçé žãããªãŠã ãæ°Žé ž
åãããªãŠã åã¯æ°Žé žåã«ãªãŠã ã®ååšã§ãšã¹ã
ã«åããããšãæããããã ææã®æ¹æ³ãšããŠåŒç¶ãè¡ãªããããããã³ã«
ã«ãã³é žèªå°äœã®å¡©ãžã®å€æã¯åæ§ã«åœæ¥è ã«å ¬
ç¥ã®æ¡ä»¶äžã§ãååç©ãççåŠçã«å®å šãªå¡©åºã§
äžåããããšã«ããè¡ãªãããã æ¬çºæã«ããæ¹æ³ã®ããã®åºçºç©è³ªã¯å ¬ç¥ã§ãª
ããåã¯èªäœå ¬ç¥ã®æ¹æ³ã§è£œé ã§ããã次ã«è©²åº
çºç©è³ªã®è£œé æ¹æ³ãæ°çš®ã®ä»£è¡šçãªååç©ã«ã€ã
ãŠèšèŒããã  ïŒâããã«âïŒïŒïŒâãžãããâïŒâã¡ãã
ã·âïŒâãããã³âïŒâã«ã«ãã³é ž ïŒâããããã·âïŒâã¡ããã·âãããªã³âïŒ
âã«ã«ãã³é ž11.0ïœïŒ50ããªã¢ã«ïŒããžã¡ãã«ã¹
ã«ããã·ã200mläžã®ç²æ«åæ°Žé žåãããªãŠã
14.0ïœïŒ351ããªã¢ã«ïŒã®æžæ¿æ¶²äžã«å ¥ããã宀
æž©ã§10åæ¹æãã次ãã§èåããã«16.1mlïŒ150
ããªã¢ã«ïŒã滎äžãããã®çµæ枩床ã¯25âãè¶ã
ãªããåŒç¶ã宀枩ã§ïŒæéæ¹æããæ°Žäžã«æ³šãã
ãã€å¡©é žã§é žæ§ã«ãããæ²æŸ±ããçæç©ãæ¿Ÿå
ããæ°Žã§æŽãã也ç¥ããã€ãžã¡ãã«ãã«ã ã¢ãã
ããåçµæ¶ãããã èç¹ïŒ160ã162âãåéïŒ9.18ïœã  ïŒâããã«âïŒïŒïŒâãžãããâïŒâããã
ãã·âïŒâãããã³âïŒâã«ã«ãã³é ž ïŒâããã«âïŒïŒïŒâãžãããâïŒâã¡ããã·
âïŒâãããã³âïŒâã«ã«ãã³é ž5.0ïœïŒ18ããª
ã¢ã«ïŒãèåæ°ŽçŽ é žïŒ48ïŒ ïŒ65mläžã§éæµäžã«ïŒ
æéç ®æ²žãããåŒç¶ãæ°Žäžã«æ³šããåºäœçæç©ã
æ¿Ÿåãããã€ãžã¡ãã«ãã«ã ã¢ããããåçµæ¶ã
ããã èç¹ïŒ228ã240âãåéïŒ3.5ïœ ïŒ£ ïŒïŒïŒâãžãããâïŒâããããã·âïŒâã¡
ãã«âïŒâãããã³âïŒâã«ã«ãã³é ž ïŒïŒïŒâãžãããâïŒâã¡ããã·âïŒâã¡ãã«
âïŒâãããã³âïŒâã«ã«ãã³é ž5.83ïœïŒ25ããª
ã¢ã«ïŒãèåæ°ŽçŽ é ž65mlãšãšãã«éæµäžã«ïŒæé
ç ®æ²žãããæ°Žäžã«æ³šããåºäœçæç©ãæ¿Ÿåããã
ã€é ¢é žããåçµæ¶ãããã èç¹ïŒ285ã293âãåéïŒ5.6ïœ ïŒ€ ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªã
ã·ïŒâïŒâãããããŒã« ïŒâãããããšããŒã«44.3ïœïŒ0.32ã¢ã«ïŒãã€
ãœãããããŒã«1.2äžã«æº¶ããããšãã¯ãã«ã
ããªã³13.7mlãæ·»å ããåŒç¶ãã€ãœãããããŒã«
250mläžã®æ°Žé žåã«ãªãŠã 17.5ïœã®æº¶æ¶²äžŠã³ã«æ°Ž
10mlãæ·»å ãããæ··åç©ãéæµäžã«48æéç ®æ²ž
ãã1/2ã®å®¹éã«æ¿åºŠããæ°Ž250mlãå ãããæ²æŸ±
ããçæç©ãæ¿Ÿåããæ°Žã§æŽãããã€ä¹Ÿç¥ããã èç¹ïŒ110âãåéïŒ24ïœ ïŒ¥ ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªã
ã·ïŒâïŒâãããããŒã« ïŒâãããããšããŒã«8.86ïœïŒ63.7ããªã¢ã«ïŒ
ãã€ãœãããããŒã«250mläžã«æº¶ããããšãã¯ã
ã«ãããªã³2.75mlïŒ35.1ããªã¢ã«ïŒãæ·»å ããåŒ
ç¶ãã€ãœãããããŒã«25mläžã®æ°Žé žåã«ãªãŠã
1.98ïœïŒ35.3ããªã¢ã«ïŒã®æº¶æ¶²äžŠã³ã«æ°ŽïŒmlãæ·»
å ãããæ··åç©ãéæµäžã«48æéç ®æ²žãã1/2ã®
容éã«æ¿çž®ããæ°Ž250mlãå ãããæ²æŸ±ããçæ
ç©ãæ¿Ÿåããã€ãœãããããŒã«ïŒãšã¿ããŒã«
ïŒïŒïŒïŒïŒããåçµæ¶ãããã èç¹ïŒ144ã145âãåéïŒ6.4ïœã 次ã«å®æœäŸã«ã€ãæ¬çºæã詳説ããã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ïœ ãããªãŠã 0.46ïœïŒ20ããªã¢ã«ïŒããšã¿ããŒ
ã«20mläžã«å ¥ãããåå¿çµçµåŸåŸããããããª
ãŠã ãšãã©ãŒã溶液ã«ïŒâãšãã«âïŒïŒïŒâãž
ãããâïŒâããããã·âïŒâãããã³âïŒâ
ã«ã«ãã³é ž2.33ïœïŒ10ããªã¢ã«ïŒã溶ãããåŒ
ç¶ããšãã¯ãã«ãããªã³0.91mlïŒ11.7ããªã¢
ã«ïŒåã³æ²åã«ãªãŠã çè·¡éãæ·»å ãããæ··å
ç©ãïŒæééæµäžã«ç ®æ²žããèžçºæ¿çž®ããã€æ®
枣ãæ°Žäžã«æº¶ããã溶液ãã¯ãããã«ã ãšé ¢é ž
ãšã¹ãã«ãšå ±ã«æ¯çªãããã€å¡©é žã§PHïŒãŸã§ã®
é žæ§ã«ãããæ²æŸ±ããçæç©ãæ¿Ÿåããæ°Žã§æŽ
æµãã也ç¥ãããã€ç±ããžã¡ãã«ãã«ã ã¢ãã
äžã«æº¶ãããçµæ¶åã®ããã«ã€ãœãããã«ãšãŒ
ãã«ãå ãããåŸãããç©è³ªã100âã§ç空äž
ã§ä¹Ÿç¥ããã èç¹ïŒ305ã310âãåéïŒ1.26ïœã ïœ ç²æ«åããæ°Žé žåã«ãªãŠã 0.17ïœïŒ3.0ããª
ã¢ã«ïŒããžã¡ãã«ã¹ã«ããã·ãïŒmläžã«æžæ¿ã
ãããã€ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·â
ïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«0.10ïœïŒ0.22ããª
ã¢ã«ïŒãè£ å ¥ããã宀枩ã§10åæ¹æãã次ãã§
ãžãšãã«ã¹ã«ããšãŒã0.17mlã滎äžããã宀枩
ã§ïŒæéæ¹æãã次ãã§æ°Žäžã«å ¥ãããã€é žæ§
ã«ãããåŸãããåºäœçæç©ãæ¿Ÿåããæ°Žã§æŽ
ããé ¢é žãšå ±ã«ç ®æ²žãããã€ãžã¡ãã«ãã«ã ã¢
ããïŒã€ãœãããã«ãšãŒãã«ããåçµæ¶ãã
ãã èç¹ïŒ305ã310âãåéïŒ0.05ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâããã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ãããªãŠã 0.0096ïœïŒ4.2ããªã¢ã«ïŒããšã¿ã
ãŒã«ïŒmläžã«å ¥ããåŒç¶ãïŒâããã«âïŒïŒïŒâ
ãžãããâïŒâããããã·âïŒâãããã³âïŒâ
ã«ã«ãã³é ž0.56ïœïŒ2.1ããªã¢ã«ïŒããšãã¯ãã«ã
ããªã³0.19mlåã³æ²åã«ãªãŠã çè·¡éãå ããã
ïŒæééæµäžã«ç ®æ²žããåŒç¶ãåå¿æ··åç©ã2N
âNaOHã§å®å šã«æº¶æ¶²ã«ãã次ãã§å¡©é žã§é žæ§
ã«ãããæ²æŸ±ããçæç©ãæ¿Ÿåããæ°Žã§æŽããã
ã€ä¹Ÿç¥ããã èç¹ïŒ255ã260âãåéïŒ0.45ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâã¡ãã«âïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ãããªãŠã 0.46ïœïŒ20ããªã¢ã«ïŒãã¡ã¿ããŒã«
20mläžã«å ¥ããåŒç¶ãïŒïŒïŒâãžããããŒïŒâã
ãããã·âïŒâã¡ãã«âïŒâãããã³âïŒâã«ã«
ãã³é ž2.00ïœïŒ9.1ããªã¢ã«ïŒããšãã¯ãã«ãããª
ã³1.21mlïŒ15.5ããªã¢ã«ïŒåã³æ²åã«ãªãŠã çè·¡
éãå ¥ãããïŒæééæµäžã«ç ®æ²žããèžçºæ¿çž®
ãããã€æ®æž£ãæ°Žäžã«æº¶ããã溶液ãã¯ãããã«
ã ãšå ±ã«æ¯çªãããã€å¡©é žã§é žæ§ã«ãããæ²æŸ±ã
ãçæç©ãæ¿Ÿåããæ°Žã§æŽãããã€ä¹Ÿç¥ããã èç¹ïŒ310âïŒå解ïŒãåéïŒ0.82ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâ
ïŒâãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªãã·ïŒ
âïŒâãããããŒã«10ïœïŒ30ããªã¢ã«ïŒãã¡ã¿ã
ãŒã«250mläžã«æº¶ããããã€PdâæšçïŒ10ïŒ ïŒïŒ
ïœã®ååšã§æ°ŽçŽ åããã觊åªãæ¿Ÿå¥ãããã€æº¶æ¶²
ãèžçºãããšãç²è£œïŒïŒïŒâãã¹ïŒïŒâã¢ããã
ãšãã«ãªãã·ïŒâïŒâãããããŒã«8.2ïœãæ®ãã
ããããšããã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ã
ã«100mlãšå ±ã«ïŒæé300âã«å ç±ããåŒç¶ãæ°Žæµ
ãã³ãã«ããç空äžã§100âã§ïŒæéå ç±ããã
éå°ã®ãšããã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ã
ã«ãç空äžã§æºå»ããæ®æž£ãããŠãã«ã
ïŒDowthermïŒïŒ¡ 100mläžã§éæµäžã«30åç ®æ²žã
ããå·åŽåŸã€ãœãããã«ãšãŒãã«ãå ãããæåº
ããç²è£œã®ïŒïŒïŒâãã¹âïŒïŒâãšããã·ã«ã«ã
ãã«âïŒïŒïŒâãžãããâïŒâãªããœâãããªã«
ãªãã·ïŒâïŒâãããããŒã«ãåé¢ãã2Nâ
NaOH150mläžã«æžæ¿ããããã€ïŒæééæµäžã«
ç ®æ²žãããå·åŽåŸæº¶æ¶²ãé ¢é žãšã¹ãã«ãšå ±ã«æ¯çª
ããå¡©é žã§é žæ§ã«ãããã€å°éã®ã¡ã¿ããŒã«ãå
ãããåŸãããçµæ¶è³ªç©è³ªãæ¿Ÿåããæ°Žã§æŽãã
ãã€ä¹Ÿç¥ããã èç¹ïŒïŒ300âãåéïŒ3.2ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâãž
ãããâïŒâãªããœâãããªã«ãªãã·ïŒâïŒâ
ãããããŒã« ïŒïŒïŒâãã¹âïŒïŒâãããããšãã«ãªãã·ïŒ
âïŒâãããããŒã«10ïœïŒ30ããªã¢ã«ïŒãã¡ã¿ã
ãŒã«äžã§PdïŒæšçïŒ10ïŒ ïŒ1.6ïœã®ååšã§æ°ŽçŽ å
ããã觊åªãæ¿Ÿå¥ãããã€æ¿Ÿæ¶²ãèžçºãããç²è£œ
ã®æ²¹ç¶ïŒïŒïŒâãã¹âïŒïŒâã¢ããããšãã«ãªã
ã·ïŒâïŒâãããããŒã«13ïœãæ®çããããããš
ããã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ãã«100ml
ãšå ±ã«ïŒæé100âã«ãåŒç¶ãæ°Žæµãã³ãã«ãã
ç空äžã§100âã«ïŒæéå ç±ãããéå°ã®ãšãã
ã·ã¡ãã¬ã³ããã³é žãžãšãã«ãšã¹ãã«ãç空äžã§
æºå»ããæ®æž£ãããŠãã«ã  150mläžã§30åé
æµäžã«ç ®æ²žãããå·åŽåŸæº¶æ¶²ã«ã€ãœãããã«ãšãŒ
ãã«ãå ãããã€æåºããåºäœçæç©ãæ¿Ÿåã
ããç²è£œïŒïŒïŒâãã¹âïŒïŒâã«ã«ããšããã·â
ïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«ãª
ãã·ïŒâïŒâãããããŒã«ïŒïœãåŸãããããã
2NâNaOH100mläžã§ïŒæééæµäžã«ç ®æ²žããã
æ²æŸ±ããæ²¹ç¶çæç©ãåé¢ãããã€åºäœã«ãªããŸ
ã§ãšãŒãã«ãšå ±ã«æ¹æãããåºäœçæç©ãæ¿Ÿå
ãããžã¡ãã«ãã«ã ã¢ããããåçµæ¶ããããã€
100âã§ç空äžã§ä¹Ÿç¥ããã èç¹ïŒïŒ300âãåé1.4ïœ äŸ ïŒ ïŒïŒïŒâãã¹ïŒïŒâãšãã«âïŒâã«ã«ããã·â
ïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã« ïŒâãšãã«âïŒïŒïŒâãžãããâïŒâãããã
ã·âïŒâãããã³âïŒâã«ã«ãã³é ž1.5ïœïŒ6.4ã
ãªã¢ã«ïŒããšã¿ããŒã«15mläžã®ãããªãŠã 0.29ïœ
ïŒ12.6ããªã¢ã«ïŒã®æº¶æ¶²äžã«å ¥ããåŒç¶ããšãã¯
ãã«ãããªã³0.58mlïŒ7.5ããªã¢ã«ïŒåã³æ²åã«
ãªãŠã 20mgãæ·»å ãããæ··åç©ãïŒæééæµäžã«
ç ®æ²žããæŸæãªæº¶æ¶²ã«ãªããŸã§2NâNaOHãå
ãã次ãã§2NâHClã§é žæ§ã«ãããæ²æŸ±ããç
æç©ãæ¿Ÿåããé ¢é žããåçµæ¶ããããã€120â
ã§ç空äžã§ä¹Ÿç¥ããã èç¹ïŒïŒ300âãåéïŒ1.3ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã« ïŒâãšãã«âïŒïŒïŒâãžãããâïŒâãããã
ã·âïŒâãããã³âïŒâã«ã«ãã³é ž0.466ïœïŒïŒ
ããªã¢ã«ïŒãã€ãœãããããŒã«10mläžã«æžæ¿ã
ãããšãã¯ãã«ãããªã³0.086mlïŒ1.1ããªã¢ã«ïŒã
åŒç¶ãã€ãœãããããŒã«ïŒmlåã³æ°ŽïŒæ»Žäžã®æ°Žé ž
åã«ãªãŠã 0.224ïœïŒ4.0ããªã¢ã«ïŒã®æº¶æ¶²ãæ·»å
ãããæ··åç©ã48æééæµäžã«ç ®æ²žãã2Nâ
NaOHãæŸæãªæº¶æ¶²ã«ãªããŸã§å ãã次ãã§2N
âHClã§äžåãããæ²æŸ±ããç©è³ªãæ¿Ÿåããæ°Žã§
æŽãããã€ç空äžã§ä¹Ÿç¥ããã èç¹ïŒ250âïŒå解ïŒãåéïŒ0.2ïœã äŸ ïŒ ïŒâã¢ã»ããã·âïŒïŒïŒâãã¹âïŒïŒâãšãã«
âïŒâã«ã«ããã·âïŒïŒïŒâãžãããâïŒâãª
ããœâïŒâãããªã«ãªãã·ïŒâãããã³ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«1.0ïœïŒ4.3ããªã¢
ã«ïŒãç¡æ°Žé ¢é ž7.5mlãšé ¢é ž7.5mlã®æ··åç©äžã§ïŒ
æé100âã«å ç±ãããåŒç¶ãæ°Žäžã«æ³šããæ²æŸ±
ããåºäœçæç©ãæ¿Ÿåããæ°Žã§æŽãããã€ç空äž
ã§100âã§ä¹Ÿç¥ããã èç¹ïŒ144ã147âãåéïŒ1.0ïœã äŸ ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒïŒâãããããŒã«ã®äºãããªãŠã å¡© ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããªã«
ãªãã·ïŒâïŒâãããããŒã«0.52ïœïŒ1.0ããªã¢
ã«ïŒã1NâNaOHâ溶液ïŒmlãšã¡ã¿ãâã«20ml
ã®æ··åç©äžã§å®€æž©ã§æº¶è§£ãããåŒç¶ãç空äžã§èž
çºãããã€æ®æž£ã掻æ§çã§è±è²äžã«æ°Žããåçµæ¶
ãããã èç¹ïŒ315âïŒå解ïŒãåéïŒ0.39ïœã äŸ 10 ãšãŒããŸã«ã®çµæ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã
å¡© 2.00ïŒ ã€ãœãã¬ããªã³ã¹ã«ããšãŒã 0.10ïŒ åŽå°è¬ãããã©ã³ãïŒPropellantïŒ12åã³ãã
ãã©ã³ã14ã®æ··åç©ïŒ60ïŒ40ïŒ å šé100.00ïŒ äŸ 11 ç²æ«èª¿å€ã®çµæ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ããã·
âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã
å¡©ã埮现åïŒã8ÎŒ 20mg ã€ãœãã¬ããªã³ã¹ã«ããšãŒãã埮现åïŒã8ÎŒ
0.1mg ã©ã¯ããŒã¹ãç²æ«å80ã120ÎŒ 15mg 衚瀺ã¯æçšåäœã«é¢ããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ äžè¬åŒïŒ ãåŒäžåºïŒãåŒã ã¯ïŒã€ã®ãããã³åºã®ïŒäœãïŒäœåã¯ïŒäœã«ååš
ãããã€ïœåã³ïœã¯ããããïŒã®æ°ãè¡šããã
R1ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢ã«ãã«
åºãè¡šãããR2ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒã
ïŒã®ã¢ã·ã«åºãè¡šããããã€ïŒžã¯æ°ŽçŽ ååãçç
åŠçã«å®å šãªå¡©åºã®ã«ããªã³åã¯ïŒ£âååæ°ïŒã
ïŒã®ã¢ã«ãã«åºãè¡šãããã®æ°èŠãããã³ã«ã«ã
ã³é žèªå°äœã ïŒ åºïŒãåŒããïŒã€ ã®ãããã³åºã®ããããïŒäœãããããïŒäœåã¯
ããããïŒäœã«ååšãããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé
èšèŒã®ååç©ã ïŒ R2ãæ°ŽçŽ ååãè¡šãããç¹èš±è«æ±ã®ç¯å²ç¬¬
ïŒé åã¯ç¬¬ïŒé ã«èšèŒã®ååç©ã ïŒ ïŒžãæ°ŽçŽ ååãã¢ã«ã«ãªéå±ã«ããªã³ãã¢ã«
ã«ãªåé¡éå±ã«ããªã³ãã¢ã³ã¢ããŠã ã«ããªã³ã
ããã©ãžãã«ã«ããªã³åã¯ïŒ®âã¡ãã«ã°ã«ã«ãã³
ã«ããªã³ãè¡šãããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ãã第
ïŒé ãŸã§ã®ããããã«èšèŒã®ååç©ã ïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ãã
ã·âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã§ãããç¹èš±è«æ±
ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ ïŒïŒïŒâãã¹âïŒïŒâããã«âïŒâã«ã«ãã
ã·âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã§ãããç¹èš±è«æ±
ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâ
ãžãããâïŒâã¡ãã«âïŒâãªãã·âïŒâãããª
ã«ãªãã·ïŒâïŒâãããããŒã«ã§ãããç¹èš±è«æ±
ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâ
ãžãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâ
ïŒâãããããŒã«ã§ãããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé
èšèŒã®ååç©ã ïŒ ïŒïŒïŒâãã¹âïŒïŒâã«ã«ããã·âïŒïŒïŒâ
ãžãããâïŒâãªããœâïŒâãããªã«ãªãã·ïŒâ
ïŒâãããããŒã«ã§ãããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé
èšèŒã®ååç©ã ïŒïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ã
ãã·âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãã
ãªã«ãªãã·ïŒâïŒâãããããŒã«ã§ããç¹èš±è«æ±
ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ã
ãã·âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãã
ãªã«ãªãã·ïŒâïŒâãããããŒã«ã§ãããç¹èš±è«
æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒïŒ ïŒâã¢ã»ããã·âïŒïŒïŒâãã¹âïŒïŒâãš
ãã«âïŒâã«ã«ããã·âïŒïŒïŒâãžãããâïŒâ
ãªããœâïŒâãããªã«ãªãã·ïŒâãããã³ã§ã
ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒïŒ ïŒïŒïŒâãã¹âïŒïŒâãšãã«âïŒâã«ã«ã
ãã·âïŒïŒïŒâãžãããâïŒâãªããœâïŒâãã
ãªã«ãªãã·ïŒâïŒâãããããŒã«ã®äºãããªãŠã
å¡©ã§ãããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒïŒ äžè¬åŒïŒ ãåŒäžåºïŒãåŒã ã¯ïŒã€ã®ãããã³åºã®ïŒäœãïŒäœåã¯ïŒäœã«ååš
ãããã€ïœåã³ïœã¯ããããïŒã®æ°ãè¡šããã
R1ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢ã«ãã«
åºãè¡šãããR2ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒã
ïŒã®ã¢ã·ã«åºãè¡šããããã€ïŒžã¯æ°ŽçŽ ååãçç
åŠçã«å®å šãªå¡©åºã®ã«ããªã³åã¯ïŒ£âååæ°ïŒã
ïŒã®ã¢ã«ãã«åºãè¡šãããã®ãããã³ã«ã«ãã³é ž
èªå°äœã補é ããæ¹æ³ã«ãããŠã äžè¬åŒïŒ ãåŒäžïœïŒïœåã³R2ã¯åèšã®ãã®ãè¡šããã
ã®ãžã¢ãã³ãäžè¬åŒïŒ ãåŒäžR3åã³R4ã¯ãããâååæ°ïŒãïŒã®
ã¢ã«ãã«åºãè¡šãããã®ããã³é žèªå°äœãçž®å
ããåŸãããäžè¬åŒïŒ ãåŒäžïœïŒïœïŒR2åã³R3ã¯åèšã®ãã®ãè¡šã
ããã®ååç©ãå ç±ãããã€ææã«ããåŸããã
ãããã³ã«ã«ãã³é žèªå°äœã鹞åãããšã¹ãã«å
ããâã¢ã«ãã«åããåã¯ççåŠçã«å®å šãªå¡©
åºãçšããŠå¡©ã«å€ããããšãç¹åŸŽãšãããæ°èŠã
ããã³ã«ã«ãã³é žèªå°äœã®è£œæ³ã ïŒïŒ äžè¬åŒïŒ ãåŒäžåºïŒãåŒã ã¯ïŒã€ã®ãããã³åºã®ïŒäœãïŒäœåã¯ïŒäœã«ååš
ãããã€ïœåã³ïœã¯ããããïŒã®æ°ãè¡šããã
R1ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒãïŒã®ã¢ã«ãã«
åºãè¡šãããR2ã¯æ°ŽçŽ åååã¯ïŒ£âååæ°ïŒã
ïŒã®ã¢ã·ã«åºãè¡šããããã€ïŒžã¯æ°ŽçŽ ååãçç
åŠçã«å®å šãªå¡©åºã®ã«ããªã³åã¯ïŒ£âååæ°ïŒã
ïŒã®ã¢ã«ãã«åºãè¡šãããã®ãããã³ã«ã«ãã³é ž
èªå°äœã補é ããæ¹æ³ã«ãããŠãäžè¬åŒïŒ ãåŒäžïŒžåã³R1ã¯åèšã®ãã®ãè¡šãããHOåº
ã¯ãããã³æ žã®ïŒäœãïŒäœåã¯ïŒäœã«äœçœ®ããã
ã®ããããã·ãããã³ã«ã«ãã³é žèªå°äœãäžè¬åŒ
ïŒ ãåŒäžïœïŒïœåã³R2ã¯åèšã®ãã®ãè¡šããã
ã¯å¡©çŽ ååãèçŽ ååãæ²çŽ ååãã¡ã·ã©ãåº
åã¯ãã·ã©ãåºãè¡šããããåã¯äžè¬åŒïŒ ãåŒäžïœåã³ïŒ¹ã¯åèšã®ãã®ãè¡šãããã®åå
ç©ãšçž®åãããã€ææã«ããåŸããããããã³ã«
ã«ãã³é žèªå°äœã鹞åãããšã¹ãã«åããâã¢
ã«ãã«åããåã¯ççåŠçã«å®å šãªå¡©åºãçšããŠ
å¡©ã«å€ããããšãç¹åŸŽãšãããæ°èŠãããã³ã«ã«
ãã³é žèªå°äœã®è£œæ³ã
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19782856908 DE2856908A1 (de) | 1978-12-28 | 1978-12-28 | Neue chinoloncarbonsaeure-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende pharmazeutische praeparate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5592372A JPS5592372A (en) | 1980-07-12 |
| JPS64951B2 true JPS64951B2 (ja) | 1989-01-10 |
Family
ID=6058774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP16948979A Granted JPS5592372A (en) | 1978-12-28 | 1979-12-27 | Novel quinolonecarboxylic acid derivative*its manufacture and medicine containing it and having antiallergic*antiinflammatory and antibacterial activity |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US4289777A (ja) |
| EP (1) | EP0012925B1 (ja) |
| JP (1) | JPS5592372A (ja) |
| AT (1) | ATE1777T1 (ja) |
| DE (2) | DE2856908A1 (ja) |
| DK (1) | DK149808C (ja) |
| GB (1) | GB2044253A (ja) |
| IE (1) | IE49498B1 (ja) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5017583A (en) * | 1983-04-21 | 1991-05-21 | Merck Frosst Canada, Inc. | Leukotriene antagonists |
| DE3427404A1 (de) * | 1984-07-25 | 1986-01-30 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von 5,6-dihydro-2h-thiopyran-3-carboxaldehyden |
| CA2317439A1 (en) | 1998-01-14 | 1999-07-22 | Wayne J. Brouillette | Methods of synthesizing and screening inhibitors of bacterial nad synthetase enzyme, compounds thereof, and methods of treating bacterial and microbial infections with inhibitors of bacterial nad synthetase enzyme |
| US6861448B2 (en) * | 1998-01-14 | 2005-03-01 | Virtual Drug Development, Inc. | NAD synthetase inhibitors and uses thereof |
| US6673827B1 (en) | 1999-06-29 | 2004-01-06 | The Uab Research Foundation | Methods of treating fungal infections with inhibitors of NAD synthetase enzyme |
| EP1109805B1 (en) * | 1998-08-25 | 2003-12-17 | The Uab Research Foundation | Inhibitors of bacterial nad synthetase |
| WO2003006628A2 (en) * | 2001-07-13 | 2003-01-23 | Virtual Drug Development, Inc. | Nad synthetase inhibitors and uses thereof |
| DE10317461A1 (de) * | 2003-04-16 | 2004-10-28 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Radioaktiv markierte Mikropartikel, Verfahren zu deren Herstellung und deren Verwendung |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1120870A (en) * | 1966-07-11 | 1968-07-24 | Ici Ltd | Quinoline derivatives |
| GB1305820A (ja) * | 1970-09-28 | 1973-02-07 | ||
| JPS5324028A (en) * | 1976-08-19 | 1978-03-06 | Sumitomo Chem Co Ltd | Systemic bactericide for plant |
-
1978
- 1978-12-28 DE DE19782856908 patent/DE2856908A1/de not_active Withdrawn
-
1979
- 1979-12-11 DE DE7979105088T patent/DE2964033D1/de not_active Expired
- 1979-12-11 AT AT79105088T patent/ATE1777T1/de active
- 1979-12-11 EP EP79105088A patent/EP0012925B1/de not_active Expired
- 1979-12-21 DK DK551179A patent/DK149808C/da not_active IP Right Cessation
- 1979-12-21 GB GB7944068A patent/GB2044253A/en not_active Withdrawn
- 1979-12-27 JP JP16948979A patent/JPS5592372A/ja active Granted
- 1979-12-27 US US06/107,676 patent/US4289777A/en not_active Expired - Lifetime
- 1979-12-28 IE IE2515/79A patent/IE49498B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE1777T1 (de) | 1982-11-15 |
| DK149808B (da) | 1986-10-06 |
| DE2964033D1 (en) | 1982-12-16 |
| IE49498B1 (en) | 1985-10-16 |
| EP0012925B1 (de) | 1982-11-10 |
| IE792515L (en) | 1980-06-28 |
| EP0012925A1 (de) | 1980-07-09 |
| US4289777A (en) | 1981-09-15 |
| DK551179A (da) | 1980-06-29 |
| JPS5592372A (en) | 1980-07-12 |
| DK149808C (da) | 1987-03-23 |
| GB2044253A (en) | 1980-10-15 |
| DE2856908A1 (de) | 1980-07-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JPS61191683A (ja) | æ°èŠãªé žæ§ã€ã³ãâã«ååç© | |
| JPS62155250A (ja) | ããšããã·ã¢ã«ãã«ã«ã«ãã³é žããã³ãšã¹ãã«ååç©ïŒãã®è£œé æ¹æ³ããã³è©²ååç©ãå«æããå»è¬çµæç© | |
| JPH0146514B2 (ja) | ||
| JPH0568476B2 (ja) | ||
| JPS64951B2 (ja) | ||
| JPH066576B2 (ja) | ã¢ãããããªã³èªå°äœåã³ãã®è£œæ³ | |
| JP3483160B2 (ja) | ããªãããªããžã³ãžãªã³é¡ããã®è£œé æ¹æ³ããã³ãããå«æããè¬å€ | |
| US4250182A (en) | Pharmaceutical composition containing acridone compounds and method of using same | |
| US4232024A (en) | 1-Oxo-1H-pyrimido[6,1-b]benzthiazole derivatives | |
| AU636087B2 (en) | Quinolinyl-benzopyran derivatives as antagonists of leukotriene d4 | |
| CA1269103A (en) | Pyrido[1,2-a]pyrimidine derivatives | |
| JPS5829309B2 (ja) | ã³ãŠã¢ã¬ã«ã®âã»ã€ãµã³ã«ã³ã·ãã«ãŽãŠããã ã»ã€ãŸãŠããŠã㊠| |
| HU181000B (en) | Process for preparing substituted 7,7-dimethyl-5h,7h-imidazo/4,5-h/-isoquinoline-4,6-diones | |
| US4808618A (en) | Substituted 1,3-dialkylpyrido[4,3-d]pyrimidine-2,4-diones | |
| CA1286665C (en) | Pyrido [1,2-a] pyrimidine derivatives | |
| US4716160A (en) | Certain 7-amino-pyrazolo[4,3-b]pyridines useful in treating inflammatory and allergic disorders | |
| JPS6222993B2 (ja) | ||
| JPH07116187B2 (ja) | äºç°åŒååç©ãããããè¬å€ãšããŠäœ¿çšããããšããããã®è£œæ³ãããã³ãããã®è£œé ã«æçšãªäžéäœ | |
| US4127573A (en) | Ditetrazole substituted acridone compounds | |
| JP2003516969A (ja) | ïŒâãã§ãã«ãããªã³èªå°äœããã®è£œæ³åã³æ²»çã«ãããäœ¿çš | |
| SK107394A3 (en) | Quinoline compounds, method of their preparation and pharmaceutical preparation which containing these compounds | |
| JPS63130570A (ja) | ïŒïŒïŒâãžç¬¬ïŒçŽããã«âïŒâããããã·æ¡ç®é žã¢ããèªå°äœ | |
| JPS63225357A (ja) | ã«ã«ãã¹ããªã«èªå°äœ | |
| JPH02108684A (ja) | ãã³ãŸãã©ã³èªå°äœã®è£œé æ³ | |
| JPS59216888A (ja) | ïŒâãªããœâïŒïŒšâãïŒããã³ãŸãã©ããïŒïŒïŒâïœãããªãžã³èªå°äœïŒãã®è£œé æ³ããã³æ²»çå€ |