JPS6254798B2 - - Google Patents
Info
- Publication number
- JPS6254798B2 JPS6254798B2 JP54171944A JP17194479A JPS6254798B2 JP S6254798 B2 JPS6254798 B2 JP S6254798B2 JP 54171944 A JP54171944 A JP 54171944A JP 17194479 A JP17194479 A JP 17194479A JP S6254798 B2 JPS6254798 B2 JP S6254798B2
- Authority
- JP
- Japan
- Prior art keywords
- aminobenzoic acid
- acetyl
- water
- added
- reaction solution
- 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
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 28
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 26
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical group COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 claims description 11
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 229930182478 glucoside Natural products 0.000 claims description 8
- 150000008265 rhamnosides Chemical class 0.000 claims description 7
- 150000005417 aminobenzoic acid derivatives Chemical class 0.000 claims description 6
- 150000008131 glucosides Chemical class 0.000 claims description 6
- 150000002402 hexoses Chemical class 0.000 claims description 6
- 150000002972 pentoses Chemical class 0.000 claims description 6
- 150000008146 mannosides Chemical class 0.000 claims description 5
- VAMXMNNIEUEQDV-UHFFFAOYSA-N methyl anthranilate Chemical compound COC(=O)C1=CC=CC=C1N VAMXMNNIEUEQDV-UHFFFAOYSA-N 0.000 claims description 5
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 150000008195 galaktosides Chemical class 0.000 claims description 3
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000000600 disaccharide group Chemical group 0.000 claims 3
- XFDUHJPVQKIXHO-UHFFFAOYSA-N 3-aminobenzoic acid Chemical compound NC1=CC=CC(C(O)=O)=C1 XFDUHJPVQKIXHO-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 72
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 68
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 66
- 239000000243 solution Substances 0.000 description 65
- 238000006243 chemical reaction Methods 0.000 description 63
- 238000004519 manufacturing process Methods 0.000 description 59
- 239000000047 product Substances 0.000 description 59
- 239000013078 crystal Substances 0.000 description 57
- 238000003756 stirring Methods 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- 239000000126 substance Substances 0.000 description 49
- 230000021736 acetylation Effects 0.000 description 42
- 238000006640 acetylation reaction Methods 0.000 description 42
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
- 239000005457 ice water Substances 0.000 description 31
- 235000019441 ethanol Nutrition 0.000 description 28
- 239000003208 petroleum Substances 0.000 description 27
- 238000000034 method Methods 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 16
- 230000010933 acylation Effects 0.000 description 15
- 238000005917 acylation reaction Methods 0.000 description 15
- 235000000346 sugar Nutrition 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 11
- 239000008280 blood Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 239000007795 chemical reaction product Substances 0.000 description 9
- 241000700159 Rattus Species 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 235000002639 sodium chloride Nutrition 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 239000002246 antineoplastic agent Substances 0.000 description 7
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 239000008187 granular material Substances 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 206010003210 Arteriosclerosis Diseases 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 206010070834 Sensitisation Diseases 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 208000011775 arteriosclerosis disease Diseases 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 230000008313 sensitization Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 244000215068 Acacia senegal Species 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- 229920000084 Gum arabic Polymers 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000000205 acacia gum Substances 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000002220 antihypertensive agent Substances 0.000 description 4
- 229940030600 antihypertensive agent Drugs 0.000 description 4
- 239000003907 antipyretic analgesic agent Substances 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 4
- 150000002016 disaccharides Chemical group 0.000 description 4
- 210000003743 erythrocyte Anatomy 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- -1 phenylacetyl group Chemical group 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- TWLLPUMZVVGILS-UHFFFAOYSA-N Ethyl 2-aminobenzoate Chemical compound CCOC(=O)C1=CC=CC=C1N TWLLPUMZVVGILS-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 241000283973 Oryctolagus cuniculus Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 206010037660 Pyrexia Diseases 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 3
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
- 230000007059 acute toxicity Effects 0.000 description 3
- 231100000403 acute toxicity Toxicity 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 229940121363 anti-inflammatory agent Drugs 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- 229940125708 antidiabetic agent Drugs 0.000 description 3
- 239000012867 bioactive agent Substances 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
- 239000008116 calcium stearate Substances 0.000 description 3
- 235000013539 calcium stearate Nutrition 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- 235000010980 cellulose Nutrition 0.000 description 3
- 235000012000 cholesterol Nutrition 0.000 description 3
- 230000009036 growth inhibition Effects 0.000 description 3
- 230000002218 hypoglycaemic effect Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 231100000053 low toxicity Toxicity 0.000 description 3
- 230000007886 mutagenicity Effects 0.000 description 3
- 231100000299 mutagenicity Toxicity 0.000 description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 210000003462 vein Anatomy 0.000 description 3
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 244000063299 Bacillus subtilis Species 0.000 description 2
- 235000014469 Bacillus subtilis Nutrition 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000233866 Fungi Species 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N Magnesium oxide Chemical compound [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- PYMYPHUHKUWMLA-LMVFSUKVSA-N aldehydo-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 125000005907 alkyl ester group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000003276 anti-hypertensive effect Effects 0.000 description 2
- 230000001754 anti-pyretic effect Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
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- IUWVALYLNVXWKX-UHFFFAOYSA-N butamben Chemical compound CCCCOC(=O)C1=CC=C(N)C=C1 IUWVALYLNVXWKX-UHFFFAOYSA-N 0.000 description 2
- HUIYGGQINIVDNW-UHFFFAOYSA-N butyl anthranilate Chemical compound CCCCOC(=O)C1=CC=CC=C1N HUIYGGQINIVDNW-UHFFFAOYSA-N 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
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- 230000004727 humoral immunity Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 230000016784 immunoglobulin production Effects 0.000 description 2
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- 238000002347 injection Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
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- WQZGKKKJIJFFOK-SVZMEOIVSA-N (+)-Galactose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-SVZMEOIVSA-N 0.000 description 1
- ZVQAVWAHRUNNPG-VPENINKCSA-N (2r,4s,5r)-oxane-2,4,5-triol Chemical compound O[C@H]1C[C@H](O)[C@H](O)CO1 ZVQAVWAHRUNNPG-VPENINKCSA-N 0.000 description 1
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- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- FOYWCEUVVIHJKD-UHFFFAOYSA-N 2-methyl-5-(1h-pyrazol-5-yl)pyridine Chemical compound C1=NC(C)=CC=C1C1=CC=NN1 FOYWCEUVVIHJKD-UHFFFAOYSA-N 0.000 description 1
- QIGJYVCQYDKYDW-UHFFFAOYSA-N 3-O-alpha-D-mannopyranosyl-D-mannopyranose Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(CO)OC(O)C1O QIGJYVCQYDKYDW-UHFFFAOYSA-N 0.000 description 1
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- GUBGYTABKSRVRQ-PZPXDAEZSA-N 4β-mannobiose Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-PZPXDAEZSA-N 0.000 description 1
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- 201000001320 Atherosclerosis Diseases 0.000 description 1
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- 241000221198 Basidiomycota Species 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 244000168525 Croton tiglium Species 0.000 description 1
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 description 1
- RFSUNEUAIZKAJO-VRPWFDPXSA-N D-Fructose Natural products OC[C@H]1OC(O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-VRPWFDPXSA-N 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-NQXXGFSBSA-N D-ribulose Chemical compound OC[C@@H](O)[C@@H](O)C(=O)CO ZAQJHHRNXZUBTE-NQXXGFSBSA-N 0.000 description 1
- LKDRXBCSQODPBY-OEXCPVAWSA-N D-tagatose Chemical compound OCC1(O)OC[C@@H](O)[C@H](O)[C@@H]1O LKDRXBCSQODPBY-OEXCPVAWSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-UHFFFAOYSA-N D-threo-2-Pentulose Natural products OCC(O)C(O)C(=O)CO ZAQJHHRNXZUBTE-UHFFFAOYSA-N 0.000 description 1
- SQNRKWHRVIAKLP-UHFFFAOYSA-N D-xylobiose Natural products O=CC(O)C(O)C(CO)OC1OCC(O)C(O)C1O SQNRKWHRVIAKLP-UHFFFAOYSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-WUJLRWPWSA-N D-xylulose Chemical compound OC[C@@H](O)[C@H](O)C(=O)CO ZAQJHHRNXZUBTE-WUJLRWPWSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000116710 Ferula foetidissima Species 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 206010018691 Granuloma Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- AYRXSINWFIIFAE-SCLMCMATSA-N Isomaltose Natural products OC[C@H]1O[C@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)[C@@H](O)[C@@H](O)[C@@H]1O AYRXSINWFIIFAE-SCLMCMATSA-N 0.000 description 1
- LKDRXBCSQODPBY-AMVSKUEXSA-N L-(-)-Sorbose Chemical compound OCC1(O)OC[C@H](O)[C@@H](O)[C@@H]1O LKDRXBCSQODPBY-AMVSKUEXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-DHVFOXMCSA-N L-galactose Chemical compound OC[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O WQZGKKKJIJFFOK-DHVFOXMCSA-N 0.000 description 1
- ZAQJHHRNXZUBTE-WVZVXSGGSA-N L-xylulose Chemical compound OC[C@H](O)[C@@H](O)C(=O)CO ZAQJHHRNXZUBTE-WVZVXSGGSA-N 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- DKXNBNKWCZZMJT-UHFFFAOYSA-N O4-alpha-D-Mannopyranosyl-D-mannose Natural products O=CC(O)C(O)C(C(O)CO)OC1OC(CO)C(O)C(O)C1O DKXNBNKWCZZMJT-UHFFFAOYSA-N 0.000 description 1
- AYRXSINWFIIFAE-UHFFFAOYSA-N O6-alpha-D-Galactopyranosyl-D-galactose Natural products OCC1OC(OCC(O)C(O)C(O)C(O)C=O)C(O)C(O)C1O AYRXSINWFIIFAE-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000000114 Pain Threshold Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 239000006159 Sabouraud's agar Substances 0.000 description 1
- 208000006268 Sarcoma 180 Diseases 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- 241001045770 Trichophyton mentagrophytes Species 0.000 description 1
- CYAYKKUWALRRPA-RQICVUQASA-N [(2r,3r,4s,5r)-3,4,5-triacetyloxy-6-bromooxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@H]1OC(Br)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O CYAYKKUWALRRPA-RQICVUQASA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004520 agglutination Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- SHZGCJCMOBCMKK-PHYPRBDBSA-N alpha-D-fucose Chemical compound C[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O SHZGCJCMOBCMKK-PHYPRBDBSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
- 150000008209 arabinosides Chemical class 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004531 blood pressure lowering effect Effects 0.000 description 1
- 239000000872 buffer Substances 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
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-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
- 239000011575 calcium Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- DLRVVLDZNNYCBX-OVEBFGLASA-N epimelibiose Chemical compound O[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](O)O1 DLRVVLDZNNYCBX-OVEBFGLASA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229930182479 fructoside Natural products 0.000 description 1
- DLRVVLDZNNYCBX-CQUJWQHSSA-N gentiobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-CQUJWQHSSA-N 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 210000004013 groin Anatomy 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000035931 haemagglutination Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- DLRVVLDZNNYCBX-RTPHMHGBSA-N isomaltose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C(O)O1 DLRVVLDZNNYCBX-RTPHMHGBSA-N 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- QIGJYVCQYDKYDW-LCOYTZNXSA-N laminarabiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1O QIGJYVCQYDKYDW-LCOYTZNXSA-N 0.000 description 1
- 235000019860 lauric fat Nutrition 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 230000037040 pain threshold Effects 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- DUCKXCGALKOSJF-UHFFFAOYSA-N pentanoyl pentanoate Chemical compound CCCCC(=O)OC(=O)CCCC DUCKXCGALKOSJF-UHFFFAOYSA-N 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000001603 reducing effect Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000012449 sabouraud dextrose agar Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000035488 systolic blood pressure Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000723 toxicological property Toxicity 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/18—Acyclic radicals, substituted by carbocyclic rings
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Emergency Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Description
本発明は下記一般式（）で表わされる化学物
質、その塩又はそのアルキルエステルに関するも
のである。
〔式中、R1はアシル化されたペントース、ヘキソ
ースまたは二糖類の残基を示す。ただしｏ、ｍ又
はｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｄ−
グルコシツド、ｐ−アミノ安息香酸メチル、エチ
ル又はブチルエステル−Ｎ−Ｏ−アセチル−Ｄ−
グルコシツド、ｏ−アミノ安息香酸メチルエステ
ル−Ｎ−Ｏ−アセチル−Ｄ−グルコシツド又はガ
ラクトシツドは除く。〕
従来、制癌剤として合成化合物や抗生物質など
が用いられてきたが、これらは殺癌効果はすぐれ
ていても正常細胞にも作用するため毒性が強く、
副作用を呈する欠点があつた。そこで最近では宿
主の免疫能を高めることにより制癌効果を発揮す
る種々の起源の多糖体が注目されるようになつ
た。本発明者等はすでに担子菌由来多糖よりなる
制癌剤を開発し社会に提供して来たが、この制癌
剤の構造並びに活性の研究中にアミノ安息香酸−
Ｎ−Ｄ−アンノシド、アミノ安息香酸−Ｎ−Ｌ−
アラビノシド、アミノ安息香酸−Ｎ−Ｄ−キシロ
シド、アミノ安息香酸−Ｎ−Ｄ−グルコシド、ア
ミノ安息香酸−Ｎ−Ｄ−ガラクトシド、アミノ安
息香酸−Ｎ−Ｌ−ラムノシドが有用な種々の生理
活性を有することを見出した。
しかし、これらの物質は長時間にわたつて薬効
を維持する点において必らずしも十分でない。そ
こで更に研究を重ねた結果低毒性でかつ薬効の高
い上記一般式（）で示される化合物が有効であ
ることを見い出し、本発明を完成したものであ
る。
一般式（）で示される化合物、その塩又はそ
のエステル（以下、“本物質”と略称する）は簡
単な構造でありながら、極めて低毒性であり且つ
抗菌活性がないので腸内菌叢撹乱などの心配がな
く、長期投与が可能である。また変異原性や細胞
性及び体液性免疫にも影響を与えず、したがつて
健康な人に対する催奇形性やアレルギー反応など
の危険もなく、極めて安全な薬剤である。加えて
本物質はいずれも血糖降下作用、血圧降下作用、
血中脂質降下作用、抗腫瘍作用、解熱鎮痛作用並
びに抗炎症作用を有しており、抗糖尿病剤、血圧
降下剤、抗動脈硬化症剤、抗腫瘍剤、解熱鎮痛
剤、抗炎症剤として有用である。
本発明のアミノ安息香酸誘導体の塩とは、前記
式（）中の−COOH基の水素原子をアルカリ
金属、アルカリ土金属、アルミニウム金属で置換
したものである。アルカリ金属ならびにアルカリ
土金属としては薬剤として許容されるものであれ
ばいずれのものでもよく、通常はNa、Ｋ、Mg、
Caなどが好ましく、特にNaが好ましい。又、本
発明のアミノ安息香酸誘導体のエステルとは、前
記式（）中の−COOH基の水素原子をアルキ
ル基で置換したものであり、アルキル基としては
メチル、エチル、プロピル、ブチル基等が好まし
い。
R1はアシル化されたペントース、ヘキソース
または二糖類の残基を示す。ここでアシル化糖類
残基とは糖類の分子中のOH基（ただし１個の
OHは除かれている）のＨをアシル基で置換した
もので、ここでアシル基はアセチル、プロピオニ
ル、ブチリル、バレリル、ベンゾイル、フエニル
アセチル基等を示す。
これらの糖はＤ又はＬ体もしくはα−アノマー
又はβ−アノマーの形またはアノマーの混合物の
形であることが出来る。したがつて本物質もα又
はβもしくはこれらの混合アノマーであることが
出来る。
ここでいう糖について１例を示すと、次のよう
なものがあげられる。
ペントースとしてはＤ−リボース、Ｄキシロー
ス、Ｄ又はＬ−アルビノース、Ｌ又はＤ−キシ
ルロース、Ｄ−リブロース。
ヘキソースとしてはＤ又はＬ−ガラクトース、Ｄ
−グルコース、Ｄ−マンノース、Ｄ−フルクト
ース、Ｌ−ソルボース、Ｄ−タガトース。
二糖類としてはマルトース、セロビオース、ラク
トース、ラミナリビオース、ゲンチオビオー
ス、メリビオース、イソマルトース、マンノビ
オース、キシロビオース、サツカロース。
本物質は下記のごとき方法によつて製造し得
る。糖又はアミノ安息香酸もしくはそのエステル
１〜10ｇを溶媒（例えば水、アルコール（例えば
メタノール、エタノール）、アセトン、クロロホ
ルム、ピリジン、ニトロメタン、DMF、THF、
ジオキサン、DMSO）２〜200ml中、触媒の存在
又は非存在下に20℃〜200℃、好ましくは50℃〜
150℃で時間は10分〜48時間、好ましくは30分〜
24時間反応させる。ここで触媒は酢酸又はその
塩、塩酸、塩化アンモン等が好ましく、上記量に
対し0.1〜５ｇに加える。
二糖類を用いての縮合反応の場合、塩化アンモ
ンは必らずしも適当でなく有効な触媒は酢酸であ
る。この場合アミノ安息香酸（塩、低級アルキル
エステルを含む）２〜６ｇ、糖１〜10ｇ、溶媒２
〜200mlに対し酢酸１〜２mlの割合で使用する場
合が最も好ましい結果を示した。
酢酸の使用量がこの範囲以下では収率が低下し
これ以上では生成物の増加がみられなかつた。上
記反応後冷却し、そのままか、あるいは濃縮して
反応生成物の結晶を析出させ、濾別後、水、メタ
ノール、アセトン、エーテル等で洗浄する。さら
に再結晶化を行ない、得られる生成物を乾燥有機
溶媒例えばベンゼン、アセトン、ジオキサン、ニ
トロメタン、ピリジン、DMSO、クロロホルム、
DMF、THF等の中でアシル化剤、酸塩化物、例
えば塩化アセチル、塩化プロピオル、塩化ブチリ
ル、塩化ベンゾイル、塩化フエニルアセチル又は
酸無水物例えば無水酢酸、無水プロピオン酸、無
水酪酸、無水吉草酸、無水安息香酸等を加え反応
させる。得られる反応液を氷水中に添加して水不
溶物を採取する。この採取した固型物を再結晶し
て本物質を得る。反応条件の１例を示すとアミノ
安息香酸またはそのエステルと糖の結合体１ｇを
有機溶媒5.0〜20ml、酸無水物又は酸塩化物２ｇ
〜20ｇと−70〜100℃好ましくは−20℃〜50℃で
反応させる。この反応生成物を冷却し氷水に加え
固型物を採取する。この固型物をアルコール、エ
ーテルその他の溶媒中で再結晶化して本物質を得
る。
又本物質は次の方法によつて得られる。アシル
化糖〔ただし１個のOH基はフリーであるか又は
Br、Cl等のハロゲンで置換したもの〕とアミノ
安息香酸又はそのエステルを有機溶媒例えばピリ
ジン、THF、DMSO、DMF、ニトロメタン、ク
ロロホルム、ジオキサン、アセトン、アルコール
中にて−70〜180℃、好ましくは−20〜50℃にて
１分〜168時間、好ましくは1.0〜24時間反応さ
せ、該反応生成物から本物質を得る。
以上の製法により得られた本物質例についての
物理化学的特性を下記表１に示す。また赤外線吸
収スペクトルを第１〜１９図に示す。なお、表１
における分析方法は次の通りである。
(1) 融点 柳本微量融点測定装置を用いて測定し
た。
(2) 元素分析 柳本CHNコーダーMT2型により
測定した。
(3) UV 日立ESP−3T型自記分光光度計によ
り、測定した。
(4) IR 日本分光DS−701G型によりKBr法で測
定した。尚、図面番号は表１の試料No.１と一致
する。
The present invention relates to a chemical substance represented by the following general formula (), a salt thereof, or an alkyl ester thereof. [In the formula, R 1 represents an acylated pentose, hexose or disaccharide residue. However, o, m or p-aminobenzoic acid-N-O-acetyl-D-
Glucoside, p-aminobenzoic acid methyl, ethyl or butyl ester -N-O-acetyl-D-
Glucoside, o-aminobenzoic acid methyl ester-N-O-acetyl-D-glucoside or galactoside are excluded. ] Conventionally, synthetic compounds and antibiotics have been used as anticancer agents, but although these have excellent cancer killing effects, they are highly toxic because they also act on normal cells.
It had the disadvantage of causing side effects. Therefore, recently, polysaccharides of various origins have attracted attention because they exhibit anticancer effects by enhancing the immune capacity of the host. The present inventors have already developed and provided to society an anticancer agent consisting of a basidiomycete-derived polysaccharide, but during research on the structure and activity of this anticancer agent, aminobenzoic acid
N-D-annoside, aminobenzoic acid-N-L-
Arabinoside, aminobenzoic acid N-D-xyloside, aminobenzoic acid N-D-glucoside, aminobenzoic acid N-D-galactoside, and aminobenzoic acid N-L-rhamnoside have various useful physiological activities. I discovered that. However, these substances are not necessarily sufficient to maintain their medicinal efficacy over a long period of time. As a result of further research, it was discovered that a compound represented by the above general formula (), which has low toxicity and high medicinal efficacy, is effective, and the present invention has been completed. Although the compound represented by the general formula (), its salt, or its ester (hereinafter referred to as "the substance") has a simple structure, it has extremely low toxicity and has no antibacterial activity, so it may cause disruption of intestinal flora. There is no need to worry about this, and long-term administration is possible. Furthermore, it is an extremely safe drug that does not have mutagenicity or affect cellular or humoral immunity, and therefore poses no risk of teratogenicity or allergic reactions to healthy people. In addition, this substance has hypoglycemic and hypotensive effects,
It has blood lipid lowering, antitumor, antipyretic and analgesic, and antiinflammatory effects, and is useful as an antidiabetic agent, antihypertensive agent, antiarteriosclerotic agent, antitumor agent, antipyretic analgesic, and antiinflammatory agent. It is. The salt of the aminobenzoic acid derivative of the present invention is one in which the hydrogen atom of the -COOH group in the above formula () is replaced with an alkali metal, an alkaline earth metal, or an aluminum metal. Any alkali metal or alkaline earth metal may be used as long as it is acceptable as a drug, and usually Na, K, Mg,
Ca is preferable, and Na is particularly preferable. In addition, the ester of the aminobenzoic acid derivative of the present invention is one in which the hydrogen atom of the -COOH group in the above formula () is replaced with an alkyl group, and the alkyl group includes methyl, ethyl, propyl, butyl group, etc. preferable. R 1 represents an acylated pentose, hexose or disaccharide residue. Here, acylated sugar residue refers to the OH group (however, one
OH is removed) and H is substituted with an acyl group, where the acyl group represents acetyl, propionyl, butyryl, valeryl, benzoyl, phenylacetyl group, etc. These sugars can be in the D or L form or in the form of the α- or β-anomer or in the form of a mixture of anomers. Therefore, the present substance can also be α or β or a mixed anomer thereof. Examples of the sugars mentioned here include the following. Pentoses include D-ribose, D-xylose, D or L-albinose, L or D-xylulose, and D-ribulose. Hexoses include D or L-galactose, D
- Glucose, D-mannose, D-fructose, L-sorbose, D-tagatose. Disaccharides include maltose, cellobiose, lactose, laminaribiose, gentiobiose, melibiose, isomaltose, mannobiose, xylobiose, and sutucarose. This substance can be produced by the following method. 1 to 10 g of sugar or aminobenzoic acid or its ester in a solvent (e.g. water, alcohol (e.g. methanol, ethanol), acetone, chloroform, pyridine, nitromethane, DMF, THF,
Dioxane, DMSO) in 2 to 200 ml in the presence or absence of a catalyst at 20°C to 200°C, preferably from 50°C to
At 150℃, the time is 10 minutes to 48 hours, preferably 30 minutes to
Allow to react for 24 hours. Here, the catalyst is preferably acetic acid or a salt thereof, hydrochloric acid, ammonium chloride, etc., and is added in an amount of 0.1 to 5 g based on the above amount. In the case of condensation reactions with disaccharides, ammonium chloride is not necessarily suitable and the effective catalyst is acetic acid. In this case, 2 to 6 g of aminobenzoic acid (including salt and lower alkyl ester), 1 to 10 g of sugar, and 2 to 10 g of solvent.
The most favorable results were obtained when 1 to 2 ml of acetic acid was used per ~200 ml. When the amount of acetic acid used was below this range, the yield decreased, and when it was above this range, no increase in the product was observed. After the above reaction, the reaction product is cooled, either as it is or concentrated to precipitate crystals of the reaction product, separated by filtration and washed with water, methanol, acetone, ether, etc. Further recrystallization is performed, and the resulting product is dried in an organic solvent such as benzene, acetone, dioxane, nitromethane, pyridine, DMSO, chloroform,
Acylating agents, acid chlorides such as acetyl chloride, propiol chloride, butyryl chloride, benzoyl chloride, phenylacetyl chloride or acid anhydrides such as acetic anhydride, propionic anhydride, butyric anhydride, valeric anhydride among DMF, THF etc. , benzoic anhydride, etc. are added and reacted. The resulting reaction solution is added to ice water to collect water-insoluble materials. This collected solid substance is recrystallized to obtain this substance. An example of the reaction conditions is 1 g of aminobenzoic acid or its ester and sugar conjugate, 5.0 to 20 ml of organic solvent, and 2 g of acid anhydride or acid chloride.
-20g at -70 to 100°C, preferably -20°C to 50°C. The reaction product is cooled and added to ice water to collect a solid substance. This solid substance is recrystallized in alcohol, ether or other solvent to obtain the substance. This substance can also be obtained by the following method. Acylated sugar [However, one OH group is free or
Br, Cl, etc.] and aminobenzoic acid or its ester in an organic solvent such as pyridine, THF, DMSO, DMF, nitromethane, chloroform, dioxane, acetone, or alcohol at -70 to 180°C, preferably The reaction is carried out at -20 to 50°C for 1 minute to 168 hours, preferably 1.0 to 24 hours, and the present substance is obtained from the reaction product. The physicochemical properties of the example of this substance obtained by the above production method are shown in Table 1 below. Further, infrared absorption spectra are shown in FIGS. 1 to 19. In addition, Table 1
The analysis method is as follows. (1) Melting point Measured using a Yanagimoto micro melting point measuring device. (2) Elemental analysis Measured using Yanagimoto CHN coder MT2 type. (3) UV Measured using a Hitachi ESP-3T self-recording spectrophotometer. (4) IR Measured using the KBr method using JASCO Model DS-701G. The drawing number corresponds to sample No. 1 in Table 1.
【表】【table】
【表】
次に本物質の毒性学的特性を示す。
(1) 急性毒性
ICR−JCL系マウスを用いて強制経口投与に
よる急性毒性を調べた。本物質は蒸溜水に溶解
又は懸濁し、これを胃ゾンデを用いて所定の量
に調整して与えた。
投与後中毒症状の観察を続け、７日目までの
経時的死亡率からLD50値を求めた。生存例、
死亡例とも解剖して所見を得た。LD50値はリ
ツチフイールド・ウイルコクソン（Litchfield
−Wilcoxon）図計算法により求めた。結果を
表２に示す。いずれもLD50値は大きく、低毒
性物質であり極めて安全性の高い薬剤であると
いえる。[Table] Next, the toxicological properties of this substance are shown. (1) Acute toxicity Acute toxicity was investigated by forced oral administration using ICR-JCL mice. This substance was dissolved or suspended in distilled water, and the solution was adjusted to a predetermined amount using a stomach tube and administered. After administration, the symptoms of toxicity were continued to be observed, and the LD 50 value was determined from the mortality rate over time up to the 7th day. Survival cases,
In both cases of death, autopsies were performed to obtain findings. LD50 values are Litchfield-Wilcoxon (Litchfield
−Wilcoxon) calculated using the graphic calculation method. The results are shown in Table 2. All have large LD 50 values, are low toxicity substances, and can be said to be extremely safe drugs.
【表】【table】
【表】
(2) 抗菌活性
本物質を50％ジメチルスルフオキシド水溶液
に溶解して２倍稀釈系列を作成し、この稀釈液
を９倍量の加温溶解した寒天培地に混和し、ペ
トリ皿に注いで平板とした。培地にはハートイ
ンヒユージヨン寒天（細菌）及びサブロー寒天
（真菌）を用い、前培養した試験菌を塗抹接種
後細菌は37℃で20〜24hr、真菌は25℃で３〜７
日間それぞれ培養して生育の有無を調べた。被
検菌ととしては次の各菌種を使用した。
緑膿菌（Pseudomonas aeruginosaIAM
1514）
大腸菌（Eschefichia coli IFO 12734）
黄色ブドウ球菌（Staphylococcus aureus
209P）
枯草菌（Bacillus subtilis IAM 1069）
パン酵母（Saccharomyces cerevisiae IAM
4207）
カンジダ酵母（Candida albicans ATCC
752）
白癬菌（Trichophyton mentagrophytes
IFO 6124）
黒かび（Aspergillus niger IAM 3001）
その結果、本物質はいずれの菌に対しても１
mg／mlの濃度で生育阻止を示さなかつた。
(3) 変異原性
まずRec−assayによる検討を行なつた。す
なわち、組換修復欠損株（Bacillus subtillis
M45）と組換修復保持株（B.subtilis H17）の
２株をＢ−寒天培地（肉エキス10ｇ、ポリペ
プトン10ｇ、NaCl5ｇ、寒天15ｇ、蒸溜水1000
ml、PH7.0）上に出発点が互いに接触しないよ
うに画線した。本物質をジメチルスルフオキシ
ドに溶解し、その0.05mlを直径８mmの円形紙
に吸収させた後、直ちに画線の開始点をおおう
ように静置し、37℃晩培養して生育阻止域の長
さを測定した。陰性対照としてカナマイシン、
陽性対照としてマイトマイシンＣを用いた。
Rec−assayの結果を表３に示す。本物質は
いずれも高濃度で作用させても変異原性を示さ
ず、安全性の高い薬剤であることが知られた。[Table] (2) Antibacterial activity Dissolve this substance in a 50% dimethyl sulfoxide aqueous solution to prepare a 2-fold dilution series, mix this dilution with 9 times the amount of heated agar medium, and place in a Petri dish. It was poured into a plate and made into a flat plate. Heart infusion agar (bacteria) and Sabouraud agar (fungi) were used as the culture medium, and after inoculation with pre-cultured test bacteria, bacteria were incubated at 37℃ for 20 to 24 hours, and fungi were incubated at 25℃ for 3 to 7 hours.
The cells were cultured for several days and the presence or absence of growth was examined. The following bacterial species were used as test bacteria. Pseudomonas aeruginosa IAM
1514) Eschefichia coli IFO 12734) Staphylococcus aureus
209P) Bacillus subtilis IAM 1069) Baker's yeast ( Saccharomyces cerevisiae IAM
4207) Candida albicans ATCC
752) Trichophyton mentagrophytes
IFO 6124) Black mold ( Aspergillus niger IAM 3001) As a result, this substance has a 1.
No growth inhibition was observed at a concentration of mg/ml. (3) Mutagenicity First, we conducted an investigation using Rec-assay. That is, the recombinant repair-deficient strain (Bacillus subtillis
M45) and a recombinant repaired strain (B. subtilis H17) were placed on B-agar medium (10 g of meat extract, 10 g of polypeptone, 5 g of NaCl, 15 g of agar, 1000 g of distilled water).
ml, PH7.0) so that the starting points did not touch each other. After dissolving this substance in dimethyl sulfoxide and absorbing 0.05 ml onto a circular paper with a diameter of 8 mm, it was immediately left to stand so as to cover the starting point of the streak, and incubated overnight at 37°C to reach the growth inhibition zone. The length was measured. kanamycin as a negative control;
Mitomycin C was used as a positive control. The results of Rec-assay are shown in Table 3. None of these substances exhibits mutagenicity even when applied at high concentrations, and is known to be a highly safe drug.
【表】
(4) 遅延型皮内反応
本物質の細胞性免疫への影響を知るために
ICR−JCLマウスを用いてヒツジ赤血球を抗原
とする足蹠反応（Foot pad reaction）を行な
つた。ヒツジ赤血球を生理食塩水に10％量懸濁
せしめ、この液0.2mlを尾静脈より注入して１
次感作を行ない、さらに７日後にヒツジ赤血球
の40％量懸濁液0.05mlを足蹠に注射して２次感
作を行ない翌日足蹠厚の測定を行なつた。本物
質は１次感作の日を中心に250ml／Kgを腹腔内
へ連日５回投与した。
その結果、本物質投与群の足蹠厚の増加は対
照（非投与）群と比較して何ら有意差は認めな
かつた。
(5) 抗体産生能
本物質の体液性免疫への影響を知るために、
ICR−JCLマウスに対し、ヒツジ赤血球の10％
量懸濁液0.2mlを尾静脈より注入して感作し、
感作後７日目に採血して赤血球凝集反応により
抗体産生能を測定した。なお本物質は感作日を
中心にして250mg／Kgを連日５回腹腔内へ投与
した。
結果は、本物質投与群と対照群の凝集価に何
ら有意差はみられなかつた。
次に本物質の薬理学的特性を述べる。
(1) 血糖降下作用
ストレプトゾトシン60mg／Kgを10週齢のウイ
スター（Wistar）系ラツトの腹腔内に投与し
て１週間後に尿糖陽性を確認し、さらにレギユ
ラーインシユリン投与により尿糖、血糖の低下
をみるものの、数日後に再び高尿糖、高血糖を
確認した動物のみを糖尿病モデル動物として用
いた。各群10匹を用いた。本物質をアラビアゴ
ム水溶液に懸濁し、300mg／Kgとなるよう経口
投与した。投与後3hr及び6hr目に血液を採取
し、グルコースの測定をRaBAキツト（中外製
酵素法）を用いて行なつた。
平均値の結果を表４に示す。投与前血糖値に
対する投与後血糖値の差、すなわち本物質投与
により実際に低下した血糖値（△値）はいずれ
の化合物でも対照より大きく血糖降下作用が認
められた。ただし、投与前の血糖総平均値は
520mg／dlであつた。[Table] (4) Delayed intradermal reaction To understand the effect of this substance on cellular immunity
A foot pad reaction using sheep red blood cells as an antigen was performed using ICR-JCL mice. Sheep red blood cells were suspended in physiological saline at a volume of 10%, and 0.2 ml of this solution was injected through the tail vein.
Secondary sensitization was performed, and 7 days later, 0.05 ml of a 40% suspension of sheep red blood cells was injected into the footpad to perform secondary sensitization, and the footpad thickness was measured the next day. This substance was administered intraperitoneally at a dose of 250 ml/Kg five times on consecutive days, mainly on the day of primary sensitization. As a result, no significant difference was observed in the increase in footpad thickness in the group administered with this substance compared to the control (non-administered) group. (5) Antibody production ability In order to understand the effect of this substance on humoral immunity,
10% of sheep red blood cells for ICR-JCL mice
Sensitize by injecting 0.2ml of the suspension through the tail vein.
Blood was collected 7 days after sensitization, and antibody production ability was measured by hemagglutination reaction. The substance was administered intraperitoneally at a dose of 250 mg/Kg five times daily, mainly on the day of sensitization. As a result, no significant difference was observed in the agglutination value between the group administered with this substance and the control group. Next, we will discuss the pharmacological properties of this substance. (1) Hypoglycemic effect Streptozotocin 60mg/Kg was administered intraperitoneally to 10-week-old Wistar rats, positive urine glucose was confirmed one week later, and regular insulin was administered to lower urine sugar and blood sugar. Only animals in which high urinary sugar and hyperglycemia were confirmed again after a few days, although a decrease was observed, were used as diabetic model animals. 10 animals were used in each group. This substance was suspended in an aqueous gum arabic solution and orally administered at a dose of 300 mg/Kg. Blood was collected 3 hours and 6 hours after administration, and glucose was measured using a RaBA kit (manufactured by Chugai Enzyme Method). The results of the average values are shown in Table 4. The difference between the pre-administration blood sugar level and the post-administration blood sugar level, that is, the blood sugar level actually lowered by administration of this substance (△ value), was greater than that of the control for all compounds, indicating a hypoglycemic effect. However, the total average blood sugar value before administration was
It was 520mg/dl.
【表】
(2) 血圧降下作用
ヒトの本能性高血圧に斎も近似し高血圧モデ
ル動物としてすぐれている自然発症高血圧ラツ
ト（SHR）に対して、アラビアゴム水溶液に
懸濁した本物質を300mg／Kgとなるよう経口投
与した。投与後3hr及び6hr目に血圧測定器（ウ
エダ製作所製、USM−105R型）を用いて血圧
として尾動脈圧を非観的に測定し、投与前後の
血圧差をもつて本物質の降圧効果とした。
尚、ラツトは20乃至25週鈴で、投与前の最高
血圧の総平均値は205mmHgで、一群５匹を用い
た。
結果を表５に示す。本物質はいずれも明らか
に降圧効果を示し、血圧降下剤として有用であ
る。[Table] (2) Blood pressure lowering effect 300 mg/Kg of this substance suspended in an aqueous gum arabic solution was administered to spontaneously hypertensive rats (SHR), which closely resembles human instinctive hypertension and is an excellent model animal for hypertension. It was administered orally so that 3 hours and 6 hours after administration, tail artery pressure was non-objectively measured as blood pressure using a blood pressure measuring device (manufactured by Ueda Seisakusho, model USM-105R), and the blood pressure difference before and after administration was used to determine the antihypertensive effect of this substance. did. The rats were 20 to 25 weeks old, the total mean systolic blood pressure before administration was 205 mmHg, and 5 rats were used per group. The results are shown in Table 5. All of these substances clearly exhibit antihypertensive effects and are useful as antihypertensive agents.
【表】
(3) 抗腫瘍作用
Sarcoma−180細胞１×106個を５週齢のICR
−JCL雌マウス（日本クレア(株)より購入）の腋
下部皮下に移植、移植24hr後より隔日に10回、
アラビアゴム水溶液に懸濁させた本物質を500
mg／Kg経口投与した。移植後25日目に腫瘍結節
を摘出し、次式により増植抑制率（I.R.％）を
算出した。尚、各群10匹を用いた。
（１−Ｔ／Ｃ）×100＝I.R.（％）
Ｔ：投与群平均腫瘍重量
Ｃ：対照群平均腫瘍重量
結果を表６に示す。試験に供した化合物はい
ずれも抗腫瘍活性を示し、制癌剤として有用で
あることが知られる。[Table] (3) Antitumor effect ICR of 1× 106 Sarcoma-180 cells at 5 weeks old
- Transplanted subcutaneously in the axillary region of JCL female mice (purchased from Nippon Clea Co., Ltd.), 10 times every other day starting 24 hours after transplantation.
500% of this substance suspended in aqueous gum arabic solution
mg/Kg was administered orally. Tumor nodules were excised on the 25th day after transplantation, and the growth inhibition rate (IR%) was calculated using the following formula. In addition, 10 animals were used in each group. (1-T/C)×100=IR (%) T: Administration group average tumor weight C: Control group average tumor weight The results are shown in Table 6. All of the compounds tested exhibited antitumor activity and are known to be useful as anticancer agents.
【表】
(4) 血中脂質降下作用
日本白色種雄性ウサギ（体重約2.5Kgのも
の）にコレステロール１％含有固型飼料（CR
−１）を経口自由摂取させ、約３ケ月後血清脂
質成分の上昇を確認してこれを実験的動脈硬化
モデル動物として使用した。このウサギの血清
コレステロール、β−LPの総平均値はそれぞ
れ1550mg／dl、1240mg／dlであつた。これら高
脂血症を示すウサギは同時に粥状動脈硬化を発
症し、動脈硬化モデル動物として従来より抗動
脈硬化症剤の効果検定に汎用されている。これ
らの動脈硬化モデル動物に、本物質をアラビア
ゴム水溶液に懸濁し、300mg／Kgを経口投与し
た。
投与後経時的に耳静脈より採血して血清脂質
分析を実施し、血液中の総コレステロールの変
化を酵素法により、又β−リポタンパクは比濁
法により測定した。結果を表７に示す。
上述した本物質の毒物学的特性および薬理学
的特性からみて、本物質は抗動脈硬化症剤とし
て実用に供せられることが理解される。[Table] (4) Blood lipid-lowering effect Japanese White male rabbits (body weight approximately 2.5 kg) were fed solid feed containing 1% cholesterol (CR).
-1) was orally administered ad libitum, and after approximately 3 months, an increase in serum lipid components was confirmed, and this animal was used as an experimental arteriosclerosis model animal. The total average values of serum cholesterol and β-LP in this rabbit were 1550 mg/dl and 1240 mg/dl, respectively. These hyperlipidemic rabbits also develop atherosclerosis, and have been commonly used as arteriosclerosis model animals to test the effects of anti-arteriosclerosis drugs. This substance was suspended in an aqueous gum arabic solution and 300 mg/Kg was orally administered to these arteriosclerosis model animals. Blood was collected from the ear vein over time after administration, and serum lipid analysis was performed.Changes in total cholesterol in the blood were measured by an enzymatic method, and β-lipoprotein was measured by a turbidimetric method. The results are shown in Table 7. In view of the above-mentioned toxicological and pharmacological properties of this substance, it is understood that this substance can be put to practical use as an anti-arteriosclerotic agent.
【表】
(5) 抗炎症作用
(1) カラゲニン浮腫抑制作用
Van Arman et.al.（1963）の方法に従
い、１群10匹の６週齢の呑竜系雌ラツト（東
京実験動物(株)より購入）に検体1000mg／Kgを
強制経口投与し、投与１時間後に右後股足足
蹠に１％Carrageenin生食懸濁液を0.1ml注射
し、経時的に足容積を測定し次式により抑制
率を求めた。
（１−Ｔ／Ｃ）×100＝I.R.（％）
Ｔ：投与群平均足蹠容積
Ｃ：対照群〃
(2) 肉芽腫抑制作用
Winter et.al.（1963）の方法に従い、１群
６匹の６週齢の呑竜系雌ラツト（東京実験動
物(株)より購入）の背部皮下に正中線を左右対
称とし30±１mgのCotton wool pelletを２個
植込み本物質を７日間連続経口投与し、８日
目に肉芽を摘出し、乾燥重量を測定し上記(1)
と同様に抑制率を求めた。
(3) 抗滲出作用
Baris et.al.（1965）らの方法に従い、１
群６匹の６週齢の呑竜系雌ラツト（東京実験
動物(株)より購入）の背部皮下に空気を注入し
てポーチを作成し、ポーチ中に１％Croton
oil（ゴマ油中）、0.5mlを注入、本物質を５日
間連続経口投与し、６日目にポーチ内の滲出
液量を測定し上記(1)と同様に抑制率を求め
た。
結果を表８に示す。この結果より本物質は抗
炎症作用があることがわかる。[Table] (5) Anti-inflammatory effect (1) Suppressive effect on carrageenan edema According to the method of Van Arman et.al. 1000 mg/Kg of the sample was administered by force orally to a human (purchased), and 1 hour after administration, 0.1 ml of 1% Carrageenin saline suspension was injected into the right hind groin and footpad.The paw volume was measured over time and the inhibition rate was calculated using the following formula. I asked for (1-T/C)×100=IR (%) T: Average footpad volume of administration group C: Control group (2) Granuloma suppression effect According to the method of Winter et.al. (1963), 6 animals per group Two 30 ± 1 mg cotton wool pellets were implanted subcutaneously on the back of 6-week-old female rats (purchased from Tokyo Experimental Animals Co., Ltd.) symmetrically on the midline, and the substance was orally administered for 7 consecutive days. On the 8th day, the granulation was removed and the dry weight was measured (see (1) above).
The suppression rate was calculated in the same manner as . (3) Anti-exudation effect According to the method of Baris et.al. (1965), 1
A pouch was created by injecting air subcutaneously into the back of a group of 6 6-week-old female rats (purchased from Tokyo Experimental Animals Co., Ltd.), and 1% Croton was added to the pouch.
0.5 ml of oil (in sesame oil) was injected, and the substance was orally administered for 5 consecutive days. On the 6th day, the amount of exudate in the pouch was measured and the inhibition rate was determined in the same manner as in (1) above. The results are shown in Table 8. This result shows that this substance has an anti-inflammatory effect.
【表】【table】
【表】
(6) 熱解、鎮痛作用
(1) 鎮痛作用
機械的刺激法（圧刺激法）
高木、亀山らの圧刺激装置（夏目製作所
製）を用いた。被験動物は６週齢のICR系マ
ウス（♀、日本クレア(株)より購入）を用い、
マウスの尾根部に圧を加え、疼痛閾値が50〜
80mmHgを示すものを選び１群10匹とした。
試料経口投与後、経時的に測定を行い、被
験動物が仮性逃避反応を示した時点までの圧
を所要時間（秒）より鎮痛効果を判定した。
化学的刺激法
ICR系マウス、５〜６週令（♀、日本クレ
ア(株)より購入）マウスを１群10匹とし、
Koster et al（1959）の方法に準拠して試料
を経口投与後30min後に0.6％酢酸溶液を0.1
ml／10ｇマウス体重当り腹腔内注執し、さら
に10min後より10min間マウスにおきる
Writhing数を計数し、次式により対照群に
対する抑制率（％）を求めた。
(2) 解熱作用
Winter et.al.（1961）の方法に準じ、１群
６匹の６週齢の呑竜ラツト（♀、東京実験動
物(株)より購入）に20％ビール酵母懸濁液を皮
下投与し、10時間絶食後、試料を経口投与し
直腸温を測定し、試料の作用最大時における
対照発熱ラツト体温に対する発熱抑制率を次
式より求めた。
Ｃ１−Ｈ／Ｃ１−Ｃ２×100＝I.R.（％）
Ｔ：投与群の平均体温（39.1℃）
C1：対照発熱ラツトの平均体温
C2：対照無処理ラツトの平均体温（37.5℃）
結果を表10に示す。この結果から本物質は解
熱鎮痛剤として有用であることがわかる。[Table] (6) Heat-reducing and analgesic effects (1) Analgesic effects Mechanical stimulation method (pressure stimulation method) Takagi, Kameyama et al.'s pressure stimulation device (manufactured by Natsume Seisakusho) was used. The test animals used were 6-week-old ICR mice (♀, purchased from Nippon Clea Co., Ltd.).
Apply pressure to the ridge of the mouse until the pain threshold is 50~
Those exhibiting 80 mmHg were selected and each group consisted of 10 animals. After oral administration of the sample, measurements were taken over time, and the analgesic effect was determined based on the pressure and time required (seconds) until the test animal showed a pseudo-escape response. Chemical stimulation method ICR mice, 5 to 6 weeks old (female, purchased from Nippon Clea Co., Ltd.), 10 mice per group.
30 min after oral administration of the sample according to the method of Koster et al (1959), add 0.1% of 0.6% acetic acid solution.
Inject intraperitoneally per ml/10g mouse body weight, and after another 10 minutes, inject into the mouse for 10 minutes.
The number of writings was counted, and the inhibition rate (%) relative to the control group was determined using the following formula. (2) Antipyretic effect According to the method of Winter et.al. (1961), a 20% brewer's yeast suspension was administered to 6-week-old Doryu rats (female, purchased from Tokyo Experimental Animals Co., Ltd.), 6 in each group. The sample was administered subcutaneously, and after fasting for 10 hours, the sample was orally administered, the rectal temperature was measured, and the rate of fever suppression relative to the body temperature of the control fever rat at the peak of the sample's effect was determined from the following formula. C 1 -H/C 1 -C 2 × 100 = IR (%) T: Average body temperature of treated group (39.1°C) C 1 : Average body temperature of control fever rats C2 : Average body temperature of control untreated rats (37.5°C) ) The results are shown in Table 10. This result shows that this substance is useful as an antipyretic analgesic.
【表】
本物質は急性毒性も少なく又他の副作用も少な
いので動物更に人用の医薬として有用である。医
薬としては抗糖尿病剤、血圧降下剤、抗動脈硬化
症剤、抗腫瘍剤、解熱鎮痛剤そして抗炎症剤とし
て人用い用いられる。
次に本物質の製剤化について述べる。
本発明は抗糖尿病剤、血圧降下剤、抗腫瘍剤、
抗動脈硬化症剤、抗炎症剤、解熱鎮痛剤として使
用する場合、疾患の種類及び症状に応じて薬効を
得るのに都合のよい形状で使用でき、そして単独
または製薬上許容し得る希釈剤及び他の薬剤との
混合物として使用できる
本物質は投薬単位形で提供することができる。
有効薬量の有効成分が含有され、その形態として
は経口用として散剤、顆粒剤、錠剤、糖衣錠剤、
カプセル剤、シロツプ剤、丸剤、懸濁液、液剤、
乳剤などである。非経口用として注射液のアンプ
ル、ビン形態などをとり得る。又座剤の形態もと
り得る。希釈剤として固体、液体、半固体状のも
のでよく、例えば次のものがあげられる。すなわ
ち、賦形剤、増量剤、結合剤、湿潤化剤、崩解
剤、表面活性剤、滑沢剤、分散剤、緩衝剤、香
料、保存料、溶解補助剤、溶剤等などである。具
体的な例としてあげると乳糖、しよ糖、ソルビツ
ト、マンニツト、でん粉、沈降性炭酸カルシウ
ム、重質酸化マグネシウム、タルク、ステアリン
酸カルシウム、ステアリン酸マグネシウム、セル
ロース又はその誘導体、アミロペクチン、ポリビ
ニルアルコール、ゼラチン、水、生理食塩水、エ
タノール、グリセリン、プロピレングリコール、
カカオ脂、ラウリン脂、ワセリン、パラフイン、
高級アルコール等である。
本発明の生理活性剤は既知のいかなる方法でも
製造し得る。本発明において用いられる組成物中
の活性成分は一般に0.01％から100wt％、好まし
くは0.05％から80％wt％含まれる。
本発明の生理活性剤は人間及び動物に経口的ま
たは非経口的に投与されるが経口投与に好まし
い。経口的投与は舌下投与を包含する。非経口的
投与は注射投与（例えば皮下、筋肉、静脈注射、
点滴）、直腸投与などを含む。
本発明の生理活性剤の投与量は動物か人間によ
り、また年令、個人差、病状などに影響されるの
で場合によつては下記範囲外量を投与する場合も
生ずるが、一般に人間を対象とする場合、本物質
の経口的投与量は体重１Kg、１日当り0.1〜500
mg、好ましくは0.5〜200mg、非経口投与量は同じ
く、0.01〜200mg、好ましくは0.1〜100mgを１回
〜４回に分けて投与する。
以下、本発明物質の製剤化例並びに製造例を示
し本発明をより詳細に説明する。下記例中の部は
重量を示す。
製剤化例 １
本物質（ｐ−アミノ安息香酸メチルエステル−Ｎ
−Ｏ−アセチル−Ｄ−キシロシツド） 10（部）
重質酸化マグネシウム 15
乳 糖 75
を均一に混合して粉末または細粒状として350μ
以下の散剤とする。またこの散剤をカプセル容器
に入れてカプセル剤とした。
製剤化例 ２
本物質（ｐ−アミノ安息香酸エチルエステル−Ｎ
−Ｏ−アセチル−Ｄ−マンノシツド） 45（部）
澱 粉 15
乳 糖 16
結晶セルロース 21
ポリビニルアルコール ３
水 30
を均一に加温混合混和後、破砕造粒して乾燥、篩
別後顆粒1410μ〜177μの大きさの剤とする。
製剤化例 ３
例２におけるｐ−アミノ安息香酸エチルエステ
ル−Ｎ−Ｏ−アセチル−Ｄ−マンノシツドのかわ
りにｐ−アミノ安息香酸ブチルエーテル−Ｎ−Ｏ
−アセチル−Ｌ−ラムノシツドを用いて同様の方
法で顆粒剤を作り、この顆粒剤96部にステアリン
酸カルシウム４部を加えて圧縮成形して直径10mm
の錠剤とする。
製剤化例 ４
製剤化例２の方法で得られた顆粒の90部に結晶
セルロース10部とステアリン酸カルシウム３部を
加え圧縮成形して直径８mmの錠剤とし、これにシ
ロツプゼラチン、沈降性炭酸カルシウムの混合懸
濁液を加えて糖衣錠とする。
製造例 １
ｏ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｄ−
リボシツドの製造法
ｏ−アミノ安息香酸−Ｎ−Ｄ−リボシツド1.5
ｇを10mlの乾燥ピリジンに分散させ10mlの無水酢
酸を加え溶解するまで撹拌する。反応液はそのま
ま放置しアセチル化を行う。アセチル化終了後反
応液を氷水中に撹拌しつつ添加、アセチル化物は
水不溶性の固形物として分離される。分離された
アセチル化物は再度水で洗浄後エチルアルコール
に溶解、少量の石油エーテルを添加、放置すると
結晶の析出をみる。同様の方法で数回再結をくり
返すと、針状の結晶を得る。
収率12.8％であつた。
製造例 ２
ｏ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−マンノシツドの製造法
ｏ−アミノ安息香酸メチルエステル−Ｎ−Ｄ−
マンノシツド1.0ｇを５mlの乾燥ピリジンに分散
させ5.0mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルアルコールに溶解、少量の石油エーテル
を添加、放置すると結晶の析出をみる。同様の方
法で数回再結をくり返すと、針状の結晶を得る。
収率は69.0％であつた。
又、ｏ−アミノ安息香酸メチルエステル1.0ｇ
を５mlの乾燥ピリジンに分散させ２・３・４・６
−テトラ−Ｏ−アセチル−Ｄ−マンノシルブロマ
イド３ｇを加え50℃で２時間反応させる。
該反応生成物を上記と同じ方法で精製し乾燥し
て収率70％でｏ−アミノ安息香酸メチルエステル
−Ｎ−Ｏ−アセチル−Ｄ−マンノシツドを得る。
製造例 ３
ｏ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−グルコシツドの製造法
ｏ−アミノ安息香酸メチルエステル−Ｎ−Ｄ−
グルコシツド1.0ｇを5.0mlの乾燥ピリジンに分散
させ5.0mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルアルコールに溶解、少量の石油エーテル
を添加、放置すると結晶の析出をみる。同様の方
法で数回再結をくり返すと、針状の結晶を得る。
収率71.6％であつた。
又ｏ−アミノ安息香酸メチルエステル1.0ｇを
５mlの乾燥ピリジンに分散させ２・３・４・６−
テトラ−Ｏ−アセチル−Ｄ−グルコシルブロマイ
ド３ｇ加え、50℃で２時間反応させる。
該反応生成物を上記と同じ方法で精製し乾燥し
て収率73％でｏ−アミノ安息香酸メチルエステル
−Ｎ−Ｏ−アセチル−Ｄ−グルコシツドを得る。
製造例 ４
ｏ−アミノ安息香酸エチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−マンノシツドの製造法
ｏ−アミノ安息香酸エチルエステル−Ｎ−Ｄ−
マンノシツド1.0ｇを5.0mlの乾燥ピリジンに分散
させ5.0mlの無水酢酸を溶解するまで撹拌する。
反応液はそのまま放置しアセチル化を行う。アセ
チル化終了後反応液を氷水中に撹拌しつつ添加、
アセチル化物は水不溶性の固形物として分離され
る。分離されたアセチル化物は再度水で洗浄後エ
チルアルコールに溶解、少量の石油エーテルを添
加、放置すると結晶の析出をみる。同様の方法で
数回再結をくり返すと、針状の結晶を得る。
収率57.8％であつた。
製造例 ５
ｏ−アミノ安息香酸エチルエステル−Ｎ−Ｏ−
アセチル−Ｌ−ラムノシツドの製造法
ｏ−アミノ安息香酸エチルエステル−Ｎ−Ｌ−
ラムノシツド3.0ｇを15mlの乾燥ピリジンに分散
させ15mlの無水酢酸を溶解するまで撹拌する。反
応液はそのまま放置しアセチル化を行う。アセチ
ル化終了後反応液を氷水中に撹拌しつつ添加、ア
セチル化物は水不溶性の固形物として分離され
る。分離されたアセチル化物は再度水で洗浄後エ
タノールに溶解、少量の石油エーテルを添加、放
置すると結晶の析出をみる。同様の方法で数回再
結晶をくり返すと、針状の結晶を得る。
収率75.2％であつた。
製造例 ６
ｏ−アミノ安息香酸ブチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−グルコシツドの製造法
ｏ−アミノ安息香酸ブチルエステル−Ｎ−Ｄ−
グルコシツド3.0ｇを15mlの乾燥ピリジンに分散
させ15mlの無水酢酸を溶解するまで撹拌する。反
応液はそのまま放置しアセチル化を行う。アセチ
ル化終了後反応を氷水中に撹拌しつつ添加、アセ
チル化物は水不溶性の固形物として分離される。
分離されたアセチル化物は再度水で洗浄後エチル
エーテルに溶解、少量の石油エーテルを添加、放
置すると結晶の析出をみる。同様の方法で数回再
結をくり返すと、針状の結晶を得る。
収率30.5％であつた。
又ｏ−アミノ安息香酸ブチルエステル1.0ｇを
５mlの乾燥ピリジンに分散させ２・３・４・６−
テトラ−Ｏ−アセチル−Ｄ−グルコシルクロライ
ド３ｇを加え50℃で２時間反応させる。
該反応生成物を上記と同じ方法で精製し乾燥し
て収率35％でｏ−アミノ安息香酸ブチルエステル
−Ｎ−Ｏ−アセチル−Ｄ−グルコシツドを得る。
製造例 ７
ｐ−アミノ安息香酸−Ｎ−Ｏ−プロピオニル−
２−デオキシ−Ｄ−リボシツドの製造法
ｐ−アミノ安息香酸−Ｎ−２−デオキシ−Ｄ−
リボシツド3.0ｇを15mlの乾燥ピリジンに分散さ
せ15mlの無水プロピオン酸を加え溶解するまで撹
拌する。反応液はそのまま放置し冷却する。アシ
ル化終了後反応液を氷水中に撹拌しつつ添加、水
不溶性の固形物として分離する。分離物を再度水
で洗浄後エチルアルコールに溶解、少量の石油エ
ーテルを添加、放置すると結晶の析出をみる。同
様の方法で数回再結をくり返すと、針状の結晶を
得る。
収率18.0％であつた。
製造例 ８
ｐ−アミノ安息香酸−Ｎ−Ｏ−ブチリル−Ｌ−
アラビノシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｌ−アラビノシツド
2.0ｇを10mlの乾燥ピリジンに分散させ10mlの無
水酪酸を加え溶解するまで撹拌する。反応液はそ
のまま放置しアシル化を行う。アシル化終了後反
応液を氷水中に撹拌しつつ添加、アシル化物は水
不溶性の固形物として分離される。分離されたア
シル化物は再度水で洗浄後エチルアルコールに溶
解、少量の石油エーテルを添加、放置すると結晶
の析出をみる。同様の方法で数回再結をくり返す
と、針状の結晶を得る。
収率12.0％であつた。
製造例 ９
ｍ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｄ−
マンノシツドの製造法
ｍ−アミノ安息香酸−Ｎ−Ｄ−マンノシツド
1.0ｇを５mlの乾燥ピリジンに分散させ５mlの無
水酢酸を加え溶解するまで撹拌する。反応液はそ
のまま放置しアセチル化を行う。アセチル化終了
後反応液を氷水中に撹拌しつつ添加、アセチル化
物は水不溶性の固形物として分離される。分離さ
れたアセチル化物は再度水で洗浄後エチルアルコ
ールに溶解、少量の石油エーテルを添加、放置す
ると結晶の析出をみる。同様の方法で数回再結を
くり返すと、針状の結晶を得る。
収率10.5％であつた。
製造例 10
ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｄ−
グルコシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｄ−グルコシツド
3.0ｇを15mlの乾燥ピリジンに分散させ15mlの無
水酢酸を加え溶解するまで撹拌する。反応液はそ
のまま放置しアセチル化を行う。アセチル化終了
後反応液を氷水中に撹拌しつつ添加、アセチル化
物は水不溶性の固形物として分離される。分離さ
れたアセチル化物は再度水で洗浄後エチルアルコ
ールに溶解、少量の石油エーテルを添加、放置す
ると結晶の析出をみる。同様の方法で数回再結を
くり返すと、針状の結晶を得る。
収率25.3％であつた。
又ｐ−アミノ安息香酸1.0ｇを５mlの乾燥ピリ
ジンに分散させ２・３・４・６−テトラ−Ｏ−ア
セチル−Ｄ−グルコシルブロマイド３ｇを加え50
℃で２時間反応させる。
該反応生成物を上記と同じ方法で精製し乾燥し
て収率26.0％でｐ−アミノ安息香酸−Ｎ−Ｏ−ア
セチル−Ｄ−グルコシツドを得る。
製造例 11
ｐ−アミノ安息香酸−Ｎ−Ｏ−ベンゾイル−Ｄ
−ガラクトシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｄ−ガラクトシツド
3.0ｇを15mlの乾燥ピリジンに分散させ15mlの無
水安息香酸を加え溶解するまで撹拌する。反応液
はそのまま放置しアシル化を行う。アシル化終了
後反応液を氷水中に撹拌しつつ添加、アシル化物
は水不溶性の固形物として分離される。分離され
たアシル化物は再度水で洗浄後エチルアルコール
に溶解、少量の石油エーテルを添加、放置すると
結晶の析出をみる。同様の方法で数回再結をくり
返すと、針状の結晶を得る。
収率23.1％であつた。
製造例 12
ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｄ−
キシロシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｄ−キシロシツド
3.0ｇを15mlの乾燥ピリジンに分散させ15mlの無
水酢酸を加え溶解するまで撹拌する。反応液はそ
のまま放置しアセチル化を行う。アセチル化終了
後反応液を氷水中に撹拌しつつ添加、アセチル化
物は水不溶性の固形物として分離される。分離さ
れたアセチル化物は再度水で洗浄後エチルアルコ
ールに溶解、少量の石油エーテルを添加、放置す
ると結晶の析出をみる。同様の方法で数回再結晶
をくり返すと、針状の結晶を得る。
収率43.9％であつた。
製造例 13
ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｌ−
ラムノシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｌ−ラムノシツド
3.0ｇを15mlの乾燥ピリジンに分散させ15mlの無
水酢酸を溶解するまで撹拌する。反応液はそのま
ま放置しアセチル化を行う。アセチル化終了後反
応液を氷水中に撹拌しつつ添加、アセチル化物は
水不溶性の固形物として分離される。分離された
アセチル化物は再度水で洗浄後エチルアルコール
に溶解、少量の石油エーテルを添加、放置すると
結晶の析出をみる。同様の方法で数回再結晶をく
り返すと、針状の結晶を得る。
収率19.3％であつた。
製造例 14
ｐ−アミノ安息香酸−Ｎ−Ｏ−バレリル−Ｌ−
フコシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｌ−フコシツド2.0
ｇを10mlの乾燥ピリジンに分散させ10mlの無水酪
酸を加え溶解するまで撹拌する。反応液はそのま
ま放置しアシル化を行う。アシル化終了後反応液
を氷水中に撹拌しつつ添加、アシル化物は水不溶
性の固形物として分離される。分離されたアシル
化物は再度水で洗浄後エチルアルコールに溶解、
少量の石油エーテルを添加、放置すると結晶の析
出をみる。同様の方法で数回再結をくり返すと、
針状の結晶を得る。
収率16.3％であつた。
製造例 15
ｐ−アミノ安息香酸−Ｎ−Ｏ−ベンゾイル−Ｄ
−フラクトシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｄ−フラクトシツド
1.0ｇを５mlの乾燥ピリジンに分散させ５mlの塩
化ベンゾイルを加え溶解するまで撹拌する。反応
液はそのまま放置しアシル化を行う。アシル化終
了後反応液を氷水中に撹拌しつつ添加、アシル化
物は水不溶性の固形物として分離される。分離さ
れたアシル化物は再度水で洗浄後エチルアルコー
ルに溶解、少量の石油エーテルを添加、放置する
と結晶の析出をみる。同様の方法で数回再結をく
り返すと、針状の結晶を得る。
収率12.1％であつた。
製造例 16
ｐ−アミノ安息香酸−Ｎ−Ｏ−フエニルアセチ
ル−Ｌ−ソルボシツドの製造法
ｐ−アミノ安息香酸−Ｎ−Ｌ−ソルボシツド
2.0ｇを10mlの乾燥ピリジンに分散させ10mlの塩
化フエニルアセチルを加え溶解するまで撹拌す
る。反応液はそのまま放置しアシル化を行う。ア
シル化終了後反応液を氷水中に撹拌しつつ添加、
アシル化物は水不溶性の固形物として分離され
る。分離されたアシル化物は再度水で洗浄後溶解
の再結晶をくり返すと、針状の結晶を得る。
収率8.9％であつた。
製造例 17
ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−セロ
ビオシツドの製造法
ｐ−アミノ安息香酸−Ｎ−セロビオシツド1.0
ｇを５mlの乾燥ピリジンに分散させ５mlの無水酢
酸を加え溶解するまで撹拌する。反応液はそのま
ま放置しアセチル化を行う。アセチル化終了後反
応液を氷水中に撹拌しつつ添加、アセチル化物は
水不溶性の固形物として分離される。分離された
アセチル化物は再度水で洗浄後エチルアルコール
に溶解、少量の石油エーテルを添加、放置すると
結晶の析出をみる。同様の方法で数回再結をくり
返すと、針状の結晶を得る。
収率19.7％であつた。
製造例 18
ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−マル
トシツドの製造法
ｐ−アミノ安息香酸−Ｎ−マルトシツド2.0ｇ
を10mlの乾燥ピリジンに分散させ10mlの無水酢酸
を加え溶解するまで撹拌する。反応液はそのまま
放置しアセチル化を行う。アセチル化終了後反応
液を氷水中に撹拌しつつ添加、アセチル化物は水
不溶性の固形物として分離される。分離されたア
セチル化物は再度水で洗浄後エチルアルコールに
溶解、少量の石油エーテルを添加、放置すると結
晶の析出をみる。同様の方法で数回再結をくり返
すと、針状の結晶を得る。
収率8.0％であつた。
製造例 19
ｐ−アミノ安息香酸−Ｎ−Ｏ−プロピオニル−
サツカロシツドの製造法
ｐ−アミノ安息香酸−Ｎ−サツカロシツド1.0
ｇを10mlの乾燥ピリジンに分散させ10mlの無水プ
ロピオン酸を加え溶解するまで撹拌する。反応液
はそのまま放置しアシル化を行う。アシル化終了
後反応液を氷水中に撹拌しつつ添加、アシル化物
は水不溶性の固形物として分離される。分離され
たアシル化物は再度水で洗浄後エチルアルコール
に溶解、少量の石油エーテルを添加、放置すると
結晶の析出をみる。同様の方法で数回再結をくり
返すと、針状の結晶を得る。
収率14.1％であつた。
製造例 20
ｐ−アミノ安息香酸−Ｎ−Ｏ−フエニルアセチ
ル−ラクトシツドの製造法
ｐ−アミノ安息香酸−Ｎ−ラクトシツド2.0ｇ
を15mlの乾燥ピリジンに分散させ15mlの塩化フエ
ニルアセチルを加え溶解するまで撹拌する。反応
液はそのまま放置しアシル化を行う。アシル化終
了後反応液を氷水中に撹拌しつつ添加、アシル化
物は水不溶性の固形物として分離される。分離さ
れたアシル化物は再度水で洗浄後の同再結晶をく
り返すと、針状の結晶を得る。
収率9.9％であつた。
製造例 21
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−マンノシツドの製造法
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｄ−
マンノシツド1.0ｇを5.0mlの乾燥ピリジンに分散
させ5.0mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルアルコールに溶解、少量の石油エーテル
を添加、放置すると結晶の析出をみる。同様の方
法で数回再結をくり返すと、針状の結晶を得る。
収率63.3％であつた。
又ｐ−アミノ安息香酸メチルエステル1.0ｇを
５mlの乾燥ピリジンに分散させ２・３・４・６−
テトラ−Ｏ−アセチル−Ｄ−マンノース３ｇを加
え100℃で３時間反応させる。
該反応生成物を上記と同じ方法で精製し乾燥し
て収率63.0％のｐ−アミノ安息香酸メチルエステ
ル−Ｎ−Ｏ−アセチル−Ｄ−マンノシツドを得
る。
製造例 22
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−グルコシツドの製造法
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｄ−
グルコシツド3.0ｇを15mlの乾燥ピリジンに分散
させ15mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルアルコールに溶解、少量の石油エーテル
を添加、放置すると結晶の析出をみる。同様の方
法で数回再結をくり返すと、針状の結晶を得る。
収率52.7％であつた。
製造例 23
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−Ｄ−キシロシツドの製造法
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｄ−
キシロシツド3.0ｇを15mlの乾燥ピリジンに分散
させ15mlの無水酢酸を溶解するまで撹拌する。反
応液はそのまま放置しアセチル化を行う。アセチ
ル化終了後反応液を氷水中に撹拌しつつ添加、ア
セチル化物は水不溶性の固形物として分離され
る。分離されたアセチル化物は再度水で洗浄後エ
チルアルコールに溶解、少量の石油エーテルを添
加、放置すると結晶の析出をみる。同様の方法で
数回再結をくり返すと、針状の結晶を得る。
収率40.5％であつた。
製造例 24
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−Ｌ−ラムノシツドの製造法
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｌ−
ラムノシツド1.0ｇを5.0mlの乾燥ピリジンに分散
させ5.0mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルアルコールに溶解、少量の石油エーテル
を添加、放置すると結晶の析出をみる。同様の方
法で数回再結をくり返すと、針状の結晶を得る。
収率42.2％であつた。
製造例 25
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−
アセチル−セロビオシツドの製造法
ｐ−アミノ安息香酸メチルエステル−Ｎ−セロ
ビオシツド2.0ｇを10mlの乾燥ピリジンに分散さ
せ10mlの無水酢酸を加え溶解するまで撹拌する。
反応液はそのまま放置しアセチル化を行う。アセ
チル化終了後反応液を氷水中に撹拌しつつ添加、
アセチル化物は水不溶性の固形物として分離され
る。分離されたアセチル化物は再度水で洗浄後エ
チルアルコールに溶解、少量の石油エーテルを添
加、放置すると結晶の析出をみる。同様の方法で
数回再結をくり返すと、針状の結晶を得る。
収率38.0％であつた。
製造例 26
ｐ−アミノ安息香酸エチルエステル−Ｎ−Ｏ−
アセチル−Ｌ−ラムノシツドの製造法
ｐ−アミノ安息香酸エチルエステル−Ｎ−Ｌ−
ラムノシツド3.0ｇを15mlの乾燥ピリジンに分散
させ15mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルエーテルに溶解、少量の石油エーテルを
添加、放置すると結晶の析出をみる。同様の方法
で数回再結をくり返すと、針状の結晶を得る。
収率59.4％であつた。
製造例 27
ｐ−アミノ安息香酸プロピルエステル−Ｎ−Ｏ
−アセチル−Ｌ−グルコシツドの製造法
ｐ−アミノ安息香酸プロピルエステル−Ｎ−Ｌ
−グルコシツド3.0ｇを15mlの乾燥ピリジンに分
散させ15mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルエーテルに溶解、少量の石油エーテルを
添加、放置すると結晶の析出をみる。同様の方法
で数回再結をくり返すと、針状の結晶を得る。
収率19.6％であつた。
製造例 28
ｐ−アミノ安息香酸プロピルエステル−Ｎ−Ｏ
−アセチル−Ｌ−ラムノシツドの製造法
ｐ−アミノ安息香酸プロピルエステル−Ｎ−Ｌ
−ラムノシツド3.0ｇを15mlの乾燥ピリジンに分
散させ15mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルエーテルに溶解、少量の石油エーテルを
添加、放置すると結晶の析出をみる。同様の方法
で数回再結をくり返すと、針状の結晶を得る。
収率49.2％であつた。
製造例 29
ｐ−アミノ安息香酸ブチルエステル−Ｎ−Ｏ−
アセチル−Ｌ−ラムノシツドの製造法
ｐ−アミノ安息香酸ブチルエステル−Ｎ−Ｌ−
ラムノシツド3.0ｇを15mlの乾燥ピリジンに分散
させ15mlの無水酢酸を加え溶解するまで撹拌す
る。反応液はそのまま放置しアセチル化を行う。
アセチル化終了後反応液を氷水中に撹拌しつつ添
加、アセチル化物は水不溶性の固形物として分離
される。分離されたアセチル化物は再度水で洗浄
後エチルエーテルに溶解、少量の石油エーテルを
添加、放置すると結晶の析出をみる。同様の方法
で数回再結をくり返すと、針状の結晶を得る。
収率70.2％であつた。[Table] This substance has low acute toxicity and few other side effects, so it is useful as a medicine for both animals and humans. As a medicine, it is used in humans as an antidiabetic agent, antihypertensive agent, antiarteriosclerotic agent, antitumor agent, antipyretic analgesic, and antiinflammatory agent. Next, we will discuss the formulation of this substance. The present invention provides antidiabetic agents, antihypertensive agents, antitumor agents,
When used as an anti-arteriosclerosis agent, anti-inflammatory agent, or antipyretic analgesic, it can be used in a form convenient for obtaining medicinal effects depending on the type and symptoms of the disease, and can be used alone or with a pharmaceutically acceptable diluent and Can be used as a mixture with other drugs The substance can be presented in dosage unit form.
Contains an effective amount of the active ingredient, and its forms include powders, granules, tablets, sugar-coated tablets, etc. for oral use.
Capsules, syrups, pills, suspensions, liquids,
Emulsions, etc. For parenteral use, it can be in the form of injection ampoules or bottles. It may also be in the form of suppositories. The diluent may be solid, liquid, or semi-solid, and includes, for example, the following: That is, excipients, fillers, binders, wetting agents, disintegrants, surfactants, lubricants, dispersants, buffers, fragrances, preservatives, solubilizing agents, solvents, and the like. Specific examples include lactose, sucrose, sorbitol, mannitrate, starch, precipitated calcium carbonate, heavy magnesium oxide, talc, calcium stearate, magnesium stearate, cellulose or its derivatives, amylopectin, polyvinyl alcohol, gelatin, water, saline, ethanol, glycerin, propylene glycol,
Cocoa butter, lauric fat, petrolatum, paraffin,
Higher alcohols, etc. The bioactive agent of the present invention can be produced by any known method. The active ingredient in the compositions used in the present invention generally comprises 0.01% to 100% wt., preferably 0.05% to 80% wt.%. The bioactive agent of the present invention can be administered orally or parenterally to humans and animals, with oral administration being preferred. Oral administration includes sublingual administration. Parenteral administration includes injection administration (e.g., subcutaneous, intramuscular, intravenous,
(intravenous drip), rectal administration, etc. The dose of the bioactive agent of the present invention depends on whether it is an animal or a human, and is influenced by age, individual differences, medical conditions, etc., so in some cases, doses outside the ranges listed below may be administered, but in general, humans are administered. In this case, the oral dosage of this substance is 0.1 to 500 per kg body weight per day.
mg, preferably 0.5 to 200 mg, and the parenteral dosage is similarly 0.01 to 200 mg, preferably 0.1 to 100 mg, administered in 1 to 4 divided doses. Hereinafter, the present invention will be explained in more detail by showing formulation examples and manufacturing examples of the substance of the present invention. Parts in the examples below indicate weight. Formulation example 1 This substance (p-aminobenzoic acid methyl ester-N
-O-acetyl-D-xyloside) 10 (parts) Heavy magnesium oxide 15 Lactose 75 are mixed uniformly and made into a powder or fine granules with a 350μ
The following powder is used. Further, this powder was put into a capsule container to form a capsule. Formulation Example 2 This substance (p-aminobenzoic acid ethyl ester-N
-O-acetyl-D-mannoside) 45 (parts) Starch 15 Lactose 16 Crystalline cellulose 21 Polyvinyl alcohol 3 Water 30 After uniformly heating and mixing, crush, granulate, dry, and sieve to obtain granules of 1410μ to 177μ The size of the agent. Formulation Example 3 p-Aminobenzoic acid butyl ether-N-O instead of p-aminobenzoic acid ethyl ester-N-O-acetyl-D-mannoside in Example 2
- Granules were made using the same method using acetyl-L-rhamnoside, 4 parts of calcium stearate was added to 96 parts of the granules, and the mixture was compression molded to a diameter of 10 mm.
tablets. Formulation Example 4 10 parts of crystalline cellulose and 3 parts of calcium stearate were added to 90 parts of the granules obtained by the method of Formulation Example 2, and compression molded to form tablets with a diameter of 8 mm, to which syrupy gelatin and precipitated calcium carbonate were mixed. Add the suspension to make sugar-coated tablets. Production example 1 o-aminobenzoic acid-N-O-acetyl-D-
Process for producing ribosides o-aminobenzoic acid-N-D-ribosides 1.5
Disperse g in 10 ml of dry pyridine, add 10 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 12.8%. Production example 2 o-aminobenzoic acid methyl ester -N-O-
Production method of acetyl-D-mannoside o-aminobenzoic acid methyl ester-N-D-
Disperse 1.0 g of mannoside in 5 ml of dry pyridine, add 5.0 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 69.0%. Also, 1.0 g of o-aminobenzoic acid methyl ester
Disperse in 5 ml of dry pyridine and add 2, 3, 4, 6.
Add 3 g of -tetra-O-acetyl-D-mannosyl bromide and react at 50°C for 2 hours. The reaction product is purified and dried in the same manner as above to obtain o-aminobenzoic acid methyl ester-N-O-acetyl-D-mannoside with a yield of 70%. Production example 3 o-aminobenzoic acid methyl ester -N-O-
Production method of acetyl-D-glucoside o-aminobenzoic acid methyl ester-N-D-
Disperse 1.0 g of glucoside in 5.0 ml of dry pyridine, add 5.0 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction mixture is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 71.6%. In addition, 1.0 g of o-aminobenzoic acid methyl ester was dispersed in 5 ml of dry pyridine and 2,3,4,6-
Add 3 g of tetra-O-acetyl-D-glucosyl bromide and react at 50°C for 2 hours. The reaction product is purified and dried in the same manner as above to obtain o-aminobenzoic acid methyl ester-N-O-acetyl-D-glucoside with a yield of 73%. Production example 4 o-aminobenzoic acid ethyl ester -N-O-
Production method of acetyl-D-mannoside o-aminobenzoic acid ethyl ester-N-D-
Disperse 1.0 g of mannoside in 5.0 ml of dry pyridine and stir until 5.0 ml of acetic anhydride is dissolved.
The reaction solution is left as is to carry out acetylation. After the acetylation is complete, add the reaction solution to ice water with stirring.
The acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 57.8%. Production example 5 o-aminobenzoic acid ethyl ester-N-O-
Production method of acetyl-L-rhamnoside o-aminobenzoic acid ethyl ester -N-L-
Disperse 3.0 g of rhamnoside in 15 ml of dry pyridine and stir until 15 ml of acetic anhydride is dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethanol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating recrystallization several times in the same manner, needle-shaped crystals are obtained. The yield was 75.2%. Production example 6 o-aminobenzoic acid butyl ester -N-O-
Production method of acetyl-D-glucoside o-aminobenzoic acid butyl ester-N-D-
Disperse 3.0 g of glucoside in 15 ml of dry pyridine and stir until 15 ml of acetic anhydride is dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction mixture is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid.
The separated acetylated product was washed again with water, dissolved in ethyl ether, added with a small amount of petroleum ether, and when left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 30.5%. In addition, 1.0 g of o-aminobenzoic acid butyl ester was dispersed in 5 ml of dry pyridine to obtain 2,3,4,6-
Add 3 g of tetra-O-acetyl-D-glucosyl chloride and react at 50°C for 2 hours. The reaction product is purified and dried in the same manner as above to obtain o-aminobenzoic acid butyl ester-N-O-acetyl-D-glucoside with a yield of 35%. Production example 7 p-aminobenzoic acid-N-O-propionyl-
Method for producing 2-deoxy-D-riboside p-aminobenzoic acid-N-2-deoxy-D-
Disperse 3.0 g of ribosides in 15 ml of dry pyridine, add 15 ml of propionic anhydride, and stir until dissolved. The reaction solution is left to cool. After the acylation is completed, the reaction solution is added to ice water with stirring and separated as a water-insoluble solid. After washing the separated product again with water, it was dissolved in ethyl alcohol, a small amount of petroleum ether was added, and when it was left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 18.0%. Production example 8 p-aminobenzoic acid-N-O-butyryl-L-
Method for producing arabinoside p-aminobenzoic acid-N-L-arabinoside
Disperse 2.0 g in 10 ml of dry pyridine, add 10 ml of butyric anhydride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After the acylation is completed, the reaction solution is added to ice water with stirring, and the acylated product is separated as a water-insoluble solid. The separated acylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 12.0%. Production example 9 m-aminobenzoic acid-N-O-acetyl-D-
Manufacturing method of mannoside m-aminobenzoic acid-N-D-mannoside
Disperse 1.0 g in 5 ml of dry pyridine, add 5 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 10.5%. Production example 10 p-aminobenzoic acid-N-O-acetyl-D-
Manufacturing method of glucoside p-aminobenzoic acid-N-D-glucoside
Disperse 3.0 g in 15 ml of dry pyridine, add 15 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 25.3%. Further, 1.0 g of p-aminobenzoic acid was dispersed in 5 ml of dry pyridine, and 3 g of 2,3,4,6-tetra-O-acetyl-D-glucosyl bromide was added to the solution.
Incubate at ℃ for 2 hours. The reaction product is purified and dried in the same manner as above to obtain p-aminobenzoic acid-N-O-acetyl-D-glucoside with a yield of 26.0%. Production example 11 p-aminobenzoic acid-N-O-benzoyl-D
-Production method of galactoside p-aminobenzoic acid-N-D-galactoside
Disperse 3.0 g in 15 ml of dry pyridine, add 15 ml of benzoic anhydride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After the acylation is completed, the reaction solution is added to ice water with stirring, and the acylated product is separated as a water-insoluble solid. The separated acylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 23.1%. Production example 12 p-aminobenzoic acid-N-O-acetyl-D-
Production method of xyloside p-aminobenzoic acid-N-D-xyloside
Disperse 3.0 g in 15 ml of dry pyridine, add 15 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating recrystallization several times in the same manner, needle-shaped crystals are obtained. The yield was 43.9%. Production example 13 p-aminobenzoic acid-N-O-acetyl-L-
Method for producing rhamnoside p-aminobenzoic acid-N-L-rhamnoside
Disperse 3.0 g in 15 ml of dry pyridine and stir until 15 ml of acetic anhydride is dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating recrystallization several times in the same manner, needle-shaped crystals are obtained. The yield was 19.3%. Production example 14 p-aminobenzoic acid-N-O-valeryl-L-
Production method of fucoside p-aminobenzoic acid-N-L-fucoside 2.0
Disperse g in 10 ml of dry pyridine, add 10 ml of butyric anhydride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After the acylation is completed, the reaction solution is added to ice water with stirring, and the acylated product is separated as a water-insoluble solid. The separated acylated product was washed again with water and then dissolved in ethyl alcohol.
When a small amount of petroleum ether is added and left to stand, crystals are observed to precipitate. After repeating reconnection several times in the same way,
Obtain needle-shaped crystals. The yield was 16.3%. Production example 15 p-aminobenzoic acid-N-O-benzoyl-D
-Production method of fructoside p-aminobenzoic acid-N-D-fructoside
Disperse 1.0 g in 5 ml of dry pyridine, add 5 ml of benzoyl chloride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After the acylation is completed, the reaction solution is added to ice water with stirring, and the acylated product is separated as a water-insoluble solid. The separated acylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 12.1%. Production Example 16 Production method of p-aminobenzoic acid-N-O-phenylacetyl-L-sorboside p-aminobenzoic acid-N-L-sorboside
Disperse 2.0 g in 10 ml of dry pyridine, add 10 ml of phenylacetyl chloride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After completing the acylation, add the reaction solution to ice water while stirring.
The acylated product is separated as a water-insoluble solid. The separated acylated product is washed again with water and then dissolved and recrystallized again to obtain needle-shaped crystals. The yield was 8.9%. Production example 17 Production method of p-aminobenzoic acid-N-O-acetyl-cellobioside p-aminobenzoic acid-N-cellobioside 1.0
Disperse g in 5 ml of dry pyridine, add 5 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 19.7%. Production example 18 Production method of p-aminobenzoic acid-N-O-acetyl-maltoside 2.0 g of p-aminobenzoic acid-N-maltoside
Disperse in 10ml of dry pyridine, add 10ml of acetic anhydride and stir until dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 8.0%. Production example 19 p-aminobenzoic acid-N-O-propionyl-
Production method of Satsukarosid p-Aminobenzoic acid-N-Satsukarosid 1.0
Disperse g in 10 ml of dry pyridine, add 10 ml of propionic anhydride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After the acylation is completed, the reaction solution is added to ice water with stirring, and the acylated product is separated as a water-insoluble solid. The separated acylated product was washed again with water, dissolved in ethyl alcohol, added with a small amount of petroleum ether, and when left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 14.1%. Production example 20 Production method of p-aminobenzoic acid-N-O-phenylacetyl-lactoside 2.0 g of p-aminobenzoic acid-N-lactoside
Disperse in 15 ml of dry pyridine, add 15 ml of phenylacetyl chloride, and stir until dissolved. The reaction solution is left as it is to carry out acylation. After the acylation is completed, the reaction solution is added to ice water with stirring, and the acylated product is separated as a water-insoluble solid. The separated acylated product is washed again with water and the same recrystallization process is repeated to obtain needle-shaped crystals. The yield was 9.9%. Production example 21 p-aminobenzoic acid methyl ester -N-O-
Method for producing acetyl-D-mannoside p-aminobenzoic acid methyl ester-N-D-
Disperse 1.0 g of mannoside in 5.0 ml of dry pyridine, add 5.0 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 63.3%. In addition, 1.0 g of p-aminobenzoic acid methyl ester was dispersed in 5 ml of dry pyridine and 2,3,4,6-
Add 3 g of tetra-O-acetyl-D-mannose and react at 100°C for 3 hours. The reaction product is purified and dried in the same manner as above to obtain p-aminobenzoic acid methyl ester-N-O-acetyl-D-mannoside with a yield of 63.0%. Production example 22 p-aminobenzoic acid methyl ester -N-O-
Method for producing acetyl-D-glucoside p-aminobenzoic acid methyl ester-N-D-
Disperse 3.0 g of glucoside in 15 ml of dry pyridine, add 15 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 52.7%. Production example 23 p-aminobenzoic acid methyl ester -N-O-
Production method of acetyl-D-xyloside p-aminobenzoic acid methyl ester-N-D-
Disperse 3.0 g of xyloside in 15 ml of dry pyridine and stir until 15 ml of acetic anhydride is dissolved. The reaction solution is left as is to carry out acetylation. After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 40.5%. Production example 24 p-aminobenzoic acid methyl ester -N-O-
Method for producing acetyl-L-rhamnoside p-aminobenzoic acid methyl ester -N-L-
Disperse 1.0 g of rhamnoside in 5.0 ml of dry pyridine, add 5.0 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 42.2%. Production example 25 p-aminobenzoic acid methyl ester -N-O-
Method for producing acetyl-cellobioside 2.0 g of p-aminobenzoic acid methyl ester-N-cellobioside is dispersed in 10 ml of dry pyridine, 10 ml of acetic anhydride is added, and the mixture is stirred until dissolved.
The reaction solution is left as is to carry out acetylation. After the acetylation is complete, add the reaction solution to ice water with stirring.
The acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl alcohol, and a small amount of petroleum ether was added. When left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 38.0%. Production example 26 p-aminobenzoic acid ethyl ester -N-O-
Production method of acetyl-L-rhamnoside p-aminobenzoic acid ethyl ester -N-L-
Disperse 3.0 g of rhamnoside in 15 ml of dry pyridine, add 15 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl ether, added with a small amount of petroleum ether, and when left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 59.4%. Production example 27 p-aminobenzoic acid propyl ester-N-O
-Production method of acetyl-L-glucoside p-aminobenzoic acid propyl ester-N-L
- Disperse 3.0 g of glucoside in 15 ml of dry pyridine, add 15 ml of acetic anhydride and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl ether, added with a small amount of petroleum ether, and when left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 19.6%. Production example 28 p-aminobenzoic acid propyl ester-N-O
-Production method of acetyl-L-rhamnoside p-aminobenzoic acid propyl ester-N-L
- Disperse 3.0 g of rhamnoside in 15 ml of dry pyridine, add 15 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product was washed again with water, dissolved in ethyl ether, added with a small amount of petroleum ether, and when left to stand, crystals were observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 49.2%. Production example 29 p-aminobenzoic acid butyl ester -N-O-
Production method of acetyl-L-rhamnoside p-aminobenzoic acid butyl ester -N-L-
Disperse 3.0 g of rhamnoside in 15 ml of dry pyridine, add 15 ml of acetic anhydride, and stir until dissolved. The reaction solution is left as is to carry out acetylation.
After the acetylation is completed, the reaction solution is added to ice water with stirring, and the acetylated product is separated as a water-insoluble solid. The separated acetylated product is washed again with water, dissolved in ethyl ether, a small amount of petroleum ether is added, and when left to stand, crystals are observed to precipitate. By repeating resetting several times in the same manner, needle-shaped crystals are obtained. The yield was 70.2%.
第１図乃至第１９図は本発明に係る下記各アミ
ノ安息香酸誘導体の赤外線吸収スペクトルを示
す。第１図〜ｏ−アミノ安息香酸メチルエステル
−Ｎ−Ｏ−アセチル−Ｄ−マンノシツド第２図〜
ｏ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−ア
セチル−Ｄ−グルコシツド第３図〜ｏ−アミノ安
息香酸エチルエステル−Ｎ−Ｏ−アセチル−Ｄ−
マンノシツド第４図〜ｏ−アミノ安息香酸エチル
エステル−Ｎ−Ｏ−アセチル−Ｌ−ラムノシツド
第５図〜ｏ−アミノ安息香酸ブチルエステル−Ｎ
−Ｏ−アセチル−Ｄ−グルコシツド第６図〜ｍ−
アミノ安息香酸−Ｎ−アセチル−Ｄ−マンノシツ
ド第７図〜ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチ
ル−Ｄ−グルコシツド第８図〜ｐ−アミノ安息香
酸−Ｎ−Ｏ−アセチル−Ｄ−キシロシツド第９図
〜ｐ−アミノ安息香酸−Ｎ−Ｏ−アセチル−Ｌ−
ラムノシツド第１０図〜ｐ−アミノ安息香酸−Ｎ
−Ｏ−アセチル−セロビオシツド第１１図〜ｐ−
アミノ安息香酸メチルエステル−Ｎ−Ｏ−アセチ
ル−Ｄ−マンノシツド第１２図〜ｐ−アミノ安息
香酸メチルエステル−Ｎ−Ｏ−アセチル−Ｄ−グ
ルコシツド第１３図〜ｐ−アミノ安息香酸メチル
エステル−Ｎ−Ｏ−アセチル−Ｄ−キシロシツド
第１４図〜ｐ−アミノ安息香酸メチルエステル−
Ｎ−Ｏ−アセチル−Ｌ−ラムノシツド第１５図〜
ｐ−アミノ安息香酸メチルエステル−Ｎ−Ｏ−ア
セチル−セロビオシツド第１６図〜ｐ−アミノ安
息香酸エチルエステル−Ｎ−Ｏ−アセチル−Ｌ−
ラムノシツド第１７図〜ｐ−アミノ安息香酸プロ
ピルエステル−Ｎ−Ｏ−アセチル−Ｄ−グルコシ
ツド第１８図〜ｐ−アミノ安息香酸プロピルエス
テル−Ｎ−Ｏ−アセチル−Ｌ−ラムノシツド第１
９図〜ｐ−アミノ安息香酸ブチルエステル−Ｎ−
Ｏ−アセチル−Ｌ−ラムノシツド。
1 to 19 show infrared absorption spectra of the following aminobenzoic acid derivatives according to the present invention. Figure 1 - o-aminobenzoic acid methyl ester -N-O-acetyl-D-mannoside Figure 2 -
o-Aminobenzoic acid methyl ester -N-O-acetyl-D-glucoside Figure 3 ~ o-Aminobenzoic acid ethyl ester -N-O-acetyl-D-
Mannoside Figure 4 - o-aminobenzoic acid ethyl ester -N-O-acetyl-L-rhamnoside Figure 5 - o-aminobenzoic acid butyl ester -N
-O-acetyl-D-glucoside Figure 6-m-
Aminobenzoic acid-N-acetyl-D-mannoside Figure 7 ~ p-aminobenzoic acid-N-O-acetyl-D-glucoside Figure 8 ~ p-aminobenzoic acid-N-O-acetyl-D-xyloside Figure 8 Figure 9 ~ p-aminobenzoic acid-N-O-acetyl-L-
Rhamnoside Figure 10 ~ p-aminobenzoic acid-N
-O-acetyl-cellobioside Figure 11~p-
Aminobenzoic acid methyl ester - N-O-acetyl-D-mannoside Figure 12 - p-Aminobenzoic acid methyl ester - N-O-acetyl-D-glucoside Figure 13 - p-Aminobenzoic acid methyl ester - N- O-acetyl-D-xyloside Figure 14 ~p-aminobenzoic acid methyl ester-
N-O-acetyl-L-rhamnoside Figure 15~
p-aminobenzoic acid methyl ester -N-O-acetyl-cellobioside Figure 16 ~ p-aminobenzoic acid ethyl ester -N-O-acetyl-L-
Rhamnoside Figure 17 - p-aminobenzoic acid propyl ester -N-O-acetyl-D-glucoside Figure 18 - p-aminobenzoic acid propyl ester -N-O-acetyl-L-rhamnoside 1st
Figure 9 ~ p-Aminobenzoic acid butyl ester-N-
O-acetyl-L-rhamnoside.
Claims (1)
ースまたは二糖類の残基を示す。ただし、ｏ−、
ｍ−またはｐ−アミノ安息香酸−Ｎ−Ｏ−アセチ
ル−Ｄ−グルコシツド、ｐ−アミノ安息香酸メチ
ル、エチル又はブチルエステル−Ｎ−Ｏ−アセチ
ル−Ｄ−グルコシツド、ｏ−アミノ安息香酸メチ
ルエステル−Ｎ−Ｏ−アセチル−Ｄ−グルコシツ
ド又はガラクトシツドは除く）で表わされるアミ
ノ安息香酸誘導体、その塩又はそのエステル。 ２ 上記一般式（）において、R1はアセチル
基によりアシル化されたペントース、ヘキソース
または二糖類の残基である特許請求の範囲第１項
に記載のアミノ安息香酸誘導体、その塩又はその
エステル。 ３ ペントース、ヘキソースまたは二糖類の残基
は、マンノシド、キシロシド、グルコシド、ラム
ノシド又はセロビオシド基である特許請求の範囲
第１項に記載のアミノ安息香酸誘導体、その塩又
はそのエステル。 ４ 前記エステルがメチル、エチル、プロピル又
はブチルエステルである特許請求の範囲第１項に
記載のアミノ安息香酸誘導体、その塩又はそのエ
ステル。[Claims] 1. General formula: (In the formula, R 1 represents an acylated pentose, hexose or disaccharide residue. However, o-,
m- or p-aminobenzoic acid -N-O-acetyl-D-glucoside, p-aminobenzoic acid methyl, ethyl or butyl ester -N-O-acetyl-D-glucoside, o-aminobenzoic acid methyl ester -N -O-acetyl-D-glucoside or galactoside), a salt thereof, or an ester thereof. 2. The aminobenzoic acid derivative, its salt, or its ester according to claim 1, wherein in the general formula (), R 1 is a pentose, hexose, or disaccharide residue acylated with an acetyl group. 3. The aminobenzoic acid derivative, its salt, or its ester according to claim 1, wherein the pentose, hexose, or disaccharide residue is a mannoside, xyloside, glucoside, rhamnoside, or cellobioside group. 4. The aminobenzoic acid derivative, its salt, or its ester according to claim 1, wherein the ester is a methyl, ethyl, propyl, or butyl ester.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17194479A JPS5695197A (en) | 1979-12-28 | 1979-12-28 | Aminobenzoic acid derivative and physiologically active agent containing the same |
| DE3048279A DE3048279C2 (en) | 1979-12-28 | 1980-12-20 | Peracetylated N-glycosides of o-, m- and p-aminobenzoic acid and drugs containing these compounds |
| FR8027307A FR2472577A1 (en) | 1979-12-28 | 1980-12-23 | Acylated mono-, di- and tri-saccharide derivs. of amino-benzoic acid - are hypoglycaemic, hypotensive, hypolipaemic, antiinflammatory, analgesic, antipyretic and antitumour cpds. |
| BE6/47361A BE886879A (en) | 1979-12-28 | 1980-12-24 | NEW AMINOBENZOIC ACID DERIVATIVES |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP17194479A JPS5695197A (en) | 1979-12-28 | 1979-12-28 | Aminobenzoic acid derivative and physiologically active agent containing the same |
Related Child Applications (6)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP661482A Division JPS57136522A (en) | 1982-01-19 | 1982-01-19 | Antitumor agent containing aminobenzoic acid derivative |
| JP661682A Division JPS609012B2 (en) | 1982-01-19 | 1982-01-19 | Anti-inflammatory agents containing aminobenzoic acid derivatives |
| JP661282A Division JPS57136520A (en) | 1982-01-19 | 1982-01-19 | Antiarteriosclerotic containing aminobenzoic acid derivative |
| JP661382A Division JPS57136521A (en) | 1982-01-19 | 1982-01-19 | Hypotensor containing aminobenzoic acid derivative |
| JP661582A Division JPS609729B2 (en) | 1982-01-19 | 1982-01-19 | Antipyretic analgesic containing aminobenzoic acid derivatives |
| JP661182A Division JPS57136519A (en) | 1982-01-19 | 1982-01-19 | Antidiabetic containing aminobenzoic acid derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS5695197A JPS5695197A (en) | 1981-08-01 |
| JPS6254798B2 true JPS6254798B2 (en) | 1987-11-17 |
Family
ID=15932694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP17194479A Granted JPS5695197A (en) | 1979-12-28 | 1979-12-28 | Aminobenzoic acid derivative and physiologically active agent containing the same |
Country Status (4)
| Country | Link |
|---|---|
| JP (1) | JPS5695197A (en) |
| BE (1) | BE886879A (en) |
| DE (1) | DE3048279C2 (en) |
| FR (1) | FR2472577A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03504281A (en) * | 1987-04-27 | 1991-09-19 | ビシーノ，ロバート ケー． | inflatable sign |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998031697A1 (en) * | 1997-01-15 | 1998-07-23 | Sankyo Company, Limited | Aryl c-glycoside compounds and sulfated esters thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH640412A5 (en) * | 1978-05-26 | 1984-01-13 | Kureha Chemical Ind Co Ltd | MEDICINE FOR TREATING HYPERGLYKAEMIA, HYPERLIPAEMIA, HYPERTENSION, INFLAMMATION, PAIN, FEVER, OR TUMOR. |
-
1979
- 1979-12-28 JP JP17194479A patent/JPS5695197A/en active Granted
-
1980
- 1980-12-20 DE DE3048279A patent/DE3048279C2/en not_active Expired
- 1980-12-23 FR FR8027307A patent/FR2472577A1/en active Granted
- 1980-12-24 BE BE6/47361A patent/BE886879A/en not_active IP Right Cessation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03504281A (en) * | 1987-04-27 | 1991-09-19 | ビシーノ，ロバート ケー． | inflatable sign |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3048279C2 (en) | 1985-04-25 |
| FR2472577A1 (en) | 1981-07-03 |
| BE886879A (en) | 1981-06-24 |
| FR2472577B1 (en) | 1983-02-18 |
| JPS5695197A (en) | 1981-08-01 |
| DE3048279A1 (en) | 1981-09-10 |
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