JPS6212221B2 - - Google Patents
Info
- Publication number
- JPS6212221B2 JPS6212221B2 JP50060111A JP6011175A JPS6212221B2 JP S6212221 B2 JPS6212221 B2 JP S6212221B2 JP 50060111 A JP50060111 A JP 50060111A JP 6011175 A JP6011175 A JP 6011175A JP S6212221 B2 JPS6212221 B2 JP S6212221B2
- Authority
- JP
- Japan
- Prior art keywords
- formula
- acid
- compounds
- compound
- reaction
- 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 76
- 239000002253 acid Substances 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- QBDOBFNOPHZPCZ-UHFFFAOYSA-N 1-benzazocine Chemical class N1=CC=CC=CC2=CC=CC=C21 QBDOBFNOPHZPCZ-UHFFFAOYSA-N 0.000 claims 1
- 150000007514 bases Chemical class 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 65
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- 238000012360 testing method Methods 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 23
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- -1 Methoxy, ethoxy, propoxy, isopropoxy Chemical group 0.000 description 18
- 238000002844 melting Methods 0.000 description 17
- 230000008018 melting Effects 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- 239000007858 starting material Substances 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 14
- 230000000202 analgesic effect Effects 0.000 description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 229910052739 hydrogen Inorganic materials 0.000 description 11
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- 229940035676 analgesics Drugs 0.000 description 8
- 239000000730 antalgic agent Substances 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 125000005210 alkyl ammonium group Chemical group 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000007363 ring formation reaction Methods 0.000 description 6
- 238000012216 screening Methods 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- 208000031481 Pathologic Constriction Diseases 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 230000003187 abdominal effect Effects 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000036262 stenosis Effects 0.000 description 5
- 208000037804 stenosis Diseases 0.000 description 5
- MMWRGWQTAMNAFC-UHFFFAOYSA-N 1,2-dihydropyridine Chemical compound C1NC=CC=C1 MMWRGWQTAMNAFC-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000906446 Theraps Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- RFQDDXWZZVRLKO-UHFFFAOYSA-N benzo[g]quinoline Chemical compound N1=CC=CC2=CC3=CC=CC=C3C=C21 RFQDDXWZZVRLKO-UHFFFAOYSA-N 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 150000004795 grignard reagents Chemical class 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
- RLQZIECDMISZHS-UHFFFAOYSA-N 2-phenylcyclohexa-2,5-diene-1,4-dione Chemical compound O=C1C=CC(=O)C(C=2C=CC=CC=2)=C1 RLQZIECDMISZHS-UHFFFAOYSA-N 0.000 description 3
- OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 150000003840 hydrochlorides Chemical group 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- PSXRWZBTVAZNSF-UHFFFAOYSA-N hydron;quinoline;chloride Chemical compound Cl.N1=CC=CC2=CC=CC=C21 PSXRWZBTVAZNSF-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- 239000003887 narcotic antagonist Substances 0.000 description 3
- 125000001979 organolithium group Chemical group 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
- PMNLUUOXGOOLSP-UHFFFAOYSA-N 2-mercaptopropanoic acid Chemical compound CC(S)C(O)=O PMNLUUOXGOOLSP-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 239000007818 Grignard reagent Substances 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- 230000003042 antagnostic effect Effects 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 125000001033 ether group Chemical group 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- SEOVTRFCIGRIMH-UHFFFAOYSA-N indole-3-acetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CNC2=C1 SEOVTRFCIGRIMH-UHFFFAOYSA-N 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229910003002 lithium salt Inorganic materials 0.000 description 2
- 159000000002 lithium salts Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- UPVCRZBVVOXMDA-UHFFFAOYSA-N trimethylazanium;formate Chemical compound OC=O.CN(C)C UPVCRZBVVOXMDA-UHFFFAOYSA-N 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- NAOLWIGVYRIGTP-UHFFFAOYSA-N 1,3,5-trihydroxyanthracene-9,10-dione Chemical compound C1=CC(O)=C2C(=O)C3=CC(O)=CC(O)=C3C(=O)C2=C1 NAOLWIGVYRIGTP-UHFFFAOYSA-N 0.000 description 1
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- VBSTXRUAXCTZBQ-UHFFFAOYSA-N 1-hexyl-4-phenylpiperazine Chemical compound C1CN(CCCCCC)CCN1C1=CC=CC=C1 VBSTXRUAXCTZBQ-UHFFFAOYSA-N 0.000 description 1
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- FVBZEIGTBYGKLB-UHFFFAOYSA-N 10-azatetracyclo[9.3.1.02,7.09,14]pentadeca-2,4,6-triene Chemical compound N1C2CC3=CC=CC=C3C3C2CCC1C3 FVBZEIGTBYGKLB-UHFFFAOYSA-N 0.000 description 1
- ZJFPQVBARDXZPX-UHFFFAOYSA-N 2,6-methano-3-benzazocine Chemical group C1=CC=C2C(C3)=CC=NC3=CC2=C1 ZJFPQVBARDXZPX-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- VYWYYJYRVSBHJQ-UHFFFAOYSA-N 3,5-dinitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 VYWYYJYRVSBHJQ-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- DMGLUDJTJZXMMG-UHFFFAOYSA-N 3-benzazocine Chemical compound C1=CN=CC=CC2=CC=CC=C21 DMGLUDJTJZXMMG-UHFFFAOYSA-N 0.000 description 1
- YCTDZYMMFQCTEO-UHFFFAOYSA-N 3-octene Chemical compound CCCCC=CCC YCTDZYMMFQCTEO-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- VJXRKZJMGVSXPX-UHFFFAOYSA-N 4-ethylpyridine Chemical compound CCC1=CC=NC=C1 VJXRKZJMGVSXPX-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- DJHGAFSJWGLOIV-UHFFFAOYSA-N Arsenic acid Chemical compound O[As](O)(O)=O DJHGAFSJWGLOIV-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 241000581650 Ivesia Species 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- JACRWUWPXAESPB-QMMMGPOBSA-N Tropic acid Natural products OC[C@H](C(O)=O)C1=CC=CC=C1 JACRWUWPXAESPB-QMMMGPOBSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 229940000488 arsenic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 238000005574 benzylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- RUEKPBLTWGFBOD-UHFFFAOYSA-N bromoethyne Chemical group BrC#C RUEKPBLTWGFBOD-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- UPDHOTIATMFGCI-UHFFFAOYSA-N butylarsonic acid Chemical compound CCCC[As](O)(O)=O UPDHOTIATMFGCI-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003874 central nervous system depressant Substances 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000006345 epimerization reaction Methods 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
- XNPCJTIURJHUPJ-UHFFFAOYSA-N ethyl 6-benzyl-2-ethyl-5-methyl-5-azabicyclo[2.2.2]oct-2-ene-8-carboxylate;hydrochloride Chemical compound Cl.CN1C(C=C2CC)C(C(=O)OCC)CC2C1CC1=CC=CC=C1 XNPCJTIURJHUPJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- YACKEPLHDIMKIO-UHFFFAOYSA-N methylphosphonic acid Chemical compound CP(O)(O)=O YACKEPLHDIMKIO-UHFFFAOYSA-N 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- ASZOJFWNMZRJLI-UHFFFAOYSA-N n,n-dimethyl-1-phenylmethanamine;formic acid Chemical compound [O-]C=O.C[NH+](C)CC1=CC=CC=C1 ASZOJFWNMZRJLI-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003401 opiate antagonist Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000000962 organic group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pentâ4âenâ2âone Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 229960000482 pethidine Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
- 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00Â -Â C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00Â -Â C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00Â -Â C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00Â -Â C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/22—Bridged ring systems
- C07D221/26—Benzomorphans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Addiction (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
Description
ãçºæã®è©³çŽ°ãªèª¬æã
æ¬çºæã¯ãé®çå€ããã³éº»è¬æ®æå€ãšããŠæçš
ãª11ïŒeqïŒâ眮æâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ã«é¢ããã 11âäœçœ®ãäœçŽã¢ã«ãã«åºã§çœ®æãããïŒïŒïŒ
âã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ã¯ç¥ãããŠããã
ïŒããšãã°ã1960幎ïŒæïŒæ¥ä»ãã®ç±³åœç¹èš±
2924603åç §ïŒãããã«ãïŒäœçœ®ã«ã±ãã³ãã«ã«ã
ããŒã«ãŸãã¯äœçŽã¢ã«ã±ãã«åºããã€ïŒïŒ14âãš
ããããã
ã³ãâãšããâããã³ãšã¿ãããã©ãããããã€
ã³ããã³ïŒïŒ14âãšã³ãâãšããâããã³ãšã¿ã
ããã©ããããªãªããã³ç³»åã«ãããååç©ãã¢
ã«ããã«å¹æµããç°åžžãªé®çåãæããããšã¯ç¥
ãããŠããããBentley et al.ïŒJ.Am.Chem.
Soc.89 3267ã3292ïŒ1967ïŒããçµå±ãïŒïŒïŒâã¡
ã¿ãâïŒâãã³ãºã¢ãŸã·ã³åé®çå€ã®11äœçœ®ã«ã
åŸè ã®ç³»åã«ååšããã±ãã³ãã«ã«ãããŒã«ãŸã
ã¯äœçŽã¢ã«ã±ãã«å®åºãå ããããšã«ãããŠé®ç
å€åéã§éåžžã«èå³ãååšãããããããåæã
ãããšããåªåã¯ãã¹ãŠäžæåã«çµã€ãã æ¬çºæã¯ãç¹å®ã®ïŒâR2âïŒïŒeqïŒâR4â
ïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâ
R1â11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãŸã·ã³ã«é¢ããããã§ïŒºã¯â
CH2COR5ã§ããããããŠR1ïŒR2ïŒR3ããã³R4ã¯
æ°ŽçŽ ãäœçŽã¢ã«ãã«ãŸãã¯ä»ã®ææ©åºã§ãããã
ããã®åºã«ã€ããŠä»¥åŸãã詳现ã«èª¬æããããã
ãã®ååç©ã¯ãé®çå€ããã³éº»è¬æ®æå€ãšããŠæ
çšã§ãããäžè¬åŒ ã§è¡šããããã ç¹å®ã®ïŒâR2âïŒïŒeqïŒâR4âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâïŒâ11ïŒaxïŒâR3
â11ïŒeqïŒâCH2ZâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ã¯ãç¹å®ã®ïŒâR2âïŒâR1âïŒâ
â4aαâR3âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒ
ïŒïŒ10ïŒ10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ãã
ã³ãŸãïœããããªã³ããã®é žãšãšãã«äžæŽ»æ§æº¶åª
äžã§ãŸãã¯ãã³ãžã«âãžâäœçŽã¢ã«ãã«ã¢ã³ã¢ã
ãŠã ãã«ã¡ãŒããããã¯ããªäœçŽã¢ã«ãã«ã¢ã³ã¢
ããŠã ãã«ã¡ãŒããšãšãã«å ç±ããããšã«ãã€
ãŠã補é ã§ããã åŒã®æ°èŠãªïŒâR2âïŒïŒeqïŒââïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâR1â
11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³ããã³ãã®è£œé ã«æçšãª
æ°èŠãªåºçºç©è³ªã¯ãæ¬çºæã«åŸããæ°èŠãªäžéäœ
ãå«ãåå転äœãå«ãæ°èŠãªåå¿ã«ãã€ãŠè£œé ã§
ããããã®åå¿ã¯äžè¬ã«æ¬¡ã®ããã«è¡šããããã ããããã
ãããã€ãŠåŒã®ïŒâR2âïŒïŒeqïŒâR4â
ïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâ
R1â11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ã¯åŒïŒåŒïœã
ïœã®äž¡æ¹ãè¡šããåŒïŒã§è¡šããããæ¬çºæã®åºçº
ç©è³ªïŒâR2âïŒâR1âïŒââïŒâR8â4aαâ
R3âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ
10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸ
ãïœããããªã³ãã補é ããããŸããã®åºçºç©è³ª
ã¯åŒã®ïŒâR1âïŒâïŒïŒâR2âãã³ãžã«ïŒâ
ïŒâR3âïŒâR4âïŒâYâ²âïŒâã¢ã¶ãã·ã¯ã
ãïŒïŒïŒïŒïŒããªã¯ãâïŒâãšã³ããåŸãããã
ã®åŒã®ååç©ã¯æšæºæäœã«åŸãåŒã®ããã²ã³
åïŒâR2âïŒâãã³ãžã«ããèªå°ãããã°ãªã
ã€ãŒã«è©Šè¬ãšåŒã®ããã²ã³åïŒâR3âïŒâR4
âïŒâR1âããªãžããŠã ãšã®åå¿ããã³çãã
åŒã®ïŒâïŒïŒâR2âãã³ãžã«ïŒâïŒâR34âïŒ
âR4âïŒïŒïŒâãžãããããªãžã³ãšãžãšããã€
ã«CH2ïŒCHYâ²ãšã®åå¿ã«ãã€ãŠè£œé ãããã äžèšåå¿åŒã«èšèŒãããæçµçæç©ãšåºçºç©è³ª
ã«ãããŠã R1ã¯æ°ŽçŽ ãäœçŽã¢ã«ãã«ãã·ã¯ãã¢ã«ãã«äœ
çŽã¢ã«ãã«ãŸãã¯ããšãã«âäœçŽã¢ã«ãã«ã§ã
ãïŒ R2ã¯æ°ŽçŽ ãããããã·ãŸãã¯äœçŽã¢ã«ã³ãã·
ã§ããïŒ R3ã¯æ°ŽçŽ ãŸãã¯äœçŽã¢ã«ãã«ã§ããïŒ R4ã¯äœçŽã¢ã«ãã«ã§ããïŒ ïŒºã¯âCH2COR5ïŒR5ã¯äœçŽã¢ã«ãã«ã§ããïŒ
ã§ããã ã¯ã«ã«ããã·ãã·ã¢ããã«ã«ãâäœçŽã¢ã«ã³
ãã·ãCOR5ãCOOâäœçŽã¢ã«ãã¬ã³âã·ã¯ãã¢
ã«ãã«ããŸãã¯COOâäœçŽã¢ã«ãã¬ã³ããšãã«
ã§ããã Yâ²ã¯ã«ã«ããã·ãã·ã¢ããã«ã«ãäœçŽã¢ã«ã³
ãã·ãŸãã¯äœçŽã¢ã«ã«ãã€ã«ã§ããããã㊠Halã¯ããã²ã³ã§ããã ããã§äœ¿çšãããäœçŽã¢ã«ãã«ããŸãã¯ãäœçŽ
ã¢ã«ã³ãã·ãã¯é£œåã§ãããã€éç°åŒã§ãã€ãŠïŒ
ãïŒåã®ççŽ ååãå«ãçŽéãŸãã¯åæéã®åºã
æå³ãããããã®äŸã¯ã¡ãã«ããšãã«ãããã
ã«ãã€ãœãããã«ãããã«ãéé£æ¥ïœâããã«ã
ã¡ããã·ããšããã·ãããããã·ãã€ãœãããã
ã·ããŸãã¯ïœâãããã·ã§ããã ããã§äœ¿çšãããäœçŽã¢ã«ã±ãã«ãããããäœçŽ
ã¢ã«ã±ãã«ãããã³ãäœçŽã¢ã«ããã«ãã¯ãïŒå
ã®äºéçµåãŸãã¯äžéçµåãå«ãççŽ æ°ïŒãïŒã®
ïŒäŸ¡ã®åºãæå³ãããããã®äŸã¯ïŒâãããã
ã«ãïŒâãããã«ãïŒâãã³ããã«ãïŒâã¡ãã«
âïŒâãããã«ãïŒâã¡ãã«âïŒâããããã«ã
ïŒâã¡ãã«âïŒâããããã«ãïŒâããããã«ã
ïŒâãããã«ãïŒâãã³ããã«ãïŒâããã·ãã«
ãªã©ã§ããããããäœçŽã¢ã«ã±ãã«ããšããçšèª
ã«ã¯ãïŒâã¯ãããšããã«ãïŒâããã¢ãšãã
ã«ãïŒïŒïŒâãžã¯ããâïŒâããããã«ãïŒâã
ãã¢âïŒâã¡ãã«ããããã«ãªã©ãå«ãŸããã ããã§äœ¿çšãããã·ã¯ãã¢ã«ãã«ãã¯ãïŒãïŒ
åã®ççŽ ååãå«ã飜åççŽ ç°åŒåºãæå³ããã
ã®äŸã¯ã·ã¯ããããã«ãã·ã¯ãããã«ãã·ã¯ãã
ã³ãã«ãã·ã¯ãããã·ã«ãïŒâã¡ãã«ã·ã¯ããã
ã«ãïŒâãšãã«ã·ã¯ãããã·ã«ãªã©ã§ããã ããã§äœ¿çšãããäœçŽã¢ã«ã«ãã€ã«ãã¯ãççŽ
æ°ïŒãïŒã®é£œåèèªæã¢ãã«ã«ãã³é žããèªå°ã
ããåºãããšãã°ãã«ãã«ãã¢ã»ãã«ãããããª
ãã«ããããªã«ãã€ãœãããªã«ãªã©ãæå³ããã ããã§äœ¿çšãããäœçŽã¢ã«ãã¬ã³ãã¯ãçŽéãŸ
ãã¯åæéã§ããããšãã§ãççŽ æ°ãïŒãïŒã®é£œ
åã®ïŒäŸ¡ã®åºãæå³ãããã®äŸã¯ã¡ãã¬ã³ãâ
CH2âãïŒïŒïŒâãšãã¬ã³ãâCH2CH2âãã
ïŒïŒïŒâãããã¬ã³ãâCH2CH2CH2âããïŒïŒ
ïŒâïŒïŒâã¡ãã«ãšãã¬ã³ïŒãâCHïŒCH3ïŒCH2
âããïŒïŒïŒâããã¬ã³ãâCH2CH2CH2CH2âã
ãªã©ã§ããã 以åŸèšèŒããæšæºã¯è¬çåŠçè©Šéšã«ãããŠæ±ºå®
ããããã
ãããããã«ãåŒã®ååç©ã¯ãæçšãªé®ç掻æ§
ããã€ããšãããããåŒã®ååç©ã®ãããã®ã¯
æçšãªéº»è¬æ®æ掻æ§ããã€ããšãããã€ãããã
ãã€ãŠãåŒã®ååç©ã¯é®çå€ããã³éº»è¬æ®æå€
ãšããŠæçšã§ããã äžèšäžè¬çèšèŒã«ããã°ãåŒã§è¡šããã
R1ïŒR2ïŒR3ïŒR4ïŒR5ããã³ïŒºãäžã«å®çŸ©ãããš
ããã§ããïŒâR2âïŒâïŒïŒeqïŒâR4âïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâR1â
11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³ã¯ãåŒã§è¡šããããïŒ
âR2âïŒâR1âïŒââïŒâR8â4aαâR3âïŒ
αâR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãª
ã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããª
ã³ããææ©æº¶åªãããšãã°ãã«ãšã³ããã·ã¬ã³ã
ããã¯ã¡ã·ãã¬ã³äžã§ã®é žãšããããã¯ãã³ãžã«
âãžâäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãŸãã¯ããªäœçŽ
ã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããšãšãã«å ç±ã
ãããšã«ãã€ãŠã補é ãããã奜ãŸãã溶åªã¯ã¡
ã·ãã¬ã³ã§ããã åèšåå¿åŒã«ç€ºãããããã«ãåŒïŒ¢ã®ååç©
ããªããŠã å¡©ãçµãŠã¢ã«ãã«åãããšãåºã®ãš
ãã¡ãªåãèµ·ãããåŒã®ååç©ã®ç°åã«ããåŸ
ããããããªåŒïŒ¢ã®ååç©äžã®åºïŒ¹ã¯åžžæ ã§Î²
âç«äœé 眮ããã¡ãããªãã¡åºïŒ¹ã¯ïŒïŒïŒâã¡ã¿
ãæ©ããã«å¯ŸããŠã·ã¹ã§ããããåŒïŒ¢ã®ååç©
ããªããŠã å¡©ãçµãŠã¢ã«ãã«åãããšããαâ
ç«äœé 眮ïŒïŒïŒïŒâã¡ã¿ãæ©ããã«å¯ŸããŠãã©ã³
ã¹ïŒã§ããïŒäœã®äœçŽã¢ã«ãã«åºãβç«äœé 眮ã§
ããååç©ãçæãããäºå®ãåŒïŒ¡ã§è¡šããã
ãαç«äœé 眮ã§ããååç©ã¯ãβâååç©
ïŒåŒïŒ¢ïŒã®ååç©ããŸã匷塩åºã§ãã€ãã§é žã§
åŠçããããšã«ãã€ãŠè£œé ã§ãããããã³
ã®ååç©ã«ãããåºïŒ¹ããã³ïŒäœã®ïŒšã®ããã
ãã¯Î±ãŸãã¯Î²ã®ç«äœé 眮ã®ãããããæºããã
ãšãã§ããåŒïŒ¡ããã³ïŒ¢ã®ååç©ã¯äžè¬ã«äž¡
åŒãå å«ããè€ååŒ åŒã§è¡šããããCOR5ã§ããååç©ããå
è¿°ã®ããã«ãææ©æº¶åªäžã§ã®é žãšãšãã«ããŸãã¯
ãã³ãžã«âãžâäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«ã¡
ãŒããããã¯ããªäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«
ã¡ãŒããšãšãã«å ç±ãããšãåŸè¿°ã®åŒã§è¡šãã
ãããåŒããåŒããŸã㯠ãåŒãã§ããïŒâR2âïŒâ R1âïŒââ4aαâR3âïŒÎ±âR4âïŒïŒïŒïŒ
ïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâïŒïŒ
ïŒâãšãããã³ãŸãïœããããªã³ãåŒïŒïŒºã¯â
CH2COR5ã§ããïŒã®ååç©ãšäžç·ã«çæããã
åŒã®ãã³ãºã¢ãŸã·ã³ã®çæéãæé«ã«ãããã
ã«ã¯ãåŒã®åºçºç©è³ª0.05ã¢ã«ããã³ã®é ž1.0ã¢
ã«ã®æ¿åºŠãçšãã¡ã·ãã¬ã³äžã§åå¿ãå®æœããã
ãšã奜ãŸããããã®æ··åç©ã¯éæµæã«çŽ120âã®
åå¿æž©åºŠãäžããåŒã®ãã³ãºã¢ãŸã·ã³ããã³åŒ
ã®ãã³ãŸãïœããããªã³ãïŒïŒïŒãïŒïŒïŒã®æ¯
ã§äžãããã®é žæ¿åºŠã挞é²çã«äœäžãããããšã«
ãããé£ç¶çã«æ²žç¹ãé«ãæ··åç©ãçæãããã®
çµæãã³ãŸãïœããããªã³ã®çžå¯Ÿéã¯æŒžé²çã«å¢
å ããã0.5ã¢ã«ããã³0.15ã¢ã«ã®ã®é žæ¿åºŠïŒã
ããŠåºçºç©è³ªæ¿åºŠ0.05ã¢ã«ïŒã«ãããŠããããã
çŽïŒïŒïŒããã³ïŒïŒïŒã®æ¯ã§ãã³ãŸãïœããããª
ã³ãçæãããåæ§ã«ãïŒã¢ã«ã®åºçºç©è³ªå¯ŸïŒã¢
ã«ã®ãã³ãžã«ãžã¡ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããŸ
ãã¯ããªã¡ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããŸãã¯ã
ãªã¡ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããŸãã¯ããªãšã
ã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒãã®æ¯ãçšãããã®æ··å
ç©ãïŒææ©æº¶åªã®äžååšäžã§ïŒ150âã«çŽ15åé
å ç±ããããšã«ããããã³ãŸãïœããããªã³ãšã
ã³ãºã¢ãŸã·ã³ãšã®æ··åç©ããããã10ïŒ ãïŒïŒ
ïŒããã³20ïŒïŒã®æ¯ã§çæããã ãã®ããã«äžå®æ¡ä»¶äžã§ïŒçš®ã®å€ç§»ãåæã«èµ·
ãããããã¯æ¬¡ã®åå¿åŒã§æãããè¡šããããã ããããã
äžåŒäžR1ïŒR2ïŒR3ïŒR4ïŒR5ããã³ïŒ±ã¯äžã«å®
矩ãããšããã§ãããäžãããããããã«ãåŒ
ã®ååç©ã¯åŒã®ååç©äžã®çµå(b)ã®åå¿æ¡ä»¶äž
ã®éè£ã«ããçããããã«å¯ŸãåŒïœã®ååç©ã¯
çµå(a)ãç Žå£ããããšãçªçŽ ååãšCOR5éšåã®
ã«ã«ããã«åºãšã®éã®éç°ã«ãã€ãŠçæããã åŒã®æçµçæç©ã®è£œé ã«ãããåºçºç©è³ªã§ã
ãåŒã®ïŒâR2âïŒâR1âïŒÎ²ââ4aαâR3
âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10a
âãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœãã
ããªã³é¡ã¯ã次ã®ããã«ããŠè£œé ããã åŒã§è¡šãããããã«ã«ããã·ãã·ã¢ããã«
ã«ãâäœçŽã¢ã«ã³ãã·ãŸãã¯COR5ïŒããã§R5ã¯
äœçŽã¢ã«ãã«ã§ãããCOOâäœçŽã¢ã«ãã¬ã³â
ã·ã¯ãã¢ã«ãã«ãŸãã¯COOâäœçŽã¢ã«ãã¬ã³â
ããšãã«ïŒã§ããååç©ã¯ãé©åœãªåŒã®ïŒâ
R1âïŒâïŒïŒâR2âïŒâR2â²ããŸãã¯R2â³ãâã
ã³ãžã«ïŒâïŒâR3âïŒâR4âïŒâYâ²âïŒâã¢ã¶
ãã·ã¯ãã2.2.2ããªã¯ãâïŒâãšã³ã®é žã觊åª
ãšããç°åã«ãã€ãŠè£œé ãããããã®åå¿ã¯åŒ
ã®ååç©ãé žãžå ãããã®åå¿æ··åç©ãçŽïŒãçŽ
10âã®æž©åºŠã«é眮ããããŸãã¯çŽ100âã«å ç±ã
ãããšã«ãã€ãŠå®æœããã奜ãŸããé žã¯å¡©é žãè
åæ°ŽçŽ é žãç¡«é žãããé žãªã©ã§ãããç¹ã«å¥œãŸã
ãé žã¯å¡©é žã§ããã åŒã®ååç©ã®åŒã®ååç©ïŒåºçºç©è³ªïŒãžã®
ç°åã¯ããã³ãžã«åºã®ïŒâãŸãã¯ïŒâäœçœ®ã§èµ·ã
ããåŒã®ååç©ãçæãããããã«ãåŒã®å
åç©ã®åŒã®ååç©ãžã®ç°åã«ãããR3ããã³
R4åºã®äž¡æ¹ãαâç«äœé 眮ã«ãããããªãã¡
ïŒïŒïŒâã¡ã¿ãæ©ããã«å¯ŸããŠãã©ã³ã¹ã«ããå
åç©ãçããã ããã«ãç°ååå¿ã®éäžããããããªãšã¹ãã«
åºãŸãã¯ãšãŒãã«åºãããšãã°ãåŒã®ååç©ã«
ãããYâ²ãŸãã¯åŒã®ååç©ã«ãããããšã¹
ãã«åºã§ãããããããã¯R2ãããšãã°äœçŽã¢
ã«ã³ãã·ã§ããååç©ãã¯ããšãã«åå¿æ··åç©
ããããšãã°èåæ°ŽçŽ é žãå ç±ãããšãããã°ã
ã°éè£ããŠå¯Ÿå¿ããã«ã«ãã³é žãŸãã¯ããšããŒã«
æ§ååç©ãšãªãããã®ãããªå Žåã«ãããŠããšã¹
ãã«ãŸãã¯ãšãŒãã«ãç®çååç©ã§ãããšããæš
æºæäœã«ããçæç©ãåãšã¹ãã«åãŸãã¯åã¢ã«
ãã«åããªããã°ãªããªãããã®ãããªããšã¯é ž
觊åªãšããŠå¡©é žã®äœ¿çšã«ãã容æã«é¿ããããšã
ã§ããã®ããåå¿æž©åºŠã¯ïŒã10âä»è¿ãšããã ã
ã§ããããã®ãã ãããªæ¡ä»¶ã«ãããŠããšã¹ãã«
ãšãšãŒãã«åºã¯åå¿äžæªå€åã®ãŸãŸã§ããã åŒã®ååç©ã補é ããäžèšæ¹æ³ã¯ãåŒã§è¡š
ããããã«ã«ããã·ãã·ã¢ããã«ã«ãäœçŽã¢ã«
ã³ãã·ãŸãã¯COR5ïŒR5ã¯äœçŽã¢ã«ãã«ã§ããïŒ
ååç©ã®è£œé ã«ãšãã«æå©ã§ããã åŒã§è¡šããããã«ã«ããã·ãã·ã¢ããŸãã¯
ã«ã«ãäœçŽã¢ã«ã³ãã·ã§ããååç©ã¯ãç°¡åãªå
åŠç転åæ³ãããšãã°ãããªã«ã®ã«ã«ãã³é žãžã®
å æ°Žå解ã«ãã€ãŠè»¢åã§ãããé žïŒïŒ¹ã¯ã«ã«ãã
ã·ïŒãŸãã¯ãšã¹ãã«ïŒïŒ¹ã¯ã«ã«ãäœçŽã¢ã«ã³ã
ããããã
ã·ãCOOâäœçŽã¢ã«ãã¬ã³ã·ã¯ãã¢ã«ãã«ã
COOâäœçŽã¢ã«ãã¬ã³ããšãã«ïŒãïŒã¢ã«ã®é©
åœãªææ©ãªããŠã R5Liãšåå¿ãããŠïŒ¹ãCOR5ã§
ããåŒã®ååç©ãçæããããšãã§ãããåŒ
ã§è¡šããããäžã«å®çŸ©ãããšããã§ããååç©
ãåŒã§è¡šããããCOR5ã§ããååç©ã®è£œé
ã«äžéäœãšããŠæçšã§ããããããŠãã®ïŒ¹ã
COR5ã§ããåŒã®ååç©ã¯åŒã®ååç©ã®è£œé
ã«ãããŠäžéäœãšããŠæçšã§ããã åŒãŸãã¯ã§è¡šãããR1ããã³ãžã«ã§ãã
ååç©ã¯ãæ¥è§Šçã«è±ãã³ãžã«åããŠãR1ãæ°Ž
çŽ ã§ãã察å¿ããååç©ãšããããšãã§ãããã€
ãã§ãåŸè ã®ååç©ã¯é©åœãªã¢ã«ãã«åå€ã§åã¢
ã«ãã«åããŠãR1ãäžã«å®çŸ©ãããšããã§ãã
ä»ã®ç°ãªãååç©ã«ããããšãã§ãããäžæŽ»æ§æº¶
åªãããšãã°ãšã¿ããŒã«ãã€ãœãããããŒã«ãªã©
äžã§40ã100ãã³ãpsiã®å§åã§éå ãå®æœããã
奜ãŸãã觊åªã¯ã掻æ§çã«æ æããããã©ãžãŠã
ã§ãããåŒã§è¡šãããR1ãæ°ŽçŽ ã§ããååç©
ã®ã¢ã«ãã«åã¯ãäžæŽ»æ§æº¶åªãããšãã°ã¢ã»ã
ã³ããšã¿ããŒã«ãŸãã¯DMFäžã§é žåäœãããšã
ã°ã¢ã«ã«ãªéå±ã®çé žå¡©ãŸãã¯éçé žå¡©ã®ååšã§
å®æœããã æåŸã«ãåŒã§è¡šããããåºçºç©è³ªã®è£œé ã«ã
ããäžéäœã§ããåŒã®ïŒâR1âïŒâïŒïŒâR2
âãã³ãžã«ïŒâïŒâR3âïŒâR4âïŒâYâ²âïŒâ
ã¢ã¶ãã·ã¯ãã2.2.2ããªã¯ãâïŒâãšã³ã¯ãåŒ
ã®ããã²ã³åïŒâR2âãã³ãžã«ããèªå°ãã
ãã°ãªãã€ãŒã«è©Šè¬ãšé©åœãªåŒã®ããã²ã³åïŒ
âR3âïŒâR4âïŒâR1âããªãžããŠã ãšãåå¿
ãããã€ãã§çããåŒã®ïŒâïŒïŒâR2âãã³
ãžã«ïŒâïŒâR3âïŒâR4âïŒïŒïŒâãžãããã
ãªãžã³ãšé©åœãªãžãšããã€ã«CH2ïŒCHYâ²ãšãã
ã€ãŒã«ã¹ã»ã¢ã«ããŒçž®åãããŠã補é ãããã ã°ãªãã€ãŒã«è©Šè¬ãçšããåå¿ã¯ïŒã25âã«ã
ããŠäžæŽ»æ§æº¶åªãããšãã°ãžãšãã«ãšãŒãã«ãã
ãã©ããããã©ã³ãŸãã¯ãžããã«ãšãŒãã«äžã§å®
æœããã°ãªãã€ãŒã«æº¶æ¶²ãåå¿æº¶åªäžã®ç¬¬åçŽå¡©
ã®ããæ¿æ¶²ãžå ããããšã«ãã€ãŠè¡ãªããçæã
ãåŒã®ãžãããååç©ã¯äžè¬ã«åé¢ããã³ç²Ÿè£œ
ãããããããžãšããã€ã«ãšã®åå¿ãå«ã次ã®å·¥
çšã«ãããŠããã«ç²Ÿè£œããã«çŽæ¥äœ¿çšãããåŒ
ã®ãžãããååç©ãšãžãšããã€ã«ãšã®åå¿ã¯æº¶åª
ãšããŠéå°éã®ãžãšããã€ã«äžã§ããããã¯äžæŽ»
æ§ææ©æº¶åªãããšãã°ãã³ãŒã³ããã«ãšã³ãŸãã¯
ãã·ã¬ã³äžã§å®æœã§ãããåå¿ã¯å¥œãŸããã¯æ··å
ç©ã®éæµæž©åºŠã«ãããŠå®æœããã åŒã®ç¬¬åçŽåç©ã補é ããã®ã«äœ¿çšããïŒâ
R3âïŒâR4âããªãžã«ãããã«ã°ãªãã€ãŒã«è©Š
è¬ã補é ããã®ã«äœ¿çšããããã²ã³åïŒâR2â
ãã³ãžã«ã¯ãç¥ãããŠããååç©ã§ããã å¡©åºæ§ã¢ããåºãååšãããããäžèšåŒã
ãããã³ã§è¡šããããéé¢å¡©åºã¯ãææ©é žã
ãã³ç¡æ©é žãšåå¿ããŠé žä»å å¡©ãçæããããã®
é žä»å å¡©ã¯ãããªãææ©é žãŸãã¯ç¡æ©é žããã補
é ã§ããããã®é žä»å å¡©ã¯ãåžžæ³ã«ãããããšã
ã°å¡©åºãšé žãçŽæ¥æ··åãããããããé©åœã§ãªã
ãšãå¡©é žãšé žã®äžæ¹ãŸãã¯äž¡æ¹ãæ°ŽãŸãã¯ææ©æº¶
åªã«å¥ã ã«æº¶ããããããã®ïŒçš®ã®æº¶æ¶²ãæ··åã
ããããããã¯å¡©åºãšé žãšãäžç·ã«æº¶åªã«æº¶è§£ã
ãããšã«ãã€ãŠåŸããããçããé žä»å å¡©ã¯ãå
å¿åªäœäžã«æº¶ããªãå Žåãéã«ããããŸãåå¿åª
äœãèžçºãããŠé žä»å å¡©ãæ®çç©ãšããŠæ®ãããš
ã«ããåé¢ãããããããã®å¡©ã®åœ¢ã®é žéšåãã
ãªãã¡é°ã€ãªã³ã¯ãããèªäœæ°èŠã§ããªãèšçç
ã§ãªãã®ã§ãå¡©åºãšå¡©ã圢æã§ãããããªãé žã®
é°ã€ãªã³ãŸãã¯é žæ§ç©è³ªã§ããããšãã§ããã é žä»å å¡©ã®çæã«ä»£è¡šçãªé žã¯ã次ã®ãšããã§
ãããã®é žãé ¢é žãã€ãœé ªé žãαâã¡ã«ã«ããã
ãããªã³é žãããªãã«ãªãé ¢é žããããé žããã
ãŒã«é žããã¯ãé žãã¹ã¯ã·ããã³é žãã¿ã³ãã³
é žãã°ã«ã¿ãã³é žãé ç³é žããããé žãããã ã·
ã³é žããããé žãä¹³é žãã°ãªã³ãŒã«é žãã°ã«ã³ã³
é žããµãã«ãªã³é žãã¢ã¹ã³ã«ãã³é žãããã·ãª
ã³ãå®æ¯éŠé žããã¿ã«é žããµãªã·ã«é žãïŒïŒïŒâ
ãžãããå®æ¯éŠé žãã¢ã³ãã©ãã«é žãã³ãªã³é žã
ïŒâããªãžã³ã«ã«ãã³é žããã¢ã€ã³é žãïŒâãã
ããã·âïŒâãããã€ã³é žããã¯ãªã³é žãããã³
é žããããã³é žãïŒâã€ã³ããŒã«é ¢é žããã«ãã
ã«é žãã¹ã«ãã¢ãã³é žãã¡ã¿ã³ã¹ã«ãã³é žããšã¿
ã³ã¹ã«ãã³é žãã€ã»ããªã³é žããã³ãŒã³ã¹ã«ãã³
é žãïœâãã«ãšã³ã¹ã«ãã³é žãããã«ã¢ã«ãœã³
é žãã¡ã¿ã³ãã¹ãã³é žãé žæ§æš¹èãããåæ°ŽçŽ
é žãå¡©åæ°ŽçŽ é žãèåæ°ŽçŽ é žããšãŒåæ°ŽçŽ é žãé
å¡©çŽ é žãç¡é žãç¡«é žãããé žããé žãªã©ã é žä»å å¡©ã®ãã¹ãŠã¯ãç¡æ©å¡©åºãšã®åå¿ã«ãã
éé¢å¡©åºã®åœ¢æ ã®æºãšããŠæçšã§ããããããã€
ãŠãäžå®ã®å¡©åºãŸãã¯é žä»å å¡©ã®ç¹æ§ãããšãã°
ããããã
溶解床ãååéãç©ççå€èŠ³ãæ¯æ§ãªã©ã®ïŒãŸã
ã¯ïŒä»¥äžãææã®ç®çã«äžé©åœã§ããå Žåããã
ãä»ã®ããé©åœãªåœ¢ã«è»¢åã§ããã補è¬äžã®ç®ç
ã§ãæ¯èŒçéæ¯æ§ã®è£œè¬äžèš±å®¹ãããé žãããšã
ã°å¡©é žãä¹³é žãé ç³é žãªã©ã®é žä»å å¡©ããã¡ãã
䜿çšã§ããã æ¬çºæã®ååç©ã¯ç«äœç°æ§äœãããªãã¡å åŠç
ç°æ§äœããã³å¹ŸäœåŠçç°æ§äœã®åœ¢ã§ååšã§ããã
å¿ èŠã«å¿ããŠãç¹å®ã®ç«äœç°æ§äœãå è¡æè¡ã§ç¥
ãããŠããäžè¬åçãå¿çšããŠåé¢ãã補é ã§ã
ããããã§äœ¿çšããåŒã®ååç©ã«çšããååœæ³
ã«ãããŠãaxãã¯ã·ã¯ããããµã³ç°å¹³é¢ã«å¯Ÿã
ãŠåçŽæ¹åã«çµåããŠããããšãæå³ãããeqã
ã¯æ°Žå¹³æ¹åã®çµåãæå³ãããããŠç«äœé 眮ã¯ã
ããè³éŠæç°ã«ã€ããŠäžãããã®ã§ãããããã
ã€ãŠãåŒã®ïŒïŒeqïŒã11ïŒaxïŒååç©ã¯ã·ã¹ç«
äœé äœã§ãããããã«å¯ŸããŠïŒïŒeqïŒã11ïŒeqïŒ
ååç©ã¯ãã©ã³ã¹ç«äœé äœã§ããã åŒã®ååç©ã«äœ¿çšããååœæ³ã«ãããŠãåã³
ç«äœé 眮ããããè³éŠæç°ã«äžããèšå·ãβãã¯
åŒã®ååç©ã®ïŒïŒïŒâã¡ã¿ãæ¶æ©ã«é¢ããŠã·ã¹
ç«äœé 眮ã瀺ããéã«ãèšå·ãαãã¯åã矀ã«é¢
ããŠãã©ã³ã¹ç«äœé 眮ã瀺ãã æšæºã®è¬çåŠçè©Šéšæäœã«ãããŠãåŒã®åå
ç©ãªãã³ã«ãããã®é žä»å å¡©ã¯äžæ¢ç¥çµç³»çµ±ã®æ
å¶å€ãšããŠæçšã§ããããšããããããšãã«é®ç
å€ãšããŠãªãã³ã«ããšããŸãªã³ãã¡ããªãžã³ãã
ã³ã¢ã«ããã®ãããªåŒ·ãé®çå€ã®æ®æå€ãšããŠæ
çšã§ããããšãããã€ããããã«åŒã®ååç©ã®
ãããã®ã¯é®çå€ãšããŠæçšã§ããããšãããã€
ãã åŒã®ååç©ã¯ãæ¢ç¥ã®é®çå€ããã³åŒ·ãé®ç
å€ã®æ®æå€ãšåãããã«ããŠãããªãã¡ããµã€ã
ã®è£œè¬ç圢æ ãããšãã°æº¶æ¶²ãããæ¿æ¶²ãé å€ã
ã«ãã»ã«ãªã©ã®åœ¢æ ã§ç®äžçã«ãŸãã¯çµå£çã«æ
äžã§ããã æ¬çºæã®ååç©ã®æçšãªæ§è³ªã¯ãè¬çåŠçè©Šéš
æäœã«ãããŠéåžžã®ç¥èããã€æè¡è ã«ãã€ãŠå®¹
æã«è¡ãªãããšãã§ããæšæºã®è¬çåŠçæäœã«ã
ã€ãŠæããã«ãããã®ã§ãç¹å®ã®è©Šéšååç©ã«ã€
ããŠã®æ°ççç©åŠçããŒã¿ã®å®éã®æž¬å®ãå®éšã
æ¡åŒµããªãã§ç¢ºèã§ããã æ¬çºæã®ååç©ã®é®ç掻æ§ããã³é®çæ®æ掻æ§
ã枬å®ããã®ã«äœ¿çšããè©Šéšæäœã¯ãå è¡æç®ã«
詳现ã«èšèŒãããŠããŠããã次ã®ããã§ãããã¢
ã»ãã«ã¯ããªã³èªçºè ¹ççªè©Šéšãããã¯Collier
et al.ïŒBritïŒJ.Pharmacol.Chemotherap.32ïŒ
295ïŒ1968ïŒã«èšèŒãããŠãããã¯ã€ãããã¿ã«
ãããŠã¢ã»ãã«ã¯ããªã³ã«ããèªçºãããè ¹ã®ç
çªãæå¶ããè©Šéšè¬å€ã®èœåã枬å®ããããã«æ¡
åºãããäž»ã«é®çã¹ã¯ãªãŒãã³ã°è©Šéšã§ãããæ
ã«ãªãžã³è©Šéšã®å€æŽæ³ãããã¯Berkowitz et al.
ïŒJ.Pharmacol.Exp.Therap.177ïŒ500â508
ïŒ1971ïŒïŒBlane et al.ïŒJ.Pharm.Pharmacol.19ïŒ
367â373ïŒ1967ïŒïŒBotha et al.ïŒEur.J.
Pharmacol.ïŒïŒ312â321ïŒ1969ïŒããã³Deffenu
et al.ïŒJ.Pharm.Pharmacol.18ïŒ135ïŒ1966ïŒã«
èšèŒãããŠãããäž»ã«é®çã¹ã¯ãªãŒãã³ã°æ³ã§ã
ããããšãã«âïœâããã³èªçºèº«ãã ãè©Šéšãã
ãã¯Pearlããã³HarrisïŒJ.Pharmacol.Exptl.
Therap.154ïŒ319â323ïŒ1966ïŒã«èšèŒãããŠã
ããã¯ã€ãããã¿ã«ãããããšãã«âïœâããã³
èªçºèº«ãã ããé²æ¢ããè©Šéšè¬å€ã®èœåã枬å®ã
ãããã«æ¡åºãããäž»ã«é®çã¹ã¯ãªãŒãã³ã°è©Š
éšãDâ²Amour and SmithïŒJ.Pharmacol.Exptl.
Therap.72ïŒ74ïŒ1941ïŒã«èšèŒãããBassããã³
Vander BrookïŒJ.Am.Pharm.Assoc.Sci.Ed.41ïŒ
569ïŒ1956ïŒã«ããå€æŽãããããã¿ã®å°Ÿã®è»œæ
ã®èŒ»å°ç±ã®é®çãã¢ãŽãã¹ãïŒagonistïŒè©Šéšã
ãããŠãããšããŸã·ã³æ®æè©Šéšãããã¯Harrisã
ãã³PiersonïŒJ.Pharmacol.Exptl.Therap.143ïŒ
141ïŒ1964ïŒã«èšèŒãããåè¿°ã®ããã¿ã®å°Ÿã®è»œ
æã®å¿çè©Šéšã«ãããããšããŸã·ã³ã®å¹æã«æ®æ
ããè©Šéšè¬å€ã®èœåã枬å®ããããã«æ¡åºããã
ãã®ã§ããã æ¬çºæã®ååç©ã®æ§é ã¯ãåææ³ãå çŽ åæã
玫å€ã¹ãã¯ãã«ãèµ€å€ã¹ãã¯ãã«ããã³æ žç£æ°å ±
鳎ã¹ãã¯ãã«ã«ãã確ç«ãããåå¿éçšãšçæç©
ã®å質æ§ã¯èå±€ã¯ãããã°ã©ãã€ãŒã«ãã確èã
ãã 次ã«åèäŸããã³å®æœäŸã«ããæ¬çºæã説æã
ããèç¹ã¯ç¹èšããªããããè£æ£ããªãã€ãã åºçºç©è³ªåæã®ããã®äžéäœã®è£œé åèäŸïŒïŒåºçºç©è³ªåæçšäžéäœã®è£œé ïŒ (A) 450mlã®ãžãšãã«ãšãŒãã«äžã®76ïœïŒ0.6ã¢
ã«ïŒã®å¡©åãã³ãžã«ã®æº¶æ¶²ãã150mlã®ä¹Ÿç¥ãš
ãŒãã«äžã®14.6ïœïŒ0.6ã¢ã«ïŒã®ãã°ãã·ãŠã
æåç©ã®æ··åç©ã«ããã ãããªéæµãç¶æãã
ããããã
ããããªé床ã§å ãããã€ãã§çãã溶液ãã
ã¬ã©ã¹ã»ãŠãŒã«ãçµããéã«ãã€ãŠã150mlã®
ãšãŒãã«äžã®75ïœïŒ0.3ã¢ã«ïŒã®ïŒâãšãã«ã
ãªãžã³ã¡ãã€ãªãã€ãã®ããæ¿æ¶²ã«å ãããã
ã®æ··åç©ã宀枩ã§ïŒæéãããŸããå¡©åã¢ã³ã¢
ããŠã ãå«ãæ°·ïŒæ°Žæ··åç©ã«æ³šãå ¥ããææ©å±€
ãåé¢ãã也ç¥ããéãããšãŒãã«ã§åžéã
ãŠ900mlã«ããã ïŒâã¡ãã«âïŒâãã³ãžã«âïŒâãšãã«â
ïŒïŒïŒâãžãããããªãžã³ãå«ã溶液ã300ml
ãã€ã®ïŒéšåã«åããåéšåãèžçºä¹Ÿç¥ããã
ããã200mlãã€ã®ãã³ãŒã³ããã«ãšã³ããã·
ã¬ã³ã«æº¶è§£ããïŒåã®æº¶æ¶²ã22mlã®ã¢ã¯ãªã«é ž
ãšãã«ã§åŠçããäžå€éæµãããå溶液ãæŸå·
ãããžãšãã«ãšãŒãã«ã§åžéãã150mlã®1N
HClã§æœåºãããæœåºæ¶²ããããããžãšãã«ãš
ãŒãã«ã§äžåæŽããã€ãã§15mlã®æ¿æ°Žé žåã¢ã³
ã¢ããŠã ã§å¡©åºæ§ã«ãã150mlã®ãžãšãã«ãšãŒ
ãã«ã§æœåºãããïŒåã®ãµã³ãã«ã®æœåºæ¶²ãã
ãããã18.2ïœã20.0ïœã19.3ïœã®çæç©ãæ²¹
ç¶ç©ãšããŠåŸããïŒåã®ãµã³ãã«ããžãšãã«ãš
ãŒãã«ã«æº¶è§£ãããšãŒãã«æ§å¡©é žã§é žæ§ã«ãã
ããŒã¿ã«ã§32.2ïœã®ãšãã«âïŒâã¡ãã«âïŒâ
ãã³ãžã«âïŒâãšãã«âïŒâã¢ã¶ãã·ã¯ã
ã2.2.2ããªã¯ãâïŒâãšã³âïŒâã«ã«ããã·ã¬
ãŒãå¡©é žå¡©ïŒmp189ã191âïŒãåŸãã åèäŸïŒ(A)ã®æ¹æ³ã§ã溶åªãšããŠãã³ãŒã³ãã
ã«ãšã³ããã·ã¬ã³ã®ããããã䜿ããåŒã®ïŒâ
R2âãã³ãžã«ãã°ãã·ãŠã ã¯ããªããåŒã®ïŒ
âR3âïŒâR4âïŒâR1âããªãžããŠã ãã©ã€
ãããžãšããã€ã«CH2ïŒCHYâ²ãã以äžã®åŒã®
ïŒâR1âïŒâïŒïŒâR2âãã³ãžã«ïŒâïŒâR3â
ïŒâR4âïŒâYâ²âïŒâã¢ã¶ãã·ã¯ãã2.2.2ããª
ã¯ãâïŒâãšã³é¡ã補é ããã ç¹èšãªãéããçæç©ã¯å¡©é žå¡©ã®åœ¢ã§åé¢ãã
ç¹æ§ã¥ãããåŒã®ïŒçŽå¡©ã®ã¢ããªã³ã¯åŒã®ïŒ
çŽå¡©ã®ééã®æ¬¡ã®ã«ãã³å ã«ç€ºãã ãã®æ现æžã®è¡šã«ãããŠãåæååç©ïŒS.M.
ïŒãšçæç©ïŒäžéäœïŒïŒProdïŒã®ééã¯âWt.
ââã§ç€ºããæ¬ã«ïœã§ç€ºããæçµçæç©ã®èç¹ã¯
åçµæ¶æº¶åªãšå ±ã«æåŸã®æ¬ã«ç€ºãã ããã€ãã®åå¿æåã®ïŒã€ã®ã¿ã®éããèšèŒã
ããŠããå Žåãä»ã®åå¿æåã®éãã¯çšããå®éš
宀çæ¹æ³ã«ã€ããŠèšèŒããå®æœäŸã«ãããŠäœ¿çšã
ãéããé©åœãªã¢ã«åºæºã§èšç®ã§ãããããå Žå
ã«ãããŠãçæç©ãèžçãŸãã¯åçµæ¶ã«ããç¹æ§
ã¥ããããããåå¿æ··åç©ããåé¢ãããŸãŸã§æ¬¡
ã®å·¥çšã«çŽæ¥äœ¿çšããã åºçºç©è³ªãŸãã¯çæç©ã®ãå¡©åºãŸãã¯å¡©ã§ãã
ç¹å®ã®åœ¢æ ããééãšãšãã«ãå¡©åºãããHClãã
ãHBrãããªã©ã§è¡šããããããã¯ããããéé¢å¡©
åºãå¡©é žå¡©ãèåæ°ŽçŽ é žå¡©ãªã©ã®å¡©ã瀺ãã ãè¡šã åèäŸïŒïŒåºçºç©è³ªã®è£œé (A) 125mlã®48ïŒ ã®èåæ°ŽçŽ é žäžã®åèäŸ1Aã«èš
ããããã
èŒãã12.3ïœïŒ0.035ã¢ã«ïŒã®ïŒâã¡ãã«âïŒ
âãã³ãžã«âïŒâãšãã«âïŒâã¢ã¶ãã·ã¯ã
ã2.2.2ããªã¯ãâïŒâãšã³âïŒâã«ã«ãã³é žãš
ãã«ã®æ··åç©ãéæµäžã«24æéãããŸããååŽ
ãããåé¢ããåºäœãéãããšã8.4ïœã®ïŒâ
ã¡ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒ
ïŒïŒ10ïŒ10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ã
ãã³ãŸãïœããããªã³âïŒÎ²âã«ã«ãã³é žèå
æ°ŽçŽ é žå¡©ãèç¹290ã293âãåŸããããããæ°Ž
ããåçµæ¶ãããšèç¹295ã299âã®ç©è³ªãåŸã
ããã åèäŸïŒ(A)ã«ãããããã«ããŠãé©åœãªåŒã®
ïŒâR1âïŒâïŒïŒâR2âãã³ãžã«ïŒâïŒâR3â
ïŒâR4âïŒâYâ²âïŒâã¢ã¶ãã·ã¯ãã2.2.2ããª
ã¯ãâïŒâãšã³ã䜿çšãããšãåŒã§è¡šãããã
次ã®ïŒâR2âïŒâR1âïŒÎ²ââ4aαâR3âïŒ
αâR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãª
ã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããª
ã³ãåŸããããïŒã15âã«ãããŠããåæ°ŽçŽ é žã
åšå²æž©åºŠã«ãããŠæ¿ç¡«é žããŸãã¯éæµæž©åºŠã«ãã
ãŠæ°·é ¢é žäžã®èåæ°ŽçŽ é žã䜿çšããŠãç°åãè¡ãª
ãããšãã§ãããåå Žåã«ãããŠåå¿ãä¿é²ãã
ããã«äœ¿çšããç¹å®ã®é žã¯ãHFãH2SO4ããã³
HBrã§äžã«è¡šç€ºãããç¹èšããªãããããçæç©
ïŒåŒã®ååç©ïŒã¯å¡©é žå¡©ãšããŠåé¢ããã ãè¡šã åèäŸ ïŒ 100mlã®ãšã¿ããŒã«äžã®21.7ïœïŒ0.06ã¢ã«ïŒã®
ïŒâãã³ãžã«âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«â
ïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãã
ãâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããªã³ïŒåè
äŸ2Cã«èšèŒããïŒã®æº¶æ¶²ãå¡©é žã§é žæ§ãšããã
ã®æº¶æ¶²ãããŒã«ïŒparrïŒæ¯ãšãè£ çœ®ã«ãã宀枩ã§
2.0ïœ10ïŒ ã®æŽ»æ§çãã©ãžãŠã ã®ååšäžã«æ°ŽçŽ ã§
éå ãããéå ãå®äºãããšãã觊åªããå»ãã
ã液ãç空æ¿çž®ä¹Ÿç¥ããæ®çç©ãã€ãœãããããŒ
ã«ããåçµæ¶ãããšã14.4ïœã®ïŒÎ²âã¢ã»ãã«â
ïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ
10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸ
ãïœããããªã³å¡©é žå¡©ãèç¹240ã241âãåŸãã
ããããã
ãã åèäŸ ïŒ 300mlã®DMFäžã®27.6ïœïŒ0.091ã¢ã«ïŒïŒÎ²âã¢
ã»ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒ
ïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ25âã¡ã¿ããã³ãŸ
ãïœããããªã³ãšãã«å¡©é žå¡©ïŒåèäŸïŒã«èšèŒã
ãïŒã14.9ïœïŒ0.11ã¢ã«ïŒã®èåã·ã¯ããããã«
ã¡ãã«ããã³16.8ïœïŒ0.20ã¢ã«ïŒã®çé žæ°ŽçŽ ãã
ãªãŠã ã®æ··åç©ããããŸããïŒæééæµããã€ã
ã§åå¿æ··åç©ãæ°Žãšãžãšãã«ãšãŒãã«ãšã«åé ã
ãããšãŒãã«å±€ãæ°ŽæŽãã也ç¥ãã掻æ§çãå
ãããéããã液ããšã¿ããŒã«ã§åžéããå¡©åæ°Ž
çŽ ã®ãšãŒãã«æº¶æ¶²ã§é žæ§ã«ãããåé¢ããåºäœã
éãããšã¿ããŒã«ïŒãšãŒãã«ããåçµæ¶ãããšã
24.1ïœã®ïŒÎ²âã¢ã»ãã«âïŒâã·ã¯ããããã«ã¡
ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ
10ïŒ10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸ
ãïœããããªã³å¡©é žå¡©ãèç¹202ã204âãåŸãã
ãã åèäŸ ïŒ (A) 390mlã®ãžãšãã«ãšãŒãã«äžã®44.1ïœïŒ0.16
ã¢ã«ïŒã®ïŒâã¡ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ
ïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããªã³âïŒÎ²â
ã«ã«ãã³é žïŒåèäŸ2Aã«ãããŠèšèŒããïŒïŒã®
æžæ¿æ¶²ã«ããžãšãã«ãšãŒãã«äžã®2.16ã¢ã«ã®ã¡
ãã«ãªããŠã 溶液230mlïŒ0.5ã¢ã«ïŒã现ãæµã
ã®åœ¢ã§å ãããæ·»å å®äºãããšãããã®æ··åç©
ãïŒæéãããŸããæ°·ïŒå¡©åã¢ã³ã¢ããŠã 氎溶
液äžã«æ³šãå ¥ãããããŠãžãšãã«ãšãŒãã«äžãž
ã®æœåºããã³æœåºæ¶²ã也ç¥ããåŸã«èžçºä¹Ÿåºã
ãŠåŠçããããã®ããã«ããŠ32.8ïœã®çæç©ã
æ²¹ç¶ç²è£œå¡©åºãšããŠåŸããããã®3.3ïœãå¡©é ž
å¡©ã«è»¢åããããããã¡ã¿ããŒã«ïŒãžãšãã«ãš
ãŒãã«ããåçµæ¶ãããšã2.3ïœã®ïŒâã¡ãã«
âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ
ïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããªã³å¡©é žå¡©ã
èç¹191âãåŸãããã åèäŸ5Aãšåæ§ãªæäœã«åŸãããåèäŸ2Aã
2Bããã³2Gã«èšèŒããåŒã®é©åœãªïŒâR2âïŒ
âR1â4aαâR3âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ
4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ25âã¡ã¿ãã
ã³ãŸãïœããããªã³âïŒÎ²âã«ã«ãã³é žãšé©åœãª
ææ©ãªããŠã R5Liã䜿çšãããšãäžè¡šïŒã«èšèŒ
ããåŒã®ååç©ãåŸããããåæååç©ã®åœ¢æ
ïŒå¡©ãŸãã¯å¡©åºïŒãåå Žåã«ãããŠã«ãã³å ã«ç€º
ãããã®ééã瀺ãããã¡ããå¡©ã¯ææ©ãªããŠã
ãšã®åå¿åã«éé¢å¡©åºã«è»¢åããããããŠåèäŸ
5Bããã³5Cã®ååç©ã®éé¢å¡©åºã«ã€ããŠãèç¹
ãèšèŒããã ãè¡šã æçµçæç©ã®è£œé å®æœäŸ ïŒ (A) 89mlã®ããªã¡ãã«ã¢ãã³ã94mlã®ã®é žã«å ã
ãŠåŸããã20mlã®æº¶æ¶²äžã®11ïœïŒ0.039ã¢ã«ïŒ
ã®ïŒâã¡ãã«âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«
âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿
ãããâ25âã¡ã¿ããã³ãŸãïœããããªã³å¡©é ž
å¡©ïŒåèäŸïŒã«èšèŒããïŒæº¶æ¶²ãã15åééæµ
æ¹æããããã®æ··åç©ãæŸå·ãã100mlã®æ°Žã
å ãã50mlã®ãžãšãã«ãšãŒãã«ã§æŽã€ããæ°Žå±€
ã15mlã®æ¿æ°Žé žåã¢ã³ã¢ããŠã ã§å¡©åºæ§ãšãã
ãžãšãã«ãšãŒãã«ã§ïŒåæœåºãããææ©æœåºæ¶²
ãäžç·ã«ããæ°Žã§ïŒåæŽãã也ç¥ããæ¿çž®ä¹Ÿç¥
ãããšã10ïœã®åºäœæ®çç©ãåŸããããããçŽ
30mlã®ç¡æ°Žãšã¿ããŒã«ã«æº¶ããã13mlã®å¡©åæ°Ž
çŽ ã®ãšãŒãã«æº¶æ¶²ã§é žæ§ã«ãã250mlã®è¿œå ã®
ãšãŒãã«ã§åžéãããåé¢ããåºäœãéã«ã
ã€ãŠé€å»ããã液ãåžæ°Žé žåã¢ã³ã¢ããŠã ã§æŽ
ããããã
ãã也ç¥ãããéãã也ç¥ãããšã3.1ïœã®æ®
çç©ãåŸãããããããžãšãã«ãšãŒãã«ã«æº¶è§£
ããå¡©åæ°ŽçŽ ã®ãšãŒãã«æº¶æ¶²ã§é žæ§ã«ãããå
é¢ããã¬ã ç¶ã®åçµæ¶æ§ç©è³ªããšã¿ããŒã«ïŒãš
ãŒãã«ããåçµæ¶ãããšã0.8ïœã®ïŒïŒeqïŒâ
ãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãã
ãâïŒâã¡ãã«â11ïŒeqïŒâïŒïŒâãªããœã
ãã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³
å¡©é žå¡©ãèç¹192ã196âãåŸãããã (B) åŒã®ååç©ããåŒã®ååç©ã補é ããå¥
æ³ã¯æ¬¡ã®ãšããã§ããã 675mlã®ã¡ãã¬ã³ããã³25mlã®ã®é žäžã®åè
äŸ9Cã«èšèŒãã10.0ïœïŒ0.03ã¢ã«ïŒã®ïŒâã¡ã
ã«âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«âïŒâãã
ããã·âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâ
ãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœãã
ããªã³ã®æ··åç©ãçŽïŒæéæ¹æéæµããæã ã®
é žãè¿œå ããŠããŸæž©åºŠã117ã119âã«ç¶æã
ããã€ãã§æ··åç©ãå·åŽããåžå¡©é žã§æœåºãã
é žæœåºæ¶²ããŸããžãšãã«ãšãŒãã«ã§æŽããæ°Žé ž
åã¢ã³ã¢ããŠã ã§å¡©åºæ§ãšããé ¢é žãšãã«ã§ã
ãäžåºŠæœåºãããææ©æœåºæ¶²ããã©ã€ã³ã§æŽ
ããèžçºä¹Ÿç¥ãããšã8.4ïœã®åºäœãåŸããã
ãããé ¢é žãšãã«ããåçµæ¶ãããšã3.7ïœã®
ïŒïŒeqïŒâãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒ
âãããµãããâ34ã¡ãã«âïŒâããããã·â
11ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ãèç¹190ã192â
ãåŸãããã å®æœäŸ1AãŸãã¯1Bãšåæ§ãªæäœã«åŸããåŒ
ã®é©åœãªïŒâR2âïŒâR1âïŒâCOR5â4aαâïŒ
αâR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãª
ã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããª
ã³ã䜿çšãããšãåŒã§è¡šããããäžè¡šïŒã«ç€ºã
ïŒâR2âïŒïŒeqïŒâR4âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒâãããµãããâïŒâR1â11ïŒaxïŒâR3â11
ïŒeqïŒâïŒãªããœâäœçŽã¢ã«ãã«ïŒâïŒïŒïŒâã¡
ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ãåŸããããå®æœäŸïŒ
ãŸãã¯1Bã«ããæäœã次ã®å®æœäŸçªå·ã«ãããŠ
ããããæå(A)ãŸãã¯(B)ã§ç€ºããç¹èšããªããã
ããçæç©ã¯éé¢å¡©åºã®åœ¢ã§åé¢ãããã®èç¹ã
èšèŒããã ãè¡šã å®æœäŸ ïŒ (A) 27.0ïœïŒ0.072ã¢ã«ïŒã®ïŒâãã³ãžã«âïŒâ
ã¡ããã·âïŒïŒeqïŒâã¡ãã«ïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
ããããã
âãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ïŒå®æœäŸ1Eã«èšèŒããïŒã®æº¶æ¶²ã
250mlã®48ïŒ èåæ°ŽçŽ é žäžã«æº¶ããããã®æ··å
ç©ãçŽïŒæééæµå ç±ããããã®æ··åç©ãç空
äžã§æ¿çž®ããŠå°å®¹ç©ã«ãã100mlã®æ°Žã§åžé
ããåã³æ¿çž®ããæåŸã«çŽ50mlã®ã€ãœãããã
ãŒã«ãšãšãã«æ²žãšããããåé¢ããåºäœãé
ãã也ç¥ãããšã23ïœã®ïŒâãã³ãžã«âïŒâã
ãããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
âãªããœããã«ïŒâ26âã¡ã¿ãâïŒâãã³ãºã¢
ãŸã·ã³èåæ°ŽçŽ é žå¡©ãèç¹156ã165âãåŸãã
ãã (B) å®æœäŸ1Hã«èšèŒãã4.0ïœã®ïŒïŒïŒïŒeqïŒâ
ãžã¡ãã«âïŒâã¡ããã·âïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒâãª
ããœãªã¯ãã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãº
ã¢ãŸã·ã³ïœâãã«ãšã³ã¹ã«ãããŒããš20mlã®48
ïŒ èåæ°ŽçŽ é žãšãåå¿ããããšãïŒïŒïŒ
ïŒeqïŒâãžã¡ãã«âïŒâããããã·âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœãªã¯ãã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒ
âãã³ãºã¢ãŸã·ã³ïŒ1.8ïœãèç¹107ã109âã
ãšã¿ããŒã«ããïŒãåæ§ã«è£œé ãããã å®æœäŸ ïŒ ïŒ¡ 150mlã®DMFäžã®23.1ïœïŒ0.05ã¢ã«ïŒã®ïŒâ
ãã³ãžã«âïŒâããããã·âïŒïŒeqïŒâã¡ã
ã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâ
11ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³èåæ°ŽçŽ é žå¡©ïŒå®
æœäŸ2Aã«èšèŒããïŒã®æº¶æ¶²ããåèäŸïŒã«èš
èŒããæäœã«ããã1.0ïœã®10ïŒ æŽ»æ§çæ æã
ã©ãžãŠã ã®ååšäžã«éå ãããåŸãããçæç©
ããšã¿ããŒã«ããåçµæ¶ãããšã16.1ïœã®ïŒâ
ããããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâ
ãã³ãºã¢ãŸã·ã³èåæ°ŽçŽ é žå¡©ãèç¹235ã237â
ïŒãšã¿ããŒã«ããïŒãåŸãããã  åæ§ã«ããŠã21.2ïœã®ïŒâãã³ãžã«âïŒâã¡
ããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
âãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ïŒå®æœäŸ1Eã«èšèŒããïŒã掻æ§ç
æ æãã©ãžãŠã ã®ååšäžã«æ°ŽçŽ ã§éå ããçæ
ç©ãå¡©é žå¡©ã®åœ¢ã§åé¢ãããš11.4ïœã®ïŒâã¡ã
ãã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒâãª
ããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢
ãŸã·ã³å¡©é žå¡©ãèç¹189ã193âïŒãšã¿ããŒã«ã
ãïŒãåŸãããã å®æœäŸ ïŒ (A) 150mlã®DMFäžã®11.4ïœïŒ0.03ã¢ã«ïŒã®ïŒâ
ããããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâ
ãã³ãºã¢ãŸã·ã³èåæ°ŽçŽ é žå¡©ïŒå®æœäŸ3Aã«èš
èŒããïŒã5.4ïœã®çé žæ°ŽçŽ ãããªãŠã ããã³
5.2ïœïŒ0.04ã¢ã«ïŒã®èåã·ã¯ããããã«ã¡ã
ã«ã®æ··åç©ãçŽïŒæééæµå ç±ããã€ãã§ç空
æ¿çž®ããŠå°å®¹ç©ã«ãããæ®çç©ãæ°Žé žåã¢ã³ã¢
ããŠã ãšé ¢é žãšãã«ãšã«åé ããææ©å±€ãåé¢
ããæ°Žå±€ãè¿œå ã®é ¢é žãšãã«ã§æœåºãããäžç·
ã«ããæœåºæ¶²ãæ°Žãã€ãã§ãã©ã€ã³ã§æŽãã也
ç¥ãããéãã也ç¥ãããšã12.1ïœã®ç²çæç©
ãåŸããããããå¡©åæ°ŽçŽ é žå¡©ã«è»¢åãããã
ã®å¡©é žå¡©ãã¢ã»ããããªã«ããïŒåãã€ãã§ãš
ã¿ããŒã«ïŒãšãŒãã«ããïŒååçµæ¶ãããšã
5.2ïœã®ïŒâã·ã¯ããããã«ã¡ãã«âïŒâãã
ããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
âãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³å¡©é žå¡©ãèç¹147ã154âãåŸãã
ãã (B) å®æœäŸ4Aãšåæ§ãªæäœã«ãããDMFäžã§ç
é žæ°ŽçŽ ãããªãŠã ã®ååšäžã«15.0ïœïŒ0.04ã¢
ã«ïŒã®ïŒâã¡ããã·âïŒïŒeqïŒâã¡ãã«â
ïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11
ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³ïŒå®æœäŸ3Bã«èšèŒã
ãïŒãšèåã·ã¯ããããã«ã¡ãã«ãšãåå¿ãã
ãŠãïŒâã·ã¯ããããã«ã¡ãã«âïŒâã¡ããã·
âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒâãããµãããâ11ïŒeqïŒâïŒïŒâãªããœ
ããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·
ã³ïŒ12.9ïœïŒã補é ããã (C) åèäŸïŒã«èšèŒããæäœã«åŸããçŽ50psiã®
æ°ŽçŽ å§äžã«ãšã¿ããŒã«äžã§æŽ»æ§çæ æãã©ãžãŠ
ããããã
ã ã®ååšäžã«11.4ïœã®ïŒâããããã·âïŒ
ïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâã
ããµãããâ11ïŒeqïŒâïŒïŒâãªããœãã
ã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³è
åæ°ŽçŽ é žå¡©ïŒå®æœäŸ3Aã«èšèŒããïŒãšãã«ã
ã¢ã«ãããããã³ããªãšãã«ã¢ãã³ãšã®éå ã¢
ã«ãã«åã«ãããïŒïŒïŒïŒeqïŒâãžã¡ãã«â
ïŒâããããã·âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâã
ããµãããâ11ïŒeqïŒâïŒïŒâãªããœãã
ã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ïœ
âãã«ãšã³ã¹ã«ãã³é žå¡©ïŒ9.9ïœïŒèç¹199ã
201âïŒãšã¿ããŒã«ããïŒãåŸãããã (D) åèäŸïŒã®æäœãçšããçŽ50psiã®æ°ŽçŽ å§äž
ã«ãšã¿ããŒã«äžã§æŽ»æ§çæ æãã©ãžãŠã ã®ååš
äžã«8.2ïœã®ïŒâã¡ããã·âïŒïŒeqïŒâã¡ãã«
âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11
ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³å¡©é žå¡©ïŒå®æœäŸ3Bã«
èšèŒããïŒãšãã«ã ã¢ã«ãããããã³ããªãšã
ã«ã¢ãã³ãšã®éå ã¢ã«ãã«åã«ãããïŒïŒïŒ
ïŒeqïŒâãžã¡ãã«âïŒâã¡ããã·âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâ
ãã³ãºã¢ãŸã·ã³ïŒ7.5ïœïŒãåŸãããã åŒã®ååç©ã¯äžè¬ã«ã¢ã»ãã«ã¯ããªã³èªçºè ¹
ççªè©ŠéšïŒAchïŒãäžæ¬¡é®çã¹ã¯ãªãŒãã³ã°è©Š
éšãããã³ããã¿ã®å°Ÿã®è»œæ茻å°ç±é®çè©Šéš
ïŒTail Flick AgonïŒã«ãããŠæŽ»æ§ã§ããããã
ã€ããããšãã«âïœâããã³èªçºãã ã
ïŒWrithingïŒè©ŠéšïŒPPQïŒããã³æã«ãªãžã³è©Šéš
ïŒBKïŒã«ãããŠè©Šéšãã掻æ§ã§ããããšãããã€
ãããããã®è©Šéšã¯äžæ¬¡é®çã¹ã¯ãªãŒãã³ã°æäœ
ã§ãããããã®ããã«ããŠåŸãããååç©ã«ã€ã
ãŠã®ããŒã¿ããåèšå®æœäŸã«é¢é£ããŠãED50
ïŒmgïŒKgãç®äžæäžïŒãŸãã¯æå¶çã§ç€ºãããã¹
ãŠã®æäžéã¯mgïŒKgã§è¡šããã ãè¡šã å®æœäŸ1Dããã³3Aã®ååç©ã¯ãããšããŸã·ã³
尟軜ææ®æè©Šéšã«ãããŠæŽ»æ§ã§ããããšããã
ãããã®ED50ïŒç®äžæäžïŒã¯ãããã®ååç©ã«
ã€ããŠãããã24ããã³0.088mgïŒKgã§ãã€ãã æåŸã«ãåŒã®ããçš®ã®ååç©ãããªãã¡åè
äŸ6Dã®ååç©ã¯ãäžæ¬¡é®çã¹ã¯ãªãŒãã³ã°è©Šéš
ã§ããã¢ã»ãã«ã¯ããªã³èªçºè ¹ççªè©Šéšããã³æ
ã«ãªãžã³è©Šéšã«ãããŠæŽ»æ§ã§ããããšããããã
ãããã€ãŠãããã¯é®çå€ãšããŠæçšã§ãããã
ãã«åŒã®çæç©ã®åºçºç©è³ªãšããŠæçšã§ããã
åèäŸ6Dã®ååç©ã®ã¢ã»ãã«ã¯ããªã³èªçºè ¹ç
çªè©Šéšã«ãããED50ã¯18mgïŒKgã§ãã€ããåè
äŸ6Dã®ååç©ã¯æã«ãªãžã³è©Šéšã«ãããŠæŽ»æ§ã§
ãã€ãã ããããã
ãª11ïŒeqïŒâ眮æâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ã«é¢ããã 11âäœçœ®ãäœçŽã¢ã«ãã«åºã§çœ®æãããïŒïŒïŒ
âã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ã¯ç¥ãããŠããã
ïŒããšãã°ã1960幎ïŒæïŒæ¥ä»ãã®ç±³åœç¹èš±
2924603åç §ïŒãããã«ãïŒäœçœ®ã«ã±ãã³ãã«ã«ã
ããŒã«ãŸãã¯äœçŽã¢ã«ã±ãã«åºããã€ïŒïŒ14âãš
ããããã
ã³ãâãšããâããã³ãšã¿ãããã©ãããããã€
ã³ããã³ïŒïŒ14âãšã³ãâãšããâããã³ãšã¿ã
ããã©ããããªãªããã³ç³»åã«ãããååç©ãã¢
ã«ããã«å¹æµããç°åžžãªé®çåãæããããšã¯ç¥
ãããŠããããBentley et al.ïŒJ.Am.Chem.
Soc.89 3267ã3292ïŒ1967ïŒããçµå±ãïŒïŒïŒâã¡
ã¿ãâïŒâãã³ãºã¢ãŸã·ã³åé®çå€ã®11äœçœ®ã«ã
åŸè ã®ç³»åã«ååšããã±ãã³ãã«ã«ãããŒã«ãŸã
ã¯äœçŽã¢ã«ã±ãã«å®åºãå ããããšã«ãããŠé®ç
å€åéã§éåžžã«èå³ãååšãããããããåæã
ãããšããåªåã¯ãã¹ãŠäžæåã«çµã€ãã æ¬çºæã¯ãç¹å®ã®ïŒâR2âïŒïŒeqïŒâR4â
ïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâ
R1â11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãŸã·ã³ã«é¢ããããã§ïŒºã¯â
CH2COR5ã§ããããããŠR1ïŒR2ïŒR3ããã³R4ã¯
æ°ŽçŽ ãäœçŽã¢ã«ãã«ãŸãã¯ä»ã®ææ©åºã§ãããã
ããã®åºã«ã€ããŠä»¥åŸãã詳现ã«èª¬æããããã
ãã®ååç©ã¯ãé®çå€ããã³éº»è¬æ®æå€ãšããŠæ
çšã§ãããäžè¬åŒ ã§è¡šããããã ç¹å®ã®ïŒâR2âïŒïŒeqïŒâR4âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâïŒâ11ïŒaxïŒâR3
â11ïŒeqïŒâCH2ZâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ã¯ãç¹å®ã®ïŒâR2âïŒâR1âïŒâ
â4aαâR3âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒ
ïŒïŒ10ïŒ10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ãã
ã³ãŸãïœããããªã³ããã®é žãšãšãã«äžæŽ»æ§æº¶åª
äžã§ãŸãã¯ãã³ãžã«âãžâäœçŽã¢ã«ãã«ã¢ã³ã¢ã
ãŠã ãã«ã¡ãŒããããã¯ããªäœçŽã¢ã«ãã«ã¢ã³ã¢
ããŠã ãã«ã¡ãŒããšãšãã«å ç±ããããšã«ãã€
ãŠã補é ã§ããã åŒã®æ°èŠãªïŒâR2âïŒïŒeqïŒââïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâR1â
11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³ããã³ãã®è£œé ã«æçšãª
æ°èŠãªåºçºç©è³ªã¯ãæ¬çºæã«åŸããæ°èŠãªäžéäœ
ãå«ãåå転äœãå«ãæ°èŠãªåå¿ã«ãã€ãŠè£œé ã§
ããããã®åå¿ã¯äžè¬ã«æ¬¡ã®ããã«è¡šããããã ããããã
ãããã€ãŠåŒã®ïŒâR2âïŒïŒeqïŒâR4â
ïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâ
R1â11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ã¯åŒïŒåŒïœã
ïœã®äž¡æ¹ãè¡šããåŒïŒã§è¡šããããæ¬çºæã®åºçº
ç©è³ªïŒâR2âïŒâR1âïŒââïŒâR8â4aαâ
R3âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ
10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸ
ãïœããããªã³ãã補é ããããŸããã®åºçºç©è³ª
ã¯åŒã®ïŒâR1âïŒâïŒïŒâR2âãã³ãžã«ïŒâ
ïŒâR3âïŒâR4âïŒâYâ²âïŒâã¢ã¶ãã·ã¯ã
ãïŒïŒïŒïŒïŒããªã¯ãâïŒâãšã³ããåŸãããã
ã®åŒã®ååç©ã¯æšæºæäœã«åŸãåŒã®ããã²ã³
åïŒâR2âïŒâãã³ãžã«ããèªå°ãããã°ãªã
ã€ãŒã«è©Šè¬ãšåŒã®ããã²ã³åïŒâR3âïŒâR4
âïŒâR1âããªãžããŠã ãšã®åå¿ããã³çãã
åŒã®ïŒâïŒïŒâR2âãã³ãžã«ïŒâïŒâR34âïŒ
âR4âïŒïŒïŒâãžãããããªãžã³ãšãžãšããã€
ã«CH2ïŒCHYâ²ãšã®åå¿ã«ãã€ãŠè£œé ãããã äžèšåå¿åŒã«èšèŒãããæçµçæç©ãšåºçºç©è³ª
ã«ãããŠã R1ã¯æ°ŽçŽ ãäœçŽã¢ã«ãã«ãã·ã¯ãã¢ã«ãã«äœ
çŽã¢ã«ãã«ãŸãã¯ããšãã«âäœçŽã¢ã«ãã«ã§ã
ãïŒ R2ã¯æ°ŽçŽ ãããããã·ãŸãã¯äœçŽã¢ã«ã³ãã·
ã§ããïŒ R3ã¯æ°ŽçŽ ãŸãã¯äœçŽã¢ã«ãã«ã§ããïŒ R4ã¯äœçŽã¢ã«ãã«ã§ããïŒ ïŒºã¯âCH2COR5ïŒR5ã¯äœçŽã¢ã«ãã«ã§ããïŒ
ã§ããã ã¯ã«ã«ããã·ãã·ã¢ããã«ã«ãâäœçŽã¢ã«ã³
ãã·ãCOR5ãCOOâäœçŽã¢ã«ãã¬ã³âã·ã¯ãã¢
ã«ãã«ããŸãã¯COOâäœçŽã¢ã«ãã¬ã³ããšãã«
ã§ããã Yâ²ã¯ã«ã«ããã·ãã·ã¢ããã«ã«ãäœçŽã¢ã«ã³
ãã·ãŸãã¯äœçŽã¢ã«ã«ãã€ã«ã§ããããã㊠Halã¯ããã²ã³ã§ããã ããã§äœ¿çšãããäœçŽã¢ã«ãã«ããŸãã¯ãäœçŽ
ã¢ã«ã³ãã·ãã¯é£œåã§ãããã€éç°åŒã§ãã€ãŠïŒ
ãïŒåã®ççŽ ååãå«ãçŽéãŸãã¯åæéã®åºã
æå³ãããããã®äŸã¯ã¡ãã«ããšãã«ãããã
ã«ãã€ãœãããã«ãããã«ãéé£æ¥ïœâããã«ã
ã¡ããã·ããšããã·ãããããã·ãã€ãœãããã
ã·ããŸãã¯ïœâãããã·ã§ããã ããã§äœ¿çšãããäœçŽã¢ã«ã±ãã«ãããããäœçŽ
ã¢ã«ã±ãã«ãããã³ãäœçŽã¢ã«ããã«ãã¯ãïŒå
ã®äºéçµåãŸãã¯äžéçµåãå«ãççŽ æ°ïŒãïŒã®
ïŒäŸ¡ã®åºãæå³ãããããã®äŸã¯ïŒâãããã
ã«ãïŒâãããã«ãïŒâãã³ããã«ãïŒâã¡ãã«
âïŒâãããã«ãïŒâã¡ãã«âïŒâããããã«ã
ïŒâã¡ãã«âïŒâããããã«ãïŒâããããã«ã
ïŒâãããã«ãïŒâãã³ããã«ãïŒâããã·ãã«
ãªã©ã§ããããããäœçŽã¢ã«ã±ãã«ããšããçšèª
ã«ã¯ãïŒâã¯ãããšããã«ãïŒâããã¢ãšãã
ã«ãïŒïŒïŒâãžã¯ããâïŒâããããã«ãïŒâã
ãã¢âïŒâã¡ãã«ããããã«ãªã©ãå«ãŸããã ããã§äœ¿çšãããã·ã¯ãã¢ã«ãã«ãã¯ãïŒãïŒ
åã®ççŽ ååãå«ã飜åççŽ ç°åŒåºãæå³ããã
ã®äŸã¯ã·ã¯ããããã«ãã·ã¯ãããã«ãã·ã¯ãã
ã³ãã«ãã·ã¯ãããã·ã«ãïŒâã¡ãã«ã·ã¯ããã
ã«ãïŒâãšãã«ã·ã¯ãããã·ã«ãªã©ã§ããã ããã§äœ¿çšãããäœçŽã¢ã«ã«ãã€ã«ãã¯ãççŽ
æ°ïŒãïŒã®é£œåèèªæã¢ãã«ã«ãã³é žããèªå°ã
ããåºãããšãã°ãã«ãã«ãã¢ã»ãã«ãããããª
ãã«ããããªã«ãã€ãœãããªã«ãªã©ãæå³ããã ããã§äœ¿çšãããäœçŽã¢ã«ãã¬ã³ãã¯ãçŽéãŸ
ãã¯åæéã§ããããšãã§ãççŽ æ°ãïŒãïŒã®é£œ
åã®ïŒäŸ¡ã®åºãæå³ãããã®äŸã¯ã¡ãã¬ã³ãâ
CH2âãïŒïŒïŒâãšãã¬ã³ãâCH2CH2âãã
ïŒïŒïŒâãããã¬ã³ãâCH2CH2CH2âããïŒïŒ
ïŒâïŒïŒâã¡ãã«ãšãã¬ã³ïŒãâCHïŒCH3ïŒCH2
âããïŒïŒïŒâããã¬ã³ãâCH2CH2CH2CH2âã
ãªã©ã§ããã 以åŸèšèŒããæšæºã¯è¬çåŠçè©Šéšã«ãããŠæ±ºå®
ããããã
ãããããã«ãåŒã®ååç©ã¯ãæçšãªé®ç掻æ§
ããã€ããšãããããåŒã®ååç©ã®ãããã®ã¯
æçšãªéº»è¬æ®æ掻æ§ããã€ããšãããã€ãããã
ãã€ãŠãåŒã®ååç©ã¯é®çå€ããã³éº»è¬æ®æå€
ãšããŠæçšã§ããã äžèšäžè¬çèšèŒã«ããã°ãåŒã§è¡šããã
R1ïŒR2ïŒR3ïŒR4ïŒR5ããã³ïŒºãäžã«å®çŸ©ãããš
ããã§ããïŒâR2âïŒâïŒïŒeqïŒâR4âïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâïŒâR1â
11ïŒaxïŒâR3â11ïŒeqïŒâCH2ZâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³ã¯ãåŒã§è¡šããããïŒ
âR2âïŒâR1âïŒââïŒâR8â4aαâR3âïŒ
αâR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãª
ã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããª
ã³ããææ©æº¶åªãããšãã°ãã«ãšã³ããã·ã¬ã³ã
ããã¯ã¡ã·ãã¬ã³äžã§ã®é žãšããããã¯ãã³ãžã«
âãžâäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãŸãã¯ããªäœçŽ
ã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããšãšãã«å ç±ã
ãããšã«ãã€ãŠã補é ãããã奜ãŸãã溶åªã¯ã¡
ã·ãã¬ã³ã§ããã åèšåå¿åŒã«ç€ºãããããã«ãåŒïŒ¢ã®ååç©
ããªããŠã å¡©ãçµãŠã¢ã«ãã«åãããšãåºã®ãš
ãã¡ãªåãèµ·ãããåŒã®ååç©ã®ç°åã«ããåŸ
ããããããªåŒïŒ¢ã®ååç©äžã®åºïŒ¹ã¯åžžæ ã§Î²
âç«äœé 眮ããã¡ãããªãã¡åºïŒ¹ã¯ïŒïŒïŒâã¡ã¿
ãæ©ããã«å¯ŸããŠã·ã¹ã§ããããåŒïŒ¢ã®ååç©
ããªããŠã å¡©ãçµãŠã¢ã«ãã«åãããšããαâ
ç«äœé 眮ïŒïŒïŒïŒâã¡ã¿ãæ©ããã«å¯ŸããŠãã©ã³
ã¹ïŒã§ããïŒäœã®äœçŽã¢ã«ãã«åºãβç«äœé 眮ã§
ããååç©ãçæãããäºå®ãåŒïŒ¡ã§è¡šããã
ãαç«äœé 眮ã§ããååç©ã¯ãβâååç©
ïŒåŒïŒ¢ïŒã®ååç©ããŸã匷塩åºã§ãã€ãã§é žã§
åŠçããããšã«ãã€ãŠè£œé ã§ãããããã³
ã®ååç©ã«ãããåºïŒ¹ããã³ïŒäœã®ïŒšã®ããã
ãã¯Î±ãŸãã¯Î²ã®ç«äœé 眮ã®ãããããæºããã
ãšãã§ããåŒïŒ¡ããã³ïŒ¢ã®ååç©ã¯äžè¬ã«äž¡
åŒãå å«ããè€ååŒ åŒã§è¡šããããCOR5ã§ããååç©ããå
è¿°ã®ããã«ãææ©æº¶åªäžã§ã®é žãšãšãã«ããŸãã¯
ãã³ãžã«âãžâäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«ã¡
ãŒããããã¯ããªäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«
ã¡ãŒããšãšãã«å ç±ãããšãåŸè¿°ã®åŒã§è¡šãã
ãããåŒããåŒããŸã㯠ãåŒãã§ããïŒâR2âïŒâ R1âïŒââ4aαâR3âïŒÎ±âR4âïŒïŒïŒïŒ
ïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâïŒïŒ
ïŒâãšãããã³ãŸãïœããããªã³ãåŒïŒïŒºã¯â
CH2COR5ã§ããïŒã®ååç©ãšäžç·ã«çæããã
åŒã®ãã³ãºã¢ãŸã·ã³ã®çæéãæé«ã«ãããã
ã«ã¯ãåŒã®åºçºç©è³ª0.05ã¢ã«ããã³ã®é ž1.0ã¢
ã«ã®æ¿åºŠãçšãã¡ã·ãã¬ã³äžã§åå¿ãå®æœããã
ãšã奜ãŸããããã®æ··åç©ã¯éæµæã«çŽ120âã®
åå¿æž©åºŠãäžããåŒã®ãã³ãºã¢ãŸã·ã³ããã³åŒ
ã®ãã³ãŸãïœããããªã³ãïŒïŒïŒãïŒïŒïŒã®æ¯
ã§äžãããã®é žæ¿åºŠã挞é²çã«äœäžãããããšã«
ãããé£ç¶çã«æ²žç¹ãé«ãæ··åç©ãçæãããã®
çµæãã³ãŸãïœããããªã³ã®çžå¯Ÿéã¯æŒžé²çã«å¢
å ããã0.5ã¢ã«ããã³0.15ã¢ã«ã®ã®é žæ¿åºŠïŒã
ããŠåºçºç©è³ªæ¿åºŠ0.05ã¢ã«ïŒã«ãããŠããããã
çŽïŒïŒïŒããã³ïŒïŒïŒã®æ¯ã§ãã³ãŸãïœããããª
ã³ãçæãããåæ§ã«ãïŒã¢ã«ã®åºçºç©è³ªå¯ŸïŒã¢
ã«ã®ãã³ãžã«ãžã¡ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããŸ
ãã¯ããªã¡ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããŸãã¯ã
ãªã¡ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããŸãã¯ããªãšã
ã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒãã®æ¯ãçšãããã®æ··å
ç©ãïŒææ©æº¶åªã®äžååšäžã§ïŒ150âã«çŽ15åé
å ç±ããããšã«ããããã³ãŸãïœããããªã³ãšã
ã³ãºã¢ãŸã·ã³ãšã®æ··åç©ããããã10ïŒ ãïŒïŒ
ïŒããã³20ïŒïŒã®æ¯ã§çæããã ãã®ããã«äžå®æ¡ä»¶äžã§ïŒçš®ã®å€ç§»ãåæã«èµ·
ãããããã¯æ¬¡ã®åå¿åŒã§æãããè¡šããããã ããããã
äžåŒäžR1ïŒR2ïŒR3ïŒR4ïŒR5ããã³ïŒ±ã¯äžã«å®
矩ãããšããã§ãããäžãããããããã«ãåŒ
ã®ååç©ã¯åŒã®ååç©äžã®çµå(b)ã®åå¿æ¡ä»¶äž
ã®éè£ã«ããçããããã«å¯ŸãåŒïœã®ååç©ã¯
çµå(a)ãç Žå£ããããšãçªçŽ ååãšCOR5éšåã®
ã«ã«ããã«åºãšã®éã®éç°ã«ãã€ãŠçæããã åŒã®æçµçæç©ã®è£œé ã«ãããåºçºç©è³ªã§ã
ãåŒã®ïŒâR2âïŒâR1âïŒÎ²ââ4aαâR3
âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10a
âãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœãã
ããªã³é¡ã¯ã次ã®ããã«ããŠè£œé ããã åŒã§è¡šãããããã«ã«ããã·ãã·ã¢ããã«
ã«ãâäœçŽã¢ã«ã³ãã·ãŸãã¯COR5ïŒããã§R5ã¯
äœçŽã¢ã«ãã«ã§ãããCOOâäœçŽã¢ã«ãã¬ã³â
ã·ã¯ãã¢ã«ãã«ãŸãã¯COOâäœçŽã¢ã«ãã¬ã³â
ããšãã«ïŒã§ããååç©ã¯ãé©åœãªåŒã®ïŒâ
R1âïŒâïŒïŒâR2âïŒâR2â²ããŸãã¯R2â³ãâã
ã³ãžã«ïŒâïŒâR3âïŒâR4âïŒâYâ²âïŒâã¢ã¶
ãã·ã¯ãã2.2.2ããªã¯ãâïŒâãšã³ã®é žã觊åª
ãšããç°åã«ãã€ãŠè£œé ãããããã®åå¿ã¯åŒ
ã®ååç©ãé žãžå ãããã®åå¿æ··åç©ãçŽïŒãçŽ
10âã®æž©åºŠã«é眮ããããŸãã¯çŽ100âã«å ç±ã
ãããšã«ãã€ãŠå®æœããã奜ãŸããé žã¯å¡©é žãè
åæ°ŽçŽ é žãç¡«é žãããé žãªã©ã§ãããç¹ã«å¥œãŸã
ãé žã¯å¡©é žã§ããã åŒã®ååç©ã®åŒã®ååç©ïŒåºçºç©è³ªïŒãžã®
ç°åã¯ããã³ãžã«åºã®ïŒâãŸãã¯ïŒâäœçœ®ã§èµ·ã
ããåŒã®ååç©ãçæãããããã«ãåŒã®å
åç©ã®åŒã®ååç©ãžã®ç°åã«ãããR3ããã³
R4åºã®äž¡æ¹ãαâç«äœé 眮ã«ãããããªãã¡
ïŒïŒïŒâã¡ã¿ãæ©ããã«å¯ŸããŠãã©ã³ã¹ã«ããå
åç©ãçããã ããã«ãç°ååå¿ã®éäžããããããªãšã¹ãã«
åºãŸãã¯ãšãŒãã«åºãããšãã°ãåŒã®ååç©ã«
ãããYâ²ãŸãã¯åŒã®ååç©ã«ãããããšã¹
ãã«åºã§ãããããããã¯R2ãããšãã°äœçŽã¢
ã«ã³ãã·ã§ããååç©ãã¯ããšãã«åå¿æ··åç©
ããããšãã°èåæ°ŽçŽ é žãå ç±ãããšãããã°ã
ã°éè£ããŠå¯Ÿå¿ããã«ã«ãã³é žãŸãã¯ããšããŒã«
æ§ååç©ãšãªãããã®ãããªå Žåã«ãããŠããšã¹
ãã«ãŸãã¯ãšãŒãã«ãç®çååç©ã§ãããšããæš
æºæäœã«ããçæç©ãåãšã¹ãã«åãŸãã¯åã¢ã«
ãã«åããªããã°ãªããªãããã®ãããªããšã¯é ž
觊åªãšããŠå¡©é žã®äœ¿çšã«ãã容æã«é¿ããããšã
ã§ããã®ããåå¿æž©åºŠã¯ïŒã10âä»è¿ãšããã ã
ã§ããããã®ãã ãããªæ¡ä»¶ã«ãããŠããšã¹ãã«
ãšãšãŒãã«åºã¯åå¿äžæªå€åã®ãŸãŸã§ããã åŒã®ååç©ã補é ããäžèšæ¹æ³ã¯ãåŒã§è¡š
ããããã«ã«ããã·ãã·ã¢ããã«ã«ãäœçŽã¢ã«
ã³ãã·ãŸãã¯COR5ïŒR5ã¯äœçŽã¢ã«ãã«ã§ããïŒ
ååç©ã®è£œé ã«ãšãã«æå©ã§ããã åŒã§è¡šããããã«ã«ããã·ãã·ã¢ããŸãã¯
ã«ã«ãäœçŽã¢ã«ã³ãã·ã§ããååç©ã¯ãç°¡åãªå
åŠç転åæ³ãããšãã°ãããªã«ã®ã«ã«ãã³é žãžã®
å æ°Žå解ã«ãã€ãŠè»¢åã§ãããé žïŒïŒ¹ã¯ã«ã«ãã
ã·ïŒãŸãã¯ãšã¹ãã«ïŒïŒ¹ã¯ã«ã«ãäœçŽã¢ã«ã³ã
ããããã
ã·ãCOOâäœçŽã¢ã«ãã¬ã³ã·ã¯ãã¢ã«ãã«ã
COOâäœçŽã¢ã«ãã¬ã³ããšãã«ïŒãïŒã¢ã«ã®é©
åœãªææ©ãªããŠã R5Liãšåå¿ãããŠïŒ¹ãCOR5ã§
ããåŒã®ååç©ãçæããããšãã§ãããåŒ
ã§è¡šããããäžã«å®çŸ©ãããšããã§ããååç©
ãåŒã§è¡šããããCOR5ã§ããååç©ã®è£œé
ã«äžéäœãšããŠæçšã§ããããããŠãã®ïŒ¹ã
COR5ã§ããåŒã®ååç©ã¯åŒã®ååç©ã®è£œé
ã«ãããŠäžéäœãšããŠæçšã§ããã åŒãŸãã¯ã§è¡šãããR1ããã³ãžã«ã§ãã
ååç©ã¯ãæ¥è§Šçã«è±ãã³ãžã«åããŠãR1ãæ°Ž
çŽ ã§ãã察å¿ããååç©ãšããããšãã§ãããã€
ãã§ãåŸè ã®ååç©ã¯é©åœãªã¢ã«ãã«åå€ã§åã¢
ã«ãã«åããŠãR1ãäžã«å®çŸ©ãããšããã§ãã
ä»ã®ç°ãªãååç©ã«ããããšãã§ãããäžæŽ»æ§æº¶
åªãããšãã°ãšã¿ããŒã«ãã€ãœãããããŒã«ãªã©
äžã§40ã100ãã³ãpsiã®å§åã§éå ãå®æœããã
奜ãŸãã觊åªã¯ã掻æ§çã«æ æããããã©ãžãŠã
ã§ãããåŒã§è¡šãããR1ãæ°ŽçŽ ã§ããååç©
ã®ã¢ã«ãã«åã¯ãäžæŽ»æ§æº¶åªãããšãã°ã¢ã»ã
ã³ããšã¿ããŒã«ãŸãã¯DMFäžã§é žåäœãããšã
ã°ã¢ã«ã«ãªéå±ã®çé žå¡©ãŸãã¯éçé žå¡©ã®ååšã§
å®æœããã æåŸã«ãåŒã§è¡šããããåºçºç©è³ªã®è£œé ã«ã
ããäžéäœã§ããåŒã®ïŒâR1âïŒâïŒïŒâR2
âãã³ãžã«ïŒâïŒâR3âïŒâR4âïŒâYâ²âïŒâ
ã¢ã¶ãã·ã¯ãã2.2.2ããªã¯ãâïŒâãšã³ã¯ãåŒ
ã®ããã²ã³åïŒâR2âãã³ãžã«ããèªå°ãã
ãã°ãªãã€ãŒã«è©Šè¬ãšé©åœãªåŒã®ããã²ã³åïŒ
âR3âïŒâR4âïŒâR1âããªãžããŠã ãšãåå¿
ãããã€ãã§çããåŒã®ïŒâïŒïŒâR2âãã³
ãžã«ïŒâïŒâR3âïŒâR4âïŒïŒïŒâãžãããã
ãªãžã³ãšé©åœãªãžãšããã€ã«CH2ïŒCHYâ²ãšãã
ã€ãŒã«ã¹ã»ã¢ã«ããŒçž®åãããŠã補é ãããã ã°ãªãã€ãŒã«è©Šè¬ãçšããåå¿ã¯ïŒã25âã«ã
ããŠäžæŽ»æ§æº¶åªãããšãã°ãžãšãã«ãšãŒãã«ãã
ãã©ããããã©ã³ãŸãã¯ãžããã«ãšãŒãã«äžã§å®
æœããã°ãªãã€ãŒã«æº¶æ¶²ãåå¿æº¶åªäžã®ç¬¬åçŽå¡©
ã®ããæ¿æ¶²ãžå ããããšã«ãã€ãŠè¡ãªããçæã
ãåŒã®ãžãããååç©ã¯äžè¬ã«åé¢ããã³ç²Ÿè£œ
ãããããããžãšããã€ã«ãšã®åå¿ãå«ã次ã®å·¥
çšã«ãããŠããã«ç²Ÿè£œããã«çŽæ¥äœ¿çšãããåŒ
ã®ãžãããååç©ãšãžãšããã€ã«ãšã®åå¿ã¯æº¶åª
ãšããŠéå°éã®ãžãšããã€ã«äžã§ããããã¯äžæŽ»
æ§ææ©æº¶åªãããšãã°ãã³ãŒã³ããã«ãšã³ãŸãã¯
ãã·ã¬ã³äžã§å®æœã§ãããåå¿ã¯å¥œãŸããã¯æ··å
ç©ã®éæµæž©åºŠã«ãããŠå®æœããã åŒã®ç¬¬åçŽåç©ã補é ããã®ã«äœ¿çšããïŒâ
R3âïŒâR4âããªãžã«ãããã«ã°ãªãã€ãŒã«è©Š
è¬ã補é ããã®ã«äœ¿çšããããã²ã³åïŒâR2â
ãã³ãžã«ã¯ãç¥ãããŠããååç©ã§ããã å¡©åºæ§ã¢ããåºãååšãããããäžèšåŒã
ãããã³ã§è¡šããããéé¢å¡©åºã¯ãææ©é žã
ãã³ç¡æ©é žãšåå¿ããŠé žä»å å¡©ãçæããããã®
é žä»å å¡©ã¯ãããªãææ©é žãŸãã¯ç¡æ©é žããã補
é ã§ããããã®é žä»å å¡©ã¯ãåžžæ³ã«ãããããšã
ã°å¡©åºãšé žãçŽæ¥æ··åãããããããé©åœã§ãªã
ãšãå¡©é žãšé žã®äžæ¹ãŸãã¯äž¡æ¹ãæ°ŽãŸãã¯ææ©æº¶
åªã«å¥ã ã«æº¶ããããããã®ïŒçš®ã®æº¶æ¶²ãæ··åã
ããããããã¯å¡©åºãšé žãšãäžç·ã«æº¶åªã«æº¶è§£ã
ãããšã«ãã€ãŠåŸããããçããé žä»å å¡©ã¯ãå
å¿åªäœäžã«æº¶ããªãå Žåãéã«ããããŸãåå¿åª
äœãèžçºãããŠé žä»å å¡©ãæ®çç©ãšããŠæ®ãããš
ã«ããåé¢ãããããããã®å¡©ã®åœ¢ã®é žéšåãã
ãªãã¡é°ã€ãªã³ã¯ãããèªäœæ°èŠã§ããªãèšçç
ã§ãªãã®ã§ãå¡©åºãšå¡©ã圢æã§ãããããªãé žã®
é°ã€ãªã³ãŸãã¯é žæ§ç©è³ªã§ããããšãã§ããã é žä»å å¡©ã®çæã«ä»£è¡šçãªé žã¯ã次ã®ãšããã§
ãããã®é žãé ¢é žãã€ãœé ªé žãαâã¡ã«ã«ããã
ãããªã³é žãããªãã«ãªãé ¢é žããããé žããã
ãŒã«é žããã¯ãé žãã¹ã¯ã·ããã³é žãã¿ã³ãã³
é žãã°ã«ã¿ãã³é žãé ç³é žããããé žãããã ã·
ã³é žããããé žãä¹³é žãã°ãªã³ãŒã«é žãã°ã«ã³ã³
é žããµãã«ãªã³é žãã¢ã¹ã³ã«ãã³é žãããã·ãª
ã³ãå®æ¯éŠé žããã¿ã«é žããµãªã·ã«é žãïŒïŒïŒâ
ãžãããå®æ¯éŠé žãã¢ã³ãã©ãã«é žãã³ãªã³é žã
ïŒâããªãžã³ã«ã«ãã³é žããã¢ã€ã³é žãïŒâãã
ããã·âïŒâãããã€ã³é žããã¯ãªã³é žãããã³
é žããããã³é žãïŒâã€ã³ããŒã«é ¢é žããã«ãã
ã«é žãã¹ã«ãã¢ãã³é žãã¡ã¿ã³ã¹ã«ãã³é žããšã¿
ã³ã¹ã«ãã³é žãã€ã»ããªã³é žããã³ãŒã³ã¹ã«ãã³
é žãïœâãã«ãšã³ã¹ã«ãã³é žãããã«ã¢ã«ãœã³
é žãã¡ã¿ã³ãã¹ãã³é žãé žæ§æš¹èãããåæ°ŽçŽ
é žãå¡©åæ°ŽçŽ é žãèåæ°ŽçŽ é žããšãŒåæ°ŽçŽ é žãé
å¡©çŽ é žãç¡é žãç¡«é žãããé žããé žãªã©ã é žä»å å¡©ã®ãã¹ãŠã¯ãç¡æ©å¡©åºãšã®åå¿ã«ãã
éé¢å¡©åºã®åœ¢æ ã®æºãšããŠæçšã§ããããããã€
ãŠãäžå®ã®å¡©åºãŸãã¯é žä»å å¡©ã®ç¹æ§ãããšãã°
ããããã
溶解床ãååéãç©ççå€èŠ³ãæ¯æ§ãªã©ã®ïŒãŸã
ã¯ïŒä»¥äžãææã®ç®çã«äžé©åœã§ããå Žåããã
ãä»ã®ããé©åœãªåœ¢ã«è»¢åã§ããã補è¬äžã®ç®ç
ã§ãæ¯èŒçéæ¯æ§ã®è£œè¬äžèš±å®¹ãããé žãããšã
ã°å¡©é žãä¹³é žãé ç³é žãªã©ã®é žä»å å¡©ããã¡ãã
䜿çšã§ããã æ¬çºæã®ååç©ã¯ç«äœç°æ§äœãããªãã¡å åŠç
ç°æ§äœããã³å¹ŸäœåŠçç°æ§äœã®åœ¢ã§ååšã§ããã
å¿ èŠã«å¿ããŠãç¹å®ã®ç«äœç°æ§äœãå è¡æè¡ã§ç¥
ãããŠããäžè¬åçãå¿çšããŠåé¢ãã補é ã§ã
ããããã§äœ¿çšããåŒã®ååç©ã«çšããååœæ³
ã«ãããŠãaxãã¯ã·ã¯ããããµã³ç°å¹³é¢ã«å¯Ÿã
ãŠåçŽæ¹åã«çµåããŠããããšãæå³ãããeqã
ã¯æ°Žå¹³æ¹åã®çµåãæå³ãããããŠç«äœé 眮ã¯ã
ããè³éŠæç°ã«ã€ããŠäžãããã®ã§ãããããã
ã€ãŠãåŒã®ïŒïŒeqïŒã11ïŒaxïŒååç©ã¯ã·ã¹ç«
äœé äœã§ãããããã«å¯ŸããŠïŒïŒeqïŒã11ïŒeqïŒ
ååç©ã¯ãã©ã³ã¹ç«äœé äœã§ããã åŒã®ååç©ã«äœ¿çšããååœæ³ã«ãããŠãåã³
ç«äœé 眮ããããè³éŠæç°ã«äžããèšå·ãβãã¯
åŒã®ååç©ã®ïŒïŒïŒâã¡ã¿ãæ¶æ©ã«é¢ããŠã·ã¹
ç«äœé 眮ã瀺ããéã«ãèšå·ãαãã¯åã矀ã«é¢
ããŠãã©ã³ã¹ç«äœé 眮ã瀺ãã æšæºã®è¬çåŠçè©Šéšæäœã«ãããŠãåŒã®åå
ç©ãªãã³ã«ãããã®é žä»å å¡©ã¯äžæ¢ç¥çµç³»çµ±ã®æ
å¶å€ãšããŠæçšã§ããããšããããããšãã«é®ç
å€ãšããŠãªãã³ã«ããšããŸãªã³ãã¡ããªãžã³ãã
ã³ã¢ã«ããã®ãããªåŒ·ãé®çå€ã®æ®æå€ãšããŠæ
çšã§ããããšãããã€ããããã«åŒã®ååç©ã®
ãããã®ã¯é®çå€ãšããŠæçšã§ããããšãããã€
ãã åŒã®ååç©ã¯ãæ¢ç¥ã®é®çå€ããã³åŒ·ãé®ç
å€ã®æ®æå€ãšåãããã«ããŠãããªãã¡ããµã€ã
ã®è£œè¬ç圢æ ãããšãã°æº¶æ¶²ãããæ¿æ¶²ãé å€ã
ã«ãã»ã«ãªã©ã®åœ¢æ ã§ç®äžçã«ãŸãã¯çµå£çã«æ
äžã§ããã æ¬çºæã®ååç©ã®æçšãªæ§è³ªã¯ãè¬çåŠçè©Šéš
æäœã«ãããŠéåžžã®ç¥èããã€æè¡è ã«ãã€ãŠå®¹
æã«è¡ãªãããšãã§ããæšæºã®è¬çåŠçæäœã«ã
ã€ãŠæããã«ãããã®ã§ãç¹å®ã®è©Šéšååç©ã«ã€
ããŠã®æ°ççç©åŠçããŒã¿ã®å®éã®æž¬å®ãå®éšã
æ¡åŒµããªãã§ç¢ºèã§ããã æ¬çºæã®ååç©ã®é®ç掻æ§ããã³é®çæ®æ掻æ§
ã枬å®ããã®ã«äœ¿çšããè©Šéšæäœã¯ãå è¡æç®ã«
詳现ã«èšèŒãããŠããŠããã次ã®ããã§ãããã¢
ã»ãã«ã¯ããªã³èªçºè ¹ççªè©Šéšãããã¯Collier
et al.ïŒBritïŒJ.Pharmacol.Chemotherap.32ïŒ
295ïŒ1968ïŒã«èšèŒãããŠãããã¯ã€ãããã¿ã«
ãããŠã¢ã»ãã«ã¯ããªã³ã«ããèªçºãããè ¹ã®ç
çªãæå¶ããè©Šéšè¬å€ã®èœåã枬å®ããããã«æ¡
åºãããäž»ã«é®çã¹ã¯ãªãŒãã³ã°è©Šéšã§ãããæ
ã«ãªãžã³è©Šéšã®å€æŽæ³ãããã¯Berkowitz et al.
ïŒJ.Pharmacol.Exp.Therap.177ïŒ500â508
ïŒ1971ïŒïŒBlane et al.ïŒJ.Pharm.Pharmacol.19ïŒ
367â373ïŒ1967ïŒïŒBotha et al.ïŒEur.J.
Pharmacol.ïŒïŒ312â321ïŒ1969ïŒããã³Deffenu
et al.ïŒJ.Pharm.Pharmacol.18ïŒ135ïŒ1966ïŒã«
èšèŒãããŠãããäž»ã«é®çã¹ã¯ãªãŒãã³ã°æ³ã§ã
ããããšãã«âïœâããã³èªçºèº«ãã ãè©Šéšãã
ãã¯Pearlããã³HarrisïŒJ.Pharmacol.Exptl.
Therap.154ïŒ319â323ïŒ1966ïŒã«èšèŒãããŠã
ããã¯ã€ãããã¿ã«ãããããšãã«âïœâããã³
èªçºèº«ãã ããé²æ¢ããè©Šéšè¬å€ã®èœåã枬å®ã
ãããã«æ¡åºãããäž»ã«é®çã¹ã¯ãªãŒãã³ã°è©Š
éšãDâ²Amour and SmithïŒJ.Pharmacol.Exptl.
Therap.72ïŒ74ïŒ1941ïŒã«èšèŒãããBassããã³
Vander BrookïŒJ.Am.Pharm.Assoc.Sci.Ed.41ïŒ
569ïŒ1956ïŒã«ããå€æŽãããããã¿ã®å°Ÿã®è»œæ
ã®èŒ»å°ç±ã®é®çãã¢ãŽãã¹ãïŒagonistïŒè©Šéšã
ãããŠãããšããŸã·ã³æ®æè©Šéšãããã¯Harrisã
ãã³PiersonïŒJ.Pharmacol.Exptl.Therap.143ïŒ
141ïŒ1964ïŒã«èšèŒãããåè¿°ã®ããã¿ã®å°Ÿã®è»œ
æã®å¿çè©Šéšã«ãããããšããŸã·ã³ã®å¹æã«æ®æ
ããè©Šéšè¬å€ã®èœåã枬å®ããããã«æ¡åºããã
ãã®ã§ããã æ¬çºæã®ååç©ã®æ§é ã¯ãåææ³ãå çŽ åæã
玫å€ã¹ãã¯ãã«ãèµ€å€ã¹ãã¯ãã«ããã³æ žç£æ°å ±
鳎ã¹ãã¯ãã«ã«ãã確ç«ãããåå¿éçšãšçæç©
ã®å質æ§ã¯èå±€ã¯ãããã°ã©ãã€ãŒã«ãã確èã
ãã 次ã«åèäŸããã³å®æœäŸã«ããæ¬çºæã説æã
ããèç¹ã¯ç¹èšããªããããè£æ£ããªãã€ãã åºçºç©è³ªåæã®ããã®äžéäœã®è£œé åèäŸïŒïŒåºçºç©è³ªåæçšäžéäœã®è£œé ïŒ (A) 450mlã®ãžãšãã«ãšãŒãã«äžã®76ïœïŒ0.6ã¢
ã«ïŒã®å¡©åãã³ãžã«ã®æº¶æ¶²ãã150mlã®ä¹Ÿç¥ãš
ãŒãã«äžã®14.6ïœïŒ0.6ã¢ã«ïŒã®ãã°ãã·ãŠã
æåç©ã®æ··åç©ã«ããã ãããªéæµãç¶æãã
ããããã
ããããªé床ã§å ãããã€ãã§çãã溶液ãã
ã¬ã©ã¹ã»ãŠãŒã«ãçµããéã«ãã€ãŠã150mlã®
ãšãŒãã«äžã®75ïœïŒ0.3ã¢ã«ïŒã®ïŒâãšãã«ã
ãªãžã³ã¡ãã€ãªãã€ãã®ããæ¿æ¶²ã«å ãããã
ã®æ··åç©ã宀枩ã§ïŒæéãããŸããå¡©åã¢ã³ã¢
ããŠã ãå«ãæ°·ïŒæ°Žæ··åç©ã«æ³šãå ¥ããææ©å±€
ãåé¢ãã也ç¥ããéãããšãŒãã«ã§åžéã
ãŠ900mlã«ããã ïŒâã¡ãã«âïŒâãã³ãžã«âïŒâãšãã«â
ïŒïŒïŒâãžãããããªãžã³ãå«ã溶液ã300ml
ãã€ã®ïŒéšåã«åããåéšåãèžçºä¹Ÿç¥ããã
ããã200mlãã€ã®ãã³ãŒã³ããã«ãšã³ããã·
ã¬ã³ã«æº¶è§£ããïŒåã®æº¶æ¶²ã22mlã®ã¢ã¯ãªã«é ž
ãšãã«ã§åŠçããäžå€éæµãããå溶液ãæŸå·
ãããžãšãã«ãšãŒãã«ã§åžéãã150mlã®1N
HClã§æœåºãããæœåºæ¶²ããããããžãšãã«ãš
ãŒãã«ã§äžåæŽããã€ãã§15mlã®æ¿æ°Žé žåã¢ã³
ã¢ããŠã ã§å¡©åºæ§ã«ãã150mlã®ãžãšãã«ãšãŒ
ãã«ã§æœåºãããïŒåã®ãµã³ãã«ã®æœåºæ¶²ãã
ãããã18.2ïœã20.0ïœã19.3ïœã®çæç©ãæ²¹
ç¶ç©ãšããŠåŸããïŒåã®ãµã³ãã«ããžãšãã«ãš
ãŒãã«ã«æº¶è§£ãããšãŒãã«æ§å¡©é žã§é žæ§ã«ãã
ããŒã¿ã«ã§32.2ïœã®ãšãã«âïŒâã¡ãã«âïŒâ
ãã³ãžã«âïŒâãšãã«âïŒâã¢ã¶ãã·ã¯ã
ã2.2.2ããªã¯ãâïŒâãšã³âïŒâã«ã«ããã·ã¬
ãŒãå¡©é žå¡©ïŒmp189ã191âïŒãåŸãã åèäŸïŒ(A)ã®æ¹æ³ã§ã溶åªãšããŠãã³ãŒã³ãã
ã«ãšã³ããã·ã¬ã³ã®ããããã䜿ããåŒã®ïŒâ
R2âãã³ãžã«ãã°ãã·ãŠã ã¯ããªããåŒã®ïŒ
âR3âïŒâR4âïŒâR1âããªãžããŠã ãã©ã€
ãããžãšããã€ã«CH2ïŒCHYâ²ãã以äžã®åŒã®
ïŒâR1âïŒâïŒïŒâR2âãã³ãžã«ïŒâïŒâR3â
ïŒâR4âïŒâYâ²âïŒâã¢ã¶ãã·ã¯ãã2.2.2ããª
ã¯ãâïŒâãšã³é¡ã補é ããã ç¹èšãªãéããçæç©ã¯å¡©é žå¡©ã®åœ¢ã§åé¢ãã
ç¹æ§ã¥ãããåŒã®ïŒçŽå¡©ã®ã¢ããªã³ã¯åŒã®ïŒ
çŽå¡©ã®ééã®æ¬¡ã®ã«ãã³å ã«ç€ºãã ãã®æ现æžã®è¡šã«ãããŠãåæååç©ïŒS.M.
ïŒãšçæç©ïŒäžéäœïŒïŒProdïŒã®ééã¯âWt.
ââã§ç€ºããæ¬ã«ïœã§ç€ºããæçµçæç©ã®èç¹ã¯
åçµæ¶æº¶åªãšå ±ã«æåŸã®æ¬ã«ç€ºãã ããã€ãã®åå¿æåã®ïŒã€ã®ã¿ã®éããèšèŒã
ããŠããå Žåãä»ã®åå¿æåã®éãã¯çšããå®éš
宀çæ¹æ³ã«ã€ããŠèšèŒããå®æœäŸã«ãããŠäœ¿çšã
ãéããé©åœãªã¢ã«åºæºã§èšç®ã§ãããããå Žå
ã«ãããŠãçæç©ãèžçãŸãã¯åçµæ¶ã«ããç¹æ§
ã¥ããããããåå¿æ··åç©ããåé¢ãããŸãŸã§æ¬¡
ã®å·¥çšã«çŽæ¥äœ¿çšããã åºçºç©è³ªãŸãã¯çæç©ã®ãå¡©åºãŸãã¯å¡©ã§ãã
ç¹å®ã®åœ¢æ ããééãšãšãã«ãå¡©åºãããHClãã
ãHBrãããªã©ã§è¡šããããããã¯ããããéé¢å¡©
åºãå¡©é žå¡©ãèåæ°ŽçŽ é žå¡©ãªã©ã®å¡©ã瀺ãã ãè¡šã åèäŸïŒïŒåºçºç©è³ªã®è£œé (A) 125mlã®48ïŒ ã®èåæ°ŽçŽ é žäžã®åèäŸ1Aã«èš
ããããã
èŒãã12.3ïœïŒ0.035ã¢ã«ïŒã®ïŒâã¡ãã«âïŒ
âãã³ãžã«âïŒâãšãã«âïŒâã¢ã¶ãã·ã¯ã
ã2.2.2ããªã¯ãâïŒâãšã³âïŒâã«ã«ãã³é žãš
ãã«ã®æ··åç©ãéæµäžã«24æéãããŸããååŽ
ãããåé¢ããåºäœãéãããšã8.4ïœã®ïŒâ
ã¡ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒ
ïŒïŒ10ïŒ10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ã
ãã³ãŸãïœããããªã³âïŒÎ²âã«ã«ãã³é žèå
æ°ŽçŽ é žå¡©ãèç¹290ã293âãåŸããããããæ°Ž
ããåçµæ¶ãããšèç¹295ã299âã®ç©è³ªãåŸã
ããã åèäŸïŒ(A)ã«ãããããã«ããŠãé©åœãªåŒã®
ïŒâR1âïŒâïŒïŒâR2âãã³ãžã«ïŒâïŒâR3â
ïŒâR4âïŒâYâ²âïŒâã¢ã¶ãã·ã¯ãã2.2.2ããª
ã¯ãâïŒâãšã³ã䜿çšãããšãåŒã§è¡šãããã
次ã®ïŒâR2âïŒâR1âïŒÎ²ââ4aαâR3âïŒ
αâR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãª
ã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããª
ã³ãåŸããããïŒã15âã«ãããŠããåæ°ŽçŽ é žã
åšå²æž©åºŠã«ãããŠæ¿ç¡«é žããŸãã¯éæµæž©åºŠã«ãã
ãŠæ°·é ¢é žäžã®èåæ°ŽçŽ é žã䜿çšããŠãç°åãè¡ãª
ãããšãã§ãããåå Žåã«ãããŠåå¿ãä¿é²ãã
ããã«äœ¿çšããç¹å®ã®é žã¯ãHFãH2SO4ããã³
HBrã§äžã«è¡šç€ºãããç¹èšããªãããããçæç©
ïŒåŒã®ååç©ïŒã¯å¡©é žå¡©ãšããŠåé¢ããã ãè¡šã åèäŸ ïŒ 100mlã®ãšã¿ããŒã«äžã®21.7ïœïŒ0.06ã¢ã«ïŒã®
ïŒâãã³ãžã«âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«â
ïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãã
ãâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããªã³ïŒåè
äŸ2Cã«èšèŒããïŒã®æº¶æ¶²ãå¡©é žã§é žæ§ãšããã
ã®æº¶æ¶²ãããŒã«ïŒparrïŒæ¯ãšãè£ çœ®ã«ãã宀枩ã§
2.0ïœ10ïŒ ã®æŽ»æ§çãã©ãžãŠã ã®ååšäžã«æ°ŽçŽ ã§
éå ãããéå ãå®äºãããšãã觊åªããå»ãã
ã液ãç空æ¿çž®ä¹Ÿç¥ããæ®çç©ãã€ãœãããããŒ
ã«ããåçµæ¶ãããšã14.4ïœã®ïŒÎ²âã¢ã»ãã«â
ïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ
10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸ
ãïœããããªã³å¡©é žå¡©ãèç¹240ã241âãåŸãã
ããããã
ãã åèäŸ ïŒ 300mlã®DMFäžã®27.6ïœïŒ0.091ã¢ã«ïŒïŒÎ²âã¢
ã»ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒ
ïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ25âã¡ã¿ããã³ãŸ
ãïœããããªã³ãšãã«å¡©é žå¡©ïŒåèäŸïŒã«èšèŒã
ãïŒã14.9ïœïŒ0.11ã¢ã«ïŒã®èåã·ã¯ããããã«
ã¡ãã«ããã³16.8ïœïŒ0.20ã¢ã«ïŒã®çé žæ°ŽçŽ ãã
ãªãŠã ã®æ··åç©ããããŸããïŒæééæµããã€ã
ã§åå¿æ··åç©ãæ°Žãšãžãšãã«ãšãŒãã«ãšã«åé ã
ãããšãŒãã«å±€ãæ°ŽæŽãã也ç¥ãã掻æ§çãå
ãããéããã液ããšã¿ããŒã«ã§åžéããå¡©åæ°Ž
çŽ ã®ãšãŒãã«æº¶æ¶²ã§é žæ§ã«ãããåé¢ããåºäœã
éãããšã¿ããŒã«ïŒãšãŒãã«ããåçµæ¶ãããšã
24.1ïœã®ïŒÎ²âã¢ã»ãã«âïŒâã·ã¯ããããã«ã¡
ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ
10ïŒ10aâãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸ
ãïœããããªã³å¡©é žå¡©ãèç¹202ã204âãåŸãã
ãã åèäŸ ïŒ (A) 390mlã®ãžãšãã«ãšãŒãã«äžã®44.1ïœïŒ0.16
ã¢ã«ïŒã®ïŒâã¡ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ
ïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããªã³âïŒÎ²â
ã«ã«ãã³é žïŒåèäŸ2Aã«ãããŠèšèŒããïŒïŒã®
æžæ¿æ¶²ã«ããžãšãã«ãšãŒãã«äžã®2.16ã¢ã«ã®ã¡
ãã«ãªããŠã 溶液230mlïŒ0.5ã¢ã«ïŒã现ãæµã
ã®åœ¢ã§å ãããæ·»å å®äºãããšãããã®æ··åç©
ãïŒæéãããŸããæ°·ïŒå¡©åã¢ã³ã¢ããŠã 氎溶
液äžã«æ³šãå ¥ãããããŠãžãšãã«ãšãŒãã«äžãž
ã®æœåºããã³æœåºæ¶²ã也ç¥ããåŸã«èžçºä¹Ÿåºã
ãŠåŠçããããã®ããã«ããŠ32.8ïœã®çæç©ã
æ²¹ç¶ç²è£œå¡©åºãšããŠåŸããããã®3.3ïœãå¡©é ž
å¡©ã«è»¢åããããããã¡ã¿ããŒã«ïŒãžãšãã«ãš
ãŒãã«ããåçµæ¶ãããšã2.3ïœã®ïŒâã¡ãã«
âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ
ïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããªã³å¡©é žå¡©ã
èç¹191âãåŸãããã åèäŸ5Aãšåæ§ãªæäœã«åŸãããåèäŸ2Aã
2Bããã³2Gã«èšèŒããåŒã®é©åœãªïŒâR2âïŒ
âR1â4aαâR3âïŒÎ±âR4âïŒïŒïŒïŒïŒïŒïŒïŒ
4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿ãããâ25âã¡ã¿ãã
ã³ãŸãïœããããªã³âïŒÎ²âã«ã«ãã³é žãšé©åœãª
ææ©ãªããŠã R5Liã䜿çšãããšãäžè¡šïŒã«èšèŒ
ããåŒã®ååç©ãåŸããããåæååç©ã®åœ¢æ
ïŒå¡©ãŸãã¯å¡©åºïŒãåå Žåã«ãããŠã«ãã³å ã«ç€º
ãããã®ééã瀺ãããã¡ããå¡©ã¯ææ©ãªããŠã
ãšã®åå¿åã«éé¢å¡©åºã«è»¢åããããããŠåèäŸ
5Bããã³5Cã®ååç©ã®éé¢å¡©åºã«ã€ããŠãèç¹
ãèšèŒããã ãè¡šã æçµçæç©ã®è£œé å®æœäŸ ïŒ (A) 89mlã®ããªã¡ãã«ã¢ãã³ã94mlã®ã®é žã«å ã
ãŠåŸããã20mlã®æº¶æ¶²äžã®11ïœïŒ0.039ã¢ã«ïŒ
ã®ïŒâã¡ãã«âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«
âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãªã¯ã¿
ãããâ25âã¡ã¿ããã³ãŸãïœããããªã³å¡©é ž
å¡©ïŒåèäŸïŒã«èšèŒããïŒæº¶æ¶²ãã15åééæµ
æ¹æããããã®æ··åç©ãæŸå·ãã100mlã®æ°Žã
å ãã50mlã®ãžãšãã«ãšãŒãã«ã§æŽã€ããæ°Žå±€
ã15mlã®æ¿æ°Žé žåã¢ã³ã¢ããŠã ã§å¡©åºæ§ãšãã
ãžãšãã«ãšãŒãã«ã§ïŒåæœåºãããææ©æœåºæ¶²
ãäžç·ã«ããæ°Žã§ïŒåæŽãã也ç¥ããæ¿çž®ä¹Ÿç¥
ãããšã10ïœã®åºäœæ®çç©ãåŸããããããçŽ
30mlã®ç¡æ°Žãšã¿ããŒã«ã«æº¶ããã13mlã®å¡©åæ°Ž
çŽ ã®ãšãŒãã«æº¶æ¶²ã§é žæ§ã«ãã250mlã®è¿œå ã®
ãšãŒãã«ã§åžéãããåé¢ããåºäœãéã«ã
ã€ãŠé€å»ããã液ãåžæ°Žé žåã¢ã³ã¢ããŠã ã§æŽ
ããããã
ãã也ç¥ãããéãã也ç¥ãããšã3.1ïœã®æ®
çç©ãåŸãããããããžãšãã«ãšãŒãã«ã«æº¶è§£
ããå¡©åæ°ŽçŽ ã®ãšãŒãã«æº¶æ¶²ã§é žæ§ã«ãããå
é¢ããã¬ã ç¶ã®åçµæ¶æ§ç©è³ªããšã¿ããŒã«ïŒãš
ãŒãã«ããåçµæ¶ãããšã0.8ïœã®ïŒïŒeqïŒâ
ãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãã
ãâïŒâã¡ãã«â11ïŒeqïŒâïŒïŒâãªããœã
ãã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³
å¡©é žå¡©ãèç¹192ã196âãåŸãããã (B) åŒã®ååç©ããåŒã®ååç©ã補é ããå¥
æ³ã¯æ¬¡ã®ãšããã§ããã 675mlã®ã¡ãã¬ã³ããã³25mlã®ã®é žäžã®åè
äŸ9Cã«èšèŒãã10.0ïœïŒ0.03ã¢ã«ïŒã®ïŒâã¡ã
ã«âïŒÎ²âã¢ã»ãã«âïŒÎ±âãšãã«âïŒâãã
ããã·âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâ
ãªã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœãã
ããªã³ã®æ··åç©ãçŽïŒæéæ¹æéæµããæã ã®
é žãè¿œå ããŠããŸæž©åºŠã117ã119âã«ç¶æã
ããã€ãã§æ··åç©ãå·åŽããåžå¡©é žã§æœåºãã
é žæœåºæ¶²ããŸããžãšãã«ãšãŒãã«ã§æŽããæ°Žé ž
åã¢ã³ã¢ããŠã ã§å¡©åºæ§ãšããé ¢é žãšãã«ã§ã
ãäžåºŠæœåºãããææ©æœåºæ¶²ããã©ã€ã³ã§æŽ
ããèžçºä¹Ÿç¥ãããšã8.4ïœã®åºäœãåŸããã
ãããé ¢é žãšãã«ããåçµæ¶ãããšã3.7ïœã®
ïŒïŒeqïŒâãšãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒ
âãããµãããâ34ã¡ãã«âïŒâããããã·â
11ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ãèç¹190ã192â
ãåŸãããã å®æœäŸ1AãŸãã¯1Bãšåæ§ãªæäœã«åŸããåŒ
ã®é©åœãªïŒâR2âïŒâR1âïŒâCOR5â4aαâïŒ
αâR4âïŒïŒïŒïŒïŒïŒïŒïŒ4aïŒïŒïŒ10ïŒ10aâãª
ã¯ã¿ãããâïŒïŒïŒâã¡ã¿ããã³ãŸãïœããããª
ã³ã䜿çšãããšãåŒã§è¡šããããäžè¡šïŒã«ç€ºã
ïŒâR2âïŒïŒeqïŒâR4âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒâãããµãããâïŒâR1â11ïŒaxïŒâR3â11
ïŒeqïŒâïŒãªããœâäœçŽã¢ã«ãã«ïŒâïŒïŒïŒâã¡
ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ãåŸããããå®æœäŸïŒ
ãŸãã¯1Bã«ããæäœã次ã®å®æœäŸçªå·ã«ãããŠ
ããããæå(A)ãŸãã¯(B)ã§ç€ºããç¹èšããªããã
ããçæç©ã¯éé¢å¡©åºã®åœ¢ã§åé¢ãããã®èç¹ã
èšèŒããã ãè¡šã å®æœäŸ ïŒ (A) 27.0ïœïŒ0.072ã¢ã«ïŒã®ïŒâãã³ãžã«âïŒâ
ã¡ããã·âïŒïŒeqïŒâã¡ãã«ïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
ããããã
âãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ïŒå®æœäŸ1Eã«èšèŒããïŒã®æº¶æ¶²ã
250mlã®48ïŒ èåæ°ŽçŽ é žäžã«æº¶ããããã®æ··å
ç©ãçŽïŒæééæµå ç±ããããã®æ··åç©ãç空
äžã§æ¿çž®ããŠå°å®¹ç©ã«ãã100mlã®æ°Žã§åžé
ããåã³æ¿çž®ããæåŸã«çŽ50mlã®ã€ãœãããã
ãŒã«ãšãšãã«æ²žãšããããåé¢ããåºäœãé
ãã也ç¥ãããšã23ïœã®ïŒâãã³ãžã«âïŒâã
ãããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
âãªããœããã«ïŒâ26âã¡ã¿ãâïŒâãã³ãºã¢
ãŸã·ã³èåæ°ŽçŽ é žå¡©ãèç¹156ã165âãåŸãã
ãã (B) å®æœäŸ1Hã«èšèŒãã4.0ïœã®ïŒïŒïŒïŒeqïŒâ
ãžã¡ãã«âïŒâã¡ããã·âïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒâãª
ããœãªã¯ãã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãº
ã¢ãŸã·ã³ïœâãã«ãšã³ã¹ã«ãããŒããš20mlã®48
ïŒ èåæ°ŽçŽ é žãšãåå¿ããããšãïŒïŒïŒ
ïŒeqïŒâãžã¡ãã«âïŒâããããã·âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœãªã¯ãã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒ
âãã³ãºã¢ãŸã·ã³ïŒ1.8ïœãèç¹107ã109âã
ãšã¿ããŒã«ããïŒãåæ§ã«è£œé ãããã å®æœäŸ ïŒ ïŒ¡ 150mlã®DMFäžã®23.1ïœïŒ0.05ã¢ã«ïŒã®ïŒâ
ãã³ãžã«âïŒâããããã·âïŒïŒeqïŒâã¡ã
ã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâ
11ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâ
ã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³èåæ°ŽçŽ é žå¡©ïŒå®
æœäŸ2Aã«èšèŒããïŒã®æº¶æ¶²ããåèäŸïŒã«èš
èŒããæäœã«ããã1.0ïœã®10ïŒ æŽ»æ§çæ æã
ã©ãžãŠã ã®ååšäžã«éå ãããåŸãããçæç©
ããšã¿ããŒã«ããåçµæ¶ãããšã16.1ïœã®ïŒâ
ããããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâ
ãã³ãºã¢ãŸã·ã³èåæ°ŽçŽ é žå¡©ãèç¹235ã237â
ïŒãšã¿ããŒã«ããïŒãåŸãããã  åæ§ã«ããŠã21.2ïœã®ïŒâãã³ãžã«âïŒâã¡
ããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
âãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³ïŒå®æœäŸ1Eã«èšèŒããïŒã掻æ§ç
æ æãã©ãžãŠã ã®ååšäžã«æ°ŽçŽ ã§éå ããçæ
ç©ãå¡©é žå¡©ã®åœ¢ã§åé¢ãããš11.4ïœã®ïŒâã¡ã
ãã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒâãª
ããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢
ãŸã·ã³å¡©é žå¡©ãèç¹189ã193âïŒãšã¿ããŒã«ã
ãïŒãåŸãããã å®æœäŸ ïŒ (A) 150mlã®DMFäžã®11.4ïœïŒ0.03ã¢ã«ïŒã®ïŒâ
ããããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâ
ãã³ãºã¢ãŸã·ã³èåæ°ŽçŽ é žå¡©ïŒå®æœäŸ3Aã«èš
èŒããïŒã5.4ïœã®çé žæ°ŽçŽ ãããªãŠã ããã³
5.2ïœïŒ0.04ã¢ã«ïŒã®èåã·ã¯ããããã«ã¡ã
ã«ã®æ··åç©ãçŽïŒæééæµå ç±ããã€ãã§ç空
æ¿çž®ããŠå°å®¹ç©ã«ãããæ®çç©ãæ°Žé žåã¢ã³ã¢
ããŠã ãšé ¢é žãšãã«ãšã«åé ããææ©å±€ãåé¢
ããæ°Žå±€ãè¿œå ã®é ¢é žãšãã«ã§æœåºãããäžç·
ã«ããæœåºæ¶²ãæ°Žãã€ãã§ãã©ã€ã³ã§æŽãã也
ç¥ãããéãã也ç¥ãããšã12.1ïœã®ç²çæç©
ãåŸããããããå¡©åæ°ŽçŽ é žå¡©ã«è»¢åãããã
ã®å¡©é žå¡©ãã¢ã»ããããªã«ããïŒåãã€ãã§ãš
ã¿ããŒã«ïŒãšãŒãã«ããïŒååçµæ¶ãããšã
5.2ïœã®ïŒâã·ã¯ããããã«ã¡ãã«âïŒâãã
ããã·âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâïŒïŒ
âãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³
ãºã¢ãŸã·ã³å¡©é žå¡©ãèç¹147ã154âãåŸãã
ãã (B) å®æœäŸ4Aãšåæ§ãªæäœã«ãããDMFäžã§ç
é žæ°ŽçŽ ãããªãŠã ã®ååšäžã«15.0ïœïŒ0.04ã¢
ã«ïŒã®ïŒâã¡ããã·âïŒïŒeqïŒâã¡ãã«â
ïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11
ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³ïŒå®æœäŸ3Bã«èšèŒã
ãïŒãšèåã·ã¯ããããã«ã¡ãã«ãšãåå¿ãã
ãŠãïŒâã·ã¯ããããã«ã¡ãã«âïŒâã¡ããã·
âïŒïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒ
ïŒâãããµãããâ11ïŒeqïŒâïŒïŒâãªããœ
ããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·
ã³ïŒ12.9ïœïŒã補é ããã (C) åèäŸïŒã«èšèŒããæäœã«åŸããçŽ50psiã®
æ°ŽçŽ å§äžã«ãšã¿ããŒã«äžã§æŽ»æ§çæ æãã©ãžãŠ
ããããã
ã ã®ååšäžã«11.4ïœã®ïŒâããããã·âïŒ
ïŒeqïŒâã¡ãã«âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâã
ããµãããâ11ïŒeqïŒâïŒïŒâãªããœãã
ã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³è
åæ°ŽçŽ é žå¡©ïŒå®æœäŸ3Aã«èšèŒããïŒãšãã«ã
ã¢ã«ãããããã³ããªãšãã«ã¢ãã³ãšã®éå ã¢
ã«ãã«åã«ãããïŒïŒïŒïŒeqïŒâãžã¡ãã«â
ïŒâããããã·âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâã
ããµãããâ11ïŒeqïŒâïŒïŒâãªããœãã
ã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâãã³ãºã¢ãŸã·ã³ïœ
âãã«ãšã³ã¹ã«ãã³é žå¡©ïŒ9.9ïœïŒèç¹199ã
201âïŒãšã¿ããŒã«ããïŒãåŸãããã (D) åèäŸïŒã®æäœãçšããçŽ50psiã®æ°ŽçŽ å§äž
ã«ãšã¿ããŒã«äžã§æŽ»æ§çæ æãã©ãžãŠã ã®ååš
äžã«8.2ïœã®ïŒâã¡ããã·âïŒïŒeqïŒâã¡ãã«
âïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11
ïŒeqïŒâïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿
ãâïŒâãã³ãºã¢ãŸã·ã³å¡©é žå¡©ïŒå®æœäŸ3Bã«
èšèŒããïŒãšãã«ã ã¢ã«ãããããã³ããªãšã
ã«ã¢ãã³ãšã®éå ã¢ã«ãã«åã«ãããïŒïŒïŒ
ïŒeqïŒâãžã¡ãã«âïŒâã¡ããã·âïŒïŒïŒïŒ
ïŒïŒïŒïŒïŒïŒïŒâãããµãããâ11ïŒeqïŒâ
ïŒïŒâãªããœããã«ïŒâïŒïŒïŒâã¡ã¿ãâïŒâ
ãã³ãºã¢ãŸã·ã³ïŒ7.5ïœïŒãåŸãããã åŒã®ååç©ã¯äžè¬ã«ã¢ã»ãã«ã¯ããªã³èªçºè ¹
ççªè©ŠéšïŒAchïŒãäžæ¬¡é®çã¹ã¯ãªãŒãã³ã°è©Š
éšãããã³ããã¿ã®å°Ÿã®è»œæ茻å°ç±é®çè©Šéš
ïŒTail Flick AgonïŒã«ãããŠæŽ»æ§ã§ããããã
ã€ããããšãã«âïœâããã³èªçºãã ã
ïŒWrithingïŒè©ŠéšïŒPPQïŒããã³æã«ãªãžã³è©Šéš
ïŒBKïŒã«ãããŠè©Šéšãã掻æ§ã§ããããšãããã€
ãããããã®è©Šéšã¯äžæ¬¡é®çã¹ã¯ãªãŒãã³ã°æäœ
ã§ãããããã®ããã«ããŠåŸãããååç©ã«ã€ã
ãŠã®ããŒã¿ããåèšå®æœäŸã«é¢é£ããŠãED50
ïŒmgïŒKgãç®äžæäžïŒãŸãã¯æå¶çã§ç€ºãããã¹
ãŠã®æäžéã¯mgïŒKgã§è¡šããã ãè¡šã å®æœäŸ1Dããã³3Aã®ååç©ã¯ãããšããŸã·ã³
尟軜ææ®æè©Šéšã«ãããŠæŽ»æ§ã§ããããšããã
ãããã®ED50ïŒç®äžæäžïŒã¯ãããã®ååç©ã«
ã€ããŠãããã24ããã³0.088mgïŒKgã§ãã€ãã æåŸã«ãåŒã®ããçš®ã®ååç©ãããªãã¡åè
äŸ6Dã®ååç©ã¯ãäžæ¬¡é®çã¹ã¯ãªãŒãã³ã°è©Šéš
ã§ããã¢ã»ãã«ã¯ããªã³èªçºè ¹ççªè©Šéšããã³æ
ã«ãªãžã³è©Šéšã«ãããŠæŽ»æ§ã§ããããšããããã
ãããã€ãŠãããã¯é®çå€ãšããŠæçšã§ãããã
ãã«åŒã®çæç©ã®åºçºç©è³ªãšããŠæçšã§ããã
åèäŸ6Dã®ååç©ã®ã¢ã»ãã«ã¯ããªã³èªçºè ¹ç
çªè©Šéšã«ãããED50ã¯18mgïŒKgã§ãã€ããåè
äŸ6Dã®ååç©ã¯æã«ãªãžã³è©Šéšã«ãããŠæŽ»æ§ã§
ãã€ãã ããããã
Claims (1)
- ãç¹èš±è«æ±ã®ç¯å²ã ïŒ åŒ ãåŒäžãR1ã¯ïŒšãäœçŽã¢ã«ãã«ãã·ã¯ãã¢ã«
ãã«äœçŽã¢ã«ãã«ãŸãã¯ããšãã«âäœçŽã¢ã«ãã«
ã§ããïŒ R2ã¯ïŒšãããããã·ãŸãã¯äœçŽã¢ã«ã³ãã·ã§
ããïŒ R3ã¯ïŒšãŸãã¯äœçŽã¢ã«ãã«ã§ããïŒ R4ã¯äœçŽã¢ã«ãã«ã§ããïŒ ïŒºã¯âCH2COR5ïŒR5ã¯äœçŽã¢ã«ãã«ã§ããïŒ
ã§ãããã§è¡šãããããã³ãŸã¢ãŸã·ã³é¡ãŸãã¯ã
ã®é žä»å å¡©ã®è£œé æ¹æ³ã«ãããŠã ã®é žãšå ±ã«äžæŽ»æ§ææ©æº¶åªäžã§ããããã¯ãã³
ãžã«ãžäœçŽã¢ã«ãã«ã¢ã³ã¢ããŠã ãŸãã¯ããªäœçŽ
ã¢ã«ãã«ã¢ã³ã¢ããŠã ãã«ã¡ãŒããšå ±ã«ãåŒïŒ ãåŒäžR1ïŒR2ïŒR3ïŒR4ã¯åèšå®çŸ©éãã§ã
ãïŒ ïŒ¹ã¯COR5ïŒããã§R5ã¯åèšã®éãïŒã§ããã
ã§ç€ºãããååç©ãå ç±ãã ææã«ããåŒã®ååç©ã®R1ããã³ãžã«åºã®
å Žåãè±ãã³ãžã«åãããŸã㯠ææã«ããåŸãããåŒã§è¡šããããå¡©åºæ§å
åç©ãé žä»å å¡©ã«è»¢åããããšããæãæ¹æ³ã
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US05/471,571 US3932422A (en) | 1974-05-20 | 1974-05-20 | 8-Methylene-3-azabicyclo[3.3.1]non-6-en-4-ones |
| US57631375A | 1975-05-12 | 1975-05-12 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS50160275A JPS50160275A (ja) | 1975-12-25 |
| JPS6212221B2 true JPS6212221B2 (ja) | 1987-03-17 |
Family
ID=27043488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP50060111A Expired JPS6212221B2 (ja) | 1974-05-20 | 1975-05-20 |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JPS6212221B2 (ja) |
| CA (1) | CA1052785A (ja) |
| GB (2) | GB1514572A (ja) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4255579A (en) * | 1974-05-20 | 1981-03-10 | Sterling Drug Inc. | 11-Substituted hexahydro-2,6-methano-3-benzazocines |
| JPS54130577A (en) * | 1978-03-31 | 1979-10-09 | Sterling Drug Inc | Novel benzazosin compound and its manufacture |
| EP0017074A1 (en) * | 1979-03-26 | 1980-10-15 | Sterling Drug Inc. | Process and intermediates for preparing 11-(alkoxy- and alkylmercapto-3-oxoalkyl)-2,6-methano-3-benzazocines |
-
1975
- 1975-05-19 GB GB27040/77A patent/GB1514572A/en not_active Expired
- 1975-05-19 GB GB21272/75A patent/GB1514571A/en not_active Expired
- 1975-05-20 CA CA227,350A patent/CA1052785A/en not_active Expired
- 1975-05-20 JP JP50060111A patent/JPS6212221B2/ja not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| CA1052785A (en) | 1979-04-17 |
| GB1514572A (en) | 1978-06-14 |
| GB1514571A (en) | 1978-06-14 |
| JPS50160275A (ja) | 1975-12-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4210749A (en) | Substituted 1,2,4,5-tetrahydro-3H,3 benzazepines | |
| US4272541A (en) | 7,8 and 7-8 Substituted 4,5α-epoxymorphinan-6-one compounds, and methods of treating pain and drug dependence with them | |
| US4128548A (en) | Process for preparing 6,7-benzomorphans | |
| JPS6051174A (ja) | æ°èŠã¢ãªâã«ãããªãžã³èªå°äœã®è£œé æ¹æ³ | |
| JPS6123790B2 (ja) | ||
| US4425353A (en) | Analgesic 5-oxygenated-6,7-benzomorphan derivatives | |
| IE41898B1 (en) | Decahydroisoquinoline derivatives, processes for their preparation and their use in pharmaceutical compositions | |
| US3513169A (en) | 5,9-diethyl benzomorphan derivatives | |
| US4255579A (en) | 11-Substituted hexahydro-2,6-methano-3-benzazocines | |
| JPH085889B2 (ja) | çµå£æŽ»æ§éèœæººæ§é®çå€ | |
| JPS6212221B2 (ja) | ||
| DE3118521A1 (de) | Dibenzo(de,g)chinolin-derivate, verfahren zu deren herstellung und deren verwendung bei der bekaempfung von erkaeltungskrankheiten und allergien | |
| US4058531A (en) | Process for the preparation of 14-hydroxymorphinan derivatives | |
| IL27871A (en) | History of benzomorphan and their preparation | |
| EP0106486A2 (en) | Improvements in or relating to novel octahydrobenz(f)isoquinolines | |
| US4139534A (en) | Process for the preparation of 14-hydroxymorphinan derivatives | |
| US3810899A (en) | 2-hydroxy-n-substituted-morphinan derivatives | |
| US4105659A (en) | 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines | |
| US4335243A (en) | Oximes of 11-(3-oxooctyl)-hexahydro-2,6-methano-3-benzazocines | |
| US4423221A (en) | 7-Carboethoxy-morphinan-6-one compounds | |
| US4296238A (en) | 2,6-Methano-3-benzazocines | |
| EP0039444A1 (en) | 7,7-Ditosyloxymethyl-4,5 alpha-epoxy-morphinan-6-ols and their use as intermediates in the production of epoxymorphinan derivatives | |
| US4202984A (en) | β-(Hexahydro-2,6-methano-3-benzazocin-11-yl)propionic acids, esters and amides | |
| US4141893A (en) | Decahydrocyclopent[c]azepines | |
| US4219652A (en) | N-Methyl and N-phenethyl-cis-decahydroisoquinolines |