JPS6311353B2 - - Google Patents
Info
- Publication number
- JPS6311353B2 JPS6311353B2 JP57017392A JP1739282A JPS6311353B2 JP S6311353 B2 JPS6311353 B2 JP S6311353B2 JP 57017392 A JP57017392 A JP 57017392A JP 1739282 A JP1739282 A JP 1739282A JP S6311353 B2 JPS6311353 B2 JP S6311353B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- piperazinyl
- group
- diphenylmethyl
- acetic acid
- 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
- 150000001875 compounds Chemical class 0.000 claims description 58
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 20
- -1 alkali metal salt Chemical class 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 18
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 11
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 10
- 239000012442 inert solvent Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- YCKSFFKKEWTLIZ-UHFFFAOYSA-N 2-(4-benzhydrylpiperazin-1-ium-1-yl)acetate Chemical compound C1CN(CC(=O)O)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 YCKSFFKKEWTLIZ-UHFFFAOYSA-N 0.000 claims description 9
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 231100000252 nontoxic Toxicity 0.000 claims description 8
- 230000003000 nontoxic effect Effects 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- 239000007788 liquid Substances 0.000 claims description 6
- 229910021529 ammonia Inorganic materials 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- NWVNXDKZIQLBNM-UHFFFAOYSA-N diphenylmethylpiperazine Chemical compound C1CNCCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 NWVNXDKZIQLBNM-UHFFFAOYSA-N 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 150000001340 alkali metals Chemical group 0.000 claims description 3
- PCSREFRBRMMIHJ-UHFFFAOYSA-N 2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 PCSREFRBRMMIHJ-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 238000000034 method Methods 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 238000004458 analytical method Methods 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 239000000243 solution Substances 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 239000000739 antihistaminic agent Substances 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 239000008194 pharmaceutical composition Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- YZGQDNOIGFBYKF-UHFFFAOYSA-N Ethoxyacetic acid Chemical compound CCOCC(O)=O YZGQDNOIGFBYKF-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- IHTYTYHXCRAMAV-UHFFFAOYSA-N acetic acid;dihydrochloride Chemical compound Cl.Cl.CC(O)=O IHTYTYHXCRAMAV-UHFFFAOYSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- GGSYGVSIXHKJLA-UHFFFAOYSA-N 2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]acetamide Chemical compound C1CN(CCOCC(=O)N)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 GGSYGVSIXHKJLA-UHFFFAOYSA-N 0.000 description 3
- 208000009079 Bronchial Spasm Diseases 0.000 description 3
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 3
- 239000013566 allergen Substances 0.000 description 3
- 230000003266 anti-allergic effect Effects 0.000 description 3
- 230000001387 anti-histamine Effects 0.000 description 3
- 230000002921 anti-spasmodic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 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
- 238000001816 cooling Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 229960001340 histamine Drugs 0.000 description 3
- 150000007529 inorganic bases Chemical class 0.000 description 3
- 231100000636 lethal dose Toxicity 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- DSRFEQQOFDQPJI-UHFFFAOYSA-N 2-(4-benzhydrylpiperazin-1-yl)acetamide Chemical compound C1CN(CC(=O)N)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 DSRFEQQOFDQPJI-UHFFFAOYSA-N 0.000 description 2
- GUKUYMOLNDMQJP-UHFFFAOYSA-N 2-[2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]ethoxy]acetic acid;dihydrochloride Chemical compound Cl.Cl.C1CN(CCOCCOCC(=O)O)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 GUKUYMOLNDMQJP-UHFFFAOYSA-N 0.000 description 2
- ZRYXLOFOMAFFIH-UHFFFAOYSA-N 2-[2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]ethoxy]acetamide;dihydrochloride Chemical compound Cl.Cl.C1CN(CCOCCOCC(=O)N)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZRYXLOFOMAFFIH-UHFFFAOYSA-N 0.000 description 2
- LVJDQBJDVOYDLA-UHFFFAOYSA-N 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetamide Chemical compound C1CN(CCOCC(=O)N)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 LVJDQBJDVOYDLA-UHFFFAOYSA-N 0.000 description 2
- UTSUJWHGUFHWKK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]acetamide Chemical compound C1CN(CC(=O)N)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 UTSUJWHGUFHWKK-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
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 208000014181 Bronchial disease Diseases 0.000 description 2
- 206010006482 Bronchospasm Diseases 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- YVNBKZUIJRWERZ-UHFFFAOYSA-N acetic acid hydrate Chemical compound O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O YVNBKZUIJRWERZ-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 230000006399 behavior Effects 0.000 description 2
- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BYCHNMFDSQCCDD-UHFFFAOYSA-N methyl 2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetate Chemical compound C1CN(CCOCC(=O)OC)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 BYCHNMFDSQCCDD-UHFFFAOYSA-N 0.000 description 2
- 229940092253 ovalbumin Drugs 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000001624 sedative effect Effects 0.000 description 2
- 229940076279 serotonin Drugs 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- UZKBSZSTDQSMDR-UHFFFAOYSA-N 1-[(4-chlorophenyl)-phenylmethyl]piperazine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)N1CCNCC1 UZKBSZSTDQSMDR-UHFFFAOYSA-N 0.000 description 1
- KQHRCXCLILUNBX-UHFFFAOYSA-N 2-(2-chloroethoxy)acetamide Chemical compound NC(=O)COCCCl KQHRCXCLILUNBX-UHFFFAOYSA-N 0.000 description 1
- IMPFZLMZRCBJTE-UHFFFAOYSA-N 2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]acetamide;dihydrochloride Chemical compound Cl.Cl.C1CN(CCOCC(=O)N)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 IMPFZLMZRCBJTE-UHFFFAOYSA-N 0.000 description 1
- OXBBIHZWNDPBMQ-UHFFFAOYSA-N 2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]ethanol Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 OXBBIHZWNDPBMQ-UHFFFAOYSA-N 0.000 description 1
- BVGHJNKEYURETK-UHFFFAOYSA-N 2-[2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]ethoxy]acetamide;dihydrochloride Chemical compound Cl.Cl.C1CN(CCOCCOCC(=O)N)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BVGHJNKEYURETK-UHFFFAOYSA-N 0.000 description 1
- GVGYRKPEGABQIB-UHFFFAOYSA-N 2-[2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]ethoxy]acetamide Chemical compound C1CN(CCOCCOCC(=O)N)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 GVGYRKPEGABQIB-UHFFFAOYSA-N 0.000 description 1
- IAEKRGFKVLXEBN-UHFFFAOYSA-N 2-[2-[2-[4-[phenyl-[4-(trifluoromethyl)phenyl]methyl]piperazin-1-yl]ethoxy]ethoxy]acetamide Chemical compound C1CN(CCOCCOCC(=O)N)CCN1C(C=1C=CC(=CC=1)C(F)(F)F)C1=CC=CC=C1 IAEKRGFKVLXEBN-UHFFFAOYSA-N 0.000 description 1
- BJZQCAYZCQPFBM-UHFFFAOYSA-N 2-[2-[4-[(2-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetamide Chemical compound C1CN(CCOCC(=O)N)CCN1C(C=1C(=CC=CC=1)Cl)C1=CC=CC=C1 BJZQCAYZCQPFBM-UHFFFAOYSA-N 0.000 description 1
- AMWZYEYIOPBLEO-UHFFFAOYSA-N 2-[2-[4-[(2-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C(=CC=CC=1)Cl)C1=CC=CC=C1 AMWZYEYIOPBLEO-UHFFFAOYSA-N 0.000 description 1
- ILNDUEYFFCVAHC-UHFFFAOYSA-N 2-[2-[4-[(4-fluorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetamide Chemical compound C1CN(CCOCC(=O)N)CCN1C(C=1C=CC(F)=CC=1)C1=CC=CC=C1 ILNDUEYFFCVAHC-UHFFFAOYSA-N 0.000 description 1
- ACMKLMXMTWDEHI-UHFFFAOYSA-N 2-[2-[4-[(4-fluorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(F)=CC=1)C1=CC=CC=C1 ACMKLMXMTWDEHI-UHFFFAOYSA-N 0.000 description 1
- QXFFCZGQTGPGKO-UHFFFAOYSA-N 2-[2-[4-[(4-methoxyphenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetamide;dihydrochloride Chemical compound Cl.Cl.C1=CC(OC)=CC=C1C(C=1C=CC=CC=1)N1CCN(CCOCC(N)=O)CC1 QXFFCZGQTGPGKO-UHFFFAOYSA-N 0.000 description 1
- NBQBQRKLQXVPIS-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]acetic acid Chemical compound C1CN(CC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 NBQBQRKLQXVPIS-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000272814 Anser sp. Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- PGLIUCLTXOYQMV-UHFFFAOYSA-N Cetirizine hydrochloride Chemical compound Cl.Cl.C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PGLIUCLTXOYQMV-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 108010058846 Ovalbumin Proteins 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 108010021119 Trichosanthin Proteins 0.000 description 1
- 150000003869 acetamides Chemical class 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000168 bronchodilator agent Substances 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
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000004706 cardiovascular dysfunction Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 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 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 229960000930 hydroxyzine Drugs 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 231100000566 intoxication Toxicity 0.000 description 1
- 230000035987 intoxication Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- RDFIZBYHUOHTQI-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)acetate Chemical compound COC(=O)COCCCl RDFIZBYHUOHTQI-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical group C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 description 1
- 229960004535 oxazepam Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- HLVJBBWMBPQZAE-UHFFFAOYSA-M potassium;2-[2-[4-[(4-chlorophenyl)-phenylmethyl]piperazin-1-yl]ethoxy]acetate Chemical compound [K+].C1CN(CCOCC(=O)[O-])CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 HLVJBBWMBPQZAE-UHFFFAOYSA-M 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000009291 secondary effect Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
ãçºæã®è©³çŽ°ãªèª¬æã
æ¬çºæã¯ãæ°èŠãªïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ãé ¢é žããã®ã¢ãããå
ã³æ¯æ§ã®ãªããè¬å€ãšããŠèš±å®¹ããããããã®å¡©
é¡ããªãã³ã«ãããã®è£œé æ¹æ³åã³ããããå«ã
è¬å€çµæç©ã«é¢ããã æ¬çºæã«ããæ°èŠååç©ã¯ãäžè¬åŒïŒ ïŒåŒäžã ã¯ããããã·ã«åºåã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠæ°ŽçŽ ååãããã²ã³ååã
çŽéãããã¯åæéã®äœçŽã¢ã«ã³ãã·åºåã¯ã
ãªãã«ãªãã¡ãã«åºãè¡šããã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã奜ãŸããã¯ïŒã§ããïŒãæãããª
ãã³ã«æ¯æ§ã®ãªããè¬å€ãšããŠèš±å®¹ããããã®å¡©
é¡ãšããŠã®æ§é ãæããã æ¬æ现æžã«çšããããçšèªãäœçŽã¢ã«ã³ãã·ã
ãšã¯ãäŸãã°ã¡ããã·ããšããã·ãããããã·ç
ã®ããã«ãïŒãïŒåã®ççŽ ååãå«ãçŽéåã¯å
åéã®ã¢ã«ã³ãŒã«ã®æ®åºãæå³ãããããã²ã³å
åã¯ãå¡©çŽ åã¯åŒçŽ ååã§ããã®ãæãŸããã æ¬æ现æžã§ãããæ¯æ§ã®ãªããè¬å€ãšããŠèš±å®¹
ãããå¡©ããšã¯ãåŒã§è¡šããããé žåã³ã¢ãã
ã®è¬å€ãšããŠèš±å®¹ãããé žãäŸãã°é ¢é žãããã
é žããã¯ãé žãã¢ã¹ã³ã«ãã³é žãå¡©åæ°ŽçŽ é žãè
åæ°ŽçŽ é žãç¡«é žåã³çé žãšã®ä»å å¡©ãæå³ããã®
ã¿ã§ãªããéå±å¡©ïŒäŸãã°ããããªãŠã åã¯ã«ãª
ãŠã å¡©ïŒãã¢ã³ã¢ããŠã å¡©ãã¢ãã³å¡©åã³ã¢ãã
é žå¡©ã®ãããªè¬å€ãšããŠèš±å®¹ãããå¡©ããæå³ã
ãã ãããã®è¬å€ãšããŠèš±å®¹ãããå¡©é¡ã¯ãããèª
äœå ¬ç¥ã®æ¹æ³ã«ãã€ãŠåŒã®ååç©ãã補é ãã
ããšãã§ããã æ¬çºæã«ãã奜ãŸããååç©ã«ã¯ã次ã®ãããª
ãã®ãããã ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšããã·ã
é ¢é žåã³ãã®ïŒå¡©é žå¡©ã ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšããã·ã
é ¢é žã«ãªãŠã ã ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ããšããã·ãé ¢é žåã³ãã®ïŒå¡©é ž
å¡©ã ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žåã³ãã®æ°Žåç©ã åŒã®ååç©ã¯ãè¬ççã«èå³ããæ§è³ªãæã
ãŠãããç¹ã«ããããã®ååç©ã¯ãæã¢ã¬ã«ã®ãŒ
å€ãæãã¹ã¿ãã³å€ãæ°ç®¡æ¯æ¡åŒµå€åã³é®çå€ãš
ããŠæçšã§ããã ããã«ãåŸæ¥ã®æãã¹ã¿ãã³å€ã®å Žåã«ãã°ã
ã°èŠãããäžæ¢ç¥çµã«å¯Ÿããåºæ¿åã¯æå§ãšãã€
ãäºæ¬¡çå¹æãæå°éã«æãããããšããç¹åŸŽã
ãããã®ååç©ã¯æããŠããããã®ãããããã
ã®ååç©ã¯ãèå³ãã麻é åã³æççæ§ã瀺ããš
å ±ã«ã倧è³åã³å¿èè¡ç®¡ã®æ©èœäžå šæã«ãå¹æã
çºæ®ããã H.B.Wrightåã³D.L.Martinã®è«æãJ.Med.
Chem.11ïŒ1968幎ïŒ390ã391é ãã§ã¯ãã³ã¬ã¹ã
ããŒã«éäžå€ãšããŠã®ïŒâãïŒâãïŒïŒâã¯ãã
ããšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ãã¢ã»ãã¢ããïŒåŒïŒïŒ¹ïŒNH2ïŒïŒžïŒïœâ
ClïŒXâ²ïŒïŒšïŒãã ãïœïŒïŒïŒã®äœçšã«ã€ããŠã®
ç 究ãçºè¡šãããŠããããåŸãããçµæã¯å¿ ãã
ããææã§ãªãã ããã«ããã«ã®ãŒç¹èš±ç¬¬763609å·æ现æžã«ã¯ã
ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãž
ãã«ãã¢ã»ãã¢ããïŒåŒïŒïŒ¹ïŒNH2ïŒïŒžïŒ
Xâ²ïŒïŒšïŒãã ãïœïŒïŒïŒã«å©å°¿äœçšã®ããããš
ãé瀺ãããŠããã該ç¹èš±ã«ã¯ãã¢ããåºã®çªçŽ
ååã眮æãããåæ§ã®ã¢ã»ãã¢ããã§ãã€ãŠã
çš®ã ã®ä»ã®è¬ççæ§è³ªãæãããã®ãèšèŒãããŠ
ããã æ¬çºæè ãè¡ã€ãè¬çè©Šéšã®çµæã§ã¯ãããã
ã®ã¢ã»ãã¢ããã察å¿ããé žã®æã¢ã¬ã«ã®ãŒãé®
çåã³æãã¹ã¿ãã³å¹æã¯ãé¢å¿ãå¯ããã»ã©ã®
ãã®ã§ãªãã€ãïŒB.Pharmacologyåç §ïŒã  補é æ¹æ³ åŒïŒïŒ¹ïŒâNH2ïŒã®ã¢ããã¯ã次ã«èš
èŒãããããªçš®ã ã®æ¹æ³ã§è£œé ããããšãã§
ããã ïŒïŒ äžèšã®æ¹çšåŒã«åŸããåŒã®ïŒâïŒãž
ããšãã«ã¡ãã«ïŒããã©ãžã³ãšåŒã®Ïâ
ããã¢ã»ãã¢ãããšãåå¿ãããã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ããããããŠïŒºã¯ããã²ã³ååã§ããã ãã®åå¿ã¯ãäžè¬ã«äžæŽ»æ§æº¶å€ïŒå¥œãŸã
ãã¯èèªæã¢ã«ã³ãŒã«ãã¡ãã«ãšãã«ã±ã
ã³ã®ãããªèèªæã±ãã³ãåã¯ãã«ãšã³ã
ããã¯ãã·ã¬ã³ã®ãããªè³éŠæçåæ°ŽçŽ ïŒ
äžã«ãããŠãé žå容äœãäŸãã°ããªãšãã«
ã¢ãã³ã®ãããªç¬¬äžææ©ã¢ãã³ãåã¯çé ž
ãããªãŠã ã®ãããªç¡æ©å¡©åºã®ååšäžã§æ°
æéåå¿æ··åç©ã80ã150âã«å ç±ããã
ãšã«ãã€ãŠè¡ãããã ïŒïŒ äžèšã®åå¿åŒã«åŸããåŒã®ÏâãïŒ
âïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãžã
ã«ãã¢ã«ã«ããŒã«ã®ã¢ã«ã«ãªéå±å¡©ãšãåŒ
ã®ïŒâããã¢ã»ãã¢ãããšãåå¿ãã
ãã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ãããã¯ããã²ã³ååã§ããããããŠ
Meã¯ã¢ã«ã«ãªéå±ååã§ããã åŒã®ã¢ã«ã«ãªéå±å¡©ãšãåŒã®ããã¢
ã»ãã¢ãããšã®éã®åå¿ã¯ããã«ãšã³ãã
ã·ã¬ã³åã¯ãžã¡ãã«ãã«ã ã¢ããã®ãããª
äžæŽ»æ§æº¶å€äžã«ãããŠãïŒâããåå¿æ··å
ç©ã®éæµæž©åºŠãŸã§ã®æž©åºŠã§å®æœãããã ãã®åå¿ã«äœ¿ãããåŒã®ã¢ã«ã«ãªéå±
å¡©ã¯ããã«ãšã³ããã·ã¬ã³åã¯ãžã¡ãã«ã
ã«ã ã¢ããã®ãããªäžæŽ»æ§æº¶å€äžã«ãã
ãŠãé©åœãªÏâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ãã¢ã«ã«ããŒã«
ãšãã¢ã«ã«ãªéå±æ°ŽçŽ åç©ãäžè¬ã«ã¯æ°ŽçŽ
åãããªãŠã ãšãåå¿ãããããšã«ãã€ãŠ
ãã®å Žã§èª¿è£œãããã åŒïŒMeïŒïŒšïŒã®ã¢ã«ã³ãŒã«ã®è£œé æ³
ã¯ãç±³åœç¹èš±ç¬¬2899436å·æ现æžã«èšèŒã
ããŠããã ïŒïŒ äžèšã®æ¹çšåŒã«åŸããã¢ã³ã¢ãã¢ãšã
ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâã
ãã©ãžãã«ãé ¢é žã®å®èœæ§èªå°äœãããªã
ã¡ãåŒã§ç€ºãããããã²ã³åç©åã¯äœçŽ
ã¢ã«ãã«ãšã¹ãã«ãšãåå¿ãããã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ããããããŠïŒ·ã¯ããã²ã³åååã¯â
ORâ²åºïŒRâ²ã¯äœçŽã¢ã«ãã«åºã§ããïŒãè¡š
ããã ããã²ã³ååã¯ãäŸãã°å¡©çŽ åã¯èçŽ å
åã§ãã€ãŠããããããŠã¢ã«ãã«åºã¯ãäŸ
ãã°ã¡ãã«åã¯ãšãã«åºã§ãã€ãŠãããã ãããã²ã³ååãè¡šããå ŽåãåŒ
ïŒïŒ¹ïŒOHïŒã®é žãåŸè¿°ã®æ¹æ³ã§æåã«
補é ãã次ã«ãã®çš®ã®ååç©ã補é ããã
ãã®åšç¥ã®æ¹æ³ã«ãããäžèšã®é žã察å¿ã
ãããã²ã³åç©ã«å€æããã次ãã§ãåŸã
ããããã²ã³åç©ãäžæŽ»æ§æº¶å€äžã§ã¢ã³ã¢
ãã¢ãšåå¿ãããã ãâORâ²åºãè¡šããå Žåã«ã¯ãåŸè¿°ã
ãæ¹æ³ã®ãã¡ã®äžã€ã«ãã€ãŠãæåã«åŒ
ã®ãšã¹ãã«ã補é ããã次ã«ãïŒâãªãã
åšå²æž©åºŠã«ãããŠãäžèšã®ãšã¹ãã«ãäžæŽ»
æ§æº¶å€äžã§ã¢ã³ã¢ãã¢ãšåå¿ãããããã®
åå¿ã¯ããããªãŠã ã¡ããã·ãã®ãããªè§Š
åªã®ååšäžã§è¡ãããšãã§ããã åŒïŒïŒ¹ïŒOHïŒã®é žã¯ãïŒâãïŒâïŒãž
ããšãã«ã¡ãã«ïŒâïŒâããã©ãžãã«ãé ¢é ž
ã®å®èœæ§èªå°äœãããªãã¡ãåŒ ãåŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ããããããŠYâ²ã¯âNH2åºåã¯âORâ²åº
ïŒRâ²ã¯äœçŽã¢ã«ãã«åºãäŸãã°ã¡ãã«ããã
ã¯ãšãã«åºãè¡šããïŒã§ããããæããã¢ã
ãåã¯äœçŽã¢ã«ãã«ãšã¹ãã«ãå¡©åºæ§åªè³ªäž
ã§å æ°Žå解ããããšã«ãã€ãŠè£œé ããããšã
ã§ããã ãã®å æ°Žå解ã¯ã20âããåå¿æ··åç©ã®éæµæž©
床ãŸã§ã®æž©åºŠã«ãããŠãæ°Žæ§åªè³ªãåã¯æ°Žæ§ã¡ã¿
ããŒã«ããšã¿ããŒã«çã®ãããªæ°Žæ§ã¢ã«ã³ãŒã«åª
質äžã§ç¡æ©å¡©åºãäŸãã°æ°Žé žåãããªãŠã åã¯ã«
ãªãŠã ãçšããŠè¡ãããã åŒïŒYâ²ïŒâNH2ïŒã®ã¢ããã¯ãåèšã®æ¹æ³
ïŒïŒãïŒïŒã®ãã¡ã®ããããã«ãã€ãŠè£œé ã
ãããšãã§ããã åŒïŒïŒ·ïŒâORâ²ïŒã®ãšã¹ãã«ãåã³åŒ
ïŒYâ²ïŒâORâ²ïŒã®ãšã¹ãã«ã¯ãçš®ã ã®æ¹æ³ã§è£œé
ããããšãã§ããã補é æ³ã®äŸãããããšæ¬¡ã®ãš
ããã§ããã (a) äžèšã®åå¿åŒã«åŸããåŒã®ïŒâïŒãžããšã
ã«ã¡ãã«ïŒããã©ãžã³ãšãåŒã®äœçŽã¢ã«ãã«
Ïâããã¢ã»ããŒããšãåå¿ãããã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§ã
ããRâ²ã¯äœçŽã¢ã«ãã«åºã§ããããããŠïŒºã¯
ããã²ã³ååã§ãããåŸã€ãŠãRâ²ã¯äŸãã°ã¡
ãã«åã¯ãšãã«åºã§ãã€ãŠãããã¯å¡©çŽ åã¯
èçŽ ååã§ãã€ãŠããã äžè¬ã«ããã®åå¿ã¯ããã³ãŒã³ããã«ãšã³å
ã¯ãã·ã¬ã³ã®ãããªäžæŽ»æ§æº¶å€äžã第äžææ©å¡©
åºãäŸãã°ããªãšãã«ã¢ãã³ãåã¯ç¡æ©å¡©åºã
äŸãã°çé žãããªãŠã ã®ãããªé žå容äœã®ååš
äžã«åå¿æ··åç©ã80ãã150âã®æž©åºŠã«æ°æéå
ç±ããããšã«ãã€ãŠè¡ãããã (b) äžèšã®åå¿åŒã«åŸããåŒã§è¡šããããÏâ
ãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãžã
ã«ãã¢ã«ã«ããŒã«ã®ã¢ã«ã«ãªéå±å¡©ãšãåŒïŒžã§
è¡šããããïŒâããé ¢é žã®äœçŽã¢ã«ãã«ãšã¹ã
ã«ãšãåå¿ãããã åŒäžãRâ²ããXâ²ãïœåã³ïœã¯åèšãšå矩
ã§ãããã¯ããã²ã³ååã§ããããããŠMe
ã¯ã¢ã«ã«ãªéå±ååãè¡šããã åŒã®ã¢ã«ã«ãªéå±å¡©ãšãåŒã®ããã²ã³åãš
ã¹ãã«ãšã®éã®åå¿ã¯ãäžæŽ»æ§æº¶å€äžãïŒâãã
åå¿æ··åç©ã®éæµæž©åºŠãŸã§ã®æž©åºŠã«ãããŠè¡ãã
ãã 以äžãäŸããããŠæ¬çºæã説æããã äŸ ïŒ ïŒåŒïŒïŒ¹ïŒâNH2ïŒã®ã¢ããã®è£œé 1.1 ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâ
ïŒâããã©ãžãã«ããšããã·ãã¢ã»ãã¢ããïŒ
å¡©é žå¡©ïŒæ¹æ³ïŒïŒïŒ 37.8ïœïŒ0.15ã¢ã«ïŒã®ïŒâïŒãžããšãã«ã¡ã
ã«ïŒããã©ãžã³ã27.5ïœïŒ0.2ã¢ã«ïŒã®ïŒâ
ïŒïŒâã¯ãããšããã·ïŒã¢ã»ãã¢ãããåã³
26.5ïœã®ç¡æ°Žçé žãããªãŠã ã®ãã·ã¬ã³120ml
äžæ··åç©ã90ãã120âã«ïŒæéå ç±ããããã®
åŸã120mlã®ãã³ãŒã³ãåå¿æ··åç©ã«å ããç
ããæ²æŸ±ãå¥ããææ©çžãåžå¡©é žïŒæ¿å¡©é ž30
mlãæ°Ž100mlã«å ãããã®ïŒã§æœåºãããæ°Žé ž
åãããªãŠã ã®æ¿å氎溶液40mlãå ããåŸãã
ã³ãŒã³ã§æœåºããããã³ãŒã³æ°Žæº¶æ¶²ãæ°ŽæŽãã
ç¡æ°Žçé žãããªãŠã ã§ä¹Ÿç¥ããŠãããã³ãŒã³ã
èžçºä¹Ÿåºããããèžçºæ®æž£ããžãšãã«ãšãŒãã«
ãšå ±ã«ããã€ã¶ããæŸçœ®ããŠçµæ¶ããããçè«
å€ã®73ïŒ ã®åçã§ïŒâãïŒâãïŒâïŒãžããšã
ã«ã¡ãã«ïŒâïŒâããã©ãžãã«ããšããã·ãã¢
ã»ãã¢ãããåŸãã mp119ã120âã ãšã¿ããŒã«äžã§è£œé ããïŒå¡©é žå¡©ã¯ã230â
ã«ãããŠå解ããªãã溶èããã C21H27N3O2ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC59.15H6.85N9.85Cl-16.63 枬å®å€ïŒ 58.99 6.80 9.79 16.46 äžèšã®æ¹æ³ãçšããäžèšã®ååç©ã補é ã
ãïŒ ïŒâãïŒâãâïŒãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒ åçã¯çè«å€ã®47ïŒ ïŒãšã¿ããŒã«ããåçµæ¶
åŸã®mp111ã112âã C21H26ClN3O2ãšããŠã®ïŒ åæå€ïŒ èšç®æž¬ïŒC65.02H6.71N10.83Cl9.14 枬å®å€ïŒ 64.59 7.00 10.82 9.54 ïŒâãïŒâãïŒâãïŒïŒãžããšãã«ã¡ãã«ïŒ
âïŒâããã©ãžãã«ããšããã·ããšããã·ãã¢
ã»ãã¢ããïŒ å®è³ªäžãå®éçã«åŸãããç²è£œç¶æ ã®çæç©
ã¯ã粟補ããªãã§ãã®ãŸãŸå¯Ÿå¿ããé žã®è£œé ã«
çšããããšãã§ããïŒäŸ2.2åç §ïŒã ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããšã
ã«ïŒããšãã«ã¡ãã«ãïŒâããã©ãžãã«ããšã
ãã·ããšããã·ãã¢ã»ãã¢ããïŒ å®è³ªäžå®éçã«åŸãããç²è£œç¶æ ã®çæç©
ã¯ã粟補ããããšãªãã«ãã®ãŸãŸå¯Ÿå¿ããé žã®
補é ã«çšããããšãã§ããïŒäŸ2.2åç §ïŒã ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒ çè«å€ã«å¯ŸããŠ54.7ïŒ ã®åçïŒã¢ã»ããããª
ã«ããæçµæ¶ããåŸã®mp105ã107âã C21H26FN3O2ã®ïŒ åæå€ïŒ èšç®å€ïŒC67.90H7.09N11.31 枬å®å€ïŒ 68.3 7.40 11.21 ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒ çè«å€ã«å¯ŸããŠ57ïŒ ã®åçïŒãã³ãŒã³ããå
çµæ¶ããåŸã®mp129ã130âã C21H26ClN3O2ã®ïŒ åæå€ïŒ èšç®å€ïŒC65.0H6.75N10.8Cl9.4 枬å®å€ïŒ 66.3 7.0 10.6 9.7 ãã®ã¢ããã®ïŒå¡©é žå¡©ã補é ããïŒè¥å¹²ã®ïŒ
å¡©é žå¡©ãå«ããã€ãœãããããŒã«ããåçµæ¶ã
ãåŸã®mp218ã220âã C21H26ClN3O2ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC54.72H6.12N9.11Cl-15.38 Clå š23.08 枬å®å€ïŒ 55.69 6.52 9.20 11.86 20.27 ïŒâãïŒâãïŒâãïŒïŒâã¡ããã·ããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒçè«å€ã®20ïŒ ã®å
çïŒã¢ã»ããããªã«ã§åçµæ¶åŸã®mp175ã176
âã C22H29N3O3ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC57.8H6.8N9.2Cl-15.5 枬å®å€ïŒ 57.8 7.2 9.5 15.9 ïŒâãïŒâãïŒâãïŒâããïŒâïŒããªãã«
ãªãã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒ
âããã©ãžãã«ããšããã·ããšããã·ãã¢ã»ã
ã¢ããïŒåçïŒ78ïŒ ïŒãã®ååç©ã®ïŒå¡©é žå¡©ã®
mpïŒ178ã181âïŒã¢ã»ããããªã«ïŒ C24H30F3N3O3.2HClãšããŠã®åæå€(%)ïŒ èšç®å€ïŒC53.53H5.99N7.80Cl-13.17 枬å®å€ïŒ 51.47 5.60 7.89 13.10 ïŒâãïŒâãïŒâãïŒâããã¹ïŒïŒâãã«ãª
ãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ããš
ããã·ããšããã·ãã¢ã»ãã¢ããïŒåçïŒ90
ïŒ ïŒãã®ååç©ã®ïŒå¡©é žå¡©ã®mpïŒ188ã190â
ïŒã¢ã»ããããªã«ïŒ C23H29F2N3O3.2HClãšããŠã®åæå€(%)ïŒ èšç®å€ïŒC54.54H6.17N8.29Cl-14.0 枬å®å€ïŒ 54.01 6.38 8.07 13.75 1.2 ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒæ¹æ³ïŒïŒïŒ 180mlã®ãžã¡ãã«ãã«ã ã¢ããäž172.9ïœ
ïŒ0.508ã¢ã«ïŒã®ïŒâãïŒâãïŒâïŒãžããšãã«
ã¡ãã«ïŒâïŒâããã©ãžãã«ããšããã·ããšã¿
ããŒã«ã®æº¶æ¶²ã«æ°ŽçŽ åãããªãŠã 24.2ïœïŒ0.53
ã¢ã«ïŒãå ãããæ·»å ãçµäºããæç¹ã§ãåå¿
æ··åç©ã40âã«30åå ç±ãããå·åŽåŸã60ïœ
ïŒ0.624ã¢ã«ïŒã®ïŒâã¯ããã¢ã»ãã¢ããã10å
éã§å ãããåå¿æ··åç©ã®æž©åºŠã40âã«äžãã
30åéãã®æž©åºŠã«ä¿ã€ãå·åŽåŸãæ°Ž30mlãå
ãã次ãã§èžçºä¹Ÿåºããããèžçºæ®æž£ãïŒã®
æ°Žã«æžæ¿ãããã®æžæ¿æ¶²ããã³ãŒã³ã§æœåºã
ããç¡æ°Žçé žã«ãªãŠã äžã§ææ©çžã也ç¥ãã
åŸãææ©çžãèžçºããããã·ãªã«ã®ã«ã©ã ïŒæº¶
é¢å€ãšããŠã容éïŒå®¹éã§95ïŒïŒã®ã¯ãããã«
ã âãšã¿ããŒã«äœ¿çšïŒãçšããã¯ãããã°ã©ã
ã€ãŒã«ãããèžçºæ®æž£ã粟補ãããåŸãããç
æç©ã45mlã®ãšã¿ããŒã«ã«æº¶è§£ããå¡©åæ°ŽçŽ é ž
ã®5.1Nãšã¿ããŒã«æº¶æ¶²24mlã該溶液ã«å ããã
çè«å€ã«å¯ŸããŠïŒïŒ ã®åçã§ïŒâãïŒâãïŒâ
ãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãžã
ã«ããšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é ž
å¡©19ïœãåŸãïŒã¢ã»ããããªã«ã§åçµæ¶åŸã®
mp196ã197âã C23H31N3O3ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC58.72H7.07N8.93Cl-15.07 枬å®å€ïŒ 58.29 6.83 8.44 15.01 äžèšã®æ¹æ³ãçšãã次ã®ååç©ã調補ããïŒ ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒ
çæç©ãã€ãœãããããŒã«ããåçµæ¶ãããã®
ã¯ãïŒååã®çµæ¶æº¶åªãå«ããçè«å€ã®11ïŒ ã®
åçïŒmp100ã102âã C23H30ClN3O3ã»C3H7OHã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC55.27H7.16N7.43Cl-12.55 Clå š18.22 枬å®å€ïŒ 53.10 6.93 7.18 12.56 18.79 1.3 ïŒâãïŒâãïŒâãïŒâïŒã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒæ¹æ³ïŒïŒïŒ ã¡ãã«ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšã
ã«ïŒããšãã«ã¡ãã«ãïŒâããã©ãžãã«ããšã
ãã·ãã¢ã»ããŒã2.3ïœïŒ0.0057ã¢ã«ïŒãç¡æ°Ž
ã¡ã¿ããŒã«100mlã«æº¶è§£ããããã®æº¶æ¶²ãïŒã
10âã®æž©åºŠã«å·åŽãã次ãã§ã¢ã³ã¢ãã¢ã20æ
éæ°æ³¡éå ¥ãããæžå§äžã«æº¶å€ãèžçºé€å»ãã
æ®æž£ããžãšãã«ãšãŒãã«ãšå ±ã«ããã€ã¶ããŠã
ãæŸçœ®ããŠçµæ¶ãããïŒâãïŒâãïŒâãïŒïŒ
âã¯ããããšãã«ïŒããšãã«ã¡ãã«ãâïŒâã
ãã©ãžãã«ãâãšããã·ãã¢ã»ãã¢ãã1.2ïœ
ãåŸãïŒçè«å€ã«å¯Ÿããåç54ïŒ ïŒmp109ã
110âã C21H26ClN3O2ã®ïŒ åæå€ïŒ èšç®å€ïŒC65.02H6.71N10.83Cl9.14 枬å®å€ïŒ 65.13 6.59 10.95 9.54 åæç©è³ªãšããŠçšããã¡ãã«ïŒâãïŒâãïŒ
âãïŒïŒâã¯ããããšãã«ïŒããšãã«ã¡ãã«ã
âïŒâããã©ãžãã«ããšããã·ãã¢ã»ããŒãã¯
次ã®ããã«è£œé ããïŒ ç¡æ°Žãã·ã¬ã³500mläžã«æº¶è§£ããã87ïœ
ïŒ0.30ã¢ã«ïŒã®ïŒâãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãããã©ãžã³ã58ïœïŒ0.38ã¢ã«ïŒ
ã®ã¡ãã«ïŒïŒâã¯ãããšããã·ïŒã¢ã»ããŒãã
åã³40.3ïœïŒ0.38ã¢ã«ïŒã®çé žãããªãŠã ãã
ãªãæ··åç©ãããæ¹æããªããéæµäžã«40æé
å ç±ããã次ã«åå¿æ··åç©ãå·åŽããŠããé
ãããããŠåºåœ¢ç©ã¯ãã³ãŒã³ã§æŽã€ãåŸã«æ£ãŠ
ãã液ãèžçºä¹Ÿåºããã·ãªã«ã®ã«ã©ã ïŒæº¶é¢
å€ãšããŠã容éïŒå®¹éã§97ïŒïŒã®ã¯ãããã«ã
âã¡ã¿ããŒã«ã䜿çšïŒãçšããã¯ãããã°ã©ã
ã€ãŒã§èžçºæ®æž£ã粟補ããææã®ã¡ãã«ãšã¹ã
ã«34ïœïŒçè«éã®27.8ïŒ ïŒãåŸãã C22H27ClN2O3ãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC65.60H6.70N6.95 枬å®å€ïŒ 63.87 6.55 6.59 ãã®ãšã¹ãã«ã®äžèšã®ä»å å¡©ïŒçš®ã補é ã
ãïŒ ïŒå¡©é žå¡©ïŒmp123ã125âã C22H27ClN2O3ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC55.50H6.10N5.89Cl-14.92 枬å®å€ïŒ 55.20 6.23 5.65 13.2 ïŒãã¬ã€ã³é žå¡©ïŒmp128ã130âã C30H35ClN2O11ãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC56.70H5.51N4.41 枬å®å€ïŒ 57.01 5.22 4.45 äŸ ïŒ ïŒåŒïŒïŒ¹ïŒOHïŒã®é žã®è£œé 2.1 ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒæ¹æ³ïŒ ç¡æ°Žãšã¿ããŒã«65mläžã«16.8ïœïŒ0.0417ã¢
ã«ïŒã®ã¡ãã«ïŒâãïŒâãïŒâãïŒïŒâã¯ãã
ããšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ããšããã·ãã¢ã»ããŒãïŒäŸ1.3ã®æ¹æ³ã§èª¿
補ãããã®ïŒã溶解ããããã®æº¶æ¶²ã«æ°Žé žåã«
ãªãŠã ã®1Nãšã¿ããŒã«æº¶æ¶²42mlãå ããåå¿
æ··åç©ãéæµäžã«ïŒæéå ç±ãããå·åŽåŸã
éããŠæ²æ®¿ãé€ãããžãšãã«ãšãŒãã«ã§æŽæµã
ãã液ãèžçºä¹Ÿåºãããžãšãã«ãšãŒãã«ãçš
ããŠèžçºæ®æž£ãããã€ã¶ããæŸçœ®ããŠçµæ¶ãã
ããåžæ¹¿æ§ã®ïŒâãïŒâãïŒâãïŒïŒâã¯ãã
ããšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ããšããã·ãé ¢é žã«ãªãŠã 10.5ïœãåŸããç
è«å€ã«å¯ŸããŠ59ïŒ ã®åçïŒmp161ã163âã C21H24ClN2O3KãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC59.0 H5.63N6.56 枬å®å€ïŒ 57.97 5.77 6.48 ãã®ã«ãªãŠã å¡©ã100mlã®æ°Žã«æº¶è§£ãã10ïŒ
ã®å¡©é žã§PHïŒã«èª¿ç¯ããããã®æº¶æ¶²ãã¯ããã
ã«ã ã§æœåºããç¡æ°Žç¡«é žãã°ãã·ãŠã ã§ä¹Ÿç¥ã
ãåŸãææ©çžãèžçºä¹Ÿåºããããèžçºæ®æž£ããž
ãšãã«ãšãŒãã«ãšå ±ã«ããã€ã¶ããæŸçœ®ããŠçµ
æ¶ããããïŒâãïŒâãïŒâãïŒïŒâã¯ããã
ãšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ããšããã·ãé ¢é ž7.5ïœãåŸããçè«å€ã«å¯Ÿ
ããŠ81ïŒ ã®åçïŒmp110ã115âã C21H25ClN2O3ã®ïŒ åæå€ïŒ èšç®å€ïŒC64.80H6.48N7.20 枬å®å€ïŒ 62.3 6.48 6.92 ãã«ãšã³äžã§å¯Ÿå¿ããïŒå¡©é žå¡©ã調補ïŒçè«
å€ã«å¯Ÿã80ïŒ ã®åçïŒmp225âã C21H25ClN2O3ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC54.60H5.85N6.07Cl-15.38 Clå š23.07 枬å®å€ïŒ 54.42 5.60 6.01 15.29 23.08 2.2 ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâ
ïŒâããã©ãžãã«ããšããã·ãé ¢é žïŒæ¹æ³ïŒ 200mlã®ãšã¿ããŒã«ã«æº¶è§£ãã19ïœïŒ0.054ã¢
ã«ïŒã®ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒ
âïŒâããã©ãžãã«ããšããã·ã¢ã»ãã¢ãã
ïŒäŸ1.1ã«èšèŒã®æ¹æ³ã§èª¿è£œãããã®ïŒãšãæ°Žé ž
åãããªãŠã ã®4Nãšã¿ããŒã«æº¶æ¶²27mlãšã®æ··
åç©ãéæµäžã«ïŒæéå ç±ããã3.61Nå¡©é ž
29.7mlã«ãŠåå¿æ··åç©ãPH6.3ã«èª¿ç¯ããåŸã
æžå§äžã«ãšã¿ããŒã«ãèžçºãããŠé€å»ãããç
ããæ²æ®¿ãå¥ããã溶å€ãèžçºãããåŸãç²
ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ããšããã·ãé ¢é ž17.4ïœãåŸãã
çè«å€ã«å¯ŸããŠåç91ïŒ ïŒmp100âã C21H26N2O3ã®ïŒ åæå€ïŒ èšç®å€ïŒC71.1H7.39N7.90 枬å®å€ïŒ 69.1 7.07 7.12 察å¿ããïŒå¡©é žå¡©ã¯ãã€ãœãããããŒã«ãã
åçµæ¶ããŠmp217ã218âã C21H26N2O3ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC59.02H6.60N6.55Cl-16.59 枬å®å€ïŒ 58.83 6.94 6.33 15.90 äžèšã®æ¹æ³ã«ããã次ã®ãããªååç©ã補é
ããã ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒçè«å€ã«å¯Ÿãåç57ïŒ ïŒ
mp85âïŒåçµä¹Ÿç¥ãããã®ïŒå解ïŒã C23H30N2O4ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC58.60H6.84N5.94Cl-15.04 枬å®å€ïŒ 56.82 7.82 6.02 16.76 ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒçè«å€ã«
察ãåç82ïŒ ïŒmp112âïŒåçµä¹Ÿç¥ãããã®ïŒã C23H29ClN2O4ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC54.6 H5.78N5.54Clå š21.03 枬å®å€ïŒ 52.48 6.10 5.72 22.19 ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žæ°Žåç©ïŒçè«å€ã«å¯Ÿããåç100ïŒ ïŒ
mpã·ã€ãŒãã«æº¶ããªãïŒ70âããããŠãã次
第ã«è»åïŒã C21H25FN2O3ã»3/2H2Oã®ïŒ åæå€ïŒ èšç®å€ïŒC63.1H7.0N7.0 枬å®å€ïŒ 63.7 7.6 6.9 ïŒâãïŒâãïŒâãïŒïŒâã¡ããã·ããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒçè«å€ã«å¯Ÿããåç35ïŒ ïŒ
mp214ã217âïŒã¢ã»ããããªã«ããçµæ¶ïŒå
解ïŒã C22H28N2O4ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC57.7H6.6N6.1Cl-15.5 枬å®å€ïŒ 53.2 6.5 6.0 17.5 ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒçè«å€ã«å¯Ÿããåç50ïŒ ïŒmp96ã
100âïŒåçµä¹Ÿç¥ãããã®ïŒã C21H25ClN2O3ã®ïŒ åæå€ïŒ èšç®å€ïŒC64.8H6.5N7.2Cl9.1 枬å®å€ïŒ 62.3 6.9 6.9 10.2 ïŒâãïŒâãïŒâãïŒâããïŒâïŒããªãã«
ãªãã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒ
âããã©ãžãã«ããšããã·ããšããã·ãé ¢é žïŒ
åçïŒ67ïŒ ïŒãã®ååç©ã®ïŒã·ãŠãŠé žå¡©ã®
mpïŒ113ã116âïŒé ¢é žãšãã«ïŒã C24H29F3N2O4ã»2C2H2O4ãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC52.01H5.14N4.33 枬å®å€ïŒ 51.24 5.20 4.27 ïŒâãïŒâãïŒâãïŒâããã¹ïŒïŒâãã«ãª
ãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ããš
ããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒåçïŒ40
ïŒ ïŒmpïŒ181ã183âïŒã¢ã»ããããªã«ïŒã C23H28F2N2O4ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC54.54H5.95N5.52Cl-13.3 枬å®å€ïŒ 54.26 6.13 5.57 15.29  è¬çè©Šéš æ¬çºæã«å±ãã次ã®ååç©ã«ã€ããŠã®è¬çè©Š
éšãè¡ããåŸè¿°ãããããªçµæãåŸãã ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒ
âããã©ãžãã«ããšããã·ãã¢ã»ãã¢ããïŒå¡©
é žå¡©ïŒååç©ïŒ¡ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒååç©ïŒ¢ãäŸ1.1åã³1.3ã§
調補ïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒååç©ïŒ£ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒååç©ïŒ€ãäŸ1.1ã§
調補ïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¡ããã·ããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒååç©ïŒ¥ãäŸ1.1ã§
調補ïŒïŒ ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒååç©ïŒŠãäŸ1.2
ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©
ïŒååç©ïŒ§ãäŸ1.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žã«ãªãŠã ïŒååç©ïŒšãäŸ2.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·é ¢é žïŒååç©ïŒ©ãäŸ2.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©ïŒªãäŸ2.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒ
âããã©ãžãã«ããšããã·é ¢é žïŒååç©ïŒ«ãäŸ
2.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©ïŒ¬ãäŸ2.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©
ïŒãäŸ2.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žæ°Žåç©ïŒååç©ïŒ®ãäŸ2.2ã§èª¿è£œïŒïŒ ïŒâãïŒãïŒâãïŒâãïŒâïŒããªãã«ãªã
ã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒâã
ãã©ãžãã«ããšããã·ããšããã·ãã¢ã»ãã¢ã
ãïŒå¡©é žå¡©ïŒååç©ïŒ¯ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâããã¹âïŒïŒâãã«
ãªãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒ
ïŒååç©ïŒ°ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâãïŒâïŒããªãã«ãª
ãã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒâ
ããã©ãžãã«ããšããã·ããšããã·ãé ¢é žïŒå
åç©ïŒ±ãäŸ2.2ã§èª¿è£œïŒã ïŒâãïŒâãïŒâãïŒâããã¹âïŒïŒâãã«
ãªãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©
ãäŸ2.2ã§èª¿è£œïŒã æ¬çºæã«å±ããªãäžèšã®ååç©ïŒäžè¬åŒã
æããããïœïŒïŒã®ãã®ïŒã«ã€ããŠããåãã
ããªè¬çè©Šéšãå®æœããã ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâãã
ã©ãžãã«ãã¢ã»ãã¢ããïŒååç©ïŒããã«ã®ãŒ
ç¹èš±ç¬¬763609å·æ现æžèšèŒã®æ¹æ³ã§èª¿è£œïŒïŒ
mp204âã ïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒããšã
ã«ã¡ãã«ãâïŒâããã©ãžãã«ãã¢ã»ãã¢ãã
ïŒååç©ïŒãH.B.Wrightåã³D.L.Martinã®å
æ²åŒçšæç®åç §ããã«ã®ãŒç¹èš±ç¬¬763609å·æ现
æžèšèŒã®æ¹æ³ã§èª¿è£œïŒïŒmp145âã ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâãã
ã©ãžãã«ãé ¢é žïŒååç©ïŒãæ¹æ³ãäŸïŒã»ïŒ
ã§èª¿è£œïŒïŒmp176âã ïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒããšã
ã«ã¡ãã«ãâïŒâããã©ãžãã«ãé ¢é žïŒååç©
ïŒãåããæ¹æ³ãäŸ2.2ã§èª¿è£œïŒïŒmp106ã
108âã (1) æã¢ã¬ã«ã®ãŒäœçš æã¢ã¬ã«ã®ãŒäœçšã«ã€ããŠã¯ãååæ§ç®è
éæçïŒpassive cutaneous anaphylaxisïŒ
è©ŠéšïŒPCAïŒãã©ããã«æœãããšã«ãã枬
å®ãããJ.Gooseåã³A.M.J.N.Blairã®
Immunologyã16ã749ã760é ïŒ1969幎ïŒã
ãªãã³ã«U.Martinåã³D.Roemerã®
ArzneimittelâForschungã28(5)ã770ã782
é ïŒ1978幎ïŒãåç §ã®ããšãã éã®ã©ãããçšãããã®æšªè ¹ã®æ¯ãäžéšå
ãèœãšããããã®æ¯ãåã€ãéšåã«IGEã®æ
ãªãã«ããã³è¡æž 0.05mlãç®å 泚å°ããŠè©Šéš
åç©ã®ååæäœïŒpassive sensitizationïŒã
ãããããããPCAè©Šéšã®æéäžã泚å°ã
ãéšäœã«çŽ100mm2ã®è¡šé¢ç©ãæããé¡èãªæ
ç¹ãçŸããçšåºŠã«åžéããè¡æž ãçšããã 泚å°ããŠãã72æéåŸã«ãçè²å€ãå«ãã¢
ã¬ã«ã²ã³ã®æº¶æ¶²0.25mlïŒå¡©åãããªãŠã ã®
0.9ïŒ æ°Žæº¶æ¶²0.25mlã«æº¶è§£ããïŒmgã®ãªãã«
ããã³åã³ïŒmgã®ãšãŽã¢ã³ã¹ãã«ãŒïŒãéè
å ã«æäžãããç®å 泚å°ãè¡ã€ãéšäœã«é¡è
ãªéè²æç¹ãçŸããã®ã§ããã®è¡šé¢ç©ã枬å®
ããã æ¬çºæã®ååç©ã®äœçšãè©Šéšããããã«
ã¯ãäžèšãšåãæé ãå®æœãããã â è¡æž ã泚å°ããŠãã72æéåŸã«ãäŸè©Šå
åç©ãçµå£æäžãã â äžèšæäžã®åŸ15åçµéããŠãããã¢ã¬ã«
ã²ã³ã®æº¶æ¶²0.25mlãéè泚å°ãã â ã¢ã¬ã«ã²ã³ãæäžããŠãã30ååŸã«ãé
è²æç¹ã®è¡šé¢ç©ã枬å®ããã äŸè©Šåç©ã®åèšæ°ã®å¹³åãšããŠãçè²æç¹
ã®è¡šé¢ç©ã50ïŒ äœäžãããããªå ç«æäžé
ïŒID50ãÎŒã¢ã«ïŒKgã§è¡šããïŒã次ã®ç¬¬ïŒè¡š
ã«ç€ºãã 第ïŒè¡šã®çµæãããæ¬çºæã®ååç©ã¯çµå£
æäžããéã«æå¹ã§ããããšãããã«å¯Ÿãã
éèæäžããã°æåæ¯äœçšãæããããšãã
ãç¥ãããŠãããããªãŠã ã¯ãã¢ã°ãªã±ãŒã
ãçµå£æäžã§ã¯å¹æã®ãªãããšãããããä»
æ¹ãååç©ïŒãïŒãïŒåã³ïŒïŒæ¬çºæã®ç¯å²
å€ã®ãã®ïŒïœïŒïŒïŒããã»ãšãã©èå³ã®å¯Ÿè±¡
ãšãªããªãããšãã第ïŒè¡šã®çµæããæãã
ã§ããã ãè¡šã (2) é®çåã³æãã¹ã¿ãã³äœçš ãããã®äœçšã«ã€ããŠã¯ãH.Konzettåã³
R.Roesslerã®æ¹æ³ãNaunynâ
Schmiedebergs Arch.exp.Path.Pharmakol.
195ã71ã74é ïŒ1940幎ïŒããã¢ã«ã¢ããã«é©
çšããŠæž¬å®ããããªãã€ãªã³ã®å¹æãšæ¯èŒã
ãã ç³é ããããŠç³çºãããã¢ã«ã¢ããã«å¯Ÿ
ãã人çºåŒåžãæœããæ°ç®¡å å§å
ïŒendotracheal pressureïŒã®èšé²ããšããã
ãããã»ãããã³åã³ãã¹ã¿ãã³ãé£ç¶çã
ãã€ã挞å¢çã«éè泚å°ããŠãå埩çãªæ°ç®¡
æ¯ãããããèµ·ãããããäŸè©Šåç©ã®å šæ°ã«
察ããå¹³åãšããŠãæ°ç®¡æ¯ããããã®50ïŒ ã
æå¶ããååç©ã®æèŠæäžéïŒÎŒã¢ã«ïŒKgã«
ããID50ïŒãäžèšã®ç¬¬ïŒè¡šã«ç€ºãã ãè¡šã æ¬çºæã®ååç©ã«ã¯ã³ãªã³äœåå¹æ
ïŒcholinergic activityïŒããªããäžèšã®ç¬¬ïŒ
è¡šãããæ¬çºæã®ååç©ããããããã»ãã
ãã³åã³ãã¹ã¿ãã³ã«ãã€ãŠèªçºãããæ°ç®¡
æ¯çããã«å¯ŸããŠããããå¹æãæããç¹ã«
ãã¹ã¿ãã³ã«å¯ŸããŠæ Œå¥ã®éžææ§ãæããã
ãšããããããããšã¯å¯Ÿç §çã«ãååç©ïŒã
ïŒãïŒåã³ïŒïŒæ¬çºæã®ç¯å²å€ïŒïœïŒïŒïŒã¯
å¹æãå£ãã ããã«ããã®è©Šéšã®çµæãããæ¬çºæã®å
åç©ã®äžã«ã¯ãäžåã®æäžã§é·æéæãã¹ã¿
ãã³å¹æã瀺ããã®ãããããšãããã€ãã
åŸãã°ãååç©ïŒªã1ÎŒã¢ã«ïŒKgã®æäžéã§
ã¢ã«ã¢ããã«éèå æäžãããšãïŒæéåŸã«
ãããŠã100ïŒ ã®å¹æãç¶æãããã (3) ããŠã¹ã®äžè¬çæåïŒIrwinã®è©ŠéšïŒ Irwinã®è©ŠéšïŒ1959幎ïŒæïŒãïŒæ¥ã«ããŠ
ãŒã»ãã³ãã³ã®ã³ã«ããŒã»ãžãŠãã¢ã»ã«ã¬ã
ãžã§éå¬ããããå»äºååŠã«ã€ããŠã®ãŽã«ã
ã³ã®ç 究äŒè°ã«ããããS.IrwinïŒâGeneral
Phylosophy and methology of
screeningïŒïœ multidimensional
approachâåç §ïŒã«ãã€ãŠæåã調ã¹ãã äžçŸ€ïŒå¹ã®éã®ããŠã¹ïŒäœé18ã22ïœïŒã«
察ããäŸè©Šååç©ããã®è ¹èå ã«æŒžå¢çã«æ
äžããäŸè©Šåç©ã®äžè¬çæåãå ¬ç¥ã®åºæºã«
åŸã€ãŠèŠ³å¯ããã äžèšã®åèååç©ã䜵çšããã â ããããã·ãžã³ïŒïŒâãïŒâãïŒâ
ãïŒïŒâã¯ããããšãã«ïŒããšãã«ã¡ãã«ã
âïŒâããã©ãžãã«ããšããã·ããšã¿ããŒ
ã«ã â ãªããµãŒãã ïŒïŒâã¯ããâïŒïŒïŒâãž
ãããâïŒâããããã·âïŒâããšãã«â
2HâïŒïŒïŒâãã³ãŸãžã¢ãŒãã³âïŒâãª
ã³ã äžèšã®ç¬¬ïŒè¡šã¯ãäŸè©Šåç©ã«ç²Ÿç¥å®å®ã®ç¬¬
ïŒå åãèªèµ·ããæäžéïŒmgïŒKgïŒã瀺ãã ãè¡šã åèååç©ã«æ¯èŒããæ¬çºæã®ååç©ã«ã¯
é®éäœçšãã»ãšãã©ãªãããšã第ïŒè¡šããæ
ããã§ããã ãªãããã®è©Šéšã«ãããŠãæ¬çºæã®ååç©
ã®æ¯æ§ãããããŠäœãããšãç«èšŒãããã äžèšã®ç¬¬ïŒè¡šã«ã¯ãããŠã¹ã®è ¹èå ã«æäž
ããæã®æ¬çºæã®ååç©ã®èŽæ»éãmgïŒKgã§
瀺ãïŒïŒå¹ã®ãã¡ã®ïŒå¹æ»äº¡ïŒã ãè¡šã ããã§ç¬¬ïŒè¡šãšç¬¬ïŒè¡šïŒç²Ÿç¥å®å®åæäžé
ãšèŽæ»éïŒãæ¯èŒãããšãããååç©ã«ãã€
ãŠã¯ãèŽæ»éã«è¿ãæäžéã§æŒžãé®éå¹æã
çŸãããŠããã (4) DL50ã®èŽæ»é æ¬çºæã®ååç©ã®æ¯æ§ãäœãããšã¯ãçµå£
æäžæã®DL50æ¯æ§ã枬å®ããããšã«ãã€ãŠ
確èªããããååç©ïŒªã®å ŽåããŠã€ã¹ã¿ãŒã«
ïŒWistarïŒã©ããã«ã€ããŠã®DL50ã¯ãéã®
ã©ããã§ã¯703mgïŒKgã§ãããéã®ã©ããã§
ã¯865mgïŒKgã§ããã ããŠã¹ã®å Žåãååç©ïŒªã®DL50ã¯ããã
ãã600mgïŒKgïŒéã®ããŠã¹ïŒåã³752mgïŒKg
ïŒéã®ããŠã¹ïŒã§ããã (5) åŠæ¹åã³æäžæ³ æ¬çºæã®ååç©ãå«ãè¬å€çµæç©ã¯ãçµå£
æäžãè žç®¡å€æäžåã¯çŽè žå æäžãè¡ãããš
ãã§ããããŸãã錻è å æ³šå ¥æ³ïŒãšã¢ãŸãŒ
ã«ïŒã§æäžããããšãã§ãããããããã¯è»
èãããã¯ã¯ãªãŒã ã®ç¶æ ã§çšããããšãã§
ãããçµå£æäžã«çšãããè¬å€çµæç©ã¯ãåº
äœåã¯æ¶²äœã§ãã€ãŠããããäŸãã°ãé²åºå
ã¯è¢«èŠãããé å€ããã«ãç³è¡£é ããŒã©ãã³
ã«ãã»ã«ã溶液ãã·ããããã®ä»ã®åœ¢æ ãšã
ãããšãã§ãããè žç®¡å€æäžã«çšãããçµæ
ç©ã¯ããã®çš®ã®æäžã«å ¬ç¥ã®ä»»æã®è¬å€çµæ
ç©ã®åœ¢æ ãäŸãã°ãæ°Žæ§åã¯æ²¹æ§ã®æº¶æ¶²ãæž
æ¿æ¶²åã¯ä¹³å€ãšããŠçšããããšãã§ãããçŽ
è žå ã«æäžããå Žåã«ã¯ãæ¬çºæã®ååç©ã
å«ãçµæç©ãäžè¬ã«åè¬ã®åœ¢æ ã§çšããã äŸãã°æ³šå°çšæº¶æ¶²ã泚å°çšæžæ¿æ¶²ãé å€ã
滎å€ãåè¬çã®åœ¢æ ã®è¬å€ã¯ãæ £çšã®è£œè¬æ¹
æ³ã§èª¿å€ããããšãã§ãããæ¬çºæã®ååç©
ããåºäœåã¯æ¶²äœã§ãã€ãŠãæ¯æ§ã®ãªããè¬
å€ãšããŠèš±å®¹ããããã€ãªã€ãŒãšæ··åãã
ãããŸããåæ£å€ããã€ã¹ã€ã³ãã°ã¬ãŒãå€
ïŒdisintegration agentïŒãå®å®å€çãšæ··åã
ãããšãã§ãããææã«ãã€ãŠã¯ãé²è å€ã
çå³æãçè²å€çãå ããããšãã§ããã è¬å€çµæç©äžã«å«ãŸãã掻æ§ååç©ã®çŸå
çã¯ãæ£è ãæäžæ¹æ³ãç¹ã«æäžã®ç床ã«å¿
ããŠåºç¯å²ã«å€åãããããšãã§ããã é å€æ³ã«ã€ããŠããã°ãåºç¯å²ã®æäžéå
äœã«ããã€ãŠå€ããããšãå¯èœã§ãããäŸã
ã°æŽ»æ§ååç©ã0.5ã250mgå«ãããã«é å€ã
ãããšãã§ããã æ¬çºæã®ååç©ãå«ãçµæç©ã®äžäŸãšã
ãŠãçµå£æäžçšãŒã©ãã³ã«ãã»ã«ã®é åäŸã
瀺ããšæ¬¡ã®ãšããã§ããã ååç©ïŒª 100mg ä¹³ ç³ 67mg ã¹ãã¢ãªã³é žãã°ãã·ãŠã ïŒmg äºé žåçªçŽ ïŒãšãŒãã·ã«ïŒ ïŒmg
ã«ïŒâïŒâããã©ãžãã«ãé ¢é žããã®ã¢ãããå
ã³æ¯æ§ã®ãªããè¬å€ãšããŠèš±å®¹ããããããã®å¡©
é¡ããªãã³ã«ãããã®è£œé æ¹æ³åã³ããããå«ã
è¬å€çµæç©ã«é¢ããã æ¬çºæã«ããæ°èŠååç©ã¯ãäžè¬åŒïŒ ïŒåŒäžã ã¯ããããã·ã«åºåã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠæ°ŽçŽ ååãããã²ã³ååã
çŽéãããã¯åæéã®äœçŽã¢ã«ã³ãã·åºåã¯ã
ãªãã«ãªãã¡ãã«åºãè¡šããã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã奜ãŸããã¯ïŒã§ããïŒãæãããª
ãã³ã«æ¯æ§ã®ãªããè¬å€ãšããŠèš±å®¹ããããã®å¡©
é¡ãšããŠã®æ§é ãæããã æ¬æ现æžã«çšããããçšèªãäœçŽã¢ã«ã³ãã·ã
ãšã¯ãäŸãã°ã¡ããã·ããšããã·ãããããã·ç
ã®ããã«ãïŒãïŒåã®ççŽ ååãå«ãçŽéåã¯å
åéã®ã¢ã«ã³ãŒã«ã®æ®åºãæå³ãããããã²ã³å
åã¯ãå¡©çŽ åã¯åŒçŽ ååã§ããã®ãæãŸããã æ¬æ现æžã§ãããæ¯æ§ã®ãªããè¬å€ãšããŠèš±å®¹
ãããå¡©ããšã¯ãåŒã§è¡šããããé žåã³ã¢ãã
ã®è¬å€ãšããŠèš±å®¹ãããé žãäŸãã°é ¢é žãããã
é žããã¯ãé žãã¢ã¹ã³ã«ãã³é žãå¡©åæ°ŽçŽ é žãè
åæ°ŽçŽ é žãç¡«é žåã³çé žãšã®ä»å å¡©ãæå³ããã®
ã¿ã§ãªããéå±å¡©ïŒäŸãã°ããããªãŠã åã¯ã«ãª
ãŠã å¡©ïŒãã¢ã³ã¢ããŠã å¡©ãã¢ãã³å¡©åã³ã¢ãã
é žå¡©ã®ãããªè¬å€ãšããŠèš±å®¹ãããå¡©ããæå³ã
ãã ãããã®è¬å€ãšããŠèš±å®¹ãããå¡©é¡ã¯ãããèª
äœå ¬ç¥ã®æ¹æ³ã«ãã€ãŠåŒã®ååç©ãã補é ãã
ããšãã§ããã æ¬çºæã«ãã奜ãŸããååç©ã«ã¯ã次ã®ãããª
ãã®ãããã ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšããã·ã
é ¢é žåã³ãã®ïŒå¡©é žå¡©ã ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšããã·ã
é ¢é žã«ãªãŠã ã ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ããšããã·ãé ¢é žåã³ãã®ïŒå¡©é ž
å¡©ã ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žåã³ãã®æ°Žåç©ã åŒã®ååç©ã¯ãè¬ççã«èå³ããæ§è³ªãæã
ãŠãããç¹ã«ããããã®ååç©ã¯ãæã¢ã¬ã«ã®ãŒ
å€ãæãã¹ã¿ãã³å€ãæ°ç®¡æ¯æ¡åŒµå€åã³é®çå€ãš
ããŠæçšã§ããã ããã«ãåŸæ¥ã®æãã¹ã¿ãã³å€ã®å Žåã«ãã°ã
ã°èŠãããäžæ¢ç¥çµã«å¯Ÿããåºæ¿åã¯æå§ãšãã€
ãäºæ¬¡çå¹æãæå°éã«æãããããšããç¹åŸŽã
ãããã®ååç©ã¯æããŠããããã®ãããããã
ã®ååç©ã¯ãèå³ãã麻é åã³æççæ§ã瀺ããš
å ±ã«ã倧è³åã³å¿èè¡ç®¡ã®æ©èœäžå šæã«ãå¹æã
çºæ®ããã H.B.Wrightåã³D.L.Martinã®è«æãJ.Med.
Chem.11ïŒ1968幎ïŒ390ã391é ãã§ã¯ãã³ã¬ã¹ã
ããŒã«éäžå€ãšããŠã®ïŒâãïŒâãïŒïŒâã¯ãã
ããšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ãã¢ã»ãã¢ããïŒåŒïŒïŒ¹ïŒNH2ïŒïŒžïŒïœâ
ClïŒXâ²ïŒïŒšïŒãã ãïœïŒïŒïŒã®äœçšã«ã€ããŠã®
ç 究ãçºè¡šãããŠããããåŸãããçµæã¯å¿ ãã
ããææã§ãªãã ããã«ããã«ã®ãŒç¹èš±ç¬¬763609å·æ现æžã«ã¯ã
ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãž
ãã«ãã¢ã»ãã¢ããïŒåŒïŒïŒ¹ïŒNH2ïŒïŒžïŒ
Xâ²ïŒïŒšïŒãã ãïœïŒïŒïŒã«å©å°¿äœçšã®ããããš
ãé瀺ãããŠããã該ç¹èš±ã«ã¯ãã¢ããåºã®çªçŽ
ååã眮æãããåæ§ã®ã¢ã»ãã¢ããã§ãã€ãŠã
çš®ã ã®ä»ã®è¬ççæ§è³ªãæãããã®ãèšèŒãããŠ
ããã æ¬çºæè ãè¡ã€ãè¬çè©Šéšã®çµæã§ã¯ãããã
ã®ã¢ã»ãã¢ããã察å¿ããé žã®æã¢ã¬ã«ã®ãŒãé®
çåã³æãã¹ã¿ãã³å¹æã¯ãé¢å¿ãå¯ããã»ã©ã®
ãã®ã§ãªãã€ãïŒB.Pharmacologyåç §ïŒã  補é æ¹æ³ åŒïŒïŒ¹ïŒâNH2ïŒã®ã¢ããã¯ã次ã«èš
èŒãããããªçš®ã ã®æ¹æ³ã§è£œé ããããšãã§
ããã ïŒïŒ äžèšã®æ¹çšåŒã«åŸããåŒã®ïŒâïŒãž
ããšãã«ã¡ãã«ïŒããã©ãžã³ãšåŒã®Ïâ
ããã¢ã»ãã¢ãããšãåå¿ãããã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ããããããŠïŒºã¯ããã²ã³ååã§ããã ãã®åå¿ã¯ãäžè¬ã«äžæŽ»æ§æº¶å€ïŒå¥œãŸã
ãã¯èèªæã¢ã«ã³ãŒã«ãã¡ãã«ãšãã«ã±ã
ã³ã®ãããªèèªæã±ãã³ãåã¯ãã«ãšã³ã
ããã¯ãã·ã¬ã³ã®ãããªè³éŠæçåæ°ŽçŽ ïŒ
äžã«ãããŠãé žå容äœãäŸãã°ããªãšãã«
ã¢ãã³ã®ãããªç¬¬äžææ©ã¢ãã³ãåã¯çé ž
ãããªãŠã ã®ãããªç¡æ©å¡©åºã®ååšäžã§æ°
æéåå¿æ··åç©ã80ã150âã«å ç±ããã
ãšã«ãã€ãŠè¡ãããã ïŒïŒ äžèšã®åå¿åŒã«åŸããåŒã®ÏâãïŒ
âïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãžã
ã«ãã¢ã«ã«ããŒã«ã®ã¢ã«ã«ãªéå±å¡©ãšãåŒ
ã®ïŒâããã¢ã»ãã¢ãããšãåå¿ãã
ãã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ãããã¯ããã²ã³ååã§ããããããŠ
Meã¯ã¢ã«ã«ãªéå±ååã§ããã åŒã®ã¢ã«ã«ãªéå±å¡©ãšãåŒã®ããã¢
ã»ãã¢ãããšã®éã®åå¿ã¯ããã«ãšã³ãã
ã·ã¬ã³åã¯ãžã¡ãã«ãã«ã ã¢ããã®ãããª
äžæŽ»æ§æº¶å€äžã«ãããŠãïŒâããåå¿æ··å
ç©ã®éæµæž©åºŠãŸã§ã®æž©åºŠã§å®æœãããã ãã®åå¿ã«äœ¿ãããåŒã®ã¢ã«ã«ãªéå±
å¡©ã¯ããã«ãšã³ããã·ã¬ã³åã¯ãžã¡ãã«ã
ã«ã ã¢ããã®ãããªäžæŽ»æ§æº¶å€äžã«ãã
ãŠãé©åœãªÏâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ãã¢ã«ã«ããŒã«
ãšãã¢ã«ã«ãªéå±æ°ŽçŽ åç©ãäžè¬ã«ã¯æ°ŽçŽ
åãããªãŠã ãšãåå¿ãããããšã«ãã€ãŠ
ãã®å Žã§èª¿è£œãããã åŒïŒMeïŒïŒšïŒã®ã¢ã«ã³ãŒã«ã®è£œé æ³
ã¯ãç±³åœç¹èš±ç¬¬2899436å·æ现æžã«èšèŒã
ããŠããã ïŒïŒ äžèšã®æ¹çšåŒã«åŸããã¢ã³ã¢ãã¢ãšã
ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâã
ãã©ãžãã«ãé ¢é žã®å®èœæ§èªå°äœãããªã
ã¡ãåŒã§ç€ºãããããã²ã³åç©åã¯äœçŽ
ã¢ã«ãã«ãšã¹ãã«ãšãåå¿ãããã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ããããããŠïŒ·ã¯ããã²ã³åååã¯â
ORâ²åºïŒRâ²ã¯äœçŽã¢ã«ãã«åºã§ããïŒãè¡š
ããã ããã²ã³ååã¯ãäŸãã°å¡©çŽ åã¯èçŽ å
åã§ãã€ãŠããããããŠã¢ã«ãã«åºã¯ãäŸ
ãã°ã¡ãã«åã¯ãšãã«åºã§ãã€ãŠãããã ãããã²ã³ååãè¡šããå ŽåãåŒ
ïŒïŒ¹ïŒOHïŒã®é žãåŸè¿°ã®æ¹æ³ã§æåã«
補é ãã次ã«ãã®çš®ã®ååç©ã補é ããã
ãã®åšç¥ã®æ¹æ³ã«ãããäžèšã®é žã察å¿ã
ãããã²ã³åç©ã«å€æããã次ãã§ãåŸã
ããããã²ã³åç©ãäžæŽ»æ§æº¶å€äžã§ã¢ã³ã¢
ãã¢ãšåå¿ãããã ãâORâ²åºãè¡šããå Žåã«ã¯ãåŸè¿°ã
ãæ¹æ³ã®ãã¡ã®äžã€ã«ãã€ãŠãæåã«åŒ
ã®ãšã¹ãã«ã補é ããã次ã«ãïŒâãªãã
åšå²æž©åºŠã«ãããŠãäžèšã®ãšã¹ãã«ãäžæŽ»
æ§æº¶å€äžã§ã¢ã³ã¢ãã¢ãšåå¿ãããããã®
åå¿ã¯ããããªãŠã ã¡ããã·ãã®ãããªè§Š
åªã®ååšäžã§è¡ãããšãã§ããã åŒïŒïŒ¹ïŒOHïŒã®é žã¯ãïŒâãïŒâïŒãž
ããšãã«ã¡ãã«ïŒâïŒâããã©ãžãã«ãé ¢é ž
ã®å®èœæ§èªå°äœãããªãã¡ãåŒ ãåŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§
ããããããŠYâ²ã¯âNH2åºåã¯âORâ²åº
ïŒRâ²ã¯äœçŽã¢ã«ãã«åºãäŸãã°ã¡ãã«ããã
ã¯ãšãã«åºãè¡šããïŒã§ããããæããã¢ã
ãåã¯äœçŽã¢ã«ãã«ãšã¹ãã«ãå¡©åºæ§åªè³ªäž
ã§å æ°Žå解ããããšã«ãã€ãŠè£œé ããããšã
ã§ããã ãã®å æ°Žå解ã¯ã20âããåå¿æ··åç©ã®éæµæž©
床ãŸã§ã®æž©åºŠã«ãããŠãæ°Žæ§åªè³ªãåã¯æ°Žæ§ã¡ã¿
ããŒã«ããšã¿ããŒã«çã®ãããªæ°Žæ§ã¢ã«ã³ãŒã«åª
質äžã§ç¡æ©å¡©åºãäŸãã°æ°Žé žåãããªãŠã åã¯ã«
ãªãŠã ãçšããŠè¡ãããã åŒïŒYâ²ïŒâNH2ïŒã®ã¢ããã¯ãåèšã®æ¹æ³
ïŒïŒãïŒïŒã®ãã¡ã®ããããã«ãã€ãŠè£œé ã
ãããšãã§ããã åŒïŒïŒ·ïŒâORâ²ïŒã®ãšã¹ãã«ãåã³åŒ
ïŒYâ²ïŒâORâ²ïŒã®ãšã¹ãã«ã¯ãçš®ã ã®æ¹æ³ã§è£œé
ããããšãã§ããã補é æ³ã®äŸãããããšæ¬¡ã®ãš
ããã§ããã (a) äžèšã®åå¿åŒã«åŸããåŒã®ïŒâïŒãžããšã
ã«ã¡ãã«ïŒããã©ãžã³ãšãåŒã®äœçŽã¢ã«ãã«
Ïâããã¢ã»ããŒããšãåå¿ãããã åŒäžããXâ²ãïœåã³ïœã¯åèšãšå矩ã§ã
ããRâ²ã¯äœçŽã¢ã«ãã«åºã§ããããããŠïŒºã¯
ããã²ã³ååã§ãããåŸã€ãŠãRâ²ã¯äŸãã°ã¡
ãã«åã¯ãšãã«åºã§ãã€ãŠãããã¯å¡©çŽ åã¯
èçŽ ååã§ãã€ãŠããã äžè¬ã«ããã®åå¿ã¯ããã³ãŒã³ããã«ãšã³å
ã¯ãã·ã¬ã³ã®ãããªäžæŽ»æ§æº¶å€äžã第äžææ©å¡©
åºãäŸãã°ããªãšãã«ã¢ãã³ãåã¯ç¡æ©å¡©åºã
äŸãã°çé žãããªãŠã ã®ãããªé žå容äœã®ååš
äžã«åå¿æ··åç©ã80ãã150âã®æž©åºŠã«æ°æéå
ç±ããããšã«ãã€ãŠè¡ãããã (b) äžèšã®åå¿åŒã«åŸããåŒã§è¡šããããÏâ
ãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãžã
ã«ãã¢ã«ã«ããŒã«ã®ã¢ã«ã«ãªéå±å¡©ãšãåŒïŒžã§
è¡šããããïŒâããé ¢é žã®äœçŽã¢ã«ãã«ãšã¹ã
ã«ãšãåå¿ãããã åŒäžãRâ²ããXâ²ãïœåã³ïœã¯åèšãšå矩
ã§ãããã¯ããã²ã³ååã§ããããããŠMe
ã¯ã¢ã«ã«ãªéå±ååãè¡šããã åŒã®ã¢ã«ã«ãªéå±å¡©ãšãåŒã®ããã²ã³åãš
ã¹ãã«ãšã®éã®åå¿ã¯ãäžæŽ»æ§æº¶å€äžãïŒâãã
åå¿æ··åç©ã®éæµæž©åºŠãŸã§ã®æž©åºŠã«ãããŠè¡ãã
ãã 以äžãäŸããããŠæ¬çºæã説æããã äŸ ïŒ ïŒåŒïŒïŒ¹ïŒâNH2ïŒã®ã¢ããã®è£œé 1.1 ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâ
ïŒâããã©ãžãã«ããšããã·ãã¢ã»ãã¢ããïŒ
å¡©é žå¡©ïŒæ¹æ³ïŒïŒïŒ 37.8ïœïŒ0.15ã¢ã«ïŒã®ïŒâïŒãžããšãã«ã¡ã
ã«ïŒããã©ãžã³ã27.5ïœïŒ0.2ã¢ã«ïŒã®ïŒâ
ïŒïŒâã¯ãããšããã·ïŒã¢ã»ãã¢ãããåã³
26.5ïœã®ç¡æ°Žçé žãããªãŠã ã®ãã·ã¬ã³120ml
äžæ··åç©ã90ãã120âã«ïŒæéå ç±ããããã®
åŸã120mlã®ãã³ãŒã³ãåå¿æ··åç©ã«å ããç
ããæ²æŸ±ãå¥ããææ©çžãåžå¡©é žïŒæ¿å¡©é ž30
mlãæ°Ž100mlã«å ãããã®ïŒã§æœåºãããæ°Žé ž
åãããªãŠã ã®æ¿å氎溶液40mlãå ããåŸãã
ã³ãŒã³ã§æœåºããããã³ãŒã³æ°Žæº¶æ¶²ãæ°ŽæŽãã
ç¡æ°Žçé žãããªãŠã ã§ä¹Ÿç¥ããŠãããã³ãŒã³ã
èžçºä¹Ÿåºããããèžçºæ®æž£ããžãšãã«ãšãŒãã«
ãšå ±ã«ããã€ã¶ããæŸçœ®ããŠçµæ¶ããããçè«
å€ã®73ïŒ ã®åçã§ïŒâãïŒâãïŒâïŒãžããšã
ã«ã¡ãã«ïŒâïŒâããã©ãžãã«ããšããã·ãã¢
ã»ãã¢ãããåŸãã mp119ã120âã ãšã¿ããŒã«äžã§è£œé ããïŒå¡©é žå¡©ã¯ã230â
ã«ãããŠå解ããªãã溶èããã C21H27N3O2ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC59.15H6.85N9.85Cl-16.63 枬å®å€ïŒ 58.99 6.80 9.79 16.46 äžèšã®æ¹æ³ãçšããäžèšã®ååç©ã補é ã
ãïŒ ïŒâãïŒâãâïŒãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒ åçã¯çè«å€ã®47ïŒ ïŒãšã¿ããŒã«ããåçµæ¶
åŸã®mp111ã112âã C21H26ClN3O2ãšããŠã®ïŒ åæå€ïŒ èšç®æž¬ïŒC65.02H6.71N10.83Cl9.14 枬å®å€ïŒ 64.59 7.00 10.82 9.54 ïŒâãïŒâãïŒâãïŒïŒãžããšãã«ã¡ãã«ïŒ
âïŒâããã©ãžãã«ããšããã·ããšããã·ãã¢
ã»ãã¢ããïŒ å®è³ªäžãå®éçã«åŸãããç²è£œç¶æ ã®çæç©
ã¯ã粟補ããªãã§ãã®ãŸãŸå¯Ÿå¿ããé žã®è£œé ã«
çšããããšãã§ããïŒäŸ2.2åç §ïŒã ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããšã
ã«ïŒããšãã«ã¡ãã«ãïŒâããã©ãžãã«ããšã
ãã·ããšããã·ãã¢ã»ãã¢ããïŒ å®è³ªäžå®éçã«åŸãããç²è£œç¶æ ã®çæç©
ã¯ã粟補ããããšãªãã«ãã®ãŸãŸå¯Ÿå¿ããé žã®
補é ã«çšããããšãã§ããïŒäŸ2.2åç §ïŒã ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒ çè«å€ã«å¯ŸããŠ54.7ïŒ ã®åçïŒã¢ã»ããããª
ã«ããæçµæ¶ããåŸã®mp105ã107âã C21H26FN3O2ã®ïŒ åæå€ïŒ èšç®å€ïŒC67.90H7.09N11.31 枬å®å€ïŒ 68.3 7.40 11.21 ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒ çè«å€ã«å¯ŸããŠ57ïŒ ã®åçïŒãã³ãŒã³ããå
çµæ¶ããåŸã®mp129ã130âã C21H26ClN3O2ã®ïŒ åæå€ïŒ èšç®å€ïŒC65.0H6.75N10.8Cl9.4 枬å®å€ïŒ 66.3 7.0 10.6 9.7 ãã®ã¢ããã®ïŒå¡©é žå¡©ã補é ããïŒè¥å¹²ã®ïŒ
å¡©é žå¡©ãå«ããã€ãœãããããŒã«ããåçµæ¶ã
ãåŸã®mp218ã220âã C21H26ClN3O2ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC54.72H6.12N9.11Cl-15.38 Clå š23.08 枬å®å€ïŒ 55.69 6.52 9.20 11.86 20.27 ïŒâãïŒâãïŒâãïŒïŒâã¡ããã·ããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒçè«å€ã®20ïŒ ã®å
çïŒã¢ã»ããããªã«ã§åçµæ¶åŸã®mp175ã176
âã C22H29N3O3ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC57.8H6.8N9.2Cl-15.5 枬å®å€ïŒ 57.8 7.2 9.5 15.9 ïŒâãïŒâãïŒâãïŒâããïŒâïŒããªãã«
ãªãã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒ
âããã©ãžãã«ããšããã·ããšããã·ãã¢ã»ã
ã¢ããïŒåçïŒ78ïŒ ïŒãã®ååç©ã®ïŒå¡©é žå¡©ã®
mpïŒ178ã181âïŒã¢ã»ããããªã«ïŒ C24H30F3N3O3.2HClãšããŠã®åæå€(%)ïŒ èšç®å€ïŒC53.53H5.99N7.80Cl-13.17 枬å®å€ïŒ 51.47 5.60 7.89 13.10 ïŒâãïŒâãïŒâãïŒâããã¹ïŒïŒâãã«ãª
ãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ããš
ããã·ããšããã·ãã¢ã»ãã¢ããïŒåçïŒ90
ïŒ ïŒãã®ååç©ã®ïŒå¡©é žå¡©ã®mpïŒ188ã190â
ïŒã¢ã»ããããªã«ïŒ C23H29F2N3O3.2HClãšããŠã®åæå€(%)ïŒ èšç®å€ïŒC54.54H6.17N8.29Cl-14.0 枬å®å€ïŒ 54.01 6.38 8.07 13.75 1.2 ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒæ¹æ³ïŒïŒïŒ 180mlã®ãžã¡ãã«ãã«ã ã¢ããäž172.9ïœ
ïŒ0.508ã¢ã«ïŒã®ïŒâãïŒâãïŒâïŒãžããšãã«
ã¡ãã«ïŒâïŒâããã©ãžãã«ããšããã·ããšã¿
ããŒã«ã®æº¶æ¶²ã«æ°ŽçŽ åãããªãŠã 24.2ïœïŒ0.53
ã¢ã«ïŒãå ãããæ·»å ãçµäºããæç¹ã§ãåå¿
æ··åç©ã40âã«30åå ç±ãããå·åŽåŸã60ïœ
ïŒ0.624ã¢ã«ïŒã®ïŒâã¯ããã¢ã»ãã¢ããã10å
éã§å ãããåå¿æ··åç©ã®æž©åºŠã40âã«äžãã
30åéãã®æž©åºŠã«ä¿ã€ãå·åŽåŸãæ°Ž30mlãå
ãã次ãã§èžçºä¹Ÿåºããããèžçºæ®æž£ãïŒã®
æ°Žã«æžæ¿ãããã®æžæ¿æ¶²ããã³ãŒã³ã§æœåºã
ããç¡æ°Žçé žã«ãªãŠã äžã§ææ©çžã也ç¥ãã
åŸãææ©çžãèžçºããããã·ãªã«ã®ã«ã©ã ïŒæº¶
é¢å€ãšããŠã容éïŒå®¹éã§95ïŒïŒã®ã¯ãããã«
ã âãšã¿ããŒã«äœ¿çšïŒãçšããã¯ãããã°ã©ã
ã€ãŒã«ãããèžçºæ®æž£ã粟補ãããåŸãããç
æç©ã45mlã®ãšã¿ããŒã«ã«æº¶è§£ããå¡©åæ°ŽçŽ é ž
ã®5.1Nãšã¿ããŒã«æº¶æ¶²24mlã該溶液ã«å ããã
çè«å€ã«å¯ŸããŠïŒïŒ ã®åçã§ïŒâãïŒâãïŒâ
ãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâããã©ãžã
ã«ããšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é ž
å¡©19ïœãåŸãïŒã¢ã»ããããªã«ã§åçµæ¶åŸã®
mp196ã197âã C23H31N3O3ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC58.72H7.07N8.93Cl-15.07 枬å®å€ïŒ 58.29 6.83 8.44 15.01 äžèšã®æ¹æ³ãçšãã次ã®ååç©ã調補ããïŒ ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒ
çæç©ãã€ãœãããããŒã«ããåçµæ¶ãããã®
ã¯ãïŒååã®çµæ¶æº¶åªãå«ããçè«å€ã®11ïŒ ã®
åçïŒmp100ã102âã C23H30ClN3O3ã»C3H7OHã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC55.27H7.16N7.43Cl-12.55 Clå š18.22 枬å®å€ïŒ 53.10 6.93 7.18 12.56 18.79 1.3 ïŒâãïŒâãïŒâãïŒâïŒã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒæ¹æ³ïŒïŒïŒ ã¡ãã«ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšã
ã«ïŒããšãã«ã¡ãã«ãïŒâããã©ãžãã«ããšã
ãã·ãã¢ã»ããŒã2.3ïœïŒ0.0057ã¢ã«ïŒãç¡æ°Ž
ã¡ã¿ããŒã«100mlã«æº¶è§£ããããã®æº¶æ¶²ãïŒã
10âã®æž©åºŠã«å·åŽãã次ãã§ã¢ã³ã¢ãã¢ã20æ
éæ°æ³¡éå ¥ãããæžå§äžã«æº¶å€ãèžçºé€å»ãã
æ®æž£ããžãšãã«ãšãŒãã«ãšå ±ã«ããã€ã¶ããŠã
ãæŸçœ®ããŠçµæ¶ãããïŒâãïŒâãïŒâãïŒïŒ
âã¯ããããšãã«ïŒããšãã«ã¡ãã«ãâïŒâã
ãã©ãžãã«ãâãšããã·ãã¢ã»ãã¢ãã1.2ïœ
ãåŸãïŒçè«å€ã«å¯Ÿããåç54ïŒ ïŒmp109ã
110âã C21H26ClN3O2ã®ïŒ åæå€ïŒ èšç®å€ïŒC65.02H6.71N10.83Cl9.14 枬å®å€ïŒ 65.13 6.59 10.95 9.54 åæç©è³ªãšããŠçšããã¡ãã«ïŒâãïŒâãïŒ
âãïŒïŒâã¯ããããšãã«ïŒããšãã«ã¡ãã«ã
âïŒâããã©ãžãã«ããšããã·ãã¢ã»ããŒãã¯
次ã®ããã«è£œé ããïŒ ç¡æ°Žãã·ã¬ã³500mläžã«æº¶è§£ããã87ïœ
ïŒ0.30ã¢ã«ïŒã®ïŒâãïŒïŒâã¯ããããšãã«ïŒã
ãšãã«ã¡ãã«ãããã©ãžã³ã58ïœïŒ0.38ã¢ã«ïŒ
ã®ã¡ãã«ïŒïŒâã¯ãããšããã·ïŒã¢ã»ããŒãã
åã³40.3ïœïŒ0.38ã¢ã«ïŒã®çé žãããªãŠã ãã
ãªãæ··åç©ãããæ¹æããªããéæµäžã«40æé
å ç±ããã次ã«åå¿æ··åç©ãå·åŽããŠããé
ãããããŠåºåœ¢ç©ã¯ãã³ãŒã³ã§æŽã€ãåŸã«æ£ãŠ
ãã液ãèžçºä¹Ÿåºããã·ãªã«ã®ã«ã©ã ïŒæº¶é¢
å€ãšããŠã容éïŒå®¹éã§97ïŒïŒã®ã¯ãããã«ã
âã¡ã¿ããŒã«ã䜿çšïŒãçšããã¯ãããã°ã©ã
ã€ãŒã§èžçºæ®æž£ã粟補ããææã®ã¡ãã«ãšã¹ã
ã«34ïœïŒçè«éã®27.8ïŒ ïŒãåŸãã C22H27ClN2O3ãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC65.60H6.70N6.95 枬å®å€ïŒ 63.87 6.55 6.59 ãã®ãšã¹ãã«ã®äžèšã®ä»å å¡©ïŒçš®ã補é ã
ãïŒ ïŒå¡©é žå¡©ïŒmp123ã125âã C22H27ClN2O3ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC55.50H6.10N5.89Cl-14.92 枬å®å€ïŒ 55.20 6.23 5.65 13.2 ïŒãã¬ã€ã³é žå¡©ïŒmp128ã130âã C30H35ClN2O11ãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC56.70H5.51N4.41 枬å®å€ïŒ 57.01 5.22 4.45 äŸ ïŒ ïŒåŒïŒïŒ¹ïŒOHïŒã®é žã®è£œé 2.1 ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒæ¹æ³ïŒ ç¡æ°Žãšã¿ããŒã«65mläžã«16.8ïœïŒ0.0417ã¢
ã«ïŒã®ã¡ãã«ïŒâãïŒâãïŒâãïŒïŒâã¯ãã
ããšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ããšããã·ãã¢ã»ããŒãïŒäŸ1.3ã®æ¹æ³ã§èª¿
補ãããã®ïŒã溶解ããããã®æº¶æ¶²ã«æ°Žé žåã«
ãªãŠã ã®1Nãšã¿ããŒã«æº¶æ¶²42mlãå ããåå¿
æ··åç©ãéæµäžã«ïŒæéå ç±ãããå·åŽåŸã
éããŠæ²æ®¿ãé€ãããžãšãã«ãšãŒãã«ã§æŽæµã
ãã液ãèžçºä¹Ÿåºãããžãšãã«ãšãŒãã«ãçš
ããŠèžçºæ®æž£ãããã€ã¶ããæŸçœ®ããŠçµæ¶ãã
ããåžæ¹¿æ§ã®ïŒâãïŒâãïŒâãïŒïŒâã¯ãã
ããšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ããšããã·ãé ¢é žã«ãªãŠã 10.5ïœãåŸããç
è«å€ã«å¯ŸããŠ59ïŒ ã®åçïŒmp161ã163âã C21H24ClN2O3KãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC59.0 H5.63N6.56 枬å®å€ïŒ 57.97 5.77 6.48 ãã®ã«ãªãŠã å¡©ã100mlã®æ°Žã«æº¶è§£ãã10ïŒ
ã®å¡©é žã§PHïŒã«èª¿ç¯ããããã®æº¶æ¶²ãã¯ããã
ã«ã ã§æœåºããç¡æ°Žç¡«é žãã°ãã·ãŠã ã§ä¹Ÿç¥ã
ãåŸãææ©çžãèžçºä¹Ÿåºããããèžçºæ®æž£ããž
ãšãã«ãšãŒãã«ãšå ±ã«ããã€ã¶ããæŸçœ®ããŠçµ
æ¶ããããïŒâãïŒâãïŒâãïŒïŒâã¯ããã
ãšãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžã
ã«ããšããã·ãé ¢é ž7.5ïœãåŸããçè«å€ã«å¯Ÿ
ããŠ81ïŒ ã®åçïŒmp110ã115âã C21H25ClN2O3ã®ïŒ åæå€ïŒ èšç®å€ïŒC64.80H6.48N7.20 枬å®å€ïŒ 62.3 6.48 6.92 ãã«ãšã³äžã§å¯Ÿå¿ããïŒå¡©é žå¡©ã調補ïŒçè«
å€ã«å¯Ÿã80ïŒ ã®åçïŒmp225âã C21H25ClN2O3ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC54.60H5.85N6.07Cl-15.38 Clå š23.07 枬å®å€ïŒ 54.42 5.60 6.01 15.29 23.08 2.2 ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâ
ïŒâããã©ãžãã«ããšããã·ãé ¢é žïŒæ¹æ³ïŒ 200mlã®ãšã¿ããŒã«ã«æº¶è§£ãã19ïœïŒ0.054ã¢
ã«ïŒã®ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒ
âïŒâããã©ãžãã«ããšããã·ã¢ã»ãã¢ãã
ïŒäŸ1.1ã«èšèŒã®æ¹æ³ã§èª¿è£œãããã®ïŒãšãæ°Žé ž
åãããªãŠã ã®4Nãšã¿ããŒã«æº¶æ¶²27mlãšã®æ··
åç©ãéæµäžã«ïŒæéå ç±ããã3.61Nå¡©é ž
29.7mlã«ãŠåå¿æ··åç©ãPH6.3ã«èª¿ç¯ããåŸã
æžå§äžã«ãšã¿ããŒã«ãèžçºãããŠé€å»ãããç
ããæ²æ®¿ãå¥ããã溶å€ãèžçºãããåŸãç²
ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ããšããã·ãé ¢é ž17.4ïœãåŸãã
çè«å€ã«å¯ŸããŠåç91ïŒ ïŒmp100âã C21H26N2O3ã®ïŒ åæå€ïŒ èšç®å€ïŒC71.1H7.39N7.90 枬å®å€ïŒ 69.1 7.07 7.12 察å¿ããïŒå¡©é žå¡©ã¯ãã€ãœãããããŒã«ãã
åçµæ¶ããŠmp217ã218âã C21H26N2O3ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC59.02H6.60N6.55Cl-16.59 枬å®å€ïŒ 58.83 6.94 6.33 15.90 äžèšã®æ¹æ³ã«ããã次ã®ãããªååç©ã補é
ããã ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒçè«å€ã«å¯Ÿãåç57ïŒ ïŒ
mp85âïŒåçµä¹Ÿç¥ãããã®ïŒå解ïŒã C23H30N2O4ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC58.60H6.84N5.94Cl-15.04 枬å®å€ïŒ 56.82 7.82 6.02 16.76 ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒçè«å€ã«
察ãåç82ïŒ ïŒmp112âïŒåçµä¹Ÿç¥ãããã®ïŒã C23H29ClN2O4ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC54.6 H5.78N5.54Clå š21.03 枬å®å€ïŒ 52.48 6.10 5.72 22.19 ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žæ°Žåç©ïŒçè«å€ã«å¯Ÿããåç100ïŒ ïŒ
mpã·ã€ãŒãã«æº¶ããªãïŒ70âããããŠãã次
第ã«è»åïŒã C21H25FN2O3ã»3/2H2Oã®ïŒ åæå€ïŒ èšç®å€ïŒC63.1H7.0N7.0 枬å®å€ïŒ 63.7 7.6 6.9 ïŒâãïŒâãïŒâãïŒïŒâã¡ããã·ããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒçè«å€ã«å¯Ÿããåç35ïŒ ïŒ
mp214ã217âïŒã¢ã»ããããªã«ããçµæ¶ïŒå
解ïŒã C22H28N2O4ã»2HClã®ïŒ åæå€ïŒ èšç®å€ïŒC57.7H6.6N6.1Cl-15.5 枬å®å€ïŒ 53.2 6.5 6.0 17.5 ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒçè«å€ã«å¯Ÿããåç50ïŒ ïŒmp96ã
100âïŒåçµä¹Ÿç¥ãããã®ïŒã C21H25ClN2O3ã®ïŒ åæå€ïŒ èšç®å€ïŒC64.8H6.5N7.2Cl9.1 枬å®å€ïŒ 62.3 6.9 6.9 10.2 ïŒâãïŒâãïŒâãïŒâããïŒâïŒããªãã«
ãªãã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒ
âããã©ãžãã«ããšããã·ããšããã·ãé ¢é žïŒ
åçïŒ67ïŒ ïŒãã®ååç©ã®ïŒã·ãŠãŠé žå¡©ã®
mpïŒ113ã116âïŒé ¢é žãšãã«ïŒã C24H29F3N2O4ã»2C2H2O4ãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC52.01H5.14N4.33 枬å®å€ïŒ 51.24 5.20 4.27 ïŒâãïŒâãïŒâãïŒâããã¹ïŒïŒâãã«ãª
ãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ããš
ããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒåçïŒ40
ïŒ ïŒmpïŒ181ã183âïŒã¢ã»ããããªã«ïŒã C23H28F2N2O4ã»2HClãšããŠã®ïŒ åæå€ïŒ èšç®å€ïŒC54.54H5.95N5.52Cl-13.3 枬å®å€ïŒ 54.26 6.13 5.57 15.29  è¬çè©Šéš æ¬çºæã«å±ãã次ã®ååç©ã«ã€ããŠã®è¬çè©Š
éšãè¡ããåŸè¿°ãããããªçµæãåŸãã ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒ
âããã©ãžãã«ããšããã·ãã¢ã»ãã¢ããïŒå¡©
é žå¡©ïŒååç©ïŒ¡ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒååç©ïŒ¢ãäŸ1.1åã³1.3ã§
調補ïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãã¢ã»ãã¢ããïŒååç©ïŒ£ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒååç©ïŒ€ãäŸ1.1ã§
調補ïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¡ããã·ããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒååç©ïŒ¥ãäŸ1.1ã§
調補ïŒïŒ ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒååç©ïŒŠãäŸ1.2
ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©
ïŒååç©ïŒ§ãäŸ1.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žã«ãªãŠã ïŒååç©ïŒšãäŸ2.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·é ¢é žïŒååç©ïŒ©ãäŸ2.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©ïŒªãäŸ2.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒ
âããã©ãžãã«ããšããã·é ¢é žïŒååç©ïŒ«ãäŸ
2.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ããšããã·ããšãã
ã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©ïŒ¬ãäŸ2.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâãïŒïŒâã¯ããããš
ãã«ïŒããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©
ïŒãäŸ2.2ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žæ°Žåç©ïŒååç©ïŒ®ãäŸ2.2ã§èª¿è£œïŒïŒ ïŒâãïŒãïŒâãïŒâãïŒâïŒããªãã«ãªã
ã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒâã
ãã©ãžãã«ããšããã·ããšããã·ãã¢ã»ãã¢ã
ãïŒå¡©é žå¡©ïŒååç©ïŒ¯ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâããã¹âïŒïŒâãã«
ãªãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãã¢ã»ãã¢ããïŒå¡©é žå¡©ïŒ
ïŒååç©ïŒ°ãäŸ1.1ã§èª¿è£œïŒïŒ ïŒâãïŒâãïŒâãïŒâãïŒâïŒããªãã«ãª
ãã¡ãã«ïŒããšãã«ãããšãã«ã¡ãã«ãâïŒâ
ããã©ãžãã«ããšããã·ããšããã·ãé ¢é žïŒå
åç©ïŒ±ãäŸ2.2ã§èª¿è£œïŒã ïŒâãïŒâãïŒâãïŒâããã¹âïŒïŒâãã«
ãªãããšãã«ïŒã¡ãã«ãâïŒâããã©ãžãã«ã
ãšããã·ããšããã·ãé ¢é žïŒå¡©é žå¡©ïŒååç©
ãäŸ2.2ã§èª¿è£œïŒã æ¬çºæã«å±ããªãäžèšã®ååç©ïŒäžè¬åŒã
æããããïœïŒïŒã®ãã®ïŒã«ã€ããŠããåãã
ããªè¬çè©Šéšãå®æœããã ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâãã
ã©ãžãã«ãã¢ã»ãã¢ããïŒååç©ïŒããã«ã®ãŒ
ç¹èš±ç¬¬763609å·æ现æžèšèŒã®æ¹æ³ã§èª¿è£œïŒïŒ
mp204âã ïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒããšã
ã«ã¡ãã«ãâïŒâããã©ãžãã«ãã¢ã»ãã¢ãã
ïŒååç©ïŒãH.B.Wrightåã³D.L.Martinã®å
æ²åŒçšæç®åç §ããã«ã®ãŒç¹èš±ç¬¬763609å·æ现
æžèšèŒã®æ¹æ³ã§èª¿è£œïŒïŒmp145âã ïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâãã
ã©ãžãã«ãé ¢é žïŒååç©ïŒãæ¹æ³ãäŸïŒã»ïŒ
ã§èª¿è£œïŒïŒmp176âã ïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒããšã
ã«ã¡ãã«ãâïŒâããã©ãžãã«ãé ¢é žïŒååç©
ïŒãåããæ¹æ³ãäŸ2.2ã§èª¿è£œïŒïŒmp106ã
108âã (1) æã¢ã¬ã«ã®ãŒäœçš æã¢ã¬ã«ã®ãŒäœçšã«ã€ããŠã¯ãååæ§ç®è
éæçïŒpassive cutaneous anaphylaxisïŒ
è©ŠéšïŒPCAïŒãã©ããã«æœãããšã«ãã枬
å®ãããJ.Gooseåã³A.M.J.N.Blairã®
Immunologyã16ã749ã760é ïŒ1969幎ïŒã
ãªãã³ã«U.Martinåã³D.Roemerã®
ArzneimittelâForschungã28(5)ã770ã782
é ïŒ1978幎ïŒãåç §ã®ããšãã éã®ã©ãããçšãããã®æšªè ¹ã®æ¯ãäžéšå
ãèœãšããããã®æ¯ãåã€ãéšåã«IGEã®æ
ãªãã«ããã³è¡æž 0.05mlãç®å 泚å°ããŠè©Šéš
åç©ã®ååæäœïŒpassive sensitizationïŒã
ãããããããPCAè©Šéšã®æéäžã泚å°ã
ãéšäœã«çŽ100mm2ã®è¡šé¢ç©ãæããé¡èãªæ
ç¹ãçŸããçšåºŠã«åžéããè¡æž ãçšããã 泚å°ããŠãã72æéåŸã«ãçè²å€ãå«ãã¢
ã¬ã«ã²ã³ã®æº¶æ¶²0.25mlïŒå¡©åãããªãŠã ã®
0.9ïŒ æ°Žæº¶æ¶²0.25mlã«æº¶è§£ããïŒmgã®ãªãã«
ããã³åã³ïŒmgã®ãšãŽã¢ã³ã¹ãã«ãŒïŒãéè
å ã«æäžãããç®å 泚å°ãè¡ã€ãéšäœã«é¡è
ãªéè²æç¹ãçŸããã®ã§ããã®è¡šé¢ç©ã枬å®
ããã æ¬çºæã®ååç©ã®äœçšãè©Šéšããããã«
ã¯ãäžèšãšåãæé ãå®æœãããã â è¡æž ã泚å°ããŠãã72æéåŸã«ãäŸè©Šå
åç©ãçµå£æäžãã â äžèšæäžã®åŸ15åçµéããŠãããã¢ã¬ã«
ã²ã³ã®æº¶æ¶²0.25mlãéè泚å°ãã â ã¢ã¬ã«ã²ã³ãæäžããŠãã30ååŸã«ãé
è²æç¹ã®è¡šé¢ç©ã枬å®ããã äŸè©Šåç©ã®åèšæ°ã®å¹³åãšããŠãçè²æç¹
ã®è¡šé¢ç©ã50ïŒ äœäžãããããªå ç«æäžé
ïŒID50ãÎŒã¢ã«ïŒKgã§è¡šããïŒã次ã®ç¬¬ïŒè¡š
ã«ç€ºãã 第ïŒè¡šã®çµæãããæ¬çºæã®ååç©ã¯çµå£
æäžããéã«æå¹ã§ããããšãããã«å¯Ÿãã
éèæäžããã°æåæ¯äœçšãæããããšãã
ãç¥ãããŠãããããªãŠã ã¯ãã¢ã°ãªã±ãŒã
ãçµå£æäžã§ã¯å¹æã®ãªãããšãããããä»
æ¹ãååç©ïŒãïŒãïŒåã³ïŒïŒæ¬çºæã®ç¯å²
å€ã®ãã®ïŒïœïŒïŒïŒããã»ãšãã©èå³ã®å¯Ÿè±¡
ãšãªããªãããšãã第ïŒè¡šã®çµæããæãã
ã§ããã ãè¡šã (2) é®çåã³æãã¹ã¿ãã³äœçš ãããã®äœçšã«ã€ããŠã¯ãH.Konzettåã³
R.Roesslerã®æ¹æ³ãNaunynâ
Schmiedebergs Arch.exp.Path.Pharmakol.
195ã71ã74é ïŒ1940幎ïŒããã¢ã«ã¢ããã«é©
çšããŠæž¬å®ããããªãã€ãªã³ã®å¹æãšæ¯èŒã
ãã ç³é ããããŠç³çºãããã¢ã«ã¢ããã«å¯Ÿ
ãã人çºåŒåžãæœããæ°ç®¡å å§å
ïŒendotracheal pressureïŒã®èšé²ããšããã
ãããã»ãããã³åã³ãã¹ã¿ãã³ãé£ç¶çã
ãã€ã挞å¢çã«éè泚å°ããŠãå埩çãªæ°ç®¡
æ¯ãããããèµ·ãããããäŸè©Šåç©ã®å šæ°ã«
察ããå¹³åãšããŠãæ°ç®¡æ¯ããããã®50ïŒ ã
æå¶ããååç©ã®æèŠæäžéïŒÎŒã¢ã«ïŒKgã«
ããID50ïŒãäžèšã®ç¬¬ïŒè¡šã«ç€ºãã ãè¡šã æ¬çºæã®ååç©ã«ã¯ã³ãªã³äœåå¹æ
ïŒcholinergic activityïŒããªããäžèšã®ç¬¬ïŒ
è¡šãããæ¬çºæã®ååç©ããããããã»ãã
ãã³åã³ãã¹ã¿ãã³ã«ãã€ãŠèªçºãããæ°ç®¡
æ¯çããã«å¯ŸããŠããããå¹æãæããç¹ã«
ãã¹ã¿ãã³ã«å¯ŸããŠæ Œå¥ã®éžææ§ãæããã
ãšããããããããšã¯å¯Ÿç §çã«ãååç©ïŒã
ïŒãïŒåã³ïŒïŒæ¬çºæã®ç¯å²å€ïŒïœïŒïŒïŒã¯
å¹æãå£ãã ããã«ããã®è©Šéšã®çµæãããæ¬çºæã®å
åç©ã®äžã«ã¯ãäžåã®æäžã§é·æéæãã¹ã¿
ãã³å¹æã瀺ããã®ãããããšãããã€ãã
åŸãã°ãååç©ïŒªã1ÎŒã¢ã«ïŒKgã®æäžéã§
ã¢ã«ã¢ããã«éèå æäžãããšãïŒæéåŸã«
ãããŠã100ïŒ ã®å¹æãç¶æãããã (3) ããŠã¹ã®äžè¬çæåïŒIrwinã®è©ŠéšïŒ Irwinã®è©ŠéšïŒ1959幎ïŒæïŒãïŒæ¥ã«ããŠ
ãŒã»ãã³ãã³ã®ã³ã«ããŒã»ãžãŠãã¢ã»ã«ã¬ã
ãžã§éå¬ããããå»äºååŠã«ã€ããŠã®ãŽã«ã
ã³ã®ç 究äŒè°ã«ããããS.IrwinïŒâGeneral
Phylosophy and methology of
screeningïŒïœ multidimensional
approachâåç §ïŒã«ãã€ãŠæåã調ã¹ãã äžçŸ€ïŒå¹ã®éã®ããŠã¹ïŒäœé18ã22ïœïŒã«
察ããäŸè©Šååç©ããã®è ¹èå ã«æŒžå¢çã«æ
äžããäŸè©Šåç©ã®äžè¬çæåãå ¬ç¥ã®åºæºã«
åŸã€ãŠèŠ³å¯ããã äžèšã®åèååç©ã䜵çšããã â ããããã·ãžã³ïŒïŒâãïŒâãïŒâ
ãïŒïŒâã¯ããããšãã«ïŒããšãã«ã¡ãã«ã
âïŒâããã©ãžãã«ããšããã·ããšã¿ããŒ
ã«ã â ãªããµãŒãã ïŒïŒâã¯ããâïŒïŒïŒâãž
ãããâïŒâããããã·âïŒâããšãã«â
2HâïŒïŒïŒâãã³ãŸãžã¢ãŒãã³âïŒâãª
ã³ã äžèšã®ç¬¬ïŒè¡šã¯ãäŸè©Šåç©ã«ç²Ÿç¥å®å®ã®ç¬¬
ïŒå åãèªèµ·ããæäžéïŒmgïŒKgïŒã瀺ãã ãè¡šã åèååç©ã«æ¯èŒããæ¬çºæã®ååç©ã«ã¯
é®éäœçšãã»ãšãã©ãªãããšã第ïŒè¡šããæ
ããã§ããã ãªãããã®è©Šéšã«ãããŠãæ¬çºæã®ååç©
ã®æ¯æ§ãããããŠäœãããšãç«èšŒãããã äžèšã®ç¬¬ïŒè¡šã«ã¯ãããŠã¹ã®è ¹èå ã«æäž
ããæã®æ¬çºæã®ååç©ã®èŽæ»éãmgïŒKgã§
瀺ãïŒïŒå¹ã®ãã¡ã®ïŒå¹æ»äº¡ïŒã ãè¡šã ããã§ç¬¬ïŒè¡šãšç¬¬ïŒè¡šïŒç²Ÿç¥å®å®åæäžé
ãšèŽæ»éïŒãæ¯èŒãããšãããååç©ã«ãã€
ãŠã¯ãèŽæ»éã«è¿ãæäžéã§æŒžãé®éå¹æã
çŸãããŠããã (4) DL50ã®èŽæ»é æ¬çºæã®ååç©ã®æ¯æ§ãäœãããšã¯ãçµå£
æäžæã®DL50æ¯æ§ã枬å®ããããšã«ãã€ãŠ
確èªããããååç©ïŒªã®å ŽåããŠã€ã¹ã¿ãŒã«
ïŒWistarïŒã©ããã«ã€ããŠã®DL50ã¯ãéã®
ã©ããã§ã¯703mgïŒKgã§ãããéã®ã©ããã§
ã¯865mgïŒKgã§ããã ããŠã¹ã®å Žåãååç©ïŒªã®DL50ã¯ããã
ãã600mgïŒKgïŒéã®ããŠã¹ïŒåã³752mgïŒKg
ïŒéã®ããŠã¹ïŒã§ããã (5) åŠæ¹åã³æäžæ³ æ¬çºæã®ååç©ãå«ãè¬å€çµæç©ã¯ãçµå£
æäžãè žç®¡å€æäžåã¯çŽè žå æäžãè¡ãããš
ãã§ããããŸãã錻è å æ³šå ¥æ³ïŒãšã¢ãŸãŒ
ã«ïŒã§æäžããããšãã§ãããããããã¯è»
èãããã¯ã¯ãªãŒã ã®ç¶æ ã§çšããããšãã§
ãããçµå£æäžã«çšãããè¬å€çµæç©ã¯ãåº
äœåã¯æ¶²äœã§ãã€ãŠããããäŸãã°ãé²åºå
ã¯è¢«èŠãããé å€ããã«ãç³è¡£é ããŒã©ãã³
ã«ãã»ã«ã溶液ãã·ããããã®ä»ã®åœ¢æ ãšã
ãããšãã§ãããè žç®¡å€æäžã«çšãããçµæ
ç©ã¯ããã®çš®ã®æäžã«å ¬ç¥ã®ä»»æã®è¬å€çµæ
ç©ã®åœ¢æ ãäŸãã°ãæ°Žæ§åã¯æ²¹æ§ã®æº¶æ¶²ãæž
æ¿æ¶²åã¯ä¹³å€ãšããŠçšããããšãã§ãããçŽ
è žå ã«æäžããå Žåã«ã¯ãæ¬çºæã®ååç©ã
å«ãçµæç©ãäžè¬ã«åè¬ã®åœ¢æ ã§çšããã äŸãã°æ³šå°çšæº¶æ¶²ã泚å°çšæžæ¿æ¶²ãé å€ã
滎å€ãåè¬çã®åœ¢æ ã®è¬å€ã¯ãæ £çšã®è£œè¬æ¹
æ³ã§èª¿å€ããããšãã§ãããæ¬çºæã®ååç©
ããåºäœåã¯æ¶²äœã§ãã€ãŠãæ¯æ§ã®ãªããè¬
å€ãšããŠèš±å®¹ããããã€ãªã€ãŒãšæ··åãã
ãããŸããåæ£å€ããã€ã¹ã€ã³ãã°ã¬ãŒãå€
ïŒdisintegration agentïŒãå®å®å€çãšæ··åã
ãããšãã§ãããææã«ãã€ãŠã¯ãé²è å€ã
çå³æãçè²å€çãå ããããšãã§ããã è¬å€çµæç©äžã«å«ãŸãã掻æ§ååç©ã®çŸå
çã¯ãæ£è ãæäžæ¹æ³ãç¹ã«æäžã®ç床ã«å¿
ããŠåºç¯å²ã«å€åãããããšãã§ããã é å€æ³ã«ã€ããŠããã°ãåºç¯å²ã®æäžéå
äœã«ããã€ãŠå€ããããšãå¯èœã§ãããäŸã
ã°æŽ»æ§ååç©ã0.5ã250mgå«ãããã«é å€ã
ãããšãã§ããã æ¬çºæã®ååç©ãå«ãçµæç©ã®äžäŸãšã
ãŠãçµå£æäžçšãŒã©ãã³ã«ãã»ã«ã®é åäŸã
瀺ããšæ¬¡ã®ãšããã§ããã ååç©ïŒª 100mg ä¹³ ç³ 67mg ã¹ãã¢ãªã³é žãã°ãã·ãŠã ïŒmg äºé žåçªçŽ ïŒãšãŒãã·ã«ïŒ ïŒmg
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ åŒ ïŒåŒäžã ã¯ããããã·ã«åºåã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãããã²ã³
ååãçŽéãããã¯åæéã®äœçŽã¢ã«ã³ã
ã·åºåã¯ããªãã«ãªãã¡ãã«åºãè¡šããã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žãããã¯ãã®ã¢ãããåã¯ç¡
æ¯æ§ã®è¬å€ãšããŠèš±å®¹ããããã®å¡©ã ïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žåã¯ãã®ç¡æ¯æ§ã®è¬å€ãšããŠèš±å®¹ããã
å¡©ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®ååç©ã ïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãâé ¢é žïŒå¡©é žå¡©ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé
ã®ååç©ã ïŒ ïŒâãïŒâãïŒâãïŒïŒâã¯ããããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žã«ãªãŠã ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®
ååç©ã ïŒ ïŒâãïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒ
âããã©ãžãã«ããšããã·ãé ¢é žåã¯ãã®ïŒå¡©é ž
å¡©ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé ã®ååç©ã ïŒ ïŒâãïŒâãïŒâãïŒïŒâãã«ãªãããšãã«ïŒ
ããšãã«ã¡ãã«ãâïŒâããã©ãžãã«ããšãã
ã·ãé ¢é žåã¯ãã®æ°Žåç©ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬
ïŒé ã®ååç©ã ïŒ åŒ ïŒåŒäžã ã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãããã²ã³
ååãçŽéãããã¯åæéã®äœçŽã¢ã«ã³ã
ã·åºåã¯ããªãã«ãªãã¡ãã«åºãè¡šããã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žã®ã¢ããã®è£œé ã«åœãã åŒ ãåŒäžãåã³Xâ²ã¯äžèšã«ããããšå矩ã§ããã
ãæããïŒâïŒãžããšãã«ã¡ãã«ïŒããã©ãžã³
ãšã ãåŒäžãïœåã³ïœã¯äžèšã«ããããšå矩ã§ããã
ãããŠïŒºã¯ããã²ã³ååã§ããããæããÏâã
ãã¢ã»ãã¢ãããšãäžæŽ»æ§æº¶åªäžã«ãŠé žå容äœã®
ååšäžã«åå¿ãããããšãããªããã®è£œé æ¹æ³ã ïŒ åŒ ïŒåŒäžã ã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãããã²ã³
ååãçŽéãããã¯åæéã®äœçŽã¢ã«ã³ã
ã·åºåã¯ããªãã«ãªãã¡ãã«åºãè¡šããã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žã®ã¢ããã®è£œé ã«åœãã åŒ ãåŒäžããXâ²ãïœåã³ïœã¯äžèšã«ããããšå
矩ã§ããããããŠMeã¯ã¢ã«ã«ãªéå±ååã瀺ãã
ãæããÏâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãã¢ã«ã«ããŒã«ã®ã¢ã«ã«ãªéå±å¡©
ãšã åŒ ïŒåŒäžãã¯ããã²ã³ååã§ããïŒãæããïŒâ
ããã¢ã»ãã¢ãããšãäžæŽ»æ§æº¶åªäžã«ãŠåå¿ãã
ãããšãããªããã®è£œé æ¹æ³ã ïŒ åŒ ïŒåŒäžã ã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãããã²ã³
ååãçŽéãããã¯åæéã®äœçŽã¢ã«ã³ã
ã·åºåã¯ããªãã«ãªãã¡ãã«åºãè¡šããã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žã®ã¢ããã®è£œé ã«åœããã¢ã³
ã¢ãã¢ãšãåŒ ãåŒäžããXâ²ãïœåã³ïœã¯äžèšã«ããããšå
矩ã§ããããããŠïŒ·ã¯ããã²ã³ååã§ããããå
ã¯ORâ²åºïŒãã ããRâ²ã¯äœçŽã¢ã«ãã«åºãè¡šã
ãïŒã§ããããæããïŒâãïŒâïŒãžããšãã«ã¡
ãã«ïŒâïŒâããã©ãžãã«ãé ¢é žã®å®èœæ§èªå°äœ
ãšãäžæŽ»æ§æº¶åªäžã«ãŠåå¿ãããããšãããªãã
ã®è£œé æ¹æ³ã ïŒïŒ åŒ ïŒåŒäžã ã¯ããããã·ã«åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãããã²ã³
ååãçŽéãããã¯åæéã®äœçŽã¢ã«ã³ã
ã·åºåã¯ããªãã«ãªãã¡ãã«åºãè¡šãã ïœã¯ïŒåã¯ïŒã§ããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žã®è£œé ã«åœãã åŒ ãåŒäžããXâ²ãïœåã³ïœã¯äžèšã«ããããšå
矩ã§ããããããŠYâ²ã¯âNH2åºã§ãããåã¯
ORâ²åºïŒãã ããRâ²ã¯äœçŽã¢ã«ãã«åºãè¡šããïŒ
ã§ããããæããïŒâãïŒâïŒãžããšãã«ã¡ã
ã«ïŒâïŒâããã©ãžãã«ãé ¢é žã®å®èœæ§èªå°äœ
ããæ°Žæ§åªè³ªåã¯æ°Žæ§ã¢ã«ã³ãŒã«æ§åªè³ªäžã«ãã
ãŠãç¡æ©å¡©åºãçšããŠå æ°Žå解ããããšãããªã
ãã®è£œé æ¹æ³ã ïŒïŒ æ²»çäžæå¹ãªéã®åŒ ïŒåŒäžã ã¯ããããã·ã«åºåã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãŸãã¯ãã
ã²ã³ååãè¡šããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žãããã¯ãã®ã¢ãããåã¯ç¡
æ¯æ§ã®è¬å€ãšããŠèš±å®¹ããããã®å¡©ããã³è¬å€ãš
ããŠèš±å®¹ãããåºäœåã¯æ¶²äœã®æ äœãå«æããæ
ã¢ã¬ã«ã®ãŒå»è¬çµæç©ã ïŒïŒ æ²»çäžæå¹ãªéã®åŒ ïŒåŒäžã ã¯ããããã·ã«åºåã¯âNH2åºã§ããã åã³Xâ²ã¯ç¬ç«ããŠãæ°ŽçŽ ååãããã²ã³
ååãäœçŽã¢ã«ã³ãã·åºåã¯ããªãã«ãªã
ã¡ãã«åºãè¡šããããã㊠ïœã¯ïŒåã¯ïŒã§ããïŒ ãæããïŒâãïŒâïŒãžããšãã«ã¡ãã«ïŒâïŒâ
ããã©ãžãã«ãé ¢é žãããã¯ãã®ã¢ãããåã¯ç¡
æ¯æ§ã®è¬å€ãšããŠèš±å®¹ããããã®å¡©ããã³è¬å€ãš
ããŠèš±å®¹ãããåºäœåã¯æ¶²äœã®æ äœãå«æããé®
çããã³æãã¹ã¿ãã³å»è¬çµæç©ã
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8103768 | 1981-02-06 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS57149282A JPS57149282A (en) | 1982-09-14 |
| JPS6311353B2 true JPS6311353B2 (ja) | 1988-03-14 |
Family
ID=10519519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57017392A Granted JPS57149282A (en) | 1981-02-06 | 1982-02-05 | 2-(4-(diphenylmethyl)-1-piperazinyl)acetic acid and their derivatives as medicine |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS57149282A (ja) |
| LT (1) | LT2553B (ja) |
| LV (1) | LV5494A3 (ja) |
| SU (1) | SU1310397A1 (ja) |
| UA (1) | UA8337A1 (ja) |
| ZA (1) | ZA82752B (ja) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2133744C1 (ru) * | 1993-07-30 | 1999-07-27 | ÐелÑÑа ЀаÑЌаÑÑÑÑОкалз, ÐМк. | ÐОпеÑазОМПвÑе ÑÐŸÐµÐŽÐžÐœÐµÐœÐžÑ |
| SE9504661D0 (sv) * | 1995-12-22 | 1995-12-22 | Astra Pharma Inc | New compounds |
| LT4430B (lt) | 1997-02-05 | 1998-12-28 | AkcinÄ BendrovÄ "Bakteriniai Preparatai" | Akių laÅ¡ai |
| EP0919550A1 (en) * | 1997-11-26 | 1999-06-02 | Ucb, S.A. | Pseudopolymorphic forms of 2-2-4-bis(4-fluorophenyl)methyl-1-piperazinyl-ethoxy acetic acid dihydrochloride |
| SK285641B6 (sk) * | 1999-11-30 | 2007-05-03 | Egis Gyï¿œGyszergyï¿œR Rt. | SpÃŽsob prÃpravy {2-[4-(alfa-fenyl-p-chlórbenzyl)piperazin-1- yl]etoxy}octovej kyseliny a nové medziprodukty |
| TR200605520T2 (tr) * | 2004-04-14 | 2006-12-21 | Lee Eun-Joo | Saç kaybı ve iyi huylu prostatik hiperplazinin tedavisine yönelik farmasötik bileÅim |
| HU227319B1 (en) * | 2005-12-08 | 2011-03-28 | Egis Gyogyszergyar Nyrt | Process for the production of (2-chloro-ethoxy)-acetic acid-n,n-dimethylamide and its intermediate and the novel intermediate |
-
1982
- 1982-02-05 UA UA3478400A patent/UA8337A1/uk unknown
- 1982-02-05 ZA ZA82752A patent/ZA82752B/xx unknown
- 1982-02-05 JP JP57017392A patent/JPS57149282A/ja active Granted
- 1982-08-18 SU SU823478400A patent/SU1310397A1/ru active
-
1993
- 1993-05-17 LV LV930358A patent/LV5494A3/xx unknown
- 1993-06-30 LT LTRP731A patent/LT2553B/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| SU1310397A1 (ru) | 1987-05-15 |
| JPS57149282A (en) | 1982-09-14 |
| ZA82752B (en) | 1982-12-29 |
| LT2553B (lt) | 1994-02-28 |
| LV5494A3 (lv) | 1994-03-10 |
| UA8337A1 (uk) | 1996-03-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4525358A (en) | 2-[4-(Diphenylmethyl)-1-piperazinyl]-acetic acids and their amides | |
| JP3880842B2 (ja) | ïŒâãïŒïŒâã¯ãããã§ãã«ïŒãã§ãã«ã¡ãã«ãããã©ãžã³ã®é¡åäœããã³ãã®è£œé æ³ | |
| US4663325A (en) | 1-(2,3,4-tri-methoxybenzyl)-4[bis(4-fluorophenyl)methyl] piperazines are useful for treating cerebrovascular disease | |
| US5589477A (en) | Pyrimidine derivatives and drugs | |
| JPS61293977A (ja) | ããã©ãžã³èªå°äœããã®è£œé æ³åã³ãããå«ãå»è¬ | |
| CA1175432A (en) | N-oxacyclyl-alkylpiperidine derivatives, process for their preparation, pharmaceutical products containing them, and their use | |
| HU206344B (en) | Process for producing new piperazino-alkyl-isothiazolone derivatives and pharmaceutical compositions containing them | |
| US4443460A (en) | 2-[4-(Diphenylmethylene)-1-piperidinyl]-acetic acids and their amides | |
| FI77456B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 3-/2-/4-(2-metoxifenyl) -1-piperazinyl/etyl/-2,4-(1h,3h)-kinazolindionderivat. | |
| US4183930A (en) | Amino derivatives of pyrazolo [1,5-a]s-triazine, and their therapeutic applications | |
| US5155116A (en) | Medicinal oxazolopyridine compounds | |
| HU196196B (en) | Process for producing new benzhydryl-piperazine derivatives and pharmaceuticals comprising the compounds | |
| JP3117183B2 (ja) | ïŒïŒïŒâãžãããâïŒïŒšâã€ãããŸãïŒïŒïŒïŒïŒâïœïœããããªã³é¡ããã®è£œé æ¹æ³ããããå«ãé®çå€ããã³äžéäœååç© | |
| SU1310397A1 (ru) | 2- @ 4-(ÐОÑеМОлЌеÑОл)-1-пОпеÑазОМОл @ -ÑкÑÑÑÐœÑе кОÑлПÑÑ ÐžÐ»Ðž ÐžÑ Ð°ÐŒÐžÐŽÑ,ОлО ÐžÑ ÐœÐµÑПкÑОÑÐœÑе ÑаÑЌаÑевÑОÑеÑкО пÑОеЌлеЌÑе ÑПлО,пÑП вл ÑÑОе ÑпазЌПлОÑОÑеÑкÑÑ Ðž аМÑОгОÑÑаЌОММÑÑ Ð°ÐºÑОвМПÑÑÑ | |
| JPH04234359A (ja) | ïŒâãžãã§ãã«ã¡ãã«ããã©ãžã³ã®æ°èŠèªå°äœããããã®è£œæ³ãåã³ãããã®å»è¬çšé | |
| JP2002534467A (ja) | 倧è³èè¡ã®äºé²ããã³æ²»çã®ããã®ïŒâ眮æãããïŒïŒïŒâãã³ãŸã€ãœãã¢ãŸãŒã«èªå°äœããã³ïŒâ眮æãããããã©ãããããªãããªããžãã³èªå°äœã®äœ¿çš | |
| JPS5825678B2 (ja) | ãªããµãŸâã«ãŠãŠããŠã¿ã€ ã ã»ã€ãŸãŠã㊠| |
| KR900001188B1 (ko) | ì¹íë íëìí¬(íŒíëŒì§ë ëë ížëªšíŒíëŒì§ë)ìí¬-í°ì¬ ë°-í°ì€ì¹Žë°ë©ìŽížì ì ì¡°ë°©ë² | |
| US5190960A (en) | Medicinal oxazolopyridine compounds | |
| JPS6323874A (ja) | ïŒïŒïŒâããã©ãžã³ãžãªã³ã®æ°ããèªå°äœããã®è£œé æ¹æ³åã³ãã®å«æå»è¬çµæç© | |
| IE59035B1 (en) | Diazine - ethenylphenyl oxamic acids and esters and salts thereof | |
| HU209930B (en) | Process for producing of 2-mercapto-2-(1-isoquinolylidene)-acetonitrile derivatives and pharmaceutical compositions comprising them | |
| JP3170273B2 (ja) | çž®åããªã¢ãžã³èªå°äœåã³ãã®äžéäœ | |
| FI77024C (fi) | Foerfarande foer framstaellning av terapeutiskt verksamma 2-/4-(difenylmetylen)-1-piperidinyl/-acetamider. | |
| SI20326A (sl) | 2-(4-(difenilmetil)-1-piperazinil)-ocetne kisline in njihovi amidi |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |