JPH0156071B2 - - Google Patents
Info
- Publication number
- JPH0156071B2 JPH0156071B2 JP55060460A JP6046080A JPH0156071B2 JP H0156071 B2 JPH0156071 B2 JP H0156071B2 JP 55060460 A JP55060460 A JP 55060460A JP 6046080 A JP6046080 A JP 6046080A JP H0156071 B2 JPH0156071 B2 JP H0156071B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- metanitrobenzyloxy
- compound
- metacyanobenzyloxy
- 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 68
- -1 3-methylbutyroxy group Chemical group 0.000 claims description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
- 238000011282 treatment Methods 0.000 claims description 9
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 6
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 claims description 4
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000000984 3-chloro-4-fluorobenzyl group Chemical group [H]C1=C(F)C(Cl)=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- VIHAEDVKXSOUAT-UHFFFAOYSA-N but-2-en-4-olide Chemical compound O=C1OCC=C1 VIHAEDVKXSOUAT-UHFFFAOYSA-N 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- LKMJVFRMDSNFRT-UHFFFAOYSA-N 2-(methoxymethyl)oxirane Chemical compound COCC1CO1 LKMJVFRMDSNFRT-UHFFFAOYSA-N 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 claims 2
- 125000005921 isopentoxy group Chemical group 0.000 claims 1
- 125000006502 nitrobenzyl group Chemical group 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000000926 separation method Methods 0.000 claims 1
- 208000024891 symptom Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 31
- 239000000243 solution Substances 0.000 description 25
- 102000010909 Monoamine Oxidase Human genes 0.000 description 17
- 108010062431 Monoamine oxidase Proteins 0.000 description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000008018 melting Effects 0.000 description 14
- 238000002844 melting Methods 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 230000000694 effects Effects 0.000 description 11
- 238000000034 method Methods 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000009833 condensation Methods 0.000 description 6
- 230000005494 condensation Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- QTHYUPNKXBZXAV-UHFFFAOYSA-N 4-(4-hydroxyphenyl)-2-(methoxymethyl)-2h-furan-5-one Chemical compound COCC1OC(=O)C(C=2C=CC(O)=CC=2)=C1 QTHYUPNKXBZXAV-UHFFFAOYSA-N 0.000 description 4
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 206010044565 Tremor Diseases 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- 239000000935 antidepressant agent Substances 0.000 description 4
- 229940005513 antidepressants Drugs 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 3
- NRPFNQUDKRYCNX-UHFFFAOYSA-N 4-methoxyphenylacetic acid Chemical compound COC1=CC=C(CC(O)=O)C=C1 NRPFNQUDKRYCNX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 206010015995 Eyelid ptosis Diseases 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 3
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 210000000744 eyelid Anatomy 0.000 description 3
- 125000003844 furanonyl group Chemical group 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 201000003004 ptosis Diseases 0.000 description 3
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 3
- 229960003147 reserpine Drugs 0.000 description 3
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 239000004342 Benzoyl peroxide Substances 0.000 description 2
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940082992 antihypertensives mao inhibitors Drugs 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- 235000019400 benzoyl peroxide Nutrition 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002695 general anesthesia Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- QZYHIOPPLUPUJF-UHFFFAOYSA-N 3-nitrotoluene Chemical compound CC1=CC=CC([N+]([O-])=O)=C1 QZYHIOPPLUPUJF-UHFFFAOYSA-N 0.000 description 1
- 208000004130 Blepharoptosis Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010053398 Clonic convulsion Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- DULCUDSUACXJJC-UHFFFAOYSA-N Ethyl phenylacetate Chemical compound CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- SUKXKLNDBLNTSW-UHFFFAOYSA-N N-(4-hydroxycyclohexyl)-6-phenylhexanamide Chemical compound OC1CCC(CC1)NC(CCCCCC1=CC=CC=C1)=O SUKXKLNDBLNTSW-UHFFFAOYSA-N 0.000 description 1
- 229910004298 SiO 2 Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000007360 debenzoylation reaction Methods 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 238000007269 dehydrobromination reaction Methods 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 229940077481 dl- 5-hydroxytryptophan Drugs 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 1
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 210000002196 fr. b Anatomy 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- SKHIBNDAFWIOPB-UHFFFAOYSA-N hydron;2-phenylethanamine;chloride Chemical compound Cl.NCCC1=CC=CC=C1 SKHIBNDAFWIOPB-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- PDZGAEAUKGKKDE-UHFFFAOYSA-N lithium;naphthalene Chemical compound [Li].C1=CC=CC2=CC=CC=C21 PDZGAEAUKGKKDE-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 238000007040 multi-step synthesis reaction Methods 0.000 description 1
- 230000001722 neurochemical effect Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- LFYCPBYLRDFURN-UHFFFAOYSA-M sodium;acetic acid;hydrogen carbonate Chemical compound [Na+].CC(O)=O.OC([O-])=O LFYCPBYLRDFURN-UHFFFAOYSA-M 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/26—Psychostimulants, e.g. nicotine, cocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D307/58—One oxygen atom, e.g. butenolide
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
Description
æ¬çºæã¯ïŒâ5Hâãã©ãã³åã³ïŒâ3Hâãžã
ãããã©ãã³ã®æ°èŠãªèªå°äœããã®ç©ã®è£œæ³åã³
ãã®ç©ã®å»è¬çšéã«é¢ãããã®ã§ããã ïŒâ3Hâãžããããã©ãã³ã®èªå°äœã¯ïŒåã®
äžæŽççŽ ååãæã¡ããããŠãã®ããïŒåã®ãžã¢
ã¹ãã¬ãªã¢ã€ãœããŒæ··åç©ã圢æããããã®ã
ããåºé¡äººã¯3Hâãžããããã©ãã³âïŒã®åèª
äœãã¯ãããã°ã©ãã€ãŒåŠçãè¡ã€ããæå Žåã«
ãããŠåäžæ§é åŒã§ãããïŒå¯Ÿã®ãžã¢ã¹ãã¬ãªã¢
ã€ãœããŒã§ããïŒçæç©ãåé¢ãããã 次ã®è©³çŽ°ãªèª¬æåã³ç¹èš±è«æ±ã®ç¯å²ã«ãããŠã
âãã©ã³ã¹âïŒæ¥µæ§å°ïŒæ§é ããã€åé¢çæåãæ
åã§è¡šç€ºããâã·ã¹âïŒæ¥µæ§å€§ïŒæ§é ããã€åé¢
çæåãæåã§è¡šç€ºãããããã¯ç«äœååŠçã«
決ããããã äžã€ã¯çžåœããïŒâ5Hâãã©ãã³ã®æ°ŽçŽ åã«
ããåŸããã極æ§æ倧ã®åå®ã«ãããã®ãä»ã¯J.
Chem.Soc Perk in I.1975.1480ã«èšèŒã®W.ãã€
ãã ãªãªã€ã¹ïŒDavid OLLISïŒã®å ±åãšé¡äŒŒ
ã«ãããã®ã 衚瀺ã®ãªã3Hâãžããããã©ãã³âïŒèªå°äœ
ã¯ïŒåã®ãžã¢ã¹ãã¬ãªã¢ã€ãœããŒã®æ··åç©ã«çžåœ
ããã æŽã«è©³çŽ°ã«ãæ¬çºæã®æ°èŠèªå°äœã¯æ¬¡ã®äžè¬åŒ
ã«çžåœããã ïŒåŒäžã
ãããã©ãã³ã®æ°èŠãªèªå°äœããã®ç©ã®è£œæ³åã³
ãã®ç©ã®å»è¬çšéã«é¢ãããã®ã§ããã ïŒâ3Hâãžããããã©ãã³ã®èªå°äœã¯ïŒåã®
äžæŽççŽ ååãæã¡ããããŠãã®ããïŒåã®ãžã¢
ã¹ãã¬ãªã¢ã€ãœããŒæ··åç©ã圢æããããã®ã
ããåºé¡äººã¯3Hâãžããããã©ãã³âïŒã®åèª
äœãã¯ãããã°ã©ãã€ãŒåŠçãè¡ã€ããæå Žåã«
ãããŠåäžæ§é åŒã§ãããïŒå¯Ÿã®ãžã¢ã¹ãã¬ãªã¢
ã€ãœããŒã§ããïŒçæç©ãåé¢ãããã 次ã®è©³çŽ°ãªèª¬æåã³ç¹èš±è«æ±ã®ç¯å²ã«ãããŠã
âãã©ã³ã¹âïŒæ¥µæ§å°ïŒæ§é ããã€åé¢çæåãæ
åã§è¡šç€ºããâã·ã¹âïŒæ¥µæ§å€§ïŒæ§é ããã€åé¢
çæåãæåã§è¡šç€ºãããããã¯ç«äœååŠçã«
決ããããã äžã€ã¯çžåœããïŒâ5Hâãã©ãã³ã®æ°ŽçŽ åã«
ããåŸããã極æ§æ倧ã®åå®ã«ãããã®ãä»ã¯J.
Chem.Soc Perk in I.1975.1480ã«èšèŒã®W.ãã€
ãã ãªãªã€ã¹ïŒDavid OLLISïŒã®å ±åãšé¡äŒŒ
ã«ãããã®ã 衚瀺ã®ãªã3Hâãžããããã©ãã³âïŒèªå°äœ
ã¯ïŒåã®ãžã¢ã¹ãã¬ãªã¢ã€ãœããŒã®æ··åç©ã«çžåœ
ããã æŽã«è©³çŽ°ã«ãæ¬çºæã®æ°èŠèªå°äœã¯æ¬¡ã®äžè¬åŒ
ã«çžåœããã ïŒåŒäžã
ãåŒãã¯
ãåŒãå
ã¯
ãåŒãã瀺ãã
ãåŒãã
ãåŒãã瀺ãå ŽåãR1ãïŒâã¡ãã«ã
ãããã·åºãã·ã¯ãããã·ã«ã¡ãããã·åºãã¡ã¿
ããããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžããã·
åºåã³ïŒâã·ã¢ãâïŒâããããã³ãžããã·åºã®
äœããäžã€ã瀺ããšãã¯ïŒ²ã¯æ°ŽçŽ ååã瀺ãã
R1ãã¡ã¿ããããã³ãžããã·åºã瀺ããšãã¯ïŒ²
ã¯ã¢ã»ãã«åºã瀺ããR1ãïŒâã¯ãããããã·
åºãïŒâã·ã¢ãããããã·åºããã³ãžããã·åºã
ã¡ã¿ããããã³ãžããã·åºãã¡ã¿ã¯ãããã³ãžã
ãã·åºãã¡ã¿ã·ã¢ããã³ãžããã·åºãïŒïŒâããª
ãžã«ïŒã¡ããã·åºãïŒâã·ã¢ãâïŒâããããã³
ãžããã·åºãïŒâã¯ããâïŒâãã«ãªããã³ãžã
ãã·åºã®äœããäžã€ã瀺ããšãã¯ïŒ²ã¯ã¡ãã«åºã
瀺ãã
ããããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžããã·
åºåã³ïŒâã·ã¢ãâïŒâããããã³ãžããã·åºã®
äœããäžã€ã瀺ããšãã¯ïŒ²ã¯æ°ŽçŽ ååã瀺ãã
R1ãã¡ã¿ããããã³ãžããã·åºã瀺ããšãã¯ïŒ²
ã¯ã¢ã»ãã«åºã瀺ããR1ãïŒâã¯ãããããã·
åºãïŒâã·ã¢ãããããã·åºããã³ãžããã·åºã
ã¡ã¿ããããã³ãžããã·åºãã¡ã¿ã¯ãããã³ãžã
ãã·åºãã¡ã¿ã·ã¢ããã³ãžããã·åºãïŒïŒâããª
ãžã«ïŒã¡ããã·åºãïŒâã·ã¢ãâïŒâããããã³
ãžããã·åºãïŒâã¯ããâïŒâãã«ãªããã³ãžã
ãã·åºã®äœããäžã€ã瀺ããšãã¯ïŒ²ã¯ã¡ãã«åºã
瀺ãã
ãåŒãã
ãåŒãã瀺ãå Ž
åãR1ãã¡ã¿ããããã³ãžããã·åºãã¡ã¿ã¯ã
ããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžããã·åºå
ã³ïŒâã¯ããâïŒâãã«ãªããã³ãžããã·åºã®äœ
ããäžã€ã瀺ããšãã¯ã¡ãã«åºã瀺ãïŒ äžè¬åŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ ã¯ãžã¹ãã¬ãªã¢ã€ãœããŒã®ãã©ã³ã¹äœãã¯
ã·ã¹äœã瀺ãã ã®ååç©ãšåŒ R2â ïŒåŒäžïŒºã¯å¡©çŽ åã¯èçŽ ååã瀺ãããããŠ
R2ã¯ïŒâã¡ãã«ããã«åºãã·ã¯ãããã·ã«ã¡ã
ã«åºãã¡ã¿ããããã³ãžã«åºãã¡ã¿ã·ã¢ããã³ãž
ã«åºåã¯ïŒâã·ã¢ãâïŒâããããã³ãžã«åºã瀺
ããïŒ ã®ããã²ã³åç©ãšçž®åãããããšã«ããæã
ã¯æ°ŽçŽ ååã瀺åŒïŒïŒã®ååç©ã補é ããæ¬çº
æã®æ¹æ³ã ãã®çž®åã¯çé žã«ãªãŠã ã®ååšäžã¢ã»ããããª
ã«äžéæµã«ãã奜é©ã«è¡ãããã 以äžã®åŠãããŠåŸãããåŒïŒïŒã®ååç©ã¯è
å±€ã¯ãããã°ã©ãåŠçã«ããåŸãããããã®å Ž
åãæäžå±€ã¯ãžã¢ã¹ãã¬ãªã¢ã€ãœããŒïŒïŒïŒ¡ãš
ïŒïŒïŒ¢ã®ïŒå¯Ÿã§ãããšç¢ºèªãããããã®æäžå±€
ã¯é«æ§èœæ¶²äœã¯ãããã°ã©ãã€ãŒïŒH.P.L.CïŒã«
ããåé¢ãããã äžèšåŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ã®
ååç©ã¯æ°èŠã§ããããããŠåŒïŒïŒïŒ¡åã¯
ïŒïŒïŒ¢åã¯åŒïŒïŒïŒ¡ãšïŒïŒïŒ¢ååç©ã®æ··å
ç©åã¯ä»ã«åŒïŒïŒã®ååç©ãš48ïŒ èåæ°ŽçŽ é žãš
åŠçããããšã«ããåŸãããã åŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ååç©
ãåæ°èŠã§ãããããã¯ãåŒïŒïŒã®ãã©ã¡ãã
ã·ããšãã«é ¢é ž ãšåŒïŒïŒã®ïŒïŒïŒâãšããã·âïŒãããã³ã ããã¿ã¬ã³ãªããŠã ãšãžãšãã«ã¢ãã³ã®ååšäž
ããã©ããããã©ã³äžéæµããåŸããã®åå¿ç²æ
ç©ãå¡©åæ°ŽçŽ é žã®æ°Žæº¶æ¶²ã§åŠçããå€å·¥çšåæã«
ããåŸããããããããŠåŸãããç²çæç©ã¯åŸã«
ãã³ãŒã³ã«ãšãããããŠãã®æº¶æ¶²ãæ°Žãå®å šã«é€
ããããŸã§éæµãããæåŸã«ãåŸãããååç©ã
H.P.L.Cã«ããã¯ãããã°ã©ãã€ãŒããã æ°èŠååç©ïŒïŒã¯åŒïŒïŒã®ãã©ã¡ããã·â
ããšãã«é ¢é žãšãã«ãšã¹ãã«ïŒ ãšåŒïŒïŒã®ïŒïŒïŒâãžãªããµã³ ïŒåŒäžZâ²ã¯èçŽ åååã¯ãã©ãã«ãšã³ã¹ã«ãã
ã«ãªãã·åã¯ã¡ãã«ã¹ã«ããã«ãªãã·åºã瀺ããïŒ
ã®çž®åã«ããåŸãããã çž®åã¯æ°ŽçŽ åãããªãŠã ã®ååšäžã§ãžã¡ãã«ã
ã«ã ã¢ããäžã§éæµããŠå¥œé©ã«è¡ããããåŸãã®
ç²åå¿çæç©ã¯80â20é ¢é žãšæ°Žæ··åç©äžã§éæµåŠ
çããã åŒïŒïŒã§ïŒ²ãã¢ã»ãã«åºã瀺ãååç©ãåŸã
æ¬çºæã®æ¹æ³ã¯ïŒ²ãæ°ŽçŽ ååâ⥠⥠ââââ â
ãéâCHâCH2âåã³R1ãã¡ã¿ããããã³ãžã
ãã·åºã瀺ãåŒïŒïŒïŒ¡åã³ïŒïŒïŒ¢ãšããã©ã
ãããã©ã³ç³»åªäœäžããªãšãã«ã¢ãã³ã®ååšäžã¢
ã»ãã«ã¯ãã©ã€ããšçž®åããããšã«ããæã€ãŠã
ãã ãã¡ãã«åºã瀺ããããŠâ⥠⥠ââââ â
ãéâCHâCH2âã瀺ããR1ããã³ãžããã·åº
ã§ããå Žåãé€ããåŒïŒïŒã®ååç©ãåŸãæ¬çº
æã®æ¹æ³ã¯åŒïŒïŒã®ååç© ãšåŒ R3â ïŒåŒäžïŒºã¯å¡©çŽ åã¯èçŽ ååã瀺ããR3ã¯ïŒ
âã¯ããããã«åºãïŒâã·ã¢ãããã«åºãã¡ã¿ã
ãããã³ãžã«åºãã¡ã¿ã¯ãããã³ãžã«åºãã¡ã¿ã·
ã¢ããã³ãžã«åºãïŒïŒâããªãžã«ïŒã¡ãã«åºãïŒ
âã·ã¢ãâïŒâããããã³ãžã«åºåã¯ïŒâã¯ãã
âïŒâãã«ãªããã³ãžã«åºã瀺ããïŒ ã®ããã²ã³åç©ãšãçž®åããããšããæã€ãŠã
ãã çž®åã¯çé žã«ãªãŠã ã®åŠãå¡©åºã®ååšäžã¢ã»ã
ãããªã«äžã§éæµããããšã«ãã€ãŠå¥œé©ã«å®æœã
ããã åŒïŒïŒã®ååç©ã®èå±€ã¯ãããã°ã©ãã€ãŒåŠ
çãè¡ããšèå¥ã§ããïŒå¯Ÿã®ãžã¢ã¹ãã¬ãªã¢ã€ãœ
ããŒïŒïŒïŒ¡åã³ïŒïŒïŒ¢ãåŸãããããããã®
äžå±€ãH.P.L.Cã«ããåé¢ãããR1ãïŒâã¯ãã
ããããã·åã³ãã³ãžããã·åºã§ç€ºãããåŒ
ïŒïŒã®ååç©ã«å¯ŸããŠã¯èå¥ã§ãããã©ã¯ã·ãš
ã³ïŒ¢ã®ã¿æ¡éããã åŒïŒïŒã®æ°èŠååç©ã¯ïŒ²ãã¡ãã«åºâ⥠⥠ââââ âãéâCHâCH2âã瀺ããR1ããã³
ãžããã·åºã瀺ãåŒïŒïŒã®ååç©äžã«è¡šã¯ãã
ãåŒïŒïŒ ããã©ãžãŠã ççŽ ã®ååšäžå æ°ŽçŽ å解ããŠåŸãã
ããååç©ïŒïŒãæ°èŠååç©ã§ãã©ãã³ãžãã
ã·ããšãã«é ¢é žåŒïŒXIïŒ ããåŒïŒïŒã®ååç©ã®åæã«çšãããšåæ§ã®æ¹
æ³ã§åŸãããã ã¯ã¡ãã«åºã瀺ããâ⥠⥠ââââ âãé
âïŒCHâã瀺ãåŒïŒïŒã®ååç©ãåŸãæ¬çº
æã®æ¹æ³ã¯åŒïŒXIIïŒã®ååç© ãšåŒ R4âOH ïŒåŒäžR4ã¯ã¡ã¿ã·ã¢ããã³ãžã«åºãã¡ã¿ã¯ã
ããã³ãžã«åºãã¡ã¿ããããã³ãžã«åºããã³ãžã«
åºåã³ïŒâã¯ããâïŒâãã«ãªãããžã«åºã瀺
ããïŒ ã®ã¢ã«ã³ãŒã«ãšçž®åãããããšã«ããæã€ãŠã
ãã ãã®çž®åã¯ããªããšãã«ãã¹ãã€ã³ïŒPÏ3ïŒå
ã³ãšãã«ãžã¢ã¶ãžã«ã«ããã·ã¬ãŒãïŒÎµtOCOâ
ïŒïŒ®âCOOεtïŒã®ååšäžããã©ããããã©ã³
ç³»åªäœäžã§å¥œé©ã«å®æœãããã æ°èŠååç©ïŒXIIïŒã¯åŒïŒïŒã®ååç© ã®å¡©é žã¡ã¿ããŒã«æº¶æ¶²ã«ããè±ãã³ãŸã€ã«åãšè±
èåæ°ŽçŽ åãåæã«è¡ãããšã«ãã€ãŠåŸãããã ååç©ïŒïŒãåæ°èŠååç©ã§åŒïŒXIïŒã®
ååç© ãåå¡©åççŽ äžéé žåãã³ãŸã€ã«ã®æº¶æ¶²ã®ååšäž
âããã¢ãµã¯ã·ã€ããïŒN.B.SïŒã§åŠçããã
ãšã«ããåŸãããã åŒïŒXIïŒã®ååç©èªäœã¯æ°èŠã§åŒïŒïŒã®å
åç©ãšãã³ãŸã€ã«ã¯ãã©ã€ããããã©ããããã©
ã³ç³»åªäœäžãããªãšãã«ã¢ãã³ã®ååšäžçž®åãã
ããšã«ããåŸãããã äžèšè£œæ³ã¯æ¬çºæã説æããããã«ç€ºãã äŸïŒïŒïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒããš
ãã«âïŒâããããã·ã¡ãã«âïŒâ3Hâãžã
ãããã©ãã³ïŒïŒã³ãŒãçªå·ïŒïŒïŒ6Aåã³
6B 第ïŒå·¥çš ïŒâãã©ã¡ããã·âïŒâã¡ããã·ã¡ã
ã«âïŒâ3Hâãžããããã©ãã³ïŒïŒ ããã©ããããã©ã³ã®100mläžã®12.8ïœã®ãã
ã¿ã¬ã³ã®æº¶æ¶²ã«ãªããŠã ã®1.4ïœãå ãããããŠ
ïŒæéå€å²ã®æž©åºŠã®æ¥è§Šããã¯ãªããåŸãžãšãã«
ã¢ãã³ã®14.6ïœãå ããããŠå šäœããªããŠã ãæ¶
ãããŸã§æ¹æãããããã©ããããã©ã³ã®30mläž
ãã©ã¡ããã·ããšãã«é ¢é žïŒïŒã®16.6ïœã®æº¶æ¶²
ãå ãã30ååïŒïŒïŒâãšããã·âïŒâã¡ããã·
ãããã³ïŒïŒã®8.8ïœã®æº¶æ¶²ãåŸã ã«å ããã
ãŠãã®æ··åç©ãïŒæééæµãããåŸãããæ°·ãšæ°Ž
æ§NaOHæ··åç©äžã«æå ¥ãããæ°Žå±€ãã€ãœãã
ãã«ãšãŒãã«ã§æŽããæ¿å¡©é žã«ããé žæ§ã«ããã
ãŠãšãã«ã¢ã»ããŒãã§æœåºãããææ©å±€ãç¡«é žã
ããªãŠã äžã§ä¹Ÿç¥ããã溶åªãèžçºããããŠåŸã
ããç²çæç©ããã³ãŒã³100mläžã«ãšããããã®
溶液ãéæµãããã®éçææ°Žãé€å»ãããåŸå·åŽ
ããé žæ§çé žãããªãŠã 氎溶液ã§æŽããç¡«æ®ãã
ãªãŠã ã§ä¹Ÿç¥ããããããŠæº¶æ¶²ãèžçºãããæ²¹ç¶
ååç©ïŒïŒ18ïœïŒ76ïŒ åçïŒãåŸããããH.
P.L.CïŒSiO212â25ÎŒïŒïŒ50ïŒ50ãšãã«ã¢ã»ããŒã
âããã¿ã³æº¶é¢ïŒã«ããã¯ãããã°ã©ãã€ãŒåŠç
ãããæ²¹ç¶ååç©ïŒïŒA7.1ïœãåŸãããã å çïŒ30ïŒ å®éšåŒïŒC13H16O4
ããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžããã·åºå
ã³ïŒâã¯ããâïŒâãã«ãªããã³ãžããã·åºã®äœ
ããäžã€ã瀺ããšãã¯ã¡ãã«åºã瀺ãïŒ äžè¬åŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ ã¯ãžã¹ãã¬ãªã¢ã€ãœããŒã®ãã©ã³ã¹äœãã¯
ã·ã¹äœã瀺ãã ã®ååç©ãšåŒ R2â ïŒåŒäžïŒºã¯å¡©çŽ åã¯èçŽ ååã瀺ãããããŠ
R2ã¯ïŒâã¡ãã«ããã«åºãã·ã¯ãããã·ã«ã¡ã
ã«åºãã¡ã¿ããããã³ãžã«åºãã¡ã¿ã·ã¢ããã³ãž
ã«åºåã¯ïŒâã·ã¢ãâïŒâããããã³ãžã«åºã瀺
ããïŒ ã®ããã²ã³åç©ãšçž®åãããããšã«ããæã
ã¯æ°ŽçŽ ååã瀺åŒïŒïŒã®ååç©ã補é ããæ¬çº
æã®æ¹æ³ã ãã®çž®åã¯çé žã«ãªãŠã ã®ååšäžã¢ã»ããããª
ã«äžéæµã«ãã奜é©ã«è¡ãããã 以äžã®åŠãããŠåŸãããåŒïŒïŒã®ååç©ã¯è
å±€ã¯ãããã°ã©ãåŠçã«ããåŸãããããã®å Ž
åãæäžå±€ã¯ãžã¢ã¹ãã¬ãªã¢ã€ãœããŒïŒïŒïŒ¡ãš
ïŒïŒïŒ¢ã®ïŒå¯Ÿã§ãããšç¢ºèªãããããã®æäžå±€
ã¯é«æ§èœæ¶²äœã¯ãããã°ã©ãã€ãŒïŒH.P.L.CïŒã«
ããåé¢ãããã äžèšåŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ã®
ååç©ã¯æ°èŠã§ããããããŠåŒïŒïŒïŒ¡åã¯
ïŒïŒïŒ¢åã¯åŒïŒïŒïŒ¡ãšïŒïŒïŒ¢ååç©ã®æ··å
ç©åã¯ä»ã«åŒïŒïŒã®ååç©ãš48ïŒ èåæ°ŽçŽ é žãš
åŠçããããšã«ããåŸãããã åŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ååç©
ãåæ°èŠã§ãããããã¯ãåŒïŒïŒã®ãã©ã¡ãã
ã·ããšãã«é ¢é ž ãšåŒïŒïŒã®ïŒïŒïŒâãšããã·âïŒãããã³ã ããã¿ã¬ã³ãªããŠã ãšãžãšãã«ã¢ãã³ã®ååšäž
ããã©ããããã©ã³äžéæµããåŸããã®åå¿ç²æ
ç©ãå¡©åæ°ŽçŽ é žã®æ°Žæº¶æ¶²ã§åŠçããå€å·¥çšåæã«
ããåŸããããããããŠåŸãããç²çæç©ã¯åŸã«
ãã³ãŒã³ã«ãšãããããŠãã®æº¶æ¶²ãæ°Žãå®å šã«é€
ããããŸã§éæµãããæåŸã«ãåŸãããååç©ã
H.P.L.Cã«ããã¯ãããã°ã©ãã€ãŒããã æ°èŠååç©ïŒïŒã¯åŒïŒïŒã®ãã©ã¡ããã·â
ããšãã«é ¢é žãšãã«ãšã¹ãã«ïŒ ãšåŒïŒïŒã®ïŒïŒïŒâãžãªããµã³ ïŒåŒäžZâ²ã¯èçŽ åååã¯ãã©ãã«ãšã³ã¹ã«ãã
ã«ãªãã·åã¯ã¡ãã«ã¹ã«ããã«ãªãã·åºã瀺ããïŒ
ã®çž®åã«ããåŸãããã çž®åã¯æ°ŽçŽ åãããªãŠã ã®ååšäžã§ãžã¡ãã«ã
ã«ã ã¢ããäžã§éæµããŠå¥œé©ã«è¡ããããåŸãã®
ç²åå¿çæç©ã¯80â20é ¢é žãšæ°Žæ··åç©äžã§éæµåŠ
çããã åŒïŒïŒã§ïŒ²ãã¢ã»ãã«åºã瀺ãååç©ãåŸã
æ¬çºæã®æ¹æ³ã¯ïŒ²ãæ°ŽçŽ ååâ⥠⥠ââââ â
ãéâCHâCH2âåã³R1ãã¡ã¿ããããã³ãžã
ãã·åºã瀺ãåŒïŒïŒïŒ¡åã³ïŒïŒïŒ¢ãšããã©ã
ãããã©ã³ç³»åªäœäžããªãšãã«ã¢ãã³ã®ååšäžã¢
ã»ãã«ã¯ãã©ã€ããšçž®åããããšã«ããæã€ãŠã
ãã ãã¡ãã«åºã瀺ããããŠâ⥠⥠ââââ â
ãéâCHâCH2âã瀺ããR1ããã³ãžããã·åº
ã§ããå Žåãé€ããåŒïŒïŒã®ååç©ãåŸãæ¬çº
æã®æ¹æ³ã¯åŒïŒïŒã®ååç© ãšåŒ R3â ïŒåŒäžïŒºã¯å¡©çŽ åã¯èçŽ ååã瀺ããR3ã¯ïŒ
âã¯ããããã«åºãïŒâã·ã¢ãããã«åºãã¡ã¿ã
ãããã³ãžã«åºãã¡ã¿ã¯ãããã³ãžã«åºãã¡ã¿ã·
ã¢ããã³ãžã«åºãïŒïŒâããªãžã«ïŒã¡ãã«åºãïŒ
âã·ã¢ãâïŒâããããã³ãžã«åºåã¯ïŒâã¯ãã
âïŒâãã«ãªããã³ãžã«åºã瀺ããïŒ ã®ããã²ã³åç©ãšãçž®åããããšããæã€ãŠã
ãã çž®åã¯çé žã«ãªãŠã ã®åŠãå¡©åºã®ååšäžã¢ã»ã
ãããªã«äžã§éæµããããšã«ãã€ãŠå¥œé©ã«å®æœã
ããã åŒïŒïŒã®ååç©ã®èå±€ã¯ãããã°ã©ãã€ãŒåŠ
çãè¡ããšèå¥ã§ããïŒå¯Ÿã®ãžã¢ã¹ãã¬ãªã¢ã€ãœ
ããŒïŒïŒïŒ¡åã³ïŒïŒïŒ¢ãåŸãããããããã®
äžå±€ãH.P.L.Cã«ããåé¢ãããR1ãïŒâã¯ãã
ããããã·åã³ãã³ãžããã·åºã§ç€ºãããåŒ
ïŒïŒã®ååç©ã«å¯ŸããŠã¯èå¥ã§ãããã©ã¯ã·ãš
ã³ïŒ¢ã®ã¿æ¡éããã åŒïŒïŒã®æ°èŠååç©ã¯ïŒ²ãã¡ãã«åºâ⥠⥠ââââ âãéâCHâCH2âã瀺ããR1ããã³
ãžããã·åºã瀺ãåŒïŒïŒã®ååç©äžã«è¡šã¯ãã
ãåŒïŒïŒ ããã©ãžãŠã ççŽ ã®ååšäžå æ°ŽçŽ å解ããŠåŸãã
ããååç©ïŒïŒãæ°èŠååç©ã§ãã©ãã³ãžãã
ã·ããšãã«é ¢é žåŒïŒXIïŒ ããåŒïŒïŒã®ååç©ã®åæã«çšãããšåæ§ã®æ¹
æ³ã§åŸãããã ã¯ã¡ãã«åºã瀺ããâ⥠⥠ââââ âãé
âïŒCHâã瀺ãåŒïŒïŒã®ååç©ãåŸãæ¬çº
æã®æ¹æ³ã¯åŒïŒXIIïŒã®ååç© ãšåŒ R4âOH ïŒåŒäžR4ã¯ã¡ã¿ã·ã¢ããã³ãžã«åºãã¡ã¿ã¯ã
ããã³ãžã«åºãã¡ã¿ããããã³ãžã«åºããã³ãžã«
åºåã³ïŒâã¯ããâïŒâãã«ãªãããžã«åºã瀺
ããïŒ ã®ã¢ã«ã³ãŒã«ãšçž®åãããããšã«ããæã€ãŠã
ãã ãã®çž®åã¯ããªããšãã«ãã¹ãã€ã³ïŒPÏ3ïŒå
ã³ãšãã«ãžã¢ã¶ãžã«ã«ããã·ã¬ãŒãïŒÎµtOCOâ
ïŒïŒ®âCOOεtïŒã®ååšäžããã©ããããã©ã³
ç³»åªäœäžã§å¥œé©ã«å®æœãããã æ°èŠååç©ïŒXIIïŒã¯åŒïŒïŒã®ååç© ã®å¡©é žã¡ã¿ããŒã«æº¶æ¶²ã«ããè±ãã³ãŸã€ã«åãšè±
èåæ°ŽçŽ åãåæã«è¡ãããšã«ãã€ãŠåŸãããã ååç©ïŒïŒãåæ°èŠååç©ã§åŒïŒXIïŒã®
ååç© ãåå¡©åççŽ äžéé žåãã³ãŸã€ã«ã®æº¶æ¶²ã®ååšäž
âããã¢ãµã¯ã·ã€ããïŒN.B.SïŒã§åŠçããã
ãšã«ããåŸãããã åŒïŒXIïŒã®ååç©èªäœã¯æ°èŠã§åŒïŒïŒã®å
åç©ãšãã³ãŸã€ã«ã¯ãã©ã€ããããã©ããããã©
ã³ç³»åªäœäžãããªãšãã«ã¢ãã³ã®ååšäžçž®åãã
ããšã«ããåŸãããã äžèšè£œæ³ã¯æ¬çºæã説æããããã«ç€ºãã äŸïŒïŒïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒããš
ãã«âïŒâããããã·ã¡ãã«âïŒâ3Hâãžã
ãããã©ãã³ïŒïŒã³ãŒãçªå·ïŒïŒïŒ6Aåã³
6B 第ïŒå·¥çš ïŒâãã©ã¡ããã·âïŒâã¡ããã·ã¡ã
ã«âïŒâ3Hâãžããããã©ãã³ïŒïŒ ããã©ããããã©ã³ã®100mläžã®12.8ïœã®ãã
ã¿ã¬ã³ã®æº¶æ¶²ã«ãªããŠã ã®1.4ïœãå ãããããŠ
ïŒæéå€å²ã®æž©åºŠã®æ¥è§Šããã¯ãªããåŸãžãšãã«
ã¢ãã³ã®14.6ïœãå ããããŠå šäœããªããŠã ãæ¶
ãããŸã§æ¹æãããããã©ããããã©ã³ã®30mläž
ãã©ã¡ããã·ããšãã«é ¢é žïŒïŒã®16.6ïœã®æº¶æ¶²
ãå ãã30ååïŒïŒïŒâãšããã·âïŒâã¡ããã·
ãããã³ïŒïŒã®8.8ïœã®æº¶æ¶²ãåŸã ã«å ããã
ãŠãã®æ··åç©ãïŒæééæµãããåŸãããæ°·ãšæ°Ž
æ§NaOHæ··åç©äžã«æå ¥ãããæ°Žå±€ãã€ãœãã
ãã«ãšãŒãã«ã§æŽããæ¿å¡©é žã«ããé žæ§ã«ããã
ãŠãšãã«ã¢ã»ããŒãã§æœåºãããææ©å±€ãç¡«é žã
ããªãŠã äžã§ä¹Ÿç¥ããã溶åªãèžçºããããŠåŸã
ããç²çæç©ããã³ãŒã³100mläžã«ãšããããã®
溶液ãéæµãããã®éçææ°Žãé€å»ãããåŸå·åŽ
ããé žæ§çé žãããªãŠã 氎溶液ã§æŽããç¡«æ®ãã
ãªãŠã ã§ä¹Ÿç¥ããããããŠæº¶æ¶²ãèžçºãããæ²¹ç¶
ååç©ïŒïŒ18ïœïŒ76ïŒ åçïŒãåŸããããH.
P.L.CïŒSiO212â25ÎŒïŒïŒ50ïŒ50ãšãã«ã¢ã»ããŒã
âããã¿ã³æº¶é¢ïŒã«ããã¯ãããã°ã©ãã€ãŒåŠç
ãããæ²¹ç¶ååç©ïŒïŒA7.1ïœãåŸãããã å çïŒ30ïŒ å®éšåŒïŒC13H16O4
ãè¡šã
ãããŠ7.4ïœã®æ²¹ç¶ååç©ïŒïŒïŒ¢
å çïŒ32ïŒ
å®éšåŒïŒC13H16O4
ãè¡šã
第ïŒå·¥çš ïŒâãã©ããããã·ããšãã«âïŒâã
ãããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³ 48ïŒ èé žã®ïŒmläžåå·¥çšã§åŸãããååç©
ïŒïŒã®0.7ïœæº¶æ¶²ãïŒæééæµããåæ°Žã®20mlå
ã³é£å¡©é£œå氎溶液20mlåã³ãšãã«ã¢ã»ããŒãã®50
mlãå ããããããé žæ§çé žãããªãŠã ã®æ°Žæº¶æ¶²
ã§äžåãã油局ãåŸçããç¡«é žãããªãŠã ã§ä¹Ÿç¥
ããããŠèžçºãããååç©ïŒïŒã®0.5ïœãåŸã
ãããïŒåç81ïŒ ïŒãããããšãã«ã¢ã»ããŒãã§å
çµæ¶ããã è ç¹ïŒ120â IRã¹ãã¯ãã«ïŒããšããŒã«åã³ã¢ã«ã³ãŒã«ã
ã³ã3440åã³3240cm-1 ã©ã¯ãã³ ãã³ã 1730cm-1 NMRã¹ãã¯ãã«ïŒDMSOïŒÎŽppmïŒ 9.65ïŒïŒ³ïŒïŒããšããŒã« ãããã³
7.04ïŒïœãåã³6.67.dïŒïŒïŒªïŒ9H2ïŒïŒïŒ
ãã³ãŒã³ ãããã³ 5.03ïŒïœïŒ1Hâãã©ãã³ç°ã®ïŒäœ 4.58ïŒïœïŒ1Hâãã©ãã³ç°ã®ïŒäœ 3.88ïŒïœïŒïŒâããããã·ã¡ãã«åºã®ïŒã¡ãã«
ãããã³ 2.42ïŒïœããã©ãã³ç°ã®ïŒäœã®ïŒãããã³ 3.62ïŒïŒ³ïŒâOH 第ïŒå·¥çš ïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒ
ããšãã«âïŒâããããã·ã¡ãã«âïŒâ3Hâ
ãžãããã©ãã³ïŒïŒ ã³ãŒãçªå·ïŒïŒïŒ6A
åã³6B ã¢ã»ããããªã«150mläžåå·¥çšã§åŸãããåå
ç©ïŒïŒã®25.8ïœãã¡ã¿ããããã«ãšã³ã¯ãã©ã€
ãã®21.2ïœåã³çé žã«ãªãŠã ã®49.6ïœã®æ··åç©ã
ïŒæééæµããåŸéããã溶åªãèžçºãããã
ãŠæ®çç©ããšãã«ã¢ã»ããŒãåã³ïœâããã¿ã³
ïŒ80â20ïŒã®æ··åç©äžã§çµæ¶åãããè¡šïŒã§è¡šã
ãããã³ãŒãçªå·ïŒã®ïŒåã®ãžã¢ã¹ãã¬ãªã¢ã€ãœ
ããŒã®æ··åç©ãåŸãããããããïŒP.L.CïŒãš
ãã«ã¢ã»ããŒã80nâããã¿ã³20ã§æº¶é¢ïŒã«ãã
ã¯ãããã°ã©ãã€ãŒãããã³ãŒãçªå·6Aã®åå
ç©ïŒïŒA11ïœ å çïŒ25ïŒ è ç¹ïŒ98â å®éšåŒïŒïŒC18H17NO6
ãããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³ 48ïŒ èé žã®ïŒmläžåå·¥çšã§åŸãããååç©
ïŒïŒã®0.7ïœæº¶æ¶²ãïŒæééæµããåæ°Žã®20mlå
ã³é£å¡©é£œå氎溶液20mlåã³ãšãã«ã¢ã»ããŒãã®50
mlãå ããããããé žæ§çé žãããªãŠã ã®æ°Žæº¶æ¶²
ã§äžåãã油局ãåŸçããç¡«é žãããªãŠã ã§ä¹Ÿç¥
ããããŠèžçºãããååç©ïŒïŒã®0.5ïœãåŸã
ãããïŒåç81ïŒ ïŒãããããšãã«ã¢ã»ããŒãã§å
çµæ¶ããã è ç¹ïŒ120â IRã¹ãã¯ãã«ïŒããšããŒã«åã³ã¢ã«ã³ãŒã«ã
ã³ã3440åã³3240cm-1 ã©ã¯ãã³ ãã³ã 1730cm-1 NMRã¹ãã¯ãã«ïŒDMSOïŒÎŽppmïŒ 9.65ïŒïŒ³ïŒïŒããšããŒã« ãããã³
7.04ïŒïœãåã³6.67.dïŒïŒïŒªïŒ9H2ïŒïŒïŒ
ãã³ãŒã³ ãããã³ 5.03ïŒïœïŒ1Hâãã©ãã³ç°ã®ïŒäœ 4.58ïŒïœïŒ1Hâãã©ãã³ç°ã®ïŒäœ 3.88ïŒïœïŒïŒâããããã·ã¡ãã«åºã®ïŒã¡ãã«
ãããã³ 2.42ïŒïœããã©ãã³ç°ã®ïŒäœã®ïŒãããã³ 3.62ïŒïŒ³ïŒâOH 第ïŒå·¥çš ïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒ
ããšãã«âïŒâããããã·ã¡ãã«âïŒâ3Hâ
ãžãããã©ãã³ïŒïŒ ã³ãŒãçªå·ïŒïŒïŒ6A
åã³6B ã¢ã»ããããªã«150mläžåå·¥çšã§åŸãããåå
ç©ïŒïŒã®25.8ïœãã¡ã¿ããããã«ãšã³ã¯ãã©ã€
ãã®21.2ïœåã³çé žã«ãªãŠã ã®49.6ïœã®æ··åç©ã
ïŒæééæµããåŸéããã溶åªãèžçºãããã
ãŠæ®çç©ããšãã«ã¢ã»ããŒãåã³ïœâããã¿ã³
ïŒ80â20ïŒã®æ··åç©äžã§çµæ¶åãããè¡šïŒã§è¡šã
ãããã³ãŒãçªå·ïŒã®ïŒåã®ãžã¢ã¹ãã¬ãªã¢ã€ãœ
ããŒã®æ··åç©ãåŸãããããããïŒP.L.CïŒãš
ãã«ã¢ã»ããŒã80nâããã¿ã³20ã§æº¶é¢ïŒã«ãã
ã¯ãããã°ã©ãã€ãŒãããã³ãŒãçªå·6Aã®åå
ç©ïŒïŒA11ïœ å çïŒ25ïŒ è ç¹ïŒ98â å®éšåŒïŒïŒC18H17NO6
ãè¡šã
åã³ã³ãŒãçªå·6Bã®ååç©ïŒïŒB12ïœãåŸ
ãããã å çïŒ30ïŒ è ç¹ïŒ115â å®éšåŒïŒO18H17NO6
ãããã å çïŒ30ïŒ è ç¹ïŒ115â å®éšåŒïŒO18H17NO6
ãè¡šã
çžåœããè©Šè¬ããåæ§ã®æ¹æ³ã«ããè¡šïŒã§è¡šã
ãããã³ãŒãçªå·ïŒïŒïŒïŒïŒ12åã³16ã®åŒïŒïŒ
ã®ååç©ãåŸãããã äŸïŒïŒïŒâãã©ããããã·ããšãã«âïŒâããã
ãã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³ïŒïŒ 第ïŒå·¥çš ïŒâãã©ã¡ããã·ããšãã«âïŒâãã
ããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒ 300mlã®ãžã¡ãã«ãã«ã ã¢ããäžãã©ã¡ããã·
ããšãã«é ¢é žãšãã«ãšã¹ãã«ïŒïŒ40.8ïœåã³ïŒ
âãã©ãã·ããã·ã¡ãã«âïŒïŒïŒâãžã¡ãã«â
ïŒïŒïŒâãžãªããµã³ïŒïŒã®æº¶æ¶²ã«æ°ŽçŽ åãããª
ãŠã ã®10ïœãã¢ã«ãŽã³äžã§å ãããåŸãã®æº¶æ¶²ã
ååå¿ã¯60âã§è¡ããåŸ90âã§ïŒæéè¡ãããã®
溶液ãæ°Ž300mlã§çšéããé ¢é žãšãã«ã§æœåºããã
ãã®æº¶åªãèžçºããããŠæ®çç©èžçããïŒEb0.1
ïŒ158â160âïŒãããããŠåŸãããçæç©ãé ¢é ž
âæ°Žæ··åç©ïŒ80â20ïŒã«å ãããããŠãã®æº¶æ¶²ã
ã45åééæµããåŸæ°·æ°Žã§çšéããããããŠæº¶æ¶²
ã®PHãé žæ§çé žãããªãŠã ã§ïŒä»¥äžã«ãããçæ
ç©ãé ¢é žãšãã«ã§æœåºããç¡«é žãããªãŠã ã§ä¹Ÿç¥
ããããŠæº¶åªãçå»ãããæ²¹ã®13ïœãåŸã ã«çµæ¶
åããã å çïŒ56ïŒ è ç¹ïŒïŒ50â å®éšåŒïŒC12H14O4
ãããã³ãŒãçªå·ïŒïŒïŒïŒïŒ12åã³16ã®åŒïŒïŒ
ã®ååç©ãåŸãããã äŸïŒïŒïŒâãã©ããããã·ããšãã«âïŒâããã
ãã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³ïŒïŒ 第ïŒå·¥çš ïŒâãã©ã¡ããã·ããšãã«âïŒâãã
ããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒ 300mlã®ãžã¡ãã«ãã«ã ã¢ããäžãã©ã¡ããã·
ããšãã«é ¢é žãšãã«ãšã¹ãã«ïŒïŒ40.8ïœåã³ïŒ
âãã©ãã·ããã·ã¡ãã«âïŒïŒïŒâãžã¡ãã«â
ïŒïŒïŒâãžãªããµã³ïŒïŒã®æº¶æ¶²ã«æ°ŽçŽ åãããª
ãŠã ã®10ïœãã¢ã«ãŽã³äžã§å ãããåŸãã®æº¶æ¶²ã
ååå¿ã¯60âã§è¡ããåŸ90âã§ïŒæéè¡ãããã®
溶液ãæ°Ž300mlã§çšéããé ¢é žãšãã«ã§æœåºããã
ãã®æº¶åªãèžçºããããŠæ®çç©èžçããïŒEb0.1
ïŒ158â160âïŒãããããŠåŸãããçæç©ãé ¢é ž
âæ°Žæ··åç©ïŒ80â20ïŒã«å ãããããŠãã®æº¶æ¶²ã
ã45åééæµããåŸæ°·æ°Žã§çšéããããããŠæº¶æ¶²
ã®PHãé žæ§çé žãããªãŠã ã§ïŒä»¥äžã«ãããçæ
ç©ãé ¢é žãšãã«ã§æœåºããç¡«é žãããªãŠã ã§ä¹Ÿç¥
ããããŠæº¶åªãçå»ãããæ²¹ã®13ïœãåŸã ã«çµæ¶
åããã å çïŒ56ïŒ è ç¹ïŒïŒ50â å®éšåŒïŒC12H14O4
ãè¡šã
第ïŒå·¥çš ïŒâãã©ããããã·ããšãã«âïŒâã
ãããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒ ãã®æ¹æ³ã¯åèšååç©ïŒïŒãçšãã以å€ã¯äŸ
ïŒã®ç¬¬ïŒå·¥çšãšåæ§ã§ããã äŸïŒïŒïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒããš
ãã«âïŒâã¢ã»ããã·ã¡ãã«âïŒâ3Hâãžã
ãããã©ãã³ïŒïŒã³ãŒãçªå·ïŒ7Aåã³7B ïŒâã«å·åŽããããã©ããããã©ã³100mläžã®
äŸïŒèšèŒã®ïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒ
ããšãã«âïŒâããããã·ã¡ãã«âïŒâ3Hâãž
ããããã©ãã³(1)ãå«ã6A溶液ã«ã¢ã»ãã«ã¯ã
ã©ã€ãã®1.5ïœãåŸããªãšãã«ã¢ãã³ã®ïŒïœãå
ãããæ®çç©ãé ¢é žãšãã«ã«ç§»ããæ°ŽæŽããç¡«é ž
ãããªãŠã ã§ä¹Ÿç¥ãã溶åªãèžçºããããŠæ®çç©
ããšãŒãã«äžã§çµæ¶åãããšååç©7Aã®ïŒïœã
åŸãããã å çïŒ79ïŒ è ç¹ïŒ78â å®éšåŒïŒC20H19NO7
ãããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒ ãã®æ¹æ³ã¯åèšååç©ïŒïŒãçšãã以å€ã¯äŸ
ïŒã®ç¬¬ïŒå·¥çšãšåæ§ã§ããã äŸïŒïŒïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒããš
ãã«âïŒâã¢ã»ããã·ã¡ãã«âïŒâ3Hâãžã
ãããã©ãã³ïŒïŒã³ãŒãçªå·ïŒ7Aåã³7B ïŒâã«å·åŽããããã©ããããã©ã³100mläžã®
äŸïŒèšèŒã®ïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒ
ããšãã«âïŒâããããã·ã¡ãã«âïŒâ3Hâãž
ããããã©ãã³(1)ãå«ã6A溶液ã«ã¢ã»ãã«ã¯ã
ã©ã€ãã®1.5ïœãåŸããªãšãã«ã¢ãã³ã®ïŒïœãå
ãããæ®çç©ãé ¢é žãšãã«ã«ç§»ããæ°ŽæŽããç¡«é ž
ãããªãŠã ã§ä¹Ÿç¥ãã溶åªãèžçºããããŠæ®çç©
ããšãŒãã«äžã§çµæ¶åãããšååç©7Aã®ïŒïœã
åŸãããã å çïŒ79ïŒ è ç¹ïŒ78â å®éšåŒïŒC20H19NO7
ãè¡šã
ååç©ïŒïŒ6Bãã以å€ã¯äŸïŒèšèŒãšåæ§ã®
æ¹æ³ã«ãã€ãŠååç©ïŒïŒ7BãåŸãã å çïŒ89ïŒ è ç¹ïŒ108â å®éšåŒïŒC20H19NO7
æ¹æ³ã«ãã€ãŠååç©ïŒïŒ7BãåŸãã å çïŒ89ïŒ è ç¹ïŒ108â å®éšåŒïŒC20H19NO7
ãè¡šã
äŸïŒïŒïŒâãã©ïŒïŒã¡ã¿ããããã³ãžããã·ïŒã
ãšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãžã
ãããã©ãã³ïŒïŒã³ãŒãçªå·ïŒïŒïŒ8Aåã³
8B 第ïŒå·¥çš ïŒâãã©ãã³ãžããã·ããšãã«âïŒâ
ã¡ããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒ ãã©ãã³ãžããã·ããšãã«é ¢é žïŒXIïŒãã以å€
ã¯äŸïŒã®ç¬¬ïŒå·¥çšèšèŒã®ååç©ïŒïŒã®åæã«çš
ããæ¹æ³ãšåæ§ã®æ¹æ³ã«ãã€ãŠååç©ïŒïŒã®65
ïŒ ãåŸãããã è ç¹ïŒ124â å®éšåŒïŒC19H20O4
ãšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãžã
ãããã©ãã³ïŒïŒã³ãŒãçªå·ïŒïŒïŒ8Aåã³
8B 第ïŒå·¥çš ïŒâãã©ãã³ãžããã·ããšãã«âïŒâ
ã¡ããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒ ãã©ãã³ãžããã·ããšãã«é ¢é žïŒXIïŒãã以å€
ã¯äŸïŒã®ç¬¬ïŒå·¥çšèšèŒã®ååç©ïŒïŒã®åæã«çš
ããæ¹æ³ãšåæ§ã®æ¹æ³ã«ãã€ãŠååç©ïŒïŒã®65
ïŒ ãåŸãããã è ç¹ïŒ124â å®éšåŒïŒC19H20O4
ãè¡šã
第ïŒå·¥çš ïŒâãã©ããããã·ããšãã«âïŒâã¡
ããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒåå·¥çšã§åŸãããååç©ïŒïŒã®4.3ïœå
ã³ãã©ãžãŠã ççŽ ïŒ10ïŒ ïŒã®4.3ïœã®ã¡ã¿ããŒ
ã«700mläžã®æžæ¿æ¶²ãæ°ŽçŽ ã®ïŒããŒã«ã®å§åäž
ã§ïŒæéå æ°ŽçŽ å解ãããåŸãããéããã
ãŠæº¶åªãèžçºãããšçæç©26ïœãåŸãããã å çïŒ87ïŒ è ç¹ïŒ75â å®éšåŒïŒC12H14O4
ããã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³
ïŒïŒåå·¥çšã§åŸãããååç©ïŒïŒã®4.3ïœå
ã³ãã©ãžãŠã ççŽ ïŒ10ïŒ ïŒã®4.3ïœã®ã¡ã¿ããŒ
ã«700mläžã®æžæ¿æ¶²ãæ°ŽçŽ ã®ïŒããŒã«ã®å§åäž
ã§ïŒæéå æ°ŽçŽ å解ãããåŸãããéããã
ãŠæº¶åªãèžçºãããšçæç©26ïœãåŸãããã å çïŒ87ïŒ è ç¹ïŒ75â å®éšåŒïŒC12H14O4
ãè¡šã
第ïŒå·¥çš ïŒâãã©ïŒã¡ã¿ããããã³ãžããã·ïŒ
ããšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãž
ããããã©ãã³ïŒïŒã³ãŒãçªå·ïŒïŒïŒ8Aå
ã³8B ååç©ïŒïŒãã以å€ã¯äŸïŒã®ç¬¬ïŒå·¥çšã«çšã
ããšåæ§ã®æ¹æ³ãçšãããããã«ããã³ãŒãçªå·
ïŒã®çæç©ãåŸããããæŽã«H.P.LïŒïŒ£ïŒæº¶é¢å€
é ¢é žãšãã«70nâããã¿ã³30ïŒã«ããåé¢ãããš
ååç©ïŒïŒïŒ¡ã8Aãã®23ïŒ è ç¹ïŒ78â å®éšåŒïŒC19H19NO6
ããšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãž
ããããã©ãã³ïŒïŒã³ãŒãçªå·ïŒïŒïŒ8Aå
ã³8B ååç©ïŒïŒãã以å€ã¯äŸïŒã®ç¬¬ïŒå·¥çšã«çšã
ããšåæ§ã®æ¹æ³ãçšãããããã«ããã³ãŒãçªå·
ïŒã®çæç©ãåŸããããæŽã«H.P.LïŒïŒ£ïŒæº¶é¢å€
é ¢é žãšãã«70nâããã¿ã³30ïŒã«ããåé¢ãããš
ååç©ïŒïŒïŒ¡ã8Aãã®23ïŒ è ç¹ïŒ78â å®éšåŒïŒC19H19NO6
ãè¡šã
ååç©ïŒïŒïŒ¢ã8Bãã®50ïŒ
ãåŸãã
è ç¹ïŒ56â
å®éšåŒïŒC19N19NO6
ãè¡šã
åæ§ã®æ¹æ³ã«ããçžåœããè©Šè¬ããè¡šã§ç€ºã
ããã³ãŒãçªå·ïŒïŒ3BïŒïŒïŒïŒïŒ5BïŒ10ïŒ10AïŒ
10BïŒ13ïŒ13AïŒ13BïŒ15ïŒ17ïŒ17AïŒ17BïŒ18ïŒ
18Aåã³18BãåŸãã äŸïŒïŒïŒâãã©ïŒã¡ã¿ã·ã¢ããã³ãžããã·ïŒããš
ãã«âïŒâã¡ããã·ã¡ãã«âïŒâ5Hâãã©ã
ã³ïŒïŒã³ãŒãçªå·ïŒ14 第ïŒå·¥çš ïŒâïŒãã©ãã³ãžããã·ïŒããšãã«â
ïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãžããããã©
ãã³ïŒïŒ ããã©ããããã©ã³25mläžäŸïŒã®ç¬¬ïŒå·¥çšã«èš
èŒãããïŒâãã©ããããã·ããšãã«âïŒâã¡ã
ãã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³ïŒïŒ
ïŒïœã®æº¶æ¶²ã«ããªãšãã«ã¢ãã³1.3ïœåŸãã³ãŸã€
ã«ã¯ãã©ã€ã0.7ïœãå ãããåžžæž©ã§20ååŸé
ããã液ãèžçºãããæ®çç©ãé ¢é žãšãã«ã«ç§»
ããé ¢æ§çé žãããªãŠã ã®é£œå氎溶液ã§æŽããç¡«
é žãããªãŠã ã§ä¹Ÿç¥ããã溶åªãèžçºããããŠæ®
çç©ããšãŒãã«ã§æŽãã å çïŒ94ïŒ è ç¹ïŒ108â å®éšåŒïŒC19H18O5
ããã³ãŒãçªå·ïŒïŒ3BïŒïŒïŒïŒïŒ5BïŒ10ïŒ10AïŒ
10BïŒ13ïŒ13AïŒ13BïŒ15ïŒ17ïŒ17AïŒ17BïŒ18ïŒ
18Aåã³18BãåŸãã äŸïŒïŒïŒâãã©ïŒã¡ã¿ã·ã¢ããã³ãžããã·ïŒããš
ãã«âïŒâã¡ããã·ã¡ãã«âïŒâ5Hâãã©ã
ã³ïŒïŒã³ãŒãçªå·ïŒ14 第ïŒå·¥çš ïŒâïŒãã©ãã³ãžããã·ïŒããšãã«â
ïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãžããããã©
ãã³ïŒïŒ ããã©ããããã©ã³25mläžäŸïŒã®ç¬¬ïŒå·¥çšã«èš
èŒãããïŒâãã©ããããã·ããšãã«âïŒâã¡ã
ãã·ã¡ãã«âïŒâ3Hâãžããããã©ãã³ïŒïŒ
ïŒïœã®æº¶æ¶²ã«ããªãšãã«ã¢ãã³1.3ïœåŸãã³ãŸã€
ã«ã¯ãã©ã€ã0.7ïœãå ãããåžžæž©ã§20ååŸé
ããã液ãèžçºãããæ®çç©ãé ¢é žãšãã«ã«ç§»
ããé ¢æ§çé žãããªãŠã ã®é£œå氎溶液ã§æŽããç¡«
é žãããªãŠã ã§ä¹Ÿç¥ããã溶åªãèžçºããããŠæ®
çç©ããšãŒãã«ã§æŽãã å çïŒ94ïŒ è ç¹ïŒ108â å®éšåŒïŒC19H18O5
ãè¡šã
第ïŒå·¥çš ïŒâããã¢âïŒâïŒãã©ãã³ãžãã
ã·ïŒããšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3H
âãžããããã©ãã³ïŒïŒ åå¡©åççŽ 350mläžåå·¥çšã§åŸãååç©ïŒïŒ
10ïœãâããã¢ãµã¯ã·ã€ãã3.4ïœåã³å°éã®
çµæ¶éé žåãã³ãŸã€ã«ã®æº¶æ¶²ãïŒæééæµããã
åŸéããã液ãèžçºããããŠæ®çç©ããšãŒã
ã«äžã§çµæ¶åãããšååç©ïŒïŒã63ïŒ åŸãã
ãã è ç¹ïŒ136â å®éšåŒïŒC19H17BrO6
ã·ïŒããšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3H
âãžããããã©ãã³ïŒïŒ åå¡©åççŽ 350mläžåå·¥çšã§åŸãååç©ïŒïŒ
10ïœãâããã¢ãµã¯ã·ã€ãã3.4ïœåã³å°éã®
çµæ¶éé žåãã³ãŸã€ã«ã®æº¶æ¶²ãïŒæééæµããã
åŸéããã液ãèžçºããããŠæ®çç©ããšãŒã
ã«äžã§çµæ¶åãããšååç©ïŒïŒã63ïŒ åŸãã
ãã è ç¹ïŒ136â å®éšåŒïŒC19H17BrO6
ãè¡šã
第ïŒå·¥çš ïŒâãã©ãããã·ããšãã«âïŒâã¡ã
ãã·ã¡ãã«âïŒâ5Hâãã©ãã³ïŒXIIïŒ ã¬ã¹ç¶å¡©åæ°ŽçŽ ã飜åãããã¡ã¿ããŒã«125ml
äžåå·¥çšã§åŸãããååç©ïŒïŒ10ïœã®æº¶æ¶²ã
ïŒæééæµãããåŸãããèžçºããæ®çç©ãé ¢é ž
ãšãã«ã«ç§»ããé žæ§çé žãããªãŠã 飜å溶液ã§æŽ
ããç¡«é žãããªãŠã ã§ä¹Ÿç¥ããããŠæº¶åªãèžçºã
ãããæ®çç©ããšãŒãã«äžã§çµæ¶åããã å çïŒ67ïŒ è ç¹ïŒ141â å®éšåŒïŒC12H12O4
ãã·ã¡ãã«âïŒâ5Hâãã©ãã³ïŒXIIïŒ ã¬ã¹ç¶å¡©åæ°ŽçŽ ã飜åãããã¡ã¿ããŒã«125ml
äžåå·¥çšã§åŸãããååç©ïŒïŒ10ïœã®æº¶æ¶²ã
ïŒæééæµãããåŸãããèžçºããæ®çç©ãé ¢é ž
ãšãã«ã«ç§»ããé žæ§çé žãããªãŠã 飜å溶液ã§æŽ
ããç¡«é žãããªãŠã ã§ä¹Ÿç¥ããããŠæº¶åªãèžçºã
ãããæ®çç©ããšãŒãã«äžã§çµæ¶åããã å çïŒ67ïŒ è ç¹ïŒ141â å®éšåŒïŒC12H12O4
ãè¡šã
第ïŒå·¥çš ïŒâãã©ïŒã¡ã¿ã·ã¢ããã³ãžããã·ïŒ
ããšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ5Hâã
ã©ãã³ïŒïŒã³ãŒãçªå·ïŒ14 ããã©ããããã©ã³ã®60mläžåå·¥çšã§åŸããã
ååç©ïŒXIIïŒ2.2ïœãããªããšãã«ãã¹ãã€ã³3.1
ïœåã³ã¡ã¿ã·ã¢ãããšãã«ã¡ã¿ããŒã«1.5ïœã®æº¶
液ãã¢ã«ãŽã³ã¬ã¹ãããŠïŒâã«å·åŽããããã®æº¶
液ã«10åéãããŠãšãã«ãžã¢ã¶âãžã«ã«ããã·ã¬
ãŒãïŒDEADCïŒïŒïœãå ãããåŸ30åïŒâã«ã
ãããŠ90ååžžæž©ã«ããã溶åªãèžçºãããããŠæ®
çç©ãã·ãªã«ã«ã©ã äžã§ã¯ãããã°ã©ãã€ãŒåŠç
ããããã«ãšã³ã«ããäžçŽç©ãé€ããåŸã¯ããã
ã°ã©ãã€ãŒåŠçãåæ¢ããããŠçæç©ãã¡ãã¬ã³
ã¯ãã©ã€ãåã³ã¡ã¿ããŒã«ã®æ··åç©ã«ããã·ãªã«
ããæœåºããã溶åªãèžçºããããŠæ®çç©ããšãŒ
ãã«äžã§åçµæ¶ããã å çïŒ30ïŒ è ç¹ïŒ70â å®éšåŒïŒC20H17NO4
ããšãã«âïŒâã¡ããã·ã¡ãã«âïŒâ5Hâã
ã©ãã³ïŒïŒã³ãŒãçªå·ïŒ14 ããã©ããããã©ã³ã®60mläžåå·¥çšã§åŸããã
ååç©ïŒXIIïŒ2.2ïœãããªããšãã«ãã¹ãã€ã³3.1
ïœåã³ã¡ã¿ã·ã¢ãããšãã«ã¡ã¿ããŒã«1.5ïœã®æº¶
液ãã¢ã«ãŽã³ã¬ã¹ãããŠïŒâã«å·åŽããããã®æº¶
液ã«10åéãããŠãšãã«ãžã¢ã¶âãžã«ã«ããã·ã¬
ãŒãïŒDEADCïŒïŒïœãå ãããåŸ30åïŒâã«ã
ãããŠ90ååžžæž©ã«ããã溶åªãèžçºãããããŠæ®
çç©ãã·ãªã«ã«ã©ã äžã§ã¯ãããã°ã©ãã€ãŒåŠç
ããããã«ãšã³ã«ããäžçŽç©ãé€ããåŸã¯ããã
ã°ã©ãã€ãŒåŠçãåæ¢ããããŠçæç©ãã¡ãã¬ã³
ã¯ãã©ã€ãåã³ã¡ã¿ããŒã«ã®æ··åç©ã«ããã·ãªã«
ããæœåºããã溶åªãèžçºããããŠæ®çç©ããšãŒ
ãã«äžã§åçµæ¶ããã å çïŒ30ïŒ è ç¹ïŒ70â å®éšåŒïŒC20H17NO4
ãè¡šã
åæ§ã®æ¹æ³ã«ããçžåœããè©Šè¬ããè¡šã§ç€ºã
ããã³ãŒãçªå·ïŒïŒïŒ11ïŒ19åã³20ãåŸãã äŸïŒïŒïŒâãã©ïŒã¡ã¿ã·ã¢ããã³ãžããã·ïŒããš
ãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãžãã
ããã©ãã³ïŒïŒâã·ã¹âã³ãŒãçªå·13B ç¡æ°Žã¡ã¿ããŒã«ã®50mläžåèšäŸïŒã§åŸãããã³
ãŒãçªå·14ã®ååç©ïŒïŒ0.5ïœæº¶æ¶²ãïŒâã§ã
ã©ãžãŠã ççŽ 0.05ïœã®ååšäžåžžå§ã§æ°ŽçŽ æ·»å ã
ããåŸ80ååå¿ãããããéãã液ãèžçºã
ãããŠâã·ã¹âååç©13B90ïŒ ãåŸãããããã
ã¯èå±€ã¯ãããã°ã©ãã€ã®ç¹åŸŽããäŸïŒïŒ13BïŒ
ã§åŸãããååç©åã³è¡šã§ç€ºãããååç©ãšå
äžã§ãããããã¯æ倧ã®æ¥µæ§ã«ããã·ã¹æ§é ãšæš
å®ãããã
ããã³ãŒãçªå·ïŒïŒïŒ11ïŒ19åã³20ãåŸãã äŸïŒïŒïŒâãã©ïŒã¡ã¿ã·ã¢ããã³ãžããã·ïŒããš
ãã«âïŒâã¡ããã·ã¡ãã«âïŒâ3Hâãžãã
ããã©ãã³ïŒïŒâã·ã¹âã³ãŒãçªå·13B ç¡æ°Žã¡ã¿ããŒã«ã®50mläžåèšäŸïŒã§åŸãããã³
ãŒãçªå·14ã®ååç©ïŒïŒ0.5ïœæº¶æ¶²ãïŒâã§ã
ã©ãžãŠã ççŽ 0.05ïœã®ååšäžåžžå§ã§æ°ŽçŽ æ·»å ã
ããåŸ80ååå¿ãããããéãã液ãèžçºã
ãããŠâã·ã¹âååç©13B90ïŒ ãåŸãããããã
ã¯èå±€ã¯ãããã°ã©ãã€ã®ç¹åŸŽããäŸïŒïŒ13BïŒ
ã§åŸãããååç©åã³è¡šã§ç€ºãããååç©ãšå
äžã§ãããããã¯æ倧ã®æ¥µæ§ã«ããã·ã¹æ§é ãšæš
å®ãããã
ãè¡šã
ãè¡šã
ãè¡šã
ãè¡šã
ãè¡šã
åŒ(1)ã®ååç©ãå®éšåç©ã§è©Šéšããåç¥çµã®å
éãç¹ã«ã¢ãã¢ãããªãã·ããŒãŒã®å¯éçæå¶æŽ»
æ§ãããããšãåã€ãã ãããã®æŽ»æ§ã¯äžèšè©Šéšã«ããæããã§ããã
è©ŠéšïŒ¡ïŒãŽãŒã¬ããåã³ããŒãã¹ïŒªã®J.ãã¢ãŒ
ãã³ã«ãGOURET C.THOMAS J.âJ.
PharmacolïŒããªïŒïŒïŒïŒ401ïŒ1973ïŒâãèšèŒã®å ±
åã«åŸã€ãŠè¡ã€ãã ããªãã¡ãããŠã¹ã«ã¬ãŒã«ãã³ïŒmgïŒKgãé泚
ããïŒæéåŸã®çŒçŒåäžïŒptosisïŒã®çµæè©Šéšã æ¬è©Šéšã¯ã10å¹ã®ããŠã¹çŸ€ã§è¡ã€ããäŸè©Šåå
ç©ãã¬ãŒã«ãã³æ³šå°ïŒæéåã«çµå£ã§æäžããã ããŠã¹ãïŒcmÃïŒcmã®æ¹åœ¢æ¿äžã«çœ®ãããã®å
ç©ã20ç§åŸç®ãå®å šã«éããïŒçŒçŒåäžïŒã瀺ã
ãªãã€ãå Žåãæ¬äŸè©Šååç©ã«ããä¿è·ãããã
ã®ãšèãããã³ã³ãããŒã«ããŠã¹ïŒãã®ããŠã¹ã¯
10ç§åŸã«ç®ãå®å šã«éãããåŠçããŠã¹ã®çŸ€ãšã®
ä¿è·ïŒïŒ°ïŒã®ããŒã»ã³ããŒãžãäžèšåŒã§ç®åºã
ãã ïŒçŒçŒåäžã瀺ããã³ã³ãããŒã«ããŠã¹æ°
âçŒçŒåäžã瀺ããåŠçããŠã¹æ°ïŒçŒçŒåäžã瀺ããã³
ã³ãããŒã«ããŠã¹æ° ED50ïŒåç©ã®ä¿è·ç50ïŒ ã®æäžéïŒã¯çæ¯æ°å
ïŒçæ¯çïŒïŒïŒã«åŸã€ãŠïŒåæäžããããšã«ãã
枬å®ããã è©ŠéšïŒ¢ïŒãŽãŒãã¬ããåã³ã¬ã€ããŠãG.
ãGOURET C.RAYNAUDG J.âJ.Pharmacol
ïŒããªïŒïŒïŒïŒ231ïŒ1974ãèšèŒã®å ±åã«åŸã€ãŠè¡ãª
ã€ããããªãã¡ãããŠã¹ã«dlâïŒâããããã·ã
ãªãããã¢ã³ïŒïŒâHTPïŒã®è ¹è å 泚å°ã«ãã
åŒãèµ·ãããå šèº«ã®ãµããã®å¢åŒ·ã ããŠã¹ãéæã®ãã©ã¹ããã¯åœã«çœ®ããè©Šéšã¯
ïŒâHTPã®æ°Žæ§æžæ¿æ¶²ã200mgïŒKgè ¹è å æäž
ããäŸè©Šååç©ã¯ïŒâHTP泚å°ã®ïŒæéåã«çµ
å£æäžããã ïŒâHTP泚å°åŸãïŒç§ã30åã60åã®é芳å¯
ãããã³ã³ãããŒã«ããŠã¹ã¯åŠäœãªããµããã瀺
ããªãããããã«ãå šèº«ã®ãµãããé代æ§çæ£çº
äœãããã®ã¯äŸè©Šååç©ã®äœçšã«ãããã®ã§ã
ãã ED50ã¯è©ŠéšïŒ¡ãšåæ§ã®æ¹æ³ãäœããã³ã³ãã
ãŒã«ããŠã¹åã³ãµããã瀺ããªãã€ãåŠçããŠã¹
ã®æ°ãšããã è©ŠéšïŒ£ïŒã¢ãã¢ãããªãã·ããŒãŒã®æå¶æŽ»æ§ã¯
R.J.ãã«ããã³åã³J.ã¢ã¯ã»ããŒããR.J.
WURTMANïŒJ.AXERODâJ.Bio.
Chem.241.2301ïŒ1966ïŒãåã³J.A.ããŒãåã³C.N.
ã®ã«ãªã¹ãJ.A.ROTHïŒC.N.GILLISâMol.
Pharmacol.11ïŒ28ã35ïŒ1975ïŒãèšèŒã®å ±åã«åŸ
ã€ãŠè¡ã€ããéã¹ãã¬ã€ãžâããŠãªã€ã©ãã
ïŒSpragueâDamley ratïŒïŒããã€ãŒãªã¹âãªããŒ
ïŒCharlesâRiverïŒãã©ã³ã¹ãã®äœé160ã190
ïœã16æé絶é£ã®ãã®ãçšããã ïŒâããããã·ãåŽéâïŒâ14Cãããªãã¿ã
ã³ ã»ã©ããã³ç¡«é žïŒ14Câ5HTïŒspec.
act.60mCiïŒïœ molïŒãã©ãžãªã±ãã«ã«ã»ã³ã¿
ãŒããããããŠãããšãã«ãšãã«ã¢ãã³å¡©é žå¡©
ïŒÎ²âã¡ãã«âïŒâ14CïŒïŒ14CâPEAïŒspec.
act.50m CiïŒïœ molïŒããŠãŒã€ã³ã°ã©ã³ãã»ã³
ã¿ãŒïŒç±³ïŒïŒNew England CentreïŒããå ¥æã
ããäŸè©Šååç©ã0.5ïŒ ã¡ãã«ã»ã«ããŒã¹ã«æžæ¿
ããŠæäžãããå¯Ÿç §æå¶å€ã¯æ°Žæº¶æ¶²ã§æäžããã
ïŒåæäžåŸã®çäœå€MAOæå¶ã¯äžèšã«åŸã€ãŠæž¬
å®ãããïŒå¹ã®åç©ã®çŸ€ãåŠçåŸç°ãªã€ãæéã§
殺ãããããŠè³ãæåºãã0.9ïŒ èæ§ãœãŒãã§ã
ãã液äœçªçŽ ã§å·åãâ20âã§è²¯èµãããçµç¹ã
0.1MãPH7.4ã®ãªã³é žç·©è¡æ¶²ã«ãã¢ã²ããŒããã
ïŒïŒïœçµç¹ïŒ16mlç·©è¡æ¶²ïŒãçµç¹ãã¢ã²ããŒããªã³
ãŒãïŒ0.1mlïŒã0.5mlã®æçµå®¹ç©ã«ãããMAO
掻æ§ã®æž¬å®ã«åã€ããåå¿ã¯0.1mlã®14CâPFAå
ã¯14Câ5HTã®æ·»å ã«ããå§ããPEAåã³ïŒâ
HTã®æçµæ¿åºŠå€«ã 12åã³480ÎŒMã§ãã€ããåå¿
ã¯37âã§PEAåã³ïŒâHTã倫ã ïŒåã³10åå¹é€
ãããå¹é€åŸåå¿æ¶²ïŒïŒ ãHClã®0.2mlã§é žæ§ãš
ããããŠæ°·å·ããããžã¢ããåããçæç©ããã«
ãšã³âé ¢é žãšãã«ïŒïŒïŒïŒïŒïœïŒïœïŒã®ïŒmläžã«
æœåºãããããŠæ¶²äœã·ã³ãã¬ãŒã·ãšã³ã«ãã
PPOïŒ0.4ïŒ ïŒå«æãã«ãšã³10mlã®æŸå°èœã枬å®ã
ãã åŒ(1)ã®ååç©ã®äžèšïŒçš®ã®è©Šéšã§åŸãããçµ
æã䞊ã³ã«å¯Ÿç §ç©è³ªã§åŸãããçµæãäžèšè¡šå
ã³ã§ç€ºãã
éãç¹ã«ã¢ãã¢ãããªãã·ããŒãŒã®å¯éçæå¶æŽ»
æ§ãããããšãåã€ãã ãããã®æŽ»æ§ã¯äžèšè©Šéšã«ããæããã§ããã
è©ŠéšïŒ¡ïŒãŽãŒã¬ããåã³ããŒãã¹ïŒªã®J.ãã¢ãŒ
ãã³ã«ãGOURET C.THOMAS J.âJ.
PharmacolïŒããªïŒïŒïŒïŒ401ïŒ1973ïŒâãèšèŒã®å ±
åã«åŸã€ãŠè¡ã€ãã ããªãã¡ãããŠã¹ã«ã¬ãŒã«ãã³ïŒmgïŒKgãé泚
ããïŒæéåŸã®çŒçŒåäžïŒptosisïŒã®çµæè©Šéšã æ¬è©Šéšã¯ã10å¹ã®ããŠã¹çŸ€ã§è¡ã€ããäŸè©Šåå
ç©ãã¬ãŒã«ãã³æ³šå°ïŒæéåã«çµå£ã§æäžããã ããŠã¹ãïŒcmÃïŒcmã®æ¹åœ¢æ¿äžã«çœ®ãããã®å
ç©ã20ç§åŸç®ãå®å šã«éããïŒçŒçŒåäžïŒã瀺ã
ãªãã€ãå Žåãæ¬äŸè©Šååç©ã«ããä¿è·ãããã
ã®ãšèãããã³ã³ãããŒã«ããŠã¹ïŒãã®ããŠã¹ã¯
10ç§åŸã«ç®ãå®å šã«éãããåŠçããŠã¹ã®çŸ€ãšã®
ä¿è·ïŒïŒ°ïŒã®ããŒã»ã³ããŒãžãäžèšåŒã§ç®åºã
ãã ïŒçŒçŒåäžã瀺ããã³ã³ãããŒã«ããŠã¹æ°
âçŒçŒåäžã瀺ããåŠçããŠã¹æ°ïŒçŒçŒåäžã瀺ããã³
ã³ãããŒã«ããŠã¹æ° ED50ïŒåç©ã®ä¿è·ç50ïŒ ã®æäžéïŒã¯çæ¯æ°å
ïŒçæ¯çïŒïŒïŒã«åŸã€ãŠïŒåæäžããããšã«ãã
枬å®ããã è©ŠéšïŒ¢ïŒãŽãŒãã¬ããåã³ã¬ã€ããŠãG.
ãGOURET C.RAYNAUDG J.âJ.Pharmacol
ïŒããªïŒïŒïŒïŒ231ïŒ1974ãèšèŒã®å ±åã«åŸã€ãŠè¡ãª
ã€ããããªãã¡ãããŠã¹ã«dlâïŒâããããã·ã
ãªãããã¢ã³ïŒïŒâHTPïŒã®è ¹è å 泚å°ã«ãã
åŒãèµ·ãããå šèº«ã®ãµããã®å¢åŒ·ã ããŠã¹ãéæã®ãã©ã¹ããã¯åœã«çœ®ããè©Šéšã¯
ïŒâHTPã®æ°Žæ§æžæ¿æ¶²ã200mgïŒKgè ¹è å æäž
ããäŸè©Šååç©ã¯ïŒâHTP泚å°ã®ïŒæéåã«çµ
å£æäžããã ïŒâHTP泚å°åŸãïŒç§ã30åã60åã®é芳å¯
ãããã³ã³ãããŒã«ããŠã¹ã¯åŠäœãªããµããã瀺
ããªãããããã«ãå šèº«ã®ãµãããé代æ§çæ£çº
äœãããã®ã¯äŸè©Šååç©ã®äœçšã«ãããã®ã§ã
ãã ED50ã¯è©ŠéšïŒ¡ãšåæ§ã®æ¹æ³ãäœããã³ã³ãã
ãŒã«ããŠã¹åã³ãµããã瀺ããªãã€ãåŠçããŠã¹
ã®æ°ãšããã è©ŠéšïŒ£ïŒã¢ãã¢ãããªãã·ããŒãŒã®æå¶æŽ»æ§ã¯
R.J.ãã«ããã³åã³J.ã¢ã¯ã»ããŒããR.J.
WURTMANïŒJ.AXERODâJ.Bio.
Chem.241.2301ïŒ1966ïŒãåã³J.A.ããŒãåã³C.N.
ã®ã«ãªã¹ãJ.A.ROTHïŒC.N.GILLISâMol.
Pharmacol.11ïŒ28ã35ïŒ1975ïŒãèšèŒã®å ±åã«åŸ
ã€ãŠè¡ã€ããéã¹ãã¬ã€ãžâããŠãªã€ã©ãã
ïŒSpragueâDamley ratïŒïŒããã€ãŒãªã¹âãªããŒ
ïŒCharlesâRiverïŒãã©ã³ã¹ãã®äœé160ã190
ïœã16æé絶é£ã®ãã®ãçšããã ïŒâããããã·ãåŽéâïŒâ14Cãããªãã¿ã
ã³ ã»ã©ããã³ç¡«é žïŒ14Câ5HTïŒspec.
act.60mCiïŒïœ molïŒãã©ãžãªã±ãã«ã«ã»ã³ã¿
ãŒããããããŠãããšãã«ãšãã«ã¢ãã³å¡©é žå¡©
ïŒÎ²âã¡ãã«âïŒâ14CïŒïŒ14CâPEAïŒspec.
act.50m CiïŒïœ molïŒããŠãŒã€ã³ã°ã©ã³ãã»ã³
ã¿ãŒïŒç±³ïŒïŒNew England CentreïŒããå ¥æã
ããäŸè©Šååç©ã0.5ïŒ ã¡ãã«ã»ã«ããŒã¹ã«æžæ¿
ããŠæäžãããå¯Ÿç §æå¶å€ã¯æ°Žæº¶æ¶²ã§æäžããã
ïŒåæäžåŸã®çäœå€MAOæå¶ã¯äžèšã«åŸã€ãŠæž¬
å®ãããïŒå¹ã®åç©ã®çŸ€ãåŠçåŸç°ãªã€ãæéã§
殺ãããããŠè³ãæåºãã0.9ïŒ èæ§ãœãŒãã§ã
ãã液äœçªçŽ ã§å·åãâ20âã§è²¯èµãããçµç¹ã
0.1MãPH7.4ã®ãªã³é žç·©è¡æ¶²ã«ãã¢ã²ããŒããã
ïŒïŒïœçµç¹ïŒ16mlç·©è¡æ¶²ïŒãçµç¹ãã¢ã²ããŒããªã³
ãŒãïŒ0.1mlïŒã0.5mlã®æçµå®¹ç©ã«ãããMAO
掻æ§ã®æž¬å®ã«åã€ããåå¿ã¯0.1mlã®14CâPFAå
ã¯14Câ5HTã®æ·»å ã«ããå§ããPEAåã³ïŒâ
HTã®æçµæ¿åºŠå€«ã 12åã³480ÎŒMã§ãã€ããåå¿
ã¯37âã§PEAåã³ïŒâHTã倫ã ïŒåã³10åå¹é€
ãããå¹é€åŸåå¿æ¶²ïŒïŒ ãHClã®0.2mlã§é žæ§ãš
ããããŠæ°·å·ããããžã¢ããåããçæç©ããã«
ãšã³âé ¢é žãšãã«ïŒïŒïŒïŒïŒïœïŒïœïŒã®ïŒmläžã«
æœåºãããããŠæ¶²äœã·ã³ãã¬ãŒã·ãšã³ã«ãã
PPOïŒ0.4ïŒ ïŒå«æãã«ãšã³10mlã®æŸå°èœã枬å®ã
ãã åŒ(1)ã®ååç©ã®äžèšïŒçš®ã®è©Šéšã§åŸãããçµ
æã䞊ã³ã«å¯Ÿç §ç©è³ªã§åŸãããçµæãäžèšè¡šå
ã³ã§ç€ºãã
ãè¡šã
ãè¡šã
è¡šã«ç€ºããã掻æ§1MAOâã掻æ§1MAO
âã¯ãMAOâïŒMAOâãæå¶ãããã®
ã§ãããMAOâïŒMAOâã¯ããã€ç çŸè±¡
äžã«ååšããããªã²ã³ã¢ãã³ã§ããïŒâHTïŒïŒ
âããããã·ããªãããã¢ã³ïŒåã³PEAïŒããšã
ã«ãšãã«ã¢ãã³ïŒã倫ã å解ãããåå ãšãªãè³
äžã«ããé µçŽ ã§ãããæ£è ããã€ç¶æ ã§ããæã
è³ã¯ïŒâHTåã³ïŒåã¯PEAãéåžžå€ããäœããª
ããïŒâHTåã³PEAãå解ãããã®é µçŽ
ïŒMAOâåã³ïŒåã¯MAOâïŒãæå¶ããã
ãšã«ãã€ãŠãã€ç ã軜æžããããšãå¯èœã§ããã è¡šã«ç€ºããã«ãæ¬çºæã®ååç©(1)ã¯MAOâ
åã³MAOâãæå¶ããããšãå¯èœã§ãã
ããMAOâã®æå¶æŽ»æ§ïŒå³ã¡1MAOâ掻
æ§ïŒãšåæ§MAOâã®æå¶æŽ»æ§ïŒå³ã¡1MAOâ
掻æ§ïŒãæããã MAOæå¶ã®äœçšã¯å¯éçåã¯äžå¯éçã«å
ããäžéçã«åãMAOæå¶å€ã¯MAOãšå ±åçµ
åããŠäžå¯éçã®æå¶äœçšãè¡ãããã®ããšã¯é µ
çŽ ïŒMAOïŒã確å®ã«ç¡å¹ãããããšãæå³ã
ããããã«å¯Ÿããæ¬çºæã®ååç©ã§ããå¯éçæ
å¶å€ã¯é µçŽ ãšã³ã³ãã¬ãã¯ã¹ã圢æãããã®ã³ã³
ãã¬ãã¯ã¹ã¯åã³åé¢ããŠé µçŽ ã¯å解ãããã«å
ã³é µçŽ äœçšãå¥ããã äžå¯éçæå¶å€ã®äœçšã¯ïŒé±éåŸã«æ¶å€±ããã
äŸãã°ãïŒé±éã®éã¯äžè¬ã®éº»é åã¯ä»ã®æãã€
åŠçœ®ãããæ£è ã«çšãããšéåžžã«å±éºã§ãããã
ãã«åããæ¬çºæã®è¬å€ã®äœçšã¯å¯éçã§ããã
ããïŒæéåŸã«æ¶å€±ããããã®ããïŒæéåŸã§ã¯
äžè¬ã®éº»é åã¯æãã€åŠçœ®ãããæ£è ã«æäžããŠ
ãå±éºããªãã çäœå ã§ã¯ãé µçŽ MAOã®æå¶ã¯ã¢ãã¢ãã³å
é§ç©ã«ããçç£ãããããã€ãã¢çå矀ã®å¢åŒ·å
å ãšãªãããã®ããã«ãããã€ãã¢ã«ãããŠïŒâ
HPã«ãã€ãŠçç£ãããäœçšã¯MAOæå¶å€ã«ã
ã€ãŠå¢åŒ·ãããããã®ãããªå¢åŒ·ã¯ïŒâHPãç¥
çµååŠã®åªäœãšããŠå«ãŸããç¥çµçŽ°èã«ããã
MAOæå¶ã®äœçšã瀺ããã®ãšèããã åæ§ã«ãã¬ãŒã«ãã³ã«ããèµ·ãããçŒçŒåäž
ïŒptosisïŒã«é¢ä¿ããMAOæå¶ã®çµæäœçšã¯ãã¢
ãã¢ãã³æ§ç¥çµäŒéãå¢åŒ·ããæå¶å€ã®åŠãèœå
ã瀺ããã®ãšèããããã è¡šã¯äŸè©Šååç©ã®å€§éšåã¯å ¬ç¥ã®æãã€å€ã®
ED50ãšåéãåã¯å°éã§ãããããã¯æ¬çºæã®
ååç©ãã¢ãã¢ãã³ãªãã·ã¿ãŒãŒïŒ¡ïŒMOAâïŒ
åã³ã¢ãã¢ãã³ãªãã·ã¿ãŒãŒïŒ¢ïŒMOAâïŒã®
æå¶æŽ»æ§ãå ¬ç¥ã®è¬å€ãšåçãåã¯ãã倧ã§ãã
ããšãæå³ãããåŸã€ãŠãæ¬çºæã®ååç©ã¯å ¬ç¥
ã®è¬å€ãšåçåã¯ããé«ãæãã€æŽ»æ§ãæã€ãŠã
ãã åŸã€ãŠãæ¬çºæã¯ãã€ç ãè人æ§å€§è³æ©èœæ¬ æ
çæ²»çè¬å€ãšããŠçšããããã ãããã¯æå¹æåã®500mgïŒæ¥ãè¶ããªãïŒå
è¬éã§é å€ããã«åã¯ã«ãã»ã«ã®åœ¢ã§çµå£æäžã
åŸããæå¹æåã®500mgïŒæ¥ãè¶ããªãïŒåè¬é
ã§æ³šå°ãåŸã液ã®åœ¢ã§æäžãåŸãã䜿çšããã溶
åªã¯ïŒçš®åã¯ïŒçš®æ··åããããäŸãã°ãæ°Žããã
ãã¬ã³ã°ãªã³ãŒã«ãããªãšãã¬ã³ã°ãªã³ãŒã«300
åã¯400åã¯ä»ã®ççç溶åªããããã®ç°ãªãæ
åã®å²åã¯è¬éã®æäžã«ãã調æŽããããæåŸ
ã«ãäžèšé å€ããã«ãã«ãã»ã«åã³æ³šå°ãåŸã溶
液ã¯æ¬çºæã®åŒïŒïŒã®ïŒåã¯ãã以äžã®ååç©
ãå«æããŠããã
âã¯ãMAOâïŒMAOâãæå¶ãããã®
ã§ãããMAOâïŒMAOâã¯ããã€ç çŸè±¡
äžã«ååšããããªã²ã³ã¢ãã³ã§ããïŒâHTïŒïŒ
âããããã·ããªãããã¢ã³ïŒåã³PEAïŒããšã
ã«ãšãã«ã¢ãã³ïŒã倫ã å解ãããåå ãšãªãè³
äžã«ããé µçŽ ã§ãããæ£è ããã€ç¶æ ã§ããæã
è³ã¯ïŒâHTåã³ïŒåã¯PEAãéåžžå€ããäœããª
ããïŒâHTåã³PEAãå解ãããã®é µçŽ
ïŒMAOâåã³ïŒåã¯MAOâïŒãæå¶ããã
ãšã«ãã€ãŠãã€ç ã軜æžããããšãå¯èœã§ããã è¡šã«ç€ºããã«ãæ¬çºæã®ååç©(1)ã¯MAOâ
åã³MAOâãæå¶ããããšãå¯èœã§ãã
ããMAOâã®æå¶æŽ»æ§ïŒå³ã¡1MAOâ掻
æ§ïŒãšåæ§MAOâã®æå¶æŽ»æ§ïŒå³ã¡1MAOâ
掻æ§ïŒãæããã MAOæå¶ã®äœçšã¯å¯éçåã¯äžå¯éçã«å
ããäžéçã«åãMAOæå¶å€ã¯MAOãšå ±åçµ
åããŠäžå¯éçã®æå¶äœçšãè¡ãããã®ããšã¯é µ
çŽ ïŒMAOïŒã確å®ã«ç¡å¹ãããããšãæå³ã
ããããã«å¯Ÿããæ¬çºæã®ååç©ã§ããå¯éçæ
å¶å€ã¯é µçŽ ãšã³ã³ãã¬ãã¯ã¹ã圢æãããã®ã³ã³
ãã¬ãã¯ã¹ã¯åã³åé¢ããŠé µçŽ ã¯å解ãããã«å
ã³é µçŽ äœçšãå¥ããã äžå¯éçæå¶å€ã®äœçšã¯ïŒé±éåŸã«æ¶å€±ããã
äŸãã°ãïŒé±éã®éã¯äžè¬ã®éº»é åã¯ä»ã®æãã€
åŠçœ®ãããæ£è ã«çšãããšéåžžã«å±éºã§ãããã
ãã«åããæ¬çºæã®è¬å€ã®äœçšã¯å¯éçã§ããã
ããïŒæéåŸã«æ¶å€±ããããã®ããïŒæéåŸã§ã¯
äžè¬ã®éº»é åã¯æãã€åŠçœ®ãããæ£è ã«æäžããŠ
ãå±éºããªãã çäœå ã§ã¯ãé µçŽ MAOã®æå¶ã¯ã¢ãã¢ãã³å
é§ç©ã«ããçç£ãããããã€ãã¢çå矀ã®å¢åŒ·å
å ãšãªãããã®ããã«ãããã€ãã¢ã«ãããŠïŒâ
HPã«ãã€ãŠçç£ãããäœçšã¯MAOæå¶å€ã«ã
ã€ãŠå¢åŒ·ãããããã®ãããªå¢åŒ·ã¯ïŒâHPãç¥
çµååŠã®åªäœãšããŠå«ãŸããç¥çµçŽ°èã«ããã
MAOæå¶ã®äœçšã瀺ããã®ãšèããã åæ§ã«ãã¬ãŒã«ãã³ã«ããèµ·ãããçŒçŒåäž
ïŒptosisïŒã«é¢ä¿ããMAOæå¶ã®çµæäœçšã¯ãã¢
ãã¢ãã³æ§ç¥çµäŒéãå¢åŒ·ããæå¶å€ã®åŠãèœå
ã瀺ããã®ãšèããããã è¡šã¯äŸè©Šååç©ã®å€§éšåã¯å ¬ç¥ã®æãã€å€ã®
ED50ãšåéãåã¯å°éã§ãããããã¯æ¬çºæã®
ååç©ãã¢ãã¢ãã³ãªãã·ã¿ãŒãŒïŒ¡ïŒMOAâïŒ
åã³ã¢ãã¢ãã³ãªãã·ã¿ãŒãŒïŒ¢ïŒMOAâïŒã®
æå¶æŽ»æ§ãå ¬ç¥ã®è¬å€ãšåçãåã¯ãã倧ã§ãã
ããšãæå³ãããåŸã€ãŠãæ¬çºæã®ååç©ã¯å ¬ç¥
ã®è¬å€ãšåçåã¯ããé«ãæãã€æŽ»æ§ãæã€ãŠã
ãã åŸã€ãŠãæ¬çºæã¯ãã€ç ãè人æ§å€§è³æ©èœæ¬ æ
çæ²»çè¬å€ãšããŠçšããããã ãããã¯æå¹æåã®500mgïŒæ¥ãè¶ããªãïŒå
è¬éã§é å€ããã«åã¯ã«ãã»ã«ã®åœ¢ã§çµå£æäžã
åŸããæå¹æåã®500mgïŒæ¥ãè¶ããªãïŒåè¬é
ã§æ³šå°ãåŸã液ã®åœ¢ã§æäžãåŸãã䜿çšããã溶
åªã¯ïŒçš®åã¯ïŒçš®æ··åããããäŸãã°ãæ°Žããã
ãã¬ã³ã°ãªã³ãŒã«ãããªãšãã¬ã³ã°ãªã³ãŒã«300
åã¯400åã¯ä»ã®ççç溶åªããããã®ç°ãªãæ
åã®å²åã¯è¬éã®æäžã«ãã調æŽããããæåŸ
ã«ãäžèšé å€ããã«ãã«ãã»ã«åã³æ³šå°ãåŸã溶
液ã¯æ¬çºæã®åŒïŒïŒã®ïŒåã¯ãã以äžã®ååç©
ãå«æããŠããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ äžè¬åŒ ïŒåŒäžããåŒãã¯ãåŒãå ã¯ãåŒãã瀺ãããåŒãã ãåŒãã瀺ãå ŽåãR1ãïŒâã¡ãã«ã ãããã·åºãã·ã¯ãããã·ã«ã¡ãããã·åºãã¡ã¿
ããããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžããã·
åºåã³ïŒâã·ã¢ãâïŒâããããã³ãžããã·åºã®
äœããäžã€ã瀺ããšãã¯ïŒ²ã¯æ°ŽçŽ ååã瀺ãã
R1ãã¡ã¿ããããã³ãžããã·åºã瀺ããšãã¯ïŒ²
ã¯ã¢ã»ãã«åºã瀺ããR1ãïŒâã¯ãããããã·
åºãïŒâã·ã¢ãããããã·åºããã³ãžããã·åºã
ã¡ã¿ããããã³ãžããã·åºãã¡ã¿ã¯ãããã³ãžã
ãã·åºãã¡ã¿ã·ã¢ããã³ãžããã·åºãïŒïŒâããª
ãžã«ïŒã¡ããã·åºãïŒâã·ã¢ãâïŒâããããã³
ãžããã·åºãïŒâã¯ããâïŒâãã«ãªããã³ãžã
ãã·åºã®äœããäžã€ã瀺ããšãã¯ïŒ²ã¯ã¡ãã«åºã
瀺ãããåŒãããåŒãã瀺ãå Ž åãR1ãã¡ã¿ããããã³ãžããã·åºãã¡ã¿ã¯ã
ããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžããã·åºå
ã³ïŒâã¯ããâïŒâãã«ãªããã³ãžããã·åºã®äœ
ããäžã€ã瀺ããšãã¯ïŒ²ã¯ã¡ãã«åºã瀺ãïŒ ãæããïŒâ5Hâãã©ãã³åã³ïŒâ3Hâãžãã
ããã©ãã³ã ïŒ äžè¬åŒ ïŒåŒäžããåŒãã¯ãåŒãå ã¯ãåŒãã瀺ãããåŒãã瀺 ãå ŽåãR1ãïŒâã¡ãã«ããããã·åºãã·ã¯ã
ããã·ã«ã¡ãããã·åºãã¡ã¿ããããã³ãžããã·
åºãã¡ã¿ã·ã¢ããã³ãžããã·åºåã³ïŒâã·ã¢ãâ
ïŒâããããã³ãžããã·åºã®äœããäžã€ã瀺ããš
ãã¯ïŒ²ã¯æ°ŽçŽ ååã瀺ããR1ãã¡ã¿ããããã³
ãžããã·åºã瀺ããšãã¯ïŒ²ã¯ã¢ã»ãã«åºã瀺ãã
R1ãïŒâã¯ãããããã·åºãïŒâã·ã¢ãããã
ãã·åºããã³ãžããã·åºãã¡ã¿ããããã³ãžãã
ã·åºãã¡ã¿ã¯ãããã³ãžããã·åºãã¡ã¿ã·ã¢ãã
ã³ãžããã·åºãïŒïŒâããªãžã«ïŒã¡ããã·åºãïŒ
âã·ã¢ãâïŒâããããã³ãžããã·åºãïŒâã¯ã
ãâïŒâãã«ãªããã³ãžããã·åºã®äœããäžã€ã
瀺ããšãã¯ïŒ²ã¯ã¡ãã«åºã瀺ãããåŒã ããåŒãã瀺ãå ŽåãR1ãã¡ã¿ããããã³ ãžããã·åºãã¡ã¿ã¯ãããã³ãžããã·åºãã¡ã¿ã·
ã¢ããã³ãžããã·åºåã³ïŒâã¯ããâïŒãã«ãªã
ãã³ãžããã·åºã®äœããäžã€ã瀺ããšãã¯ïŒ²ã¯ã¡
ãã«åºã瀺ãïŒ ãæããïŒâ5Hâãã©ãã³åã³ïŒâ3Hâãžãã
ããã©ãã³èªå°äœã®å°ããšãäžã€ãçççæ äœäž
ã«å«æããããšãç¹åŸŽãšãããã€ç ãè人æ§å€§è³
æ©èœæ¬ æçç¶ãæ²»çããå»è¬çµæç©ã ïŒ äžè¬åŒïŒïŒïŒ¡ïŒïŒïŒïŒ¢åã¯ïŒïŒïŒ¡ïŒïŒ¢ ïŒåŒã®æšç€ºã®ïŒ¡ã¯ãžã¹ãã¬ãªã¢ã€ãœããŒã®ãã©
ã³ã¹äœãã¯åã·ã¹äœïŒãšåŒR2âïŒåŒäžïŒºã¯å¡©
çŽ åã¯èçŽ ååã瀺ããR2ã¯ã€ãœãã³ãã«åºã
ã·ã¯ãããã·ã«ã¡ãã«åºãã¡ã¿ããããã³ãžã«
åºãã¡ã¿ã·ã¢ããã³ãžã«åºåã¯ïŒâã·ã¢ãâïŒâ
ããããã³ãžã«åºã瀺ããïŒ ã®ããã²ã³åç©ãšçž®åãããèŠããã°åŸãçæç©
ãé«æ§èœæ¶²äœã¯ãããã°ã©ãã€ãŒåŠçããŠãžã¢ã¹
ãã¬ãªã¢ã€ãœããŒã®ïŒå¯Ÿã«åé¢ããããšãç¹åŸŽãš
ããäžè¬åŒ ïŒåŒäžãR1ã¯ã€ãœãã³ããã·åºãã·ã¯ããã
ã·ã«ã¡ãããã·åºãã¡ã¿ããããã³ãžããã·åºã
ã¡ã¿ã·ã¢ããã³ãžããã·åºåã¯ïŒâã·ã¢ãâïŒâ
ããããã³ãžããã·åºã瀺ããïŒ ãæããååç©ã®è£œæ³ã ïŒ åŒ(1)åã³(1) ïŒåŒã®æšç€ºã®ïŒ¡ã¯ãžã¹ãã¬ãªã¢ã€ãœããŒã®ãã©
ã³ã¹äœãã¯åã·ã¹äœïŒãæããååç©ãããã©
ããããã©ã³åªäœäžã§ããªãšãã«ã¢ãã³ã®ååšäž
ã¢ã»ãã«ã¯ãã©ã€ããšçž®åãããããšãç¹åŸŽãšã
ã ãæããååç©ã®è£œæ³ã ïŒ åŒïŒïŒ ãæããååç©ãåŒR3â ïŒåŒäžãã¯å¡©çŽ åã¯èçŽ ååã瀺ããR3ã¯
ïŒâã¯ããããã«åºãïŒâã·ã¢ãããã«åºãã¡ã¿
ããããã³ãžã«åºãã¡ã¿ã¯ããããžã«åºãã¡ã¿ã·
ã¢ããã³ãžã«åºãïŒïŒâããªãžã«ïŒã¡ãã«åºãïŒ
âã·ã¢ãâïŒâããããã³ãžã«åºåã¯ïŒâã¯ãã
âïŒâãã«ãªããã³ãžã«åºã瀺ããïŒ ã®ããã²ã³åç©ãšçž®åããèŠããã°çæç©ãé«æ§
èœæ¶²äœã¯ãããã°ã©ãã€ãŒåŠçã«ãã€ãŠãžã¢ã¹ã
ã¬ãªã¢ã€ãœããŒã®ïŒå¯Ÿã«åé¢ããããšãç¹åŸŽãšã
ãåŒ ïŒåŒäžãR1ã¯ïŒâã¯ãããããã·åºãïŒâã·
ã¢ããããã·åºãã¡ã¿ããããã³ãžããã·åºãã¡
ã¿ã¯ãããã³ãžããã·åºãã¡ã¿ã·ã¢ããã³ãžãã
ã·åºãïŒïŒâããªãžã«ïŒã¡ããã·åºãïŒâã·ã¢ã
âïŒâããããã³ãžããã·åºåã¯ïŒâã¯ããâïŒ
âãã«ãªããã³ãžããã·åºã瀺ããïŒ ãæããååç©ã®è£œæ³ã ïŒ åŒ ãæããååç©ãšåŒ ã®ïŒïŒïŒâãšããã·âïŒâã¡ããã·ãããã³ãçž®
åããèŠããã°çæç©ãé«æ§èœæ¶²äœã¯ãããã°ã©
ãã€ãŒåŠçã«ãããã©ã¯ã·ãšã³ãåé¢ããããš
ãç¹åŸŽãšãã ïŒåŒäžãR1ã¯ãã³ãžããã·åºã瀺ããïŒ ãæããååç©ã®è£œæ³ã ïŒ åŒïŒXIIïŒ ãæããååç©ãšåŒ R4âOH ïŒåŒäžãR4ã¯ã¡ã¿ã·ã¢ããã³ãžã«åºãã¡ã¿ã¯
ãããã³ãžã«åºãã¡ã¿ããããã³ãžã«åºããã³ãž
ã«åºåã¯ïŒâã¯ããâïŒâãã«ãªããã³ãžã«åºã
瀺ãïŒ ã®ã¢ã«ã³ãŒã«ãçž®åããããšãç¹åŸŽãšãã ïŒåŒäžãR1ã¯ã¡ã¿ã·ã¢ããã³ãžããã·åºãã¡
ã¿ã¯ãããã³ãžããã·åºãã¡ã¿ããããã³ãžãã
ã·åºããã³ãžããã·åºåã¯ïŒâã¯ããâïŒâãã«
ãªããã³ãžããã·åºã瀺ããïŒ ãæããååç©ã®è£œæ³ã
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR7911453A FR2456097A1 (fr) | 1979-05-07 | 1979-05-07 | Nouveaux derives de la 5 h-furanone-2 et de la 3 h-dihydrofuranone-2, leur procede de preparation et leur application en therapeutique |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55149272A JPS55149272A (en) | 1980-11-20 |
| JPH0156071B2 true JPH0156071B2 (ja) | 1989-11-28 |
Family
ID=9225124
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6046080A Granted JPS55149272A (en) | 1979-05-07 | 1980-05-07 | Novel 5hhfuranonee2 and 3hhdihydrofuranonee2 derivative* their manufacture and use as medicine |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4346102A (ja) |
| JP (1) | JPS55149272A (ja) |
| FR (1) | FR2456097A1 (ja) |
| ZA (1) | ZA802673B (ja) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4351839A (en) * | 1981-03-30 | 1982-09-28 | Rohm And Haas Company | Fungicidal 2-aryl-2-1-H-azoyl-(alkyl)-gamma-butyrolactones |
| JPS5916884A (ja) * | 1982-07-19 | 1984-01-28 | Fujisawa Pharmaceut Co Ltd | æ°èŠãã©ã³ååç© |
| US5708169A (en) * | 1995-09-15 | 1998-01-13 | Pharmacia & Upjohn Company | 5-amidomethyl α,β-saturated and -unsaturated 3-aryl butyrolactone antibacterial agents |
| GB9601666D0 (en) * | 1996-01-27 | 1996-03-27 | Zeneca Ltd | Chemical compounds |
| GB9702213D0 (en) | 1996-02-24 | 1997-03-26 | Zeneca Ltd | Chemical compounds |
| GB9609919D0 (en) | 1996-05-11 | 1996-07-17 | Zeneca Ltd | Chemical compounds |
| GB9717807D0 (en) * | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| GB9717804D0 (en) | 1997-08-22 | 1997-10-29 | Zeneca Ltd | Chemical compounds |
| GB9725244D0 (en) | 1997-11-29 | 1998-01-28 | Zeneca Ltd | Chemical compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2356422A1 (fr) * | 1976-03-01 | 1978-01-27 | Delalande Sa | Nouveaux hydroxymethyl-5 oxazolidinone-2, leur procede de preparation et leur application en therapeutique |
-
1979
- 1979-05-07 FR FR7911453A patent/FR2456097A1/fr active Granted
-
1980
- 1980-04-28 US US06/144,075 patent/US4346102A/en not_active Expired - Lifetime
- 1980-05-05 ZA ZA00802673A patent/ZA802673B/xx unknown
- 1980-05-07 JP JP6046080A patent/JPS55149272A/ja active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| US4346102A (en) | 1982-08-24 |
| JPS55149272A (en) | 1980-11-20 |
| FR2456097A1 (fr) | 1980-12-05 |
| FR2456097B1 (ja) | 1983-01-14 |
| ZA802673B (en) | 1981-05-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2107484C (fr) | Nouveaux arylalkyl(thio)amides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent | |
| CH653999A5 (fr) | Derives aminomethyl-5 oxazolidiniques, procede de preparation et composition pharmaceutique. | |
| CH620436A5 (ja) | ||
| CH637927A5 (fr) | Derives de 4-amino-5-alkylsulfonyl ortho-anisamides et leurs procedes de preparation. | |
| EP0286516B1 (fr) | Nouveaux dérivés de l'amino tétrahydro-5,6,7,8 naphto [2,3b] furanne, leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent | |
| EP0833822A1 (fr) | Derives de 4-phenylaminothiazole, leur procede de preparation et les compositions pharmaceutiques les contenant | |
| US4207343A (en) | 1-Phenyl-3-(substituted phenoxy)propylamines | |
| JPS59108749A (ja) | ïŒâïœïŒïœïŒâïŒâããããã·âïŒâãïŒïœïŒâïŒïŒâã¡ãã«âïŒâããšãã«ãããã«ïŒã¢ããããšãã«ïœãµã«ãã«ã¢ãããŸãã¯ãã®è¬çåŠçã«èš±å®¹ãããé žä»å å¡©ã®è£œé æ¹æ³ | |
| FR2674849A1 (fr) | Nouveaux derives de n-cyclohexyl benzamides ou thiobenzamides, leurs preparations et leurs applications en therapeutique. | |
| EP2300424B1 (fr) | Utilisation de derives d'indole comme activateurs de nurr-1, pour le traitement de la maladie de parkinson | |
| FR2548666A1 (fr) | Nouveaux derives du nor-tropane et du granatane, leur procede de preparation et leur application en therapeutique | |
| CA1228359A (fr) | Procede de preparation de nouveaux derives de la quinoleine | |
| FR2883000A1 (fr) | Derives de trifluoromethylbenzamide et leurs utilisations en therapeutique | |
| CA2000091A1 (fr) | Derives de la benzoxazolinone, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent | |
| JPH03101643A (ja) | ããã²ãã¢ã«ãã«ãã§ãã«ã¢ã«ã³ãŒã«ãã±ãã³ããã³ãããã®æ°Žåç© | |
| JPH0314548A (ja) | ïŒâã¢ããâïŒâããããã·ããã©ãªã³ã«ã«ããã·ã¢ã«ãã«ãšãŒãã«é¡ããã³ãã®è£œé æ¹æ³ | |
| CA2178302C (fr) | Nouveaux derives de l'indole, de l'indazole et du benzisoxazole,leur pr ocede de preparation et les compositions pharmaceutiques qui les contiennent | |
| JPH05506236A (ja) | ç°ç¶ãããããµã é žããã³ãã®çšé | |
| JPS5980668A (ja) | âã¢ãªã«åãªããµãŸãªãžã³âïŒâãªã³ã®å åŠæŽ»æ§ãªèªå°äœã該èªå°äœã®è£œæ³åã³è©²èªå°äœã«ããè¬å€ | |
| BE885303A (fr) | Glycinamides | |
| WO2000058301A1 (fr) | Derives de n-[2-(4-aminophenyl)ethyl]-2,3-dihydro-1,4-benzodioxine-2-methanamine, leur preparation et leur application en therapeutique | |
| JPS61165323A (ja) | ãâãã³ãœã³çŸæ£æ²»çå€ | |
| FR2679907A1 (fr) | Nouveaux n-[(isoquinolein-5 yl)sulfonyl] azacycloalcanes, leur procede de preparation et les compositions pharmaceutiques les contenant. | |
| CA1062265A (fr) | Procede de preparation de nouvelles benzylamines | |
| FR2514003A1 (fr) | Nouvelles xanthines a activite pharmacologique, leur procede d'obtention, les compositions pharmaceutiques qui les contiennent et leur utilisation en medecine humaine |