JPS633857B2 - - Google Patents
Info
- Publication number
- JPS633857B2 JPS633857B2 JP53160026A JP16002678A JPS633857B2 JP S633857 B2 JPS633857 B2 JP S633857B2 JP 53160026 A JP53160026 A JP 53160026A JP 16002678 A JP16002678 A JP 16002678A JP S633857 B2 JPS633857 B2 JP S633857B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- compound
- reaction
- acid
- temperature
- 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 104
- 150000003839 salts Chemical class 0.000 claims description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 7
- LPCWDYWZIWDTCV-UHFFFAOYSA-N 1-phenylisoquinoline Chemical class C1=CC=CC=C1C1=NC=CC2=CC=CC=C12 LPCWDYWZIWDTCV-UHFFFAOYSA-N 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 description 27
- -1 n- Butyl Chemical group 0.000 description 21
- 239000003795 chemical substances by application Substances 0.000 description 20
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 230000000202 analgesic effect Effects 0.000 description 12
- 239000002168 alkylating agent Substances 0.000 description 11
- 229940100198 alkylating agent Drugs 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 230000003110 anti-inflammatory effect Effects 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000005804 alkylation reaction Methods 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 230000002140 halogenating effect Effects 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 6
- 238000005658 halogenation reaction Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 5
- 239000003513 alkali Substances 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 230000026030 halogenation Effects 0.000 description 5
- 239000008096 xylene Substances 0.000 description 5
- GUUVPOWQJOLRAS-UHFFFAOYSA-N Diphenyl disulfide Chemical compound C=1C=CC=CC=1SSC1=CC=CC=C1 GUUVPOWQJOLRAS-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 238000006356 dehydrogenation reaction Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000006798 ring closing metathesis reaction Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 235000019260 propionic acid Nutrition 0.000 description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- ZFVJGTNFYAMXQP-UHFFFAOYSA-N 2-(1-phenylisoquinolin-5-yl)acetic acid Chemical compound N1=CC=C2C(CC(=O)O)=CC=CC2=C1C1=CC=CC=C1 ZFVJGTNFYAMXQP-UHFFFAOYSA-N 0.000 description 2
- RZBOMSOHMOVUES-UHFFFAOYSA-N 2-(2-chlorophenyl)ethanamine Chemical compound NCCC1=CC=CC=C1Cl RZBOMSOHMOVUES-UHFFFAOYSA-N 0.000 description 2
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 2
- OWOUKRYOZIZVFK-UHFFFAOYSA-N 2-methylphenethylamine Chemical compound CC1=CC=CC=C1CCN OWOUKRYOZIZVFK-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-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
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 description 2
- 239000012670 alkaline solution Substances 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 230000002152 alkylating effect Effects 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- 229940102396 methyl bromide Drugs 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 230000001546 nitrifying effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 229960002895 phenylbutazone Drugs 0.000 description 2
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 1
- DBGRGWBLYNNKNM-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)isoquinolin-3-yl]acetamide Chemical compound N=1C(CC(=O)N)=CC2=CC=CC=C2C=1C1=CC=C(Cl)C=C1 DBGRGWBLYNNKNM-UHFFFAOYSA-N 0.000 description 1
- VBHHXOSSOFDPIX-UHFFFAOYSA-N 2-[1-(4-chlorophenyl)isoquinolin-5-yl]propanoic acid Chemical compound N1=CC=C2C(C(C(O)=O)C)=CC=CC2=C1C1=CC=C(Cl)C=C1 VBHHXOSSOFDPIX-UHFFFAOYSA-N 0.000 description 1
- FDRMMWATBRUAHP-UHFFFAOYSA-N 2-[1-(4-methoxyphenyl)isoquinolin-5-yl]propanoic acid Chemical compound C1=CC(OC)=CC=C1C1=NC=CC2=C(C(C)C(O)=O)C=CC=C12 FDRMMWATBRUAHP-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
- 241000699670 Mus sp. Species 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- CYTYCFOTNPOANT-UHFFFAOYSA-N Perchloroethylene Chemical group ClC(Cl)=C(Cl)Cl CYTYCFOTNPOANT-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
- 229910001863 barium hydroxide Inorganic materials 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- RRKTZKIUPZVBMF-IBTVXLQLSA-N brucine Chemical compound O([C@@H]1[C@H]([C@H]2C3)[C@@H]4N(C(C1)=O)C=1C=C(C(=CC=11)OC)OC)CC=C2CN2[C@@H]3[C@]41CC2 RRKTZKIUPZVBMF-IBTVXLQLSA-N 0.000 description 1
- RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 125000004181 carboxyalkyl group Chemical group 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
- 230000000911 decarboxylating effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 229940008406 diethyl sulfate Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229960003750 ethyl chloride Drugs 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002537 isoquinolines Chemical class 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Description
æ¬çºæã¯æ°èŠãªã€ãœãããªã³èªå°äœã«é¢ããã
ãã«è©³ããã¯ãïŒâäœã«ã«ã«ããã·ã«ã¢ã«ãã«åº
ãæããæ°èŠãªïŒâããšãã«ã€ãœãããªã³èªå°
äœããã®è£œé æ¹æ³ãåã³ãã®é®çæççå€ãšããŠ
ã®çšéã«é¢ããã ïŒâããšãã«ã€ãœãããªã³èªå°äœãšããŠããã
æè¿ã«ãªã€ãŠäžèšåŒ ã§ç€ºãããïŒâïŒïŒâã¯ããããšãã«ïŒâïŒâã«ã«
ãã¢ã€ã«ã¡ãã«ã€ãœãããªã³ãé®çæççäœçšã
æããããšãå ±åãããŠãããDavid A.Walsh
et al.ïŒJournal of Medicinal ChemistryïŒ
1978ãVol.21ãNo.ïŒãpp582ã585åç §ãã æ¬çºæã¯ãéåžžã«é«ãé®çåã³æççäœçšãæ
ããæ°èŠãªïŒâããšãã«ã€ãœãããªã³èªå°äœãšã
ãŠãäžèšäžè¬åŒ åŒäžãR1ã¯æ°ŽçŽ åååã¯äœçŽã¢ã«ãã«åºãè¡š
ãããR2ã¯æ°ŽçŽ ååãããã²ã³åååã¯äœçŽã¢
ã«ã³ãã·åºãè¡šããã ã§ç€ºãããååç©åã³ãã®å¡©ãæäŸãããã®ã§ã
ãã æ¬æ现æžã«ãããŠããäœçŽããªãèªã¯ããã®èª
ãä»ãããåºåã¯ååç©ãïŒå以äžã奜ãŸããã¯
ïŒå以äžã®ççŽ ååãæããããšãæå³ããã ããããŠããäœçŽã¢ã«ãã«åºãã¯çŽéç¶åã¯å
å²éç¶ã®ããããã§ããããšãã§ããäŸãã°ã¡ã
ã«ããšãã«ãïœâãããã«ãã€ãœãããã«ãïœâ
ããã«ãã€ãœããã«ãsecâããã«ãtertâãã
ã«åºçãå å«ããããäœçŽã¢ã«ã³ãã·åºããšããŠ
ã¯äŸãã°ã¡ããã·ããšããã·ãïœâããããã·ã
ã€ãœããããã·ãïœâãããã·ãã€ãœãããã·åº
çãæããããããŸãããããã²ã³ååããšããŠ
ã¯ãããçŽ ãå¡©çŽ ãèçŽ åã³ãšãŠçŽ ã®ïŒçš®ãå å«
ãããç¹ã«å¡©çŽ ååã奜é©ã§ããã æ¬çºæã«ãããŠæäŸãããäžèšåŒïŒïŒã§ç€ºã
ããååç©ã®ãã¡ã奜é©ãªçŸ€ã®ååç©ã¯ãR1ã
æ°ŽçŽ åååã¯ã¡ãã«åºãæ®ã«æ°ŽçŽ ååãè¡šããå Ž
åã®ååç©ã䞊ã³ã«R2ãæ°ŽçŽ ååãå¡©çŽ ååå
ã¯ã¡ããã·åºãè¡šããå Žåã®ååç©ã§ãããç¹ã«
奜é©ãªååç©ã¯ãR1ãæ°ŽçŽ ååã§ããäžã€R2ã
å¡©çŽ åååã¯ã¡ããã·åºãè¡šããå Žåã®åŒïŒïŒ
ã§ç€ºãããååç©ã§ããã åèšäžè¬åŒïŒïŒã§ç€ºãããååç©ã®ä»£è¡šäŸã
æããã°æ¬¡ã®ãšããã§ããïŒ ïŒâããšãã«ã€ãœãããªã³âïŒâã€ã«é ¢é žã ïŒâïŒïŒâãã«ãªãããšãã«ïŒã€ãœãããªã³âïŒ
âã€ã«é ¢é žã ïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³âïŒâ
ã€ã«é ¢é žã ïŒâïŒïŒâããã¢ããšãã«ïŒã€ãœãããªã³âïŒâ
ã€ã«é ¢é žã ïŒâïŒïŒâã¡ããã·ããšãã«ïŒã€ãœãããªã³âïŒ
âã€ã«é ¢é žã ïŒâïŒïŒâãšããã·ããšãã«ïŒã€ãœãããªã³âïŒ
âã€ã«é ¢é žã ïŒâïŒïŒâããšãã«ã€ãœãããªã³âïŒâã€ã«ïŒã
ãããªã³é žã ïŒâãïŒâïŒïŒâãã«ãªãããšãã«ïŒã€ãœãããªã³
âïŒâã€ã«ãããããªã³é žã ïŒâãïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³â
ïŒâã€ã«ãããããªã³é žã ïŒâãïŒâïŒïŒâã¡ããã·ããšãã«ïŒã€ãœãããªã³
âïŒâã€ã«ãããããªã³é žã ïŒâãïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³â
ïŒâã€ã«ãé ªé žã äžèšåŒïŒïŒã®ååç©ã®ã«ã«ããã·ã«åºã¯å¡©ã
圢æããŠããããšãã§ãããããå¡©ã®äŸãšããŠ
ã¯ããããªãŠã å¡©ãã«ãªãŠã å¡©ããªããŠã å¡©ãã«
ã«ã·ãŠã å¡©ããã°ãã·ãŠã å¡©ãã¢ã«ãããŠã å¡©ã
ã¢ã³ã¢ããŠã å¡©çã®ç¡æ©å¡©ãæãã¯ãžãšãã«ã¢ã
ã³ãããªãšãã«ã¢ãã³ããããªãžã³ããããªãž
ã³ãã¢ã«ããªã³ãããªãžã³ããã«ã·ã³ãã¢ã«ãã€
ã³çã®ææ©å¡©åºãšã®å¡©ãå å«ãããäžã§ããããª
ãŠã å¡©ãã«ãªãŠã å¡©ãã¢ã«ãããŠã å¡©çã®ççåŠ
çã«èš±å®¹ãããå¡©ã奜é©ã§ããã ãŸããåŒïŒïŒã®ååç©ã¯ãã€ãœãããªã³éªšæ Œ
äžã®ïŒ®ååã«ç±æ¥ããŠå¡©åºæ§ãåããã®ã§ãé žä»
å å¡©åã³ç¬¬ïŒçŽå¡©ã圢æããããšãã§ããããã
ãé žä»å å¡©ã®äŸãšããŠã¯ãå¡©é žå¡©ãç¡«é žå¡©ããªã³
é žå¡©çã®ç¡æ©é žå¡©ãæãã¯é ¢é žå¡©ãããããªã³é ž
å¡©çã®ææ©é žå¡©ãå å«ããããŸãã第ïŒçŽå¡©ã®äŸ
ãšããŠã¯ããšãŠåã¡ãã«ãèåã¡ãã«ãå¡©åã¡ã
ã«ããšãŠåãšãã«ãèåãšãã«ãå¡©åãšãã«çã®
ããã²ã³åã¢ã«ãã«ãšã®å¡©ãå å«ãããäžã§ãå¡©
é žå¡©ããªã³é žå¡©ãèåã¡ãã«ç¬¬ïŒçŽå¡©ãçã®çç
åŠçã«èš±å®¹ãåŸãé žä»å å¡©åã¯ç¬¬ïŒçŽå¡©ã奜é©ã§
ããã äžèšåŒïŒïŒã®ååç©ã¯ãäŸãã°ãå ¬ç¥ã®ïŒâ
ã¢ããâïŒâïŒïŒâã¡ãã«ããšãã«ïŒãšã¿ã³ãåŒ
ïŒâïŒïŒãåã¯ïŒâã¢ããâïŒâïŒïŒâã¯ããã
ãšãã«ïŒãšã¿ã³ãåŒïŒâïŒïŒãåã³ãã³ãŸã€ã«
ãã©ã€ãèªå°äœãåŒïŒïŒããåºçºåæãšããŠäž
èšåå¿åŒïŒ¡ã«ç€ºãåæçµè·¯ã«ãã€ãŠè£œé ããããš
ãã§ããã äžèšååŒäžãR11ã¯äœçŽã¢ã«ãã«åºãè¡šããã
X1åã³X2ã¯ããããããã²ã³ååã§ãããR2ã¯
åèšã®æå³ãæããã ãåæçµè·¯ ã äžèšåæçµè·¯ã«ãããŠããŸãåŒïŒâïŒïŒã®
ïŒâã¢ããâïŒâïŒïŒâã¡ãã«ããšãã«ïŒãšã¿ã³
ãšåŒïŒïŒã®ãã³ãŸã€ã«ãã©ã€ãèªå°äœãšãåå¿
ããããããããã®åå¿ã¯éåžžãäžæŽ»æ§ææ©æº¶åª
äžãäŸãã°ãžã¯ããã¡ã¿ã³ãã¯ãããã«ã ãåå¡©
åççŽ çã®ããã²ã³åçåæ°ŽçŽ é¡ïŒãã³ãŒã³ãã
ã«ãšã³ããã·ã¬ã³çã®è³éŠæçåæ°ŽçŽ é¡ïŒããªãš
ãã«ã¢ãã³ããžã¡ãã«ã¢ããªã³ãããªãžã³çã®æ
æ©å¡©åºé¡çã®äžåã¯ãããææ©æº¶åªãçµåããç³»
ã®äžã§ã宀枩ä¹è³å æž©äžã奜ãŸããã¯çŽ15âãçŽ
100âã®æž©åºŠã«ãããŠè¡ãªãããšãã§ãããåŒ
ïŒâïŒïŒã®ååç©ãšåŒïŒïŒã®ååç©ãšã®äœ¿çš
å²åã¯ç¹ã«å¶éããããã®ã§ã¯ãªãããäžè¬ã«ã¯
åŒïŒâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠãåŒïŒïŒ
ã®ååç©ãïŒã10ã¢ã«ã奜ãŸããã¯1.1ãïŒã¢ã«
ã®ç¯å²ã§æ·»å ããã®ã奜ãŸããã çæããåŒïŒâïŒïŒã®ååç©ã¯æ¬¡ãã§è±æ°Žé
ç°ããããããã®è±æ°Žéç°ã¯éåžžçž®åå€ã®ååšäž
ã«å°ãªããšãçŽ50âã®æž©åºŠã奜é©ã«ã¯çŽ140âã
çŽ250âã®æž©åºŠã«è¡ãªãããšãã§ããã䜿çšãã
ãçž®åå€ãšããŠã¯ãäŸãã°ããªãã·å¡©åãªã³ããª
ãã·èåãªã³ãç¡«é žããªã³é žãäºé žåãªã³ãããª
ãªã³é žçãæããããäžã§ããªãã·å¡©åãªã³ãäº
é žåãªã³ã®äœ¿çšãæå©ã§ããããããçž®åå€ã¯è©²
åŒïŒâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠãå°ãªããš
ãïŒåœéã奜ãŸããã¯ïŒã10åœéã®éã§äœ¿çšãã
ããšãæãŸããã ãŸããäžèšè±æ°Žéç°åå¿ã¯æº¶åªã®äžåšäžã«è¡ãª
ãããšãã§ããããå¿ èŠã«å¿ããŠé©åœãªäžæŽ»æ§æ
æ©æº¶åªäžãäŸãã°ããã³ãŒã³ããã«ãšã³ããã·ã¬
ã³çã®äžã§è¡ãªã€ãŠãããã äžèšè±æ°Žéç°ã«ãã€ãŠåŸãããåŒïŒâïŒïŒã®
ååç©ã¯è±æ°ŽçŽ åå¿ã«ä»ããããšã«ãã€ãŠåŒïŒ
âïŒïŒã®ååç©ã«å€ãããããæ¬è±æ°ŽçŽ åå¿ã¯ã
溶åªã®äžåšäžã«åã¯é©åœãªäžæŽ»æ§æº¶åªäžãäŸãã°
ããã©ãªã³ããã³ãŒã³ããã«ãšã³ããã·ã¬ã³ãã¡
ã·ãã¬ã³çã®çåæ°ŽçŽ é¡ïŒæ°ŽïŒé ¢é žïŒïœâãã¿ã
ãŒã«ãïœâã¢ãã«ã¢ã«ã³ãŒã«ãªã©ã®ã¢ã«ã³ãŒã«é¡
çã®äžã§ãåŒïŒâïŒïŒã®ååç©ãè±æ°ŽçŽ å€ã§åŠ
çããããšã«ããè¡ãªãããã䜿çšãããè±æ°ŽçŽ
å€ãšããŠã¯ãäŸãã°ããžããšãã«ãžã¹ã«ãã€ãã
ïŒïŒïŒâãžã¯ããâïŒïŒïŒâãžã·ã¢ããã³ãŸãã
ã³ãããã©ã¯ããâïŒïŒïŒâãã³ãŸããã³ãç¡«
é»ããŒã¬ã³ãã¯ãã é žãéãã³ã¬ã³é žã«ãªãŠã ç
ãæããããäžã§ããžããšãã«ãžã¹ã«ãã€ãã奜
é©ã§ããã該è±æ°ŽçŽ å€ã®äœ¿çšéã¯ãçšããè±æ°ŽçŽ
å€ã®çš®é¡çã«ããç°ãªããäžè¬ã«ã¯ã該åŒïŒâ
ïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšãïŒåœéã
奜ãŸããã¯1.1ã10åœéã®ç¯å²å ã§äœ¿çšããããš
ãã§ããã ãŸããåå¿æž©åºŠã¯èšççã§ã¯ãªããçšããè±æ°Ž
çŽ å€ã®çš®é¡çã«å¿ããŠåºç¯ã«å€ããããšãã§ãã
ããäžè¬ã«ã¯ãçŽïŒâãçŽ300âã奜ãŸããã¯å®€
æž©ãçŽ210âéã®æž©åºŠã䜿çšããããšãã§ããã
äžèšæ¡ä»¶äžã«æ¬è±æ°ŽçŽ åå¿ã¯å€§äœ0.5ã30æéã§
çµãããããšãã§ããã ããããŠåŒïŒâïŒïŒã®ååç©ãåŸããããã®
ååç©ã¯æ¬¡ãã§ããã²ã³åããããšã«ãã€ãŠãåŒ
ïŒïŒã®ååç©ã«å€ããããšãã§ãããæ¬ããã²
ã³åã¯æº¶åªã®äžåšäžã«åã¯é©åœãªäžæŽ»æ§ææ©æº¶
åªãäŸãã°ãåå¡©åççŽ ãã¯ãããã«ã ãããŒã¯
ãããšãã¬ã³çã®ããã²ã³åçåæ°ŽçŽ ã®äžã§ãåŒ
ïŒïŒã®ååç©ãããã²ã³åå€ã§åŠçããããšã«
ããè¡ãªããããæ¬ããã²ã³ååå¿ã«ãããŠãå
å¿ãä¿é²ãããããã«ãå ã®ç §å°äžã«éé¢åºçºç
è©Šå€ãäŸãã°éé žåãã³ãŸã€ã«ã®åŠãææ©éé žã
å°éå ãåå¿ãããããšã奜ãŸããã æ¬ããã²ã³ã³åã®éã®åå¿æž©åºŠã¯ç¹ã«å¶éãã
ããã®ã§ã¯ãªããåºç¯ã«å€ãããããäžè¬ã«ã¯ã
宀枩ä¹è³åå¿æ··åç©ã®éæµæž©åºŠã奜ãŸããã¯çŽ50
âä¹è³éæµæž©åºŠéã®æž©åºŠã«ãããŠåå¿ãè¡ãªãã
ãšãæãŸããã ãŸãã䜿çšãããããã²ã³åå€ãšããŠã¯ãäŸã
ã°ïŒ®âã¯ããã³ãã¯é žã€ãããâããã¢ã³ãã¯
é žã€ããçã®ïŒ®âããé žã€ããé¡ïŒå¡©çŽ ãèçŽ ç
ã®ååç¶ããã²ã³ïŒïŒ®âããã¢ã¢ã»ãã¢ããã
âã¯ããã¢ã»ãã¢ããçã®ïŒ®âããé žã¢ããé¡ç
ãæããããäžã§ãâããã¢ã³ãã¯é žã€ããã®
䜿çšã奜ãŸããã該ããã²ã³åå€ã®äœ¿çšéã¯å³å¯
ã«å¶çŽããããã®ã§ã¯ãªããçšããããã²ã³åå€
ã®çš®é¡çã«å¿ããŠåºç¯ã«å€ããããšãã§ãããã
äžè¬ã«ã¯ãåŒïŒâïŒïŒã®ååç©ïŒã¢ã«ã«å¯Ÿã
ãŠãå°ãªããšãïŒåœéã奜ãŸããã¯ïŒãïŒåœéã®
å²åã§äœ¿çšããã®ã奜ãŸããã çæããåŒïŒïŒã®ååç©ã¯æ¬¡ãã§ãããªã«å
ããããšã«ãããåŒïŒâïŒâïœïŒã®ååç©ã«å€
ããããããã®ãããªã«ååå¿ã¯ãéåžžäžæŽ»æ§æ
æ©æº¶åªäžãäŸãã°ãžã¡ãã«ã¹ã«ããã·ãããžã¡ã
ã«ãã«ã ã¢ããããšã¿ããŒã«ãã¡ã¿ããŒã«ãå«æ°Ž
ãšã¿ããŒã«çã®äžã§ãåŒïŒïŒã®ååç©ãé©åœãª
ãããªã«åå€ã§åŠçããããšã«ããéæããããš
ãã§ããã 䜿çšå¯èœãªãããªã«åå€ãšããŠã¯ãäŸãã°ã·ã¢
ã³åãããªãŠã ãã·ã¢ã³åã«ãªãŠã ãã·ã¢ã³åé
çãæããããäžã§ãã·ã¢ã³åãããªãŠã ã奜é©
ã§ããã該ãããªã«åå€ã®äœ¿çšéã¯éåžžãåŒ
ïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšãïŒåœéã
奜ãŸããã¯1.1ãïŒåœéã®ç¯å²ãšããããšãã§ã
ãã ãŸãã該ãããªã«åã®åå¿æž©åºŠã¯èšççã§ã¯ãª
ãåºç¯ã«å€ããããšãã§ããããäžè¬ã«ã¯ãçŽïŒ
âãçŽ200âã奜ãŸããã¯ã»ãŒå®€æž©ä¹è³åå¿æ··å
ç©ã®éæµæž©åºŠéã®æž©åºŠã§åå¿ãè¡ãªãããšã奜ãŸ
ããã ããããŠåŸãããåŒïŒâïŒâïœïŒã®ååç©ã¯
ããèªäœå ¬ç¥ã®æ¹æ³ãäŸãã°éãé å¿åé¢ãæœ
åºãåçµæ¶ãã¯ãããã°ã©ãã€ãŒçã«ããåå¿æ··
åç©ããåé¢ãåã³ïŒåã¯ç²Ÿè£œããããšãã§ã
ãã ãã®åŒïŒâïŒâïœïŒã®ååç©ã¯ããèªäœé®ç
æçç掻æ§ãæããè¬å€ãšããŠã®çšéãèããã
ããã該åŒïŒâïŒâïœïŒã®ååç©ã¯ããã«å æ°Ž
å解ããããšã«ãããããé®çæçç掻æ§ã®é«ã
åŒïŒâïŒâïœïŒã®ååç©ã«å€ããããšãã§ã
ãã åŒïŒâïŒâïœïŒã®ååç©ã®å æ°Žå解ã¯ã溶åª
ã®äžåšäžã«åã¯æ°Žæ··åæ§ææ©æº¶åªäŸãã°ã¡ã¿ããŒ
ã«ããšã¿ããŒã«ãã»ããœã«ãã®åŠãã¢ã«ã³ãŒã«
é¡ãã¢ã»ãã³ãã¡ãã«ãšãã«ã±ãã³ã®åŠãã±ãã³
é¡ãããã©ããããã©ã³ããžã¡ããã·ãšã¿ã³ããž
ãªããµã³ã®åŠããšãŒãã«é¡ããžã¡ãã«ã¹ã«ããã·
ããªã©ã®ååšåã¯äžåšäžã«ãã¢ã«ã«ãªæ°Žæº¶æ¶²åã¯
é žæ°Žæº¶æ¶²ãçšããŠè¡ãªãããšãã§ããã å æ°Žå解ã«éããŠäœ¿çšãåŸãã¢ã«ã«ãªãšããŠ
ã¯ãäŸãã°ãæ°Žé žåãããªãŠã ãæ°Žé žåã«ãªãŠ
ã ãæ°Žé žåããªãŠã ãªã©ã®æ°Žé žåã¢ã«ã«ãªéå±å
ã¯æ°Žé žåã¢ã«ã«ãªåé¡éå±ãçé žãããªãŠã ãç
é žã«ãªãŠã ã®åŠãçé žã¢ã«ã«ãªéå±ãªã©ãå å«ã
ãããŸãã䜿çšãããé žãšããŠã¯ãå¡©é žãç¡«é žã
ïœâãã«ãšã³ã¹ã«ãã³é žããªã³é žãããªãã«ãªã
ã¡ã¿ã³ã¹ã«ãã³é žçãæããããã ãããé žåã¯ã¢ã«ã«ãªã¯ãåŒïŒâïŒâïœïŒã®
ååç©ïŒã¢ã«ã«å¯ŸããŠéåžžå°ãªããšãïŒåœéã奜
ãŸããã¯ïŒã50åœéã®å²åã§äœ¿çšãåŸãã å æ°Žå解ã¯çŽïŒâä¹è³åå¿æ··åç©ã®éæµæž©åºŠã«
ãããŠè¡ãªãããšãã§ããããäžè¬ã«50ã120â
ã®æž©åºŠç¯å²ã奜é©ã§ããã ããããŠãåŒïŒâïŒâïœïŒã®ååç©åã¯ãã®
å¡©ãçæãããã®ãã®ã¯åžžæ³ã«åŸããäŸãã°
éãé å¿åé¢ãæœåºãåçµæ¶ãã¯ãããã°ã©ãã€
ãŒçã«ãããåå¿æ··åç©ããåé¢ãåã³ïŒåã¯ç²Ÿ
補ããããšãã§ããã ãŸãäžæ¹ãåèšã®åŠãããŠçæããããããåŒ
ïŒâïŒâïœïŒã®ååç©ã¯ããã«ãäœçŽã¢ã«ãã«
åããããšã«ãããæ¬çºæã®åŒïŒâïŒâïœïŒã®
ååç©ãçµãŠãæçµã®åŒïŒâïŒâïœïŒã®ååç©
ã«å°ãããšãã§ããã 該äœçŽã¢ã«ãã«åã«çšãããäœçŽã¢ã«ãã«åå€
ãšããŠã¯ãèèªæã®æŽ»æ§ççŽ ååã®ã¢ã«ãã«åã®
ããã«é垞䜿çšãããã¢ã«ãã«åå€ã¯ãããã䜿
çšå¯èœã§ãããäŸãã°ãäœçŽã¢ã«ãã«ãã©ã€ã
ïŒäŸãã°ããšãŠåã¡ãã«ããšãŠåãšãã«ããšãŠå
ãããã«ãªã©ïŒãç¡«é žäœçŽã¢ã«ãã«ãšã¹ãã«ïŒäŸ
ãã°ãžã¡ãã«ç¡«é žããžãšãã«ç¡«é žãªã©ïŒãé©ããŠ
ããã ãããã¢ã«ãã«åå€ã«ããã¢ã«ãã«åã«éããŠ
ã¯ãã·ã¢ãã¡ãã«åºã®ã¡ãã¬ã³åºéšåã®ïŒåã®æ°Ž
çŽ ååã®ãã¡ïŒåã®ã¿ã容æã«äžã€éžæçã«ã¢ã«
ãã«åããããããïŒåã®æ°ŽçŽ ååããäŸãã°äž
èšåå¿åŒïŒ¢ã«ç€ºãåŠãæ¹æ³ã«åŸã€ãŠäºã掻æ§åã
ãããæãã¯å察ã«ä¿è·ããŠããããããåŸã¢ã«
ãã«åããããšãæãŸããã äžèšåŒäžãR3ã¯äœçŽã¢ã«ãã«åºãè¡šãããïŒ
ã¯ã¢ã«ã«ãªéå±ïŒäŸãã°ãããªãŠã ãã«ãªãŠã å
ã¯ãªããŠã ïŒãè¡šãããR11åã³R2ã¯åèšã®æå³
ãæããã äžèšåŒïŒâïŒâïœïŒã®ååç©ã®ã¢ã«ã«ãªéå±
æ°ŽçŽ åç©åã¯ã¢ã«ã«ãªéå±ã¢ããïŒäŸãã°æ°ŽçŽ å
ãããªãŠã ãæ°ŽçŽ åã«ãªãŠã ããããªãŠã ã¢ã
ããã«ãªãŠã ã¢ãããªã©ïŒã«ããåŠçã䞊ã³ã«ã
ãã«åŒç¶ãçé žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«åã¯
ããã®é žäœçŽã¢ã«ãã«ïŒäŸãã°çé žãžã¡ãã«ãç
é žãžãšãã«ãã¯ããã®é žã¡ãã«ãã¯ããã®é žãšã
ã«ãã¯ããã®é žã€ãœãããã«ãã¯ããã®é žã€ãœã
ãã«ãªã©ïŒã«ããåŠçã¯ã段éçã«è¡ãªã€ãŠãã
ãããéåžžã¯äžæ®µéã§ãããªãã¡ãåŒïŒâïŒâ
ïœïŒã®ååç©ã«ãåžžæ³ã«åŸããã¢ã«ã«ãªéå±æ°ŽçŽ
åç©åã¯ã¢ã«ã«ãªéå±ã¢ããã®ååšäžã«ãçé žãž
ïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«åã¯ããã®é žäœçŽã¢ã«
ãã«ãäœçšãããããšã«ãããåŒïŒâïŒâïœâ
ïŒïŒã®ååç©ã«å€ããããšãã§ããã äžèšã®åå¿ã¯æº¶åªã®ååšäžåã¯äžåšäžã®ããã
ã«ãããŠãè¡ãªãããšãã§ãã溶åªã䜿çšããå Ž
åã®æº¶åªãšããŠã¯äŸãã°ãžãšãã«ãšãŒãã«ããã
ã©ããããã©ã³ããžãªããµã³ããžã¡ããã·ãšã¿
ã³ããžãšãã¬ã³ã°ãªã³ãŒã«ãžã¡ãã«ãšãŒãã«ãªã©
ã®ãšãŒãã«é¡ããããã¯ãžã¡ãã«ã¹ã«ããã·ããª
ã©ã®ã¹ã«ããã·ãé¡ããã³ãŒã³ããã«ãšã³ãªã©ã®
è³éŠæçåæ°ŽçŽ é¡ãªã©ãé©ããŠãããåå¿æž©åºŠãš
ããŠã¯çŽïŒâä¹è³åå¿æ··åç©ã®éæµæž©åºŠã奜ãŸã
ãã¯ïŒã180âã®ç¯å²ã®æž©åºŠã奜ãŸãããæå宀
æž©ã§ãã°ããæŸçœ®ããŠãããŠãã50ã150âã®æž©
床ã«å ç±ããªããåå¿ãè¡ãªãããšãã§ããã ããããŠåŸããã該ã·ã¢ãã¡ãã«åºã®ã¡ãã¬ã³
éšåã®æ°ŽçŽ ååã®ïŒã€ãã¢ã«ã³ãã·ã«ã«ããã«åº
ïŒâCOOR3ïŒã§ä¿è·ãããåŒïŒâïŒâïœâïŒïŒ
ã®ååç©ã¯ã次ãã§åèšããåŠãäœçŽã¢ã«ãã«å
å€ãšåå¿ããããããã ãã®ã¢ã«ãã«ååå¿ããŸã溶åªã®ååšäžåã¯äž
åšäžã®ãããã«ãããŠãè¡ãªãããšãã§ãã䜿çš
ãåŸã溶åªãšããŠã¯äžèšã®ãã®ãæãããããã
ã®ã¢ã«ãã«ååå¿ã®æž©åºŠã¯èšççã§ã¯ãªãã䜿çš
ããã¢ã«ãã«åå€ã®çš®é¡ã«å¿ããŠåºç¯ã«å€ããã
ãšãã§ããããäžè¬ã«å®€æž©ä¹è³åå¿æ··åç©ã®éæµ
枩床ãç¹ã«50ã150âã®ç¯å²ã奜ãŸããã 該äœçŽã¢ã«ãã«åå€ã®äœ¿çšéããŸãèšççãªã
ã®ã§ã¯ãªããäœçŽã¢ã«ãã«åå€ã®çš®é¡ãåå¿æ¡ä»¶
çã«å¿ããŠåºç¯ã«å€ããããšãã§ããããäžè¬ã«
åŒïŒâïŒâïœâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°
ãªããšã1.0ã¢ã«ã奜ãŸããã¯ïŒã10ã¢ã«ã®å²å
ã§äœ¿çšããããšãã§ããã ããããŠåŸãããåŒïŒâïŒâïœâïŒïŒã®ã¢ã«
ãã«åçæç©ã¯å æ°Žå解ããããšã«ãããäŸãã°
ææ©æº¶åªãæ°Žåã¯ãããã®æ··åç©äžã§ãã«ã»ã€ãœ
ãŒããªã©ã®ã¢ã«ã«ãªæ°Žæº¶æ¶²æãã¯å¡©é žãç¡«é žãªã©
ã®ç¡æ©é žã®ååšäžã«å ç±ããããšã«ããã容æã«
åŒïŒâïŒâïœâïŒïŒã®ååç©ã«è»¢æããã次ã
ã§ãã®ååç©ã¯ãé垞溶åªã®äžåšäžã«äžã€ã¢ã«ã«
ãªãç¹ã«æ°Žé žåãããªãŠã ãæ°Žé žåã«ãªãŠã ã®åŠ
ãã¢ã«ã«ãªéå±æ°Žé žåç©ã®ååšäžåã¯äžåšäžã«å
ç±ããŠè±çé žããããšã«ãããç®çãšããR1ã
äœçŽã¢ã«ãã«åºãè¡šããå Žåã®åŒïŒïŒã®åå
ç©ãããªãã¡åŒïŒâïŒâïœïŒã®ååç©ã«å€ãã
ããšãã§ããããã®å Žåã®å ç±æž©åºŠãšããŠã¯ã該
ã¢ã«ã«ãªã®äžåšäžã§ã¯ãåŒïŒâïŒâïœâïŒïŒã®
ååç©ã®èç¹ä»¥äžçæããåŒïŒâïŒâïœïŒã®å
åç©ã®å解枩床æªæºãšããããšãã§ããäžæ¹ã¢ã«
ã«ãªã®ååšäžã§ã¯ããã¡ããèç¹ä»¥äžã«å ç±ãã
ããšãã§ããããäžè¬ã«èç¹ããäœã枩床ãäŸã
ã°50ã120âã®æž©åºŠã«å ç±ããããšã«ãã€ãŠãè±
çé žãéæããããšãã§ããã ãã®åŒïŒâïŒâïœïŒã®ååç©ã¯ããèªäœé®ç
æçç掻æ§ãæããè¬å€ãšããŠäœ¿çšãããããã
ãã«å æ°Žå解ããããšã«ãããé®çæçç掻æ§ã
ããé«ããåŒïŒâïŒâïœïŒã®ååç©ã«å€ããã
ãšãã§ããããã®åŒïŒâïŒâïœïŒã®ååç©ã®å
æ°Žå解ã¯ãåèšåŒïŒâïŒâïœïŒã®ååç©ã®å æ°Ž
å解ã«ã€ããŠåè¿°ãããšåæ§ã«ããŠè¡ãªãããšã
ã§ããã ãªããåŒïŒâïŒâïœâïŒïŒã®ååç©ã®å æ°Žå
解ãåèšè±çé žåå¿ã«ã€ããŠè¿°ã¹ã枩床æ¡ä»¶äžã«
ãããŠè¡ãªãã°ãåŒïŒâïŒâïœïŒã®ç®çååç©
ãäžæ°ã«åŸãããšãã§ããã ããã«äžèšåå¿åŒïŒ¢ã§ç€ºãäžé£ã®åå¿ã«ãã
ãŠãåŒïŒâïŒâïœïŒã®ååç©ãã該åŒïŒâïŒ
âïœïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠïŒåœéåã¯ãã以
äžã®ã¢ã«ã«ãªéå±æ°ŽçŽ åç©åã¯ã¢ã«ã«ãªéå±ã¢ã
ããäœçšãããããšã«ããæå©ã«åŸãããäžèšåŒ åŒäžãR2åã³ïŒã¯åèšã®æå³ãæããã ã®ååç©ã«åèšããåŠãäœçŽã¢ã«ãã«åå€ãäœçš
ãããããšã«ãã€ãŠããåŒïŒâïŒâïœïŒã®åå
ç©ã補é ããããšãã§ããã äžèšåŒïŒâïŒâïœâïŒïŒã®ååç©ã®ã¢ã«ãã«
åã¯æº¶åªã®äžåšäžåã¯äžèšããåŠã溶åªã®ååšäž
ã«ãåŒïŒâïŒâïœâïŒïŒã®ååç©ã«äœçŽã¢ã«ã
ã«åå€ãåå¿ãããããšã«ããè¡ãªãããšãã§ã
ãããã®éã®åå¿æž©åºŠã¯èšççã§ã¯ãªããçšãã
ã¢ã«ãã«åå€ã®çš®é¡çã«å¿ããŠåºç¯ã«å€ããããš
ãã§ããããäžè¬ã«â10âä¹è³åå¿æ··åç©ã®éæµ
枩床ã奜ãŸããã¯ïŒâã30âã®ç¯å²ãé©åºŠã§ã
ãããŸããäœçŽã¢ã«ãã«åå€ã®äœ¿çšéãèšççã§
ã¯ãªããåºç¯ã«å€ããããšãã§ããããäžè¬ã«åŒ
ïŒâïŒâïœâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãª
ããšãçã¢ã«ãç¹ã«ïŒã10ã¢ã«ã®å²åã§äœ¿çšãã
ã®ãæå©ã§ããã çæããåŒïŒâïŒâïœïŒã®ååç©ã¯åèšãšå
æ§ã«å æ°Žå解ããããšã«ãããåŒïŒâïŒâïœïŒ
ã®ååç©ã«å€ããããšãã§ããã ããã«ãŸãå¥æ³ãšããŠãåèšã®åŠãããŠåŸãåŒ
ïŒâïŒâïœïŒã®ååç©ã«å¯ŸããŠãåèšåå¿åŒïŒ¢
ã«ç€ºãäœçŽã¢ã«ãã«ååå¿ãè¡ãªãããšãã§ãã
ããã«ãã€ãŠããåŒïŒâïŒâïœïŒã®ååç©ãåŸ
ãããã 以äžã®åŠãããŠåŸãããåŒïŒâïŒâïœïŒã®å
åç©ã¯åèšã®åŠãããŠåå¿æ··åç©ããåé¢ãå
ã³ïŒåã¯ç²Ÿè£œããããšãã§ããã ãåæçµè·¯ ã åèšåå¿åŒïŒ¡ã«ãããåæçµè·¯ã«ãããŠãåŒ
ïŒâïŒïŒã®ïŒâã¢ããâïŒâïŒïŒâã¯ããããšã
ã«ïŒãšã¿ã³ãšåŒïŒïŒã®ãã³ãŸã€ã«ãã©ã€ãèªå°
äœã®åå¿ãåŸãããåŒïŒâïŒïŒã®ååç©ã®è±æ°Ž
éç°ãããã«æ¬¡ãåŒïŒâïŒïŒã®ååç©ã®è±æ°ŽçŽ
ã¯ãäžèšåæçµè·¯ã«ãããŠè¿°ã¹ããšåæ§ã«ããŠ
è¡ãªãããšãã§ããã ããããŠåŸãããåŒïŒâïŒïŒã®ååç©ã¯ãã
ããªã«åããããšã«ããåŒïŒïŒã®ååç©ã«å€ã
ãããšãã§ããããã®ãããªã«åã¯ãåèšåæçµ
è·¯ã«ãããŠåŒïŒïŒã®ååç©ã®ãããªã«åã«ã€
ããŠåè¿°ãããšã»ãŒåæ§ã®æ¡ä»¶äžã«è¡ãªãããšã
ã§ããããã«ããåŒïŒïŒã®ååç©ãåŸãããã ãã®åŒïŒïŒã®ååç©ã¯æ¬¡ãã§å æ°Žå解ããã
ãšã«ããåŒïŒïŒã®ååç©ã«å€ããããããã®å
æ°Žå解ã¯ãåŒïŒâïŒâïœïŒã®ååç©ã®å æ°Žå解
ã«ã€ããŠåè¿°ãããšåæ§ã«ããŠè¡ãªãããšãã§
ããããã«ãã€ãŠåŒïŒïŒã®ååç©ãçæããã
ãããšãã§ããã åŸãããåŒïŒïŒã®ååç©åã¯ãã®ãšã¹ãã«ã¯
éå ããããšã«ããåŒïŒïŒã®ååç©ã«å€ããã
ããåŒïŒïŒã®ååç©åã¯ãã®ãšã¹ãã«ã®éå
ã¯ãéåžžãäžæŽ»æ§æº¶åªãäŸãã°ãšãã«ãšãŒãã«ã
ãããã«ãšãŒãã«ãããã©ããããã©ã³ããžãªã
ãµã³ããžã¡ããã·ãšã¿ã³çã®ãšãŒãã«é¡ïŒãã³ãŒ
ã³ããã«ãšã³ããã·ã¬ã³çã®è³éŠæçåæ°ŽçŽ çã®
äžã§ãåŒïŒïŒã®ååç©åã¯ãã®ãšã¹ãã«ãã宀
æž©ä¹è³åå¿æ··åç©ã®éæµæž©åºŠã«ãããŠããªããŠã
ã¢ã«ãããŠã ãããªãããžãããâãã¹ïŒïŒâã¡
ããã·ãšããã·ïŒã¢ã«ãããŠã ãããªãŠã çã®åŠ
ãé¯éå±æ°ŽçŽ åç©ãšæ¥è§Šããããããšã«ããè¡ãª
ãããšãã§ããã çæããåŒïŒïŒã®ååç©ã¯ããã«ããã²ã³å
ããããšã«ããåŒïŒïŒã®ååç©ã«ããããšãã§
ããããã®ããã²ã³åã¯ã溶åªã®äžåšäžã«åã¯é©
åœãªæº¶åªäŸãã°æ°Žããžã¯ããã¡ã¿ã³ãã¯ãããã«
ã ãåå¡©åççŽ ããã³ãŒã³ããã«ãšã³ããã·ã¬ã³
çã®ååšäžã«ãåŒïŒïŒã®ååç©ãããã²ã³åå€
ã§åŠçããããšã«ããè¡ãªãããšãã§ããã çšãããããã²ã³åå€ãšããŠã¯ãäŸãã°å¡©åæ°Ž
çŽ ãããªãã«ã¯ããªããäžå¡©åãªã³ãèåæ°ŽçŽ ã
ããªãã«ãããããäžèåãªã³ããªãã·èåãªã³
çãæãããããããããã²ã³åå€ã¯ãåŒïŒïŒ
ã®ååç©ïŒã¢ã«ã«å¯ŸããŠäžè¬ã«å°ãªããšãïŒåœ
éã奜ãŸããã¯1.1ã10åœéã®ç¯å²ã§äœ¿çšããã
ãšãã§ããã ãŸããæ¬ããã²ã³åã¯äžè¬ã«ã»ãŒå®€æž©ä¹è³åå¿
æ··åç©ã®éæµæž©åºŠã奜ãŸããã¯çŽ50âãçŽ150â
ã®æž©åºŠã«ãããŠãçŽïŒã10æéè¡ãªãã®ãæå©ã§
ããã ããããŠåŸãããåŒïŒïŒã®ååç©ã¯ãåèšå
æçµè·¯ã«èšèŒããåŠãããŠãåŒïŒâïŒâïœïŒ
åã³ïŒâïŒâïœïŒäžŠã³ã«åŒïŒâïŒâïœïŒåã³
ïŒâïŒâïœïŒã®ååç©ã«å€ããããšãã§ããã ããã«ãäžèšåæçµè·¯ã®å·¥çšéäžã§åŸããã
åŒïŒâïŒïŒã®ååç©ãããªãã¡äžèšåŒ åŒäžãR2ã¯åèšã®æå³ãæããã ã§ç€ºãããååç©ã¯ãã¢ã»ããããªã«ïŒCH3CNïŒ
ãšåå¿ãããããšã«ãããçŽæ¥ã«äžèšåŒ åŒäžãR2ã¯åèšã®æå³ãæããã ã§ç€ºãããååç©ã«å€ããããšãã§ããã äžèšåå¿ã¯é©åœãªäžæŽ»æ§æº¶åªäžãäŸãã°æ¶²äœã¢
ã³ã¢ãã¢ãã¡ãã«ã¢ãã³ããšãã«ã¢ãã³ããžã¡ã
ã«ã¹ã«ããã·ãããžã¡ãã«ãã«ã ã¢ããçã®äž
ã§ãåŒïŒâïŒïŒã®ååç©ãã¢ã»ããããªã«ãšæ¥
觊ããããããšã«ããè¡ãªãããšãã§ããã åå¿æž©åºŠã¯èšççã§ã¯ãªãåºç¯ã«å€ããããšã
ã§ããããäžè¬ã«ã¯â40âã200âã奜ãŸããã¯
â30âä¹è³å®€æž©éã®æž©åºŠã«ãããŠè¡ãªãããšãæ
ãŸããããŸããã¢ã»ããããªã«ã¯éåžžãåŒïŒâ
ïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšãïŒã¢ã«ã
奜ãŸããã¯1.5ãïŒã¢ã«ã®éã§äœ¿çšããã®ãæå©
ã§ããã äžèšã¢ã»ããããªã«ãšã®åå¿ã¯ãæå©ã«ã¯ãè±
ããã²ã³åå€ãšããŠãå°ãªããšãåœéä¹è³éå°é
ã®äŸãã°ãããªãŠã ã¢ãããã«ãªãŠã ã¢ãããã«
ãªãŠã ãããã·ãããããªãŠã ã¡ããã·ããã«ãª
ãŠã ãšããã·ãçã®ååšäžã«ãäžã€ä¿é²å€ãšããŠ
å°éã®äžå¡©åéçã®ååšäžã«è¡ãªãããã ããããŠåŸãããåŒïŒâïŒâïœïŒã®ååç©
ã¯ãåèšãšåæ§ã«ããŠãåŒïŒâïŒâïœïŒäžŠã³ã«
åŒïŒâïŒâïœïŒåã³ïŒâïŒâïœïŒã®ååç©ã«
å€ããããšãã§ããã 以äžè¿°ã¹ãåŠãããŠè£œé ãããåŒïŒïŒãããª
ãã¡ãåŒïŒâïŒâïœïŒåã³ïŒâïŒâïœïŒãã®
ååç©ã¯éåžžã®æ¹æ³ãäŸãã°æœåºãéãåçµ
æ¶ãã¯ãããã°ã©ãã€ãŒçã«ããåé¢ç²Ÿè£œããã
ãšãã§ããã åŒïŒïŒã®ååç©ã¯ãéé¢é žåã¯éé¢å¡©åºã®ç¶
æ ã«ãããšãã«ã¯ãåžžæ³ã«åŸãããã®å¡©ã«å€ãã
ããšãã§ãããŸãéã«ãå¡©ã®ç¶æ ã«ãããšãã«
ã¯ãåžžæ³ã«åŸãéé¢é žåã¯éé¢å¡©åºã«å€ããããš
ãã§ããã 以äžã«èª¬æããæ¬çºæã®åŒïŒïŒã®ååç©ã¯äž
è¬ã«ãåªããé®çåã³ïŒåã¯æççäœçšãæããŠ
ããããã®äžã§ãç¹ã«ãR1ãæ°ŽçŽ ååã§ããå Ž
åã®åŒïŒïŒã®ååç©åã¯ãã®å¡©ã¯ãçŸåšé®çæ
ççå€ãšããŠèšåºå»åŠäžæšæºçãªãã®ãšããŠèªã
ãããŠããããšãã«ãã¿ãŸã³ãåã³ã€ã³ãã¡ã¿ã·
ã³ãããã¯ããã«åªããé®çåã³ïŒåã¯æççäœ
çšãæããŠãããããããã®äžãåŸæ¥ããå®çšã«
äŸãããŠããã¢ã¹ããªã³ãããšãã«ãã¿ãŸã³ãã€
ã³ãã¡ã¿ã·ã³çã®å ¬ç¥ã®é®çæççå€ã®ãããã
ããªãã²ã©ãæ¶ååšé害ã䌎ãã®ã«å¯ŸããŠãæ¬çº
æã®äžèšåŒïŒïŒã®ååç©ã¯æ¶ååšé害ãéåžžã«
埮匱ã§ãããšãããæ²»çåŠçã«é¡èãªå©ç¹ãæã
ãŠããã æ¬çºæã®äžèšååç©ãéåžžã«åªããé®çäœçšå
ã³æççäœçšãæããããšã䞊ã³ã«æ¥µããŠåŸ®åŒ±ãª
æ¶ååšé害èªçºäœçšãããããªãããšã¯ã以äžã®
åç©å®éšã«ããç«èšŒãããã ãªãã以äžã®åç©å®éšã«çšããæ¬çºæã®ååç©
ã¯æ¬¡ã®ç¬Šå·ã§ä»£è¡šãããã ååç© ïŒ¡ïŒïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³â
ïŒâã€ã«é ¢é ž ïŒïŒâïŒïŒâã¡ããã·ããšãã«ïŒã€ãœãããªã³
âïŒâã€ã«é ¢é ž ïŒïŒâãïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããª
ã³âïŒâã€ã«ãããããªã³é ž ïŒïŒâããšãã«ã€ãœãããªã³âïŒâã€ã«é ¢é ž (1) é®çäœçš äœé18ã22ïœã®ddYç³»éæ§ããŠã¹ãïŒçŸ€10å¹ãš
ããŠçšããå ãã被æ€è¬ãåæäžéã«å¿ããŠçµå£
æäžãããçµå£æäžã¯è¢«æ€è¬ã溶åªïŒ0.5ïŒ ã«ã«
ããã·ã¡ãã«ã»ã«ããŒã¹åã³2.0ïŒ ãã€ã³80ã溶
解ãã氎溶液ïŒã«åæ£ããããã®æžæ¿æ¶²ããŸã³ã
ã«ããæäžããã被æ€è¬æäžïŒæéåŸã«0.6ïŒ é ¢
é žãè ¹è å ã«0.1mlïŒ10ïœäœéã®éã§æäžããæ
äžåŸ20åéã«äºã€ãŠçããã©ã€ãžã³ã°
ïŒwrithingïŒæ°ã枬å®ããã溶åªæäžå¯Ÿç §çŸ€ïŒè¢«
æ€è¬ãé€ãã溶åªã®ã¿ã®æäžçŸ€ïŒã«å¯Ÿãã被æ€è¬
æäžçŸ€ã®æå¶çãäžèšåŒã«åŸã€ãŠæ±ãããã®æ°å€
ãããªãããã€ãŒã«ãâãŠã€ã«ã³ãã¯ãœã³
ïŒLitchfieldâWilcoxonïŒæ³ã«åŸã€ãŠED50å€ãç®
åºããã被æ€è¬ã®åã ã®ED50å€ãäžèšè¡šïŒã«ç€º
ãã
ãã«è©³ããã¯ãïŒâäœã«ã«ã«ããã·ã«ã¢ã«ãã«åº
ãæããæ°èŠãªïŒâããšãã«ã€ãœãããªã³èªå°
äœããã®è£œé æ¹æ³ãåã³ãã®é®çæççå€ãšããŠ
ã®çšéã«é¢ããã ïŒâããšãã«ã€ãœãããªã³èªå°äœãšããŠããã
æè¿ã«ãªã€ãŠäžèšåŒ ã§ç€ºãããïŒâïŒïŒâã¯ããããšãã«ïŒâïŒâã«ã«
ãã¢ã€ã«ã¡ãã«ã€ãœãããªã³ãé®çæççäœçšã
æããããšãå ±åãããŠãããDavid A.Walsh
et al.ïŒJournal of Medicinal ChemistryïŒ
1978ãVol.21ãNo.ïŒãpp582ã585åç §ãã æ¬çºæã¯ãéåžžã«é«ãé®çåã³æççäœçšãæ
ããæ°èŠãªïŒâããšãã«ã€ãœãããªã³èªå°äœãšã
ãŠãäžèšäžè¬åŒ åŒäžãR1ã¯æ°ŽçŽ åååã¯äœçŽã¢ã«ãã«åºãè¡š
ãããR2ã¯æ°ŽçŽ ååãããã²ã³åååã¯äœçŽã¢
ã«ã³ãã·åºãè¡šããã ã§ç€ºãããååç©åã³ãã®å¡©ãæäŸãããã®ã§ã
ãã æ¬æ现æžã«ãããŠããäœçŽããªãèªã¯ããã®èª
ãä»ãããåºåã¯ååç©ãïŒå以äžã奜ãŸããã¯
ïŒå以äžã®ççŽ ååãæããããšãæå³ããã ããããŠããäœçŽã¢ã«ãã«åºãã¯çŽéç¶åã¯å
å²éç¶ã®ããããã§ããããšãã§ããäŸãã°ã¡ã
ã«ããšãã«ãïœâãããã«ãã€ãœãããã«ãïœâ
ããã«ãã€ãœããã«ãsecâããã«ãtertâãã
ã«åºçãå å«ããããäœçŽã¢ã«ã³ãã·åºããšããŠ
ã¯äŸãã°ã¡ããã·ããšããã·ãïœâããããã·ã
ã€ãœããããã·ãïœâãããã·ãã€ãœãããã·åº
çãæããããããŸãããããã²ã³ååããšããŠ
ã¯ãããçŽ ãå¡©çŽ ãèçŽ åã³ãšãŠçŽ ã®ïŒçš®ãå å«
ãããç¹ã«å¡©çŽ ååã奜é©ã§ããã æ¬çºæã«ãããŠæäŸãããäžèšåŒïŒïŒã§ç€ºã
ããååç©ã®ãã¡ã奜é©ãªçŸ€ã®ååç©ã¯ãR1ã
æ°ŽçŽ åååã¯ã¡ãã«åºãæ®ã«æ°ŽçŽ ååãè¡šããå Ž
åã®ååç©ã䞊ã³ã«R2ãæ°ŽçŽ ååãå¡©çŽ ååå
ã¯ã¡ããã·åºãè¡šããå Žåã®ååç©ã§ãããç¹ã«
奜é©ãªååç©ã¯ãR1ãæ°ŽçŽ ååã§ããäžã€R2ã
å¡©çŽ åååã¯ã¡ããã·åºãè¡šããå Žåã®åŒïŒïŒ
ã§ç€ºãããååç©ã§ããã åèšäžè¬åŒïŒïŒã§ç€ºãããååç©ã®ä»£è¡šäŸã
æããã°æ¬¡ã®ãšããã§ããïŒ ïŒâããšãã«ã€ãœãããªã³âïŒâã€ã«é ¢é žã ïŒâïŒïŒâãã«ãªãããšãã«ïŒã€ãœãããªã³âïŒ
âã€ã«é ¢é žã ïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³âïŒâ
ã€ã«é ¢é žã ïŒâïŒïŒâããã¢ããšãã«ïŒã€ãœãããªã³âïŒâ
ã€ã«é ¢é žã ïŒâïŒïŒâã¡ããã·ããšãã«ïŒã€ãœãããªã³âïŒ
âã€ã«é ¢é žã ïŒâïŒïŒâãšããã·ããšãã«ïŒã€ãœãããªã³âïŒ
âã€ã«é ¢é žã ïŒâïŒïŒâããšãã«ã€ãœãããªã³âïŒâã€ã«ïŒã
ãããªã³é žã ïŒâãïŒâïŒïŒâãã«ãªãããšãã«ïŒã€ãœãããªã³
âïŒâã€ã«ãããããªã³é žã ïŒâãïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³â
ïŒâã€ã«ãããããªã³é žã ïŒâãïŒâïŒïŒâã¡ããã·ããšãã«ïŒã€ãœãããªã³
âïŒâã€ã«ãããããªã³é žã ïŒâãïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³â
ïŒâã€ã«ãé ªé žã äžèšåŒïŒïŒã®ååç©ã®ã«ã«ããã·ã«åºã¯å¡©ã
圢æããŠããããšãã§ãããããå¡©ã®äŸãšããŠ
ã¯ããããªãŠã å¡©ãã«ãªãŠã å¡©ããªããŠã å¡©ãã«
ã«ã·ãŠã å¡©ããã°ãã·ãŠã å¡©ãã¢ã«ãããŠã å¡©ã
ã¢ã³ã¢ããŠã å¡©çã®ç¡æ©å¡©ãæãã¯ãžãšãã«ã¢ã
ã³ãããªãšãã«ã¢ãã³ããããªãžã³ããããªãž
ã³ãã¢ã«ããªã³ãããªãžã³ããã«ã·ã³ãã¢ã«ãã€
ã³çã®ææ©å¡©åºãšã®å¡©ãå å«ãããäžã§ããããª
ãŠã å¡©ãã«ãªãŠã å¡©ãã¢ã«ãããŠã å¡©çã®ççåŠ
çã«èš±å®¹ãããå¡©ã奜é©ã§ããã ãŸããåŒïŒïŒã®ååç©ã¯ãã€ãœãããªã³éªšæ Œ
äžã®ïŒ®ååã«ç±æ¥ããŠå¡©åºæ§ãåããã®ã§ãé žä»
å å¡©åã³ç¬¬ïŒçŽå¡©ã圢æããããšãã§ããããã
ãé žä»å å¡©ã®äŸãšããŠã¯ãå¡©é žå¡©ãç¡«é žå¡©ããªã³
é žå¡©çã®ç¡æ©é žå¡©ãæãã¯é ¢é žå¡©ãããããªã³é ž
å¡©çã®ææ©é žå¡©ãå å«ããããŸãã第ïŒçŽå¡©ã®äŸ
ãšããŠã¯ããšãŠåã¡ãã«ãèåã¡ãã«ãå¡©åã¡ã
ã«ããšãŠåãšãã«ãèåãšãã«ãå¡©åãšãã«çã®
ããã²ã³åã¢ã«ãã«ãšã®å¡©ãå å«ãããäžã§ãå¡©
é žå¡©ããªã³é žå¡©ãèåã¡ãã«ç¬¬ïŒçŽå¡©ãçã®çç
åŠçã«èš±å®¹ãåŸãé žä»å å¡©åã¯ç¬¬ïŒçŽå¡©ã奜é©ã§
ããã äžèšåŒïŒïŒã®ååç©ã¯ãäŸãã°ãå ¬ç¥ã®ïŒâ
ã¢ããâïŒâïŒïŒâã¡ãã«ããšãã«ïŒãšã¿ã³ãåŒ
ïŒâïŒïŒãåã¯ïŒâã¢ããâïŒâïŒïŒâã¯ããã
ãšãã«ïŒãšã¿ã³ãåŒïŒâïŒïŒãåã³ãã³ãŸã€ã«
ãã©ã€ãèªå°äœãåŒïŒïŒããåºçºåæãšããŠäž
èšåå¿åŒïŒ¡ã«ç€ºãåæçµè·¯ã«ãã€ãŠè£œé ããããš
ãã§ããã äžèšååŒäžãR11ã¯äœçŽã¢ã«ãã«åºãè¡šããã
X1åã³X2ã¯ããããããã²ã³ååã§ãããR2ã¯
åèšã®æå³ãæããã ãåæçµè·¯ ã äžèšåæçµè·¯ã«ãããŠããŸãåŒïŒâïŒïŒã®
ïŒâã¢ããâïŒâïŒïŒâã¡ãã«ããšãã«ïŒãšã¿ã³
ãšåŒïŒïŒã®ãã³ãŸã€ã«ãã©ã€ãèªå°äœãšãåå¿
ããããããããã®åå¿ã¯éåžžãäžæŽ»æ§ææ©æº¶åª
äžãäŸãã°ãžã¯ããã¡ã¿ã³ãã¯ãããã«ã ãåå¡©
åççŽ çã®ããã²ã³åçåæ°ŽçŽ é¡ïŒãã³ãŒã³ãã
ã«ãšã³ããã·ã¬ã³çã®è³éŠæçåæ°ŽçŽ é¡ïŒããªãš
ãã«ã¢ãã³ããžã¡ãã«ã¢ããªã³ãããªãžã³çã®æ
æ©å¡©åºé¡çã®äžåã¯ãããææ©æº¶åªãçµåããç³»
ã®äžã§ã宀枩ä¹è³å æž©äžã奜ãŸããã¯çŽ15âãçŽ
100âã®æž©åºŠã«ãããŠè¡ãªãããšãã§ãããåŒ
ïŒâïŒïŒã®ååç©ãšåŒïŒïŒã®ååç©ãšã®äœ¿çš
å²åã¯ç¹ã«å¶éããããã®ã§ã¯ãªãããäžè¬ã«ã¯
åŒïŒâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠãåŒïŒïŒ
ã®ååç©ãïŒã10ã¢ã«ã奜ãŸããã¯1.1ãïŒã¢ã«
ã®ç¯å²ã§æ·»å ããã®ã奜ãŸããã çæããåŒïŒâïŒïŒã®ååç©ã¯æ¬¡ãã§è±æ°Žé
ç°ããããããã®è±æ°Žéç°ã¯éåžžçž®åå€ã®ååšäž
ã«å°ãªããšãçŽ50âã®æž©åºŠã奜é©ã«ã¯çŽ140âã
çŽ250âã®æž©åºŠã«è¡ãªãããšãã§ããã䜿çšãã
ãçž®åå€ãšããŠã¯ãäŸãã°ããªãã·å¡©åãªã³ããª
ãã·èåãªã³ãç¡«é žããªã³é žãäºé žåãªã³ãããª
ãªã³é žçãæããããäžã§ããªãã·å¡©åãªã³ãäº
é žåãªã³ã®äœ¿çšãæå©ã§ããããããçž®åå€ã¯è©²
åŒïŒâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠãå°ãªããš
ãïŒåœéã奜ãŸããã¯ïŒã10åœéã®éã§äœ¿çšãã
ããšãæãŸããã ãŸããäžèšè±æ°Žéç°åå¿ã¯æº¶åªã®äžåšäžã«è¡ãª
ãããšãã§ããããå¿ èŠã«å¿ããŠé©åœãªäžæŽ»æ§æ
æ©æº¶åªäžãäŸãã°ããã³ãŒã³ããã«ãšã³ããã·ã¬
ã³çã®äžã§è¡ãªã€ãŠãããã äžèšè±æ°Žéç°ã«ãã€ãŠåŸãããåŒïŒâïŒïŒã®
ååç©ã¯è±æ°ŽçŽ åå¿ã«ä»ããããšã«ãã€ãŠåŒïŒ
âïŒïŒã®ååç©ã«å€ãããããæ¬è±æ°ŽçŽ åå¿ã¯ã
溶åªã®äžåšäžã«åã¯é©åœãªäžæŽ»æ§æº¶åªäžãäŸãã°
ããã©ãªã³ããã³ãŒã³ããã«ãšã³ããã·ã¬ã³ãã¡
ã·ãã¬ã³çã®çåæ°ŽçŽ é¡ïŒæ°ŽïŒé ¢é žïŒïœâãã¿ã
ãŒã«ãïœâã¢ãã«ã¢ã«ã³ãŒã«ãªã©ã®ã¢ã«ã³ãŒã«é¡
çã®äžã§ãåŒïŒâïŒïŒã®ååç©ãè±æ°ŽçŽ å€ã§åŠ
çããããšã«ããè¡ãªãããã䜿çšãããè±æ°ŽçŽ
å€ãšããŠã¯ãäŸãã°ããžããšãã«ãžã¹ã«ãã€ãã
ïŒïŒïŒâãžã¯ããâïŒïŒïŒâãžã·ã¢ããã³ãŸãã
ã³ãããã©ã¯ããâïŒïŒïŒâãã³ãŸããã³ãç¡«
é»ããŒã¬ã³ãã¯ãã é žãéãã³ã¬ã³é žã«ãªãŠã ç
ãæããããäžã§ããžããšãã«ãžã¹ã«ãã€ãã奜
é©ã§ããã該è±æ°ŽçŽ å€ã®äœ¿çšéã¯ãçšããè±æ°ŽçŽ
å€ã®çš®é¡çã«ããç°ãªããäžè¬ã«ã¯ã該åŒïŒâ
ïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšãïŒåœéã
奜ãŸããã¯1.1ã10åœéã®ç¯å²å ã§äœ¿çšããããš
ãã§ããã ãŸããåå¿æž©åºŠã¯èšççã§ã¯ãªããçšããè±æ°Ž
çŽ å€ã®çš®é¡çã«å¿ããŠåºç¯ã«å€ããããšãã§ãã
ããäžè¬ã«ã¯ãçŽïŒâãçŽ300âã奜ãŸããã¯å®€
æž©ãçŽ210âéã®æž©åºŠã䜿çšããããšãã§ããã
äžèšæ¡ä»¶äžã«æ¬è±æ°ŽçŽ åå¿ã¯å€§äœ0.5ã30æéã§
çµãããããšãã§ããã ããããŠåŒïŒâïŒïŒã®ååç©ãåŸããããã®
ååç©ã¯æ¬¡ãã§ããã²ã³åããããšã«ãã€ãŠãåŒ
ïŒïŒã®ååç©ã«å€ããããšãã§ãããæ¬ããã²
ã³åã¯æº¶åªã®äžåšäžã«åã¯é©åœãªäžæŽ»æ§ææ©æº¶
åªãäŸãã°ãåå¡©åççŽ ãã¯ãããã«ã ãããŒã¯
ãããšãã¬ã³çã®ããã²ã³åçåæ°ŽçŽ ã®äžã§ãåŒ
ïŒïŒã®ååç©ãããã²ã³åå€ã§åŠçããããšã«
ããè¡ãªããããæ¬ããã²ã³ååå¿ã«ãããŠãå
å¿ãä¿é²ãããããã«ãå ã®ç §å°äžã«éé¢åºçºç
è©Šå€ãäŸãã°éé žåãã³ãŸã€ã«ã®åŠãææ©éé žã
å°éå ãåå¿ãããããšã奜ãŸããã æ¬ããã²ã³ã³åã®éã®åå¿æž©åºŠã¯ç¹ã«å¶éãã
ããã®ã§ã¯ãªããåºç¯ã«å€ãããããäžè¬ã«ã¯ã
宀枩ä¹è³åå¿æ··åç©ã®éæµæž©åºŠã奜ãŸããã¯çŽ50
âä¹è³éæµæž©åºŠéã®æž©åºŠã«ãããŠåå¿ãè¡ãªãã
ãšãæãŸããã ãŸãã䜿çšãããããã²ã³åå€ãšããŠã¯ãäŸã
ã°ïŒ®âã¯ããã³ãã¯é žã€ãããâããã¢ã³ãã¯
é žã€ããçã®ïŒ®âããé žã€ããé¡ïŒå¡©çŽ ãèçŽ ç
ã®ååç¶ããã²ã³ïŒïŒ®âããã¢ã¢ã»ãã¢ããã
âã¯ããã¢ã»ãã¢ããçã®ïŒ®âããé žã¢ããé¡ç
ãæããããäžã§ãâããã¢ã³ãã¯é žã€ããã®
䜿çšã奜ãŸããã該ããã²ã³åå€ã®äœ¿çšéã¯å³å¯
ã«å¶çŽããããã®ã§ã¯ãªããçšããããã²ã³åå€
ã®çš®é¡çã«å¿ããŠåºç¯ã«å€ããããšãã§ãããã
äžè¬ã«ã¯ãåŒïŒâïŒïŒã®ååç©ïŒã¢ã«ã«å¯Ÿã
ãŠãå°ãªããšãïŒåœéã奜ãŸããã¯ïŒãïŒåœéã®
å²åã§äœ¿çšããã®ã奜ãŸããã çæããåŒïŒïŒã®ååç©ã¯æ¬¡ãã§ãããªã«å
ããããšã«ãããåŒïŒâïŒâïœïŒã®ååç©ã«å€
ããããããã®ãããªã«ååå¿ã¯ãéåžžäžæŽ»æ§æ
æ©æº¶åªäžãäŸãã°ãžã¡ãã«ã¹ã«ããã·ãããžã¡ã
ã«ãã«ã ã¢ããããšã¿ããŒã«ãã¡ã¿ããŒã«ãå«æ°Ž
ãšã¿ããŒã«çã®äžã§ãåŒïŒïŒã®ååç©ãé©åœãª
ãããªã«åå€ã§åŠçããããšã«ããéæããããš
ãã§ããã 䜿çšå¯èœãªãããªã«åå€ãšããŠã¯ãäŸãã°ã·ã¢
ã³åãããªãŠã ãã·ã¢ã³åã«ãªãŠã ãã·ã¢ã³åé
çãæããããäžã§ãã·ã¢ã³åãããªãŠã ã奜é©
ã§ããã該ãããªã«åå€ã®äœ¿çšéã¯éåžžãåŒ
ïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšãïŒåœéã
奜ãŸããã¯1.1ãïŒåœéã®ç¯å²ãšããããšãã§ã
ãã ãŸãã該ãããªã«åã®åå¿æž©åºŠã¯èšççã§ã¯ãª
ãåºç¯ã«å€ããããšãã§ããããäžè¬ã«ã¯ãçŽïŒ
âãçŽ200âã奜ãŸããã¯ã»ãŒå®€æž©ä¹è³åå¿æ··å
ç©ã®éæµæž©åºŠéã®æž©åºŠã§åå¿ãè¡ãªãããšã奜ãŸ
ããã ããããŠåŸãããåŒïŒâïŒâïœïŒã®ååç©ã¯
ããèªäœå ¬ç¥ã®æ¹æ³ãäŸãã°éãé å¿åé¢ãæœ
åºãåçµæ¶ãã¯ãããã°ã©ãã€ãŒçã«ããåå¿æ··
åç©ããåé¢ãåã³ïŒåã¯ç²Ÿè£œããããšãã§ã
ãã ãã®åŒïŒâïŒâïœïŒã®ååç©ã¯ããèªäœé®ç
æçç掻æ§ãæããè¬å€ãšããŠã®çšéãèããã
ããã該åŒïŒâïŒâïœïŒã®ååç©ã¯ããã«å æ°Ž
å解ããããšã«ãããããé®çæçç掻æ§ã®é«ã
åŒïŒâïŒâïœïŒã®ååç©ã«å€ããããšãã§ã
ãã åŒïŒâïŒâïœïŒã®ååç©ã®å æ°Žå解ã¯ã溶åª
ã®äžåšäžã«åã¯æ°Žæ··åæ§ææ©æº¶åªäŸãã°ã¡ã¿ããŒ
ã«ããšã¿ããŒã«ãã»ããœã«ãã®åŠãã¢ã«ã³ãŒã«
é¡ãã¢ã»ãã³ãã¡ãã«ãšãã«ã±ãã³ã®åŠãã±ãã³
é¡ãããã©ããããã©ã³ããžã¡ããã·ãšã¿ã³ããž
ãªããµã³ã®åŠããšãŒãã«é¡ããžã¡ãã«ã¹ã«ããã·
ããªã©ã®ååšåã¯äžåšäžã«ãã¢ã«ã«ãªæ°Žæº¶æ¶²åã¯
é žæ°Žæº¶æ¶²ãçšããŠè¡ãªãããšãã§ããã å æ°Žå解ã«éããŠäœ¿çšãåŸãã¢ã«ã«ãªãšããŠ
ã¯ãäŸãã°ãæ°Žé žåãããªãŠã ãæ°Žé žåã«ãªãŠ
ã ãæ°Žé žåããªãŠã ãªã©ã®æ°Žé žåã¢ã«ã«ãªéå±å
ã¯æ°Žé žåã¢ã«ã«ãªåé¡éå±ãçé žãããªãŠã ãç
é žã«ãªãŠã ã®åŠãçé žã¢ã«ã«ãªéå±ãªã©ãå å«ã
ãããŸãã䜿çšãããé žãšããŠã¯ãå¡©é žãç¡«é žã
ïœâãã«ãšã³ã¹ã«ãã³é žããªã³é žãããªãã«ãªã
ã¡ã¿ã³ã¹ã«ãã³é žçãæããããã ãããé žåã¯ã¢ã«ã«ãªã¯ãåŒïŒâïŒâïœïŒã®
ååç©ïŒã¢ã«ã«å¯ŸããŠéåžžå°ãªããšãïŒåœéã奜
ãŸããã¯ïŒã50åœéã®å²åã§äœ¿çšãåŸãã å æ°Žå解ã¯çŽïŒâä¹è³åå¿æ··åç©ã®éæµæž©åºŠã«
ãããŠè¡ãªãããšãã§ããããäžè¬ã«50ã120â
ã®æž©åºŠç¯å²ã奜é©ã§ããã ããããŠãåŒïŒâïŒâïœïŒã®ååç©åã¯ãã®
å¡©ãçæãããã®ãã®ã¯åžžæ³ã«åŸããäŸãã°
éãé å¿åé¢ãæœåºãåçµæ¶ãã¯ãããã°ã©ãã€
ãŒçã«ãããåå¿æ··åç©ããåé¢ãåã³ïŒåã¯ç²Ÿ
補ããããšãã§ããã ãŸãäžæ¹ãåèšã®åŠãããŠçæããããããåŒ
ïŒâïŒâïœïŒã®ååç©ã¯ããã«ãäœçŽã¢ã«ãã«
åããããšã«ãããæ¬çºæã®åŒïŒâïŒâïœïŒã®
ååç©ãçµãŠãæçµã®åŒïŒâïŒâïœïŒã®ååç©
ã«å°ãããšãã§ããã 該äœçŽã¢ã«ãã«åã«çšãããäœçŽã¢ã«ãã«åå€
ãšããŠã¯ãèèªæã®æŽ»æ§ççŽ ååã®ã¢ã«ãã«åã®
ããã«é垞䜿çšãããã¢ã«ãã«åå€ã¯ãããã䜿
çšå¯èœã§ãããäŸãã°ãäœçŽã¢ã«ãã«ãã©ã€ã
ïŒäŸãã°ããšãŠåã¡ãã«ããšãŠåãšãã«ããšãŠå
ãããã«ãªã©ïŒãç¡«é žäœçŽã¢ã«ãã«ãšã¹ãã«ïŒäŸ
ãã°ãžã¡ãã«ç¡«é žããžãšãã«ç¡«é žãªã©ïŒãé©ããŠ
ããã ãããã¢ã«ãã«åå€ã«ããã¢ã«ãã«åã«éããŠ
ã¯ãã·ã¢ãã¡ãã«åºã®ã¡ãã¬ã³åºéšåã®ïŒåã®æ°Ž
çŽ ååã®ãã¡ïŒåã®ã¿ã容æã«äžã€éžæçã«ã¢ã«
ãã«åããããããïŒåã®æ°ŽçŽ ååããäŸãã°äž
èšåå¿åŒïŒ¢ã«ç€ºãåŠãæ¹æ³ã«åŸã€ãŠäºã掻æ§åã
ãããæãã¯å察ã«ä¿è·ããŠããããããåŸã¢ã«
ãã«åããããšãæãŸããã äžèšåŒäžãR3ã¯äœçŽã¢ã«ãã«åºãè¡šãããïŒ
ã¯ã¢ã«ã«ãªéå±ïŒäŸãã°ãããªãŠã ãã«ãªãŠã å
ã¯ãªããŠã ïŒãè¡šãããR11åã³R2ã¯åèšã®æå³
ãæããã äžèšåŒïŒâïŒâïœïŒã®ååç©ã®ã¢ã«ã«ãªéå±
æ°ŽçŽ åç©åã¯ã¢ã«ã«ãªéå±ã¢ããïŒäŸãã°æ°ŽçŽ å
ãããªãŠã ãæ°ŽçŽ åã«ãªãŠã ããããªãŠã ã¢ã
ããã«ãªãŠã ã¢ãããªã©ïŒã«ããåŠçã䞊ã³ã«ã
ãã«åŒç¶ãçé žãžïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«åã¯
ããã®é žäœçŽã¢ã«ãã«ïŒäŸãã°çé žãžã¡ãã«ãç
é žãžãšãã«ãã¯ããã®é žã¡ãã«ãã¯ããã®é žãšã
ã«ãã¯ããã®é žã€ãœãããã«ãã¯ããã®é žã€ãœã
ãã«ãªã©ïŒã«ããåŠçã¯ã段éçã«è¡ãªã€ãŠãã
ãããéåžžã¯äžæ®µéã§ãããªãã¡ãåŒïŒâïŒâ
ïœïŒã®ååç©ã«ãåžžæ³ã«åŸããã¢ã«ã«ãªéå±æ°ŽçŽ
åç©åã¯ã¢ã«ã«ãªéå±ã¢ããã®ååšäžã«ãçé žãž
ïŒäœçŽã¢ã«ãã«ïŒãšã¹ãã«åã¯ããã®é žäœçŽã¢ã«
ãã«ãäœçšãããããšã«ãããåŒïŒâïŒâïœâ
ïŒïŒã®ååç©ã«å€ããããšãã§ããã äžèšã®åå¿ã¯æº¶åªã®ååšäžåã¯äžåšäžã®ããã
ã«ãããŠãè¡ãªãããšãã§ãã溶åªã䜿çšããå Ž
åã®æº¶åªãšããŠã¯äŸãã°ãžãšãã«ãšãŒãã«ããã
ã©ããããã©ã³ããžãªããµã³ããžã¡ããã·ãšã¿
ã³ããžãšãã¬ã³ã°ãªã³ãŒã«ãžã¡ãã«ãšãŒãã«ãªã©
ã®ãšãŒãã«é¡ããããã¯ãžã¡ãã«ã¹ã«ããã·ããª
ã©ã®ã¹ã«ããã·ãé¡ããã³ãŒã³ããã«ãšã³ãªã©ã®
è³éŠæçåæ°ŽçŽ é¡ãªã©ãé©ããŠãããåå¿æž©åºŠãš
ããŠã¯çŽïŒâä¹è³åå¿æ··åç©ã®éæµæž©åºŠã奜ãŸã
ãã¯ïŒã180âã®ç¯å²ã®æž©åºŠã奜ãŸãããæå宀
æž©ã§ãã°ããæŸçœ®ããŠãããŠãã50ã150âã®æž©
床ã«å ç±ããªããåå¿ãè¡ãªãããšãã§ããã ããããŠåŸããã該ã·ã¢ãã¡ãã«åºã®ã¡ãã¬ã³
éšåã®æ°ŽçŽ ååã®ïŒã€ãã¢ã«ã³ãã·ã«ã«ããã«åº
ïŒâCOOR3ïŒã§ä¿è·ãããåŒïŒâïŒâïœâïŒïŒ
ã®ååç©ã¯ã次ãã§åèšããåŠãäœçŽã¢ã«ãã«å
å€ãšåå¿ããããããã ãã®ã¢ã«ãã«ååå¿ããŸã溶åªã®ååšäžåã¯äž
åšäžã®ãããã«ãããŠãè¡ãªãããšãã§ãã䜿çš
ãåŸã溶åªãšããŠã¯äžèšã®ãã®ãæãããããã
ã®ã¢ã«ãã«ååå¿ã®æž©åºŠã¯èšççã§ã¯ãªãã䜿çš
ããã¢ã«ãã«åå€ã®çš®é¡ã«å¿ããŠåºç¯ã«å€ããã
ãšãã§ããããäžè¬ã«å®€æž©ä¹è³åå¿æ··åç©ã®éæµ
枩床ãç¹ã«50ã150âã®ç¯å²ã奜ãŸããã 該äœçŽã¢ã«ãã«åå€ã®äœ¿çšéããŸãèšççãªã
ã®ã§ã¯ãªããäœçŽã¢ã«ãã«åå€ã®çš®é¡ãåå¿æ¡ä»¶
çã«å¿ããŠåºç¯ã«å€ããããšãã§ããããäžè¬ã«
åŒïŒâïŒâïœâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°
ãªããšã1.0ã¢ã«ã奜ãŸããã¯ïŒã10ã¢ã«ã®å²å
ã§äœ¿çšããããšãã§ããã ããããŠåŸãããåŒïŒâïŒâïœâïŒïŒã®ã¢ã«
ãã«åçæç©ã¯å æ°Žå解ããããšã«ãããäŸãã°
ææ©æº¶åªãæ°Žåã¯ãããã®æ··åç©äžã§ãã«ã»ã€ãœ
ãŒããªã©ã®ã¢ã«ã«ãªæ°Žæº¶æ¶²æãã¯å¡©é žãç¡«é žãªã©
ã®ç¡æ©é žã®ååšäžã«å ç±ããããšã«ããã容æã«
åŒïŒâïŒâïœâïŒïŒã®ååç©ã«è»¢æããã次ã
ã§ãã®ååç©ã¯ãé垞溶åªã®äžåšäžã«äžã€ã¢ã«ã«
ãªãç¹ã«æ°Žé žåãããªãŠã ãæ°Žé žåã«ãªãŠã ã®åŠ
ãã¢ã«ã«ãªéå±æ°Žé žåç©ã®ååšäžåã¯äžåšäžã«å
ç±ããŠè±çé žããããšã«ãããç®çãšããR1ã
äœçŽã¢ã«ãã«åºãè¡šããå Žåã®åŒïŒïŒã®åå
ç©ãããªãã¡åŒïŒâïŒâïœïŒã®ååç©ã«å€ãã
ããšãã§ããããã®å Žåã®å ç±æž©åºŠãšããŠã¯ã該
ã¢ã«ã«ãªã®äžåšäžã§ã¯ãåŒïŒâïŒâïœâïŒïŒã®
ååç©ã®èç¹ä»¥äžçæããåŒïŒâïŒâïœïŒã®å
åç©ã®å解枩床æªæºãšããããšãã§ããäžæ¹ã¢ã«
ã«ãªã®ååšäžã§ã¯ããã¡ããèç¹ä»¥äžã«å ç±ãã
ããšãã§ããããäžè¬ã«èç¹ããäœã枩床ãäŸã
ã°50ã120âã®æž©åºŠã«å ç±ããããšã«ãã€ãŠãè±
çé žãéæããããšãã§ããã ãã®åŒïŒâïŒâïœïŒã®ååç©ã¯ããèªäœé®ç
æçç掻æ§ãæããè¬å€ãšããŠäœ¿çšãããããã
ãã«å æ°Žå解ããããšã«ãããé®çæçç掻æ§ã
ããé«ããåŒïŒâïŒâïœïŒã®ååç©ã«å€ããã
ãšãã§ããããã®åŒïŒâïŒâïœïŒã®ååç©ã®å
æ°Žå解ã¯ãåèšåŒïŒâïŒâïœïŒã®ååç©ã®å æ°Ž
å解ã«ã€ããŠåè¿°ãããšåæ§ã«ããŠè¡ãªãããšã
ã§ããã ãªããåŒïŒâïŒâïœâïŒïŒã®ååç©ã®å æ°Žå
解ãåèšè±çé žåå¿ã«ã€ããŠè¿°ã¹ã枩床æ¡ä»¶äžã«
ãããŠè¡ãªãã°ãåŒïŒâïŒâïœïŒã®ç®çååç©
ãäžæ°ã«åŸãããšãã§ããã ããã«äžèšåå¿åŒïŒ¢ã§ç€ºãäžé£ã®åå¿ã«ãã
ãŠãåŒïŒâïŒâïœïŒã®ååç©ãã該åŒïŒâïŒ
âïœïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠïŒåœéåã¯ãã以
äžã®ã¢ã«ã«ãªéå±æ°ŽçŽ åç©åã¯ã¢ã«ã«ãªéå±ã¢ã
ããäœçšãããããšã«ããæå©ã«åŸãããäžèšåŒ åŒäžãR2åã³ïŒã¯åèšã®æå³ãæããã ã®ååç©ã«åèšããåŠãäœçŽã¢ã«ãã«åå€ãäœçš
ãããããšã«ãã€ãŠããåŒïŒâïŒâïœïŒã®åå
ç©ã補é ããããšãã§ããã äžèšåŒïŒâïŒâïœâïŒïŒã®ååç©ã®ã¢ã«ãã«
åã¯æº¶åªã®äžåšäžåã¯äžèšããåŠã溶åªã®ååšäž
ã«ãåŒïŒâïŒâïœâïŒïŒã®ååç©ã«äœçŽã¢ã«ã
ã«åå€ãåå¿ãããããšã«ããè¡ãªãããšãã§ã
ãããã®éã®åå¿æž©åºŠã¯èšççã§ã¯ãªããçšãã
ã¢ã«ãã«åå€ã®çš®é¡çã«å¿ããŠåºç¯ã«å€ããããš
ãã§ããããäžè¬ã«â10âä¹è³åå¿æ··åç©ã®éæµ
枩床ã奜ãŸããã¯ïŒâã30âã®ç¯å²ãé©åºŠã§ã
ãããŸããäœçŽã¢ã«ãã«åå€ã®äœ¿çšéãèšççã§
ã¯ãªããåºç¯ã«å€ããããšãã§ããããäžè¬ã«åŒ
ïŒâïŒâïœâïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãª
ããšãçã¢ã«ãç¹ã«ïŒã10ã¢ã«ã®å²åã§äœ¿çšãã
ã®ãæå©ã§ããã çæããåŒïŒâïŒâïœïŒã®ååç©ã¯åèšãšå
æ§ã«å æ°Žå解ããããšã«ãããåŒïŒâïŒâïœïŒ
ã®ååç©ã«å€ããããšãã§ããã ããã«ãŸãå¥æ³ãšããŠãåèšã®åŠãããŠåŸãåŒ
ïŒâïŒâïœïŒã®ååç©ã«å¯ŸããŠãåèšåå¿åŒïŒ¢
ã«ç€ºãäœçŽã¢ã«ãã«ååå¿ãè¡ãªãããšãã§ãã
ããã«ãã€ãŠããåŒïŒâïŒâïœïŒã®ååç©ãåŸ
ãããã 以äžã®åŠãããŠåŸãããåŒïŒâïŒâïœïŒã®å
åç©ã¯åèšã®åŠãããŠåå¿æ··åç©ããåé¢ãå
ã³ïŒåã¯ç²Ÿè£œããããšãã§ããã ãåæçµè·¯ ã åèšåå¿åŒïŒ¡ã«ãããåæçµè·¯ã«ãããŠãåŒ
ïŒâïŒïŒã®ïŒâã¢ããâïŒâïŒïŒâã¯ããããšã
ã«ïŒãšã¿ã³ãšåŒïŒïŒã®ãã³ãŸã€ã«ãã©ã€ãèªå°
äœã®åå¿ãåŸãããåŒïŒâïŒïŒã®ååç©ã®è±æ°Ž
éç°ãããã«æ¬¡ãåŒïŒâïŒïŒã®ååç©ã®è±æ°ŽçŽ
ã¯ãäžèšåæçµè·¯ã«ãããŠè¿°ã¹ããšåæ§ã«ããŠ
è¡ãªãããšãã§ããã ããããŠåŸãããåŒïŒâïŒïŒã®ååç©ã¯ãã
ããªã«åããããšã«ããåŒïŒïŒã®ååç©ã«å€ã
ãããšãã§ããããã®ãããªã«åã¯ãåèšåæçµ
è·¯ã«ãããŠåŒïŒïŒã®ååç©ã®ãããªã«åã«ã€
ããŠåè¿°ãããšã»ãŒåæ§ã®æ¡ä»¶äžã«è¡ãªãããšã
ã§ããããã«ããåŒïŒïŒã®ååç©ãåŸãããã ãã®åŒïŒïŒã®ååç©ã¯æ¬¡ãã§å æ°Žå解ããã
ãšã«ããåŒïŒïŒã®ååç©ã«å€ããããããã®å
æ°Žå解ã¯ãåŒïŒâïŒâïœïŒã®ååç©ã®å æ°Žå解
ã«ã€ããŠåè¿°ãããšåæ§ã«ããŠè¡ãªãããšãã§
ããããã«ãã€ãŠåŒïŒïŒã®ååç©ãçæããã
ãããšãã§ããã åŸãããåŒïŒïŒã®ååç©åã¯ãã®ãšã¹ãã«ã¯
éå ããããšã«ããåŒïŒïŒã®ååç©ã«å€ããã
ããåŒïŒïŒã®ååç©åã¯ãã®ãšã¹ãã«ã®éå
ã¯ãéåžžãäžæŽ»æ§æº¶åªãäŸãã°ãšãã«ãšãŒãã«ã
ãããã«ãšãŒãã«ãããã©ããããã©ã³ããžãªã
ãµã³ããžã¡ããã·ãšã¿ã³çã®ãšãŒãã«é¡ïŒãã³ãŒ
ã³ããã«ãšã³ããã·ã¬ã³çã®è³éŠæçåæ°ŽçŽ çã®
äžã§ãåŒïŒïŒã®ååç©åã¯ãã®ãšã¹ãã«ãã宀
æž©ä¹è³åå¿æ··åç©ã®éæµæž©åºŠã«ãããŠããªããŠã
ã¢ã«ãããŠã ãããªãããžãããâãã¹ïŒïŒâã¡
ããã·ãšããã·ïŒã¢ã«ãããŠã ãããªãŠã çã®åŠ
ãé¯éå±æ°ŽçŽ åç©ãšæ¥è§Šããããããšã«ããè¡ãª
ãããšãã§ããã çæããåŒïŒïŒã®ååç©ã¯ããã«ããã²ã³å
ããããšã«ããåŒïŒïŒã®ååç©ã«ããããšãã§
ããããã®ããã²ã³åã¯ã溶åªã®äžåšäžã«åã¯é©
åœãªæº¶åªäŸãã°æ°Žããžã¯ããã¡ã¿ã³ãã¯ãããã«
ã ãåå¡©åççŽ ããã³ãŒã³ããã«ãšã³ããã·ã¬ã³
çã®ååšäžã«ãåŒïŒïŒã®ååç©ãããã²ã³åå€
ã§åŠçããããšã«ããè¡ãªãããšãã§ããã çšãããããã²ã³åå€ãšããŠã¯ãäŸãã°å¡©åæ°Ž
çŽ ãããªãã«ã¯ããªããäžå¡©åãªã³ãèåæ°ŽçŽ ã
ããªãã«ãããããäžèåãªã³ããªãã·èåãªã³
çãæãããããããããã²ã³åå€ã¯ãåŒïŒïŒ
ã®ååç©ïŒã¢ã«ã«å¯ŸããŠäžè¬ã«å°ãªããšãïŒåœ
éã奜ãŸããã¯1.1ã10åœéã®ç¯å²ã§äœ¿çšããã
ãšãã§ããã ãŸããæ¬ããã²ã³åã¯äžè¬ã«ã»ãŒå®€æž©ä¹è³åå¿
æ··åç©ã®éæµæž©åºŠã奜ãŸããã¯çŽ50âãçŽ150â
ã®æž©åºŠã«ãããŠãçŽïŒã10æéè¡ãªãã®ãæå©ã§
ããã ããããŠåŸãããåŒïŒïŒã®ååç©ã¯ãåèšå
æçµè·¯ã«èšèŒããåŠãããŠãåŒïŒâïŒâïœïŒ
åã³ïŒâïŒâïœïŒäžŠã³ã«åŒïŒâïŒâïœïŒåã³
ïŒâïŒâïœïŒã®ååç©ã«å€ããããšãã§ããã ããã«ãäžèšåæçµè·¯ã®å·¥çšéäžã§åŸããã
åŒïŒâïŒïŒã®ååç©ãããªãã¡äžèšåŒ åŒäžãR2ã¯åèšã®æå³ãæããã ã§ç€ºãããååç©ã¯ãã¢ã»ããããªã«ïŒCH3CNïŒ
ãšåå¿ãããããšã«ãããçŽæ¥ã«äžèšåŒ åŒäžãR2ã¯åèšã®æå³ãæããã ã§ç€ºãããååç©ã«å€ããããšãã§ããã äžèšåå¿ã¯é©åœãªäžæŽ»æ§æº¶åªäžãäŸãã°æ¶²äœã¢
ã³ã¢ãã¢ãã¡ãã«ã¢ãã³ããšãã«ã¢ãã³ããžã¡ã
ã«ã¹ã«ããã·ãããžã¡ãã«ãã«ã ã¢ããçã®äž
ã§ãåŒïŒâïŒïŒã®ååç©ãã¢ã»ããããªã«ãšæ¥
觊ããããããšã«ããè¡ãªãããšãã§ããã åå¿æž©åºŠã¯èšççã§ã¯ãªãåºç¯ã«å€ããããšã
ã§ããããäžè¬ã«ã¯â40âã200âã奜ãŸããã¯
â30âä¹è³å®€æž©éã®æž©åºŠã«ãããŠè¡ãªãããšãæ
ãŸããããŸããã¢ã»ããããªã«ã¯éåžžãåŒïŒâ
ïŒïŒã®ååç©ïŒã¢ã«ã«å¯ŸããŠå°ãªããšãïŒã¢ã«ã
奜ãŸããã¯1.5ãïŒã¢ã«ã®éã§äœ¿çšããã®ãæå©
ã§ããã äžèšã¢ã»ããããªã«ãšã®åå¿ã¯ãæå©ã«ã¯ãè±
ããã²ã³åå€ãšããŠãå°ãªããšãåœéä¹è³éå°é
ã®äŸãã°ãããªãŠã ã¢ãããã«ãªãŠã ã¢ãããã«
ãªãŠã ãããã·ãããããªãŠã ã¡ããã·ããã«ãª
ãŠã ãšããã·ãçã®ååšäžã«ãäžã€ä¿é²å€ãšããŠ
å°éã®äžå¡©åéçã®ååšäžã«è¡ãªãããã ããããŠåŸãããåŒïŒâïŒâïœïŒã®ååç©
ã¯ãåèšãšåæ§ã«ããŠãåŒïŒâïŒâïœïŒäžŠã³ã«
åŒïŒâïŒâïœïŒåã³ïŒâïŒâïœïŒã®ååç©ã«
å€ããããšãã§ããã 以äžè¿°ã¹ãåŠãããŠè£œé ãããåŒïŒïŒãããª
ãã¡ãåŒïŒâïŒâïœïŒåã³ïŒâïŒâïœïŒãã®
ååç©ã¯éåžžã®æ¹æ³ãäŸãã°æœåºãéãåçµ
æ¶ãã¯ãããã°ã©ãã€ãŒçã«ããåé¢ç²Ÿè£œããã
ãšãã§ããã åŒïŒïŒã®ååç©ã¯ãéé¢é žåã¯éé¢å¡©åºã®ç¶
æ ã«ãããšãã«ã¯ãåžžæ³ã«åŸãããã®å¡©ã«å€ãã
ããšãã§ãããŸãéã«ãå¡©ã®ç¶æ ã«ãããšãã«
ã¯ãåžžæ³ã«åŸãéé¢é žåã¯éé¢å¡©åºã«å€ããããš
ãã§ããã 以äžã«èª¬æããæ¬çºæã®åŒïŒïŒã®ååç©ã¯äž
è¬ã«ãåªããé®çåã³ïŒåã¯æççäœçšãæããŠ
ããããã®äžã§ãç¹ã«ãR1ãæ°ŽçŽ ååã§ããå Ž
åã®åŒïŒïŒã®ååç©åã¯ãã®å¡©ã¯ãçŸåšé®çæ
ççå€ãšããŠèšåºå»åŠäžæšæºçãªãã®ãšããŠèªã
ãããŠããããšãã«ãã¿ãŸã³ãåã³ã€ã³ãã¡ã¿ã·
ã³ãããã¯ããã«åªããé®çåã³ïŒåã¯æççäœ
çšãæããŠãããããããã®äžãåŸæ¥ããå®çšã«
äŸãããŠããã¢ã¹ããªã³ãããšãã«ãã¿ãŸã³ãã€
ã³ãã¡ã¿ã·ã³çã®å ¬ç¥ã®é®çæççå€ã®ãããã
ããªãã²ã©ãæ¶ååšé害ã䌎ãã®ã«å¯ŸããŠãæ¬çº
æã®äžèšåŒïŒïŒã®ååç©ã¯æ¶ååšé害ãéåžžã«
埮匱ã§ãããšãããæ²»çåŠçã«é¡èãªå©ç¹ãæã
ãŠããã æ¬çºæã®äžèšååç©ãéåžžã«åªããé®çäœçšå
ã³æççäœçšãæããããšã䞊ã³ã«æ¥µããŠåŸ®åŒ±ãª
æ¶ååšé害èªçºäœçšãããããªãããšã¯ã以äžã®
åç©å®éšã«ããç«èšŒãããã ãªãã以äžã®åç©å®éšã«çšããæ¬çºæã®ååç©
ã¯æ¬¡ã®ç¬Šå·ã§ä»£è¡šãããã ååç© ïŒ¡ïŒïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããªã³â
ïŒâã€ã«é ¢é ž ïŒïŒâïŒïŒâã¡ããã·ããšãã«ïŒã€ãœãããªã³
âïŒâã€ã«é ¢é ž ïŒïŒâãïŒâïŒïŒâã¯ããããšãã«ïŒã€ãœãããª
ã³âïŒâã€ã«ãããããªã³é ž ïŒïŒâããšãã«ã€ãœãããªã³âïŒâã€ã«é ¢é ž (1) é®çäœçš äœé18ã22ïœã®ddYç³»éæ§ããŠã¹ãïŒçŸ€10å¹ãš
ããŠçšããå ãã被æ€è¬ãåæäžéã«å¿ããŠçµå£
æäžãããçµå£æäžã¯è¢«æ€è¬ã溶åªïŒ0.5ïŒ ã«ã«
ããã·ã¡ãã«ã»ã«ããŒã¹åã³2.0ïŒ ãã€ã³80ã溶
解ãã氎溶液ïŒã«åæ£ããããã®æžæ¿æ¶²ããŸã³ã
ã«ããæäžããã被æ€è¬æäžïŒæéåŸã«0.6ïŒ é ¢
é žãè ¹è å ã«0.1mlïŒ10ïœäœéã®éã§æäžããæ
äžåŸ20åéã«äºã€ãŠçããã©ã€ãžã³ã°
ïŒwrithingïŒæ°ã枬å®ããã溶åªæäžå¯Ÿç §çŸ€ïŒè¢«
æ€è¬ãé€ãã溶åªã®ã¿ã®æäžçŸ€ïŒã«å¯Ÿãã被æ€è¬
æäžçŸ€ã®æå¶çãäžèšåŒã«åŸã€ãŠæ±ãããã®æ°å€
ãããªãããã€ãŒã«ãâãŠã€ã«ã³ãã¯ãœã³
ïŒLitchfieldâWilcoxonïŒæ³ã«åŸã€ãŠED50å€ãç®
åºããã被æ€è¬ã®åã ã®ED50å€ãäžèšè¡šïŒã«ç€º
ãã
ãè¡šã
ãå¹³åã©ã€ãžã³ã°æ°ã
ãåã©ã€ãžã³ã°æ° ã
æå¶çïŒïŒ ïŒïŒ
ãåã©ã€ãžã³ã°æ° ã
æå¶çïŒïŒ ïŒïŒ
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ äžè¬åŒ åŒäžãR1ã¯æ°ŽçŽ åååã¯äœçŽã¢ã«ãã«åºãè¡š
ãããR2ã¯æ°ŽçŽ ååãããã²ã³åååã¯äœçŽã¢
ã«ã³ãã·åºãè¡šããã ã§ç€ºãããïŒâããšãã«ã€ãœãããªã³èªå°äœåã³
ãã®å¡©ã ïŒ R1ãæ°ŽçŽ åååã¯ã¡ãã«åºãè¡šãããR2ã
æ°ŽçŽ ååãå¡©çŽ åååã¯ã¡ããã·åºãè¡šããç¹èš±
è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã ïŒ R1ãæ°ŽçŽ ååã§ãããR2ã¯æ°ŽçŽ ååãå¡©çŽ
åååã¯ã¡ããã·åºãè¡šããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒ
é èšèŒã®ååç©ã ïŒ åŒ ã§ç€ºãããååç©åã³ãã®ççåŠçã«èš±å®¹ããã
å¡©ã§ããç¹èš±è«æ±ã®ç¯å²ç¬¬ïŒé èšèŒã®ååç©ã
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP16002678A JPS5587771A (en) | 1978-12-27 | 1978-12-27 | 1-phenylisoquinoline derivative |
EP79105326A EP0013411A1 (en) | 1978-12-27 | 1979-12-21 | Isoquinoline derivatives, process for their preparation and pharmaceutical compositions containing them |
AU54179/79A AU5417979A (en) | 1978-12-27 | 1979-12-24 | Isoquinoline derivatives and their use as anti-inflammatory and analgesic agents |
US06/107,613 US4337256A (en) | 1978-12-27 | 1979-12-27 | 1-Phenyl isoquinoline-5-acetic acid compounds and analgesic compositions thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP16002678A JPS5587771A (en) | 1978-12-27 | 1978-12-27 | 1-phenylisoquinoline derivative |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5587771A JPS5587771A (en) | 1980-07-02 |
JPS633857B2 true JPS633857B2 (ja) | 1988-01-26 |
Family
ID=15706350
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP16002678A Granted JPS5587771A (en) | 1978-12-27 | 1978-12-27 | 1-phenylisoquinoline derivative |
Country Status (4)
Country | Link |
---|---|
US (1) | US4337256A (ja) |
EP (1) | EP0013411A1 (ja) |
JP (1) | JPS5587771A (ja) |
AU (1) | AU5417979A (ja) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS57203068A (en) * | 1981-06-08 | 1982-12-13 | Teikoku Hormone Mfg Co Ltd | Novel 1-phenylisoquinoline derivative |
DE3206660A1 (de) * | 1982-02-25 | 1983-09-01 | Basf Ag, 6700 Ludwigshafen | Verfahren zur herstellung von o-acylamidomethylbenzyl-halogeniden |
US4520025A (en) * | 1982-07-21 | 1985-05-28 | William H. Rorer, Inc. | Bicyclic nitrogen heterocyclic ethers and thioethers, and their pharmaceutical uses |
US4518779A (en) * | 1982-09-27 | 1985-05-21 | Pennwalt Corporation | 1,2,3,4-Tetrahydro-1-aminomethyl-4-phenyl isoquinolines |
KR930703259A (ko) * | 1990-12-17 | 1993-11-29 | ìë² ë¥Ží¬ì€ ë¹í¬ë¬Žì€ ììë€ì€ ì©šì€ížëŒí | ìŽê· ì± ìŽìíŽë늰 ì ë첎 |
ES2319886T3 (es) * | 2002-02-20 | 2009-05-14 | Abbott Laboratories | Compuestos azabiciclicos condensados que inhiben el sutipo 1 del receptor valinoide (vr1). |
US6933311B2 (en) * | 2003-02-11 | 2005-08-23 | Abbott Laboratories | Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor |
TW200824687A (en) | 2006-08-25 | 2008-06-16 | Abbott Lab | Compounds that inhibit TRPV1 and uses thereof |
WO2008036540A2 (en) | 2006-09-20 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
JP2012525386A (ja) | 2009-05-01 | 2012-10-22 | ã¢ãšãªãšã»ãã¡ãŒãã·ã¥ãŒãã£ã«ã«ãºã»ã€ã³ã³ãŒãã¬ãŒããã | çŸæ£ã®æ²»çã®ããã®äºéæ©æ§é»å®³å€ |
CN109528721B (zh) | 2013-03-15 | 2021-10-01 | ç±çå¶è¯å ¬åž | èåæ²»ç |
US9643927B1 (en) | 2015-11-17 | 2017-05-09 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
US10550087B2 (en) | 2015-11-17 | 2020-02-04 | Aerie Pharmaceuticals, Inc. | Process for the preparation of kinase inhibitors and intermediates thereof |
KR102568082B1 (ko) | 2016-08-31 | 2023-08-17 | ììŽëŠ¬ íë§ìí°ì»¬ìŠ, ìžìœí¬ë ìŽí°ë | ìê³Œì© ì¡°ì±ë¬Œ |
AU2018243687C1 (en) | 2017-03-31 | 2020-12-24 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
US11427563B2 (en) | 2018-09-14 | 2022-08-30 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
CN117466729A (zh) * | 2023-12-28 | 2024-01-30 | å±±äžåœéŠè¯äžæéå ¬åž | äžç§2,4,5-äžæ°è¯ä¹é žçåææ¹æ³ |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3991061A (en) * | 1975-07-16 | 1976-11-09 | G. D. Searle & Co. | Azanaphthaleneacetic acid derivatives |
JPS5398973A (en) * | 1976-12-30 | 1978-08-29 | Chinoin Gyogyszer Es Vegyeszet | Isoquinolineacetoamide derivative |
JPS53101382A (en) * | 1977-02-14 | 1978-09-04 | Teijin Ltd | Tetrahydroisoquinoline-3-acetic acids and process for their preparation |
-
1978
- 1978-12-27 JP JP16002678A patent/JPS5587771A/ja active Granted
-
1979
- 1979-12-21 EP EP79105326A patent/EP0013411A1/en not_active Ceased
- 1979-12-24 AU AU54179/79A patent/AU5417979A/en not_active Abandoned
- 1979-12-27 US US06/107,613 patent/US4337256A/en not_active Expired - Lifetime
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3991061A (en) * | 1975-07-16 | 1976-11-09 | G. D. Searle & Co. | Azanaphthaleneacetic acid derivatives |
JPS5398973A (en) * | 1976-12-30 | 1978-08-29 | Chinoin Gyogyszer Es Vegyeszet | Isoquinolineacetoamide derivative |
JPS53101382A (en) * | 1977-02-14 | 1978-09-04 | Teijin Ltd | Tetrahydroisoquinoline-3-acetic acids and process for their preparation |
Also Published As
Publication number | Publication date |
---|---|
JPS5587771A (en) | 1980-07-02 |
US4337256A (en) | 1982-06-29 |
AU5417979A (en) | 1980-07-03 |
EP0013411A1 (en) | 1980-07-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JPS633857B2 (ja) | ||
US3896145A (en) | Carbazoles | |
FI66368B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 6,1-dihydro-11-oxodibens(b,e)oxepin-2-aettiksyraderivat | |
JPS582935B2 (ja) | ïŒââã¢ãã€ã«ããâã«èªå°äœã®è£œé æ³ | |
HU176955B (hu) | Sposob poluchenija 4-skobka-di-n-propil-skobka zakryta-amino-1,3,4,5-tetragidro-benz-kvadratnaja skobka-cd-kvadratnaja skobka zakryta-indolov | |
US4457927A (en) | Pyrido[2,1-b]quinazolinone derivatives and the preparation and use thereof | |
GB1592996A (en) | Acylated pyrrole carboxylic acids and derivatives thereof | |
US4247706A (en) | Dibenzothiepin derivatives and a process for producing the same | |
US4616028A (en) | Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid derivatives, compositions and use | |
US4496735A (en) | Certain pyridyloxy-or-thio-phenyl propenoic acid derivatives | |
EP0350990A1 (en) | Pyridazinone derivatives | |
EP0008446B1 (en) | Process for the preparation of carbazoles and novel carbazole derivatives utilized therein | |
Santilli et al. | 8, 9, 10, 11-Tetrahydro-12H-benzo [5, 6] quinoxalino-[2, 3-e][1, 4] diazepin-12-ones. Examples of a New Heterocyclic Ring System | |
JPH07121944B2 (ja) | â²äžïŒâŒâã¡ãã«âïŒïŒÎ±âã¡ããã·ã«ããªã»ã«ãŽãŒã«ã®è£œé æ¹æ³ | |
SU577994A3 (ru) | СпПÑПб пПлÑÑеМО пÑПОзвПЎМÑÑ ÑеМПÑОазОМа ОлО ÐžÑ ÑПлей | |
HU192661B (en) | Process for preparing sulphur containing derivatives of 6-oxo-prostaglandin | |
US4584312A (en) | Substituted 2,3,4,9-tetrahydro-1H-carbazole-1-acetic acid, compositions and use | |
HU187471B (en) | Process for preparing n-acyl-triptamine derivatives and pharmaceutical compositions containing them as active agents | |
US3390150A (en) | Process for the preparation of 1-(beta-hydroxyethyl)-5-nitroimidazole-2-carboxylic acid gamma-lactone | |
US3763169A (en) | Isonipecotic acid compounds | |
US3644392A (en) | 1-substituted-5-nitroimidazole-2-carboximidates | |
US3972883A (en) | 1,6-Dimethyl-8β-[2' or 3'-pyrroyloxyethyl or substituted pyrroyloxyethyl]-10α-methoxyergolene compounds | |
US4697013A (en) | Condensed as-triazine derivatives | |
CA1099721A (en) | 1-phenyl-4-acetoxy-1,2-dihydroquinolin-2-one compounds and processes for their preparation | |
US3657281A (en) | 4-aryl-1-dibenzofuran-alkanoic acids and salts thereof |