JP4568527B2 - Benzofuran derivative and external preparation for skin containing the same - Google Patents
Benzofuran derivative and external preparation for skin containing the same Download PDFInfo
- Publication number
- JP4568527B2 JP4568527B2 JP2004127055A JP2004127055A JP4568527B2 JP 4568527 B2 JP4568527 B2 JP 4568527B2 JP 2004127055 A JP2004127055 A JP 2004127055A JP 2004127055 A JP2004127055 A JP 2004127055A JP 4568527 B2 JP4568527 B2 JP 4568527B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- skin
- external preparation
- group
- methyl
- 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 - Lifetime
Links
- 238000002360 preparation method Methods 0.000 title description 57
- 150000001907 coumarones Chemical class 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims description 81
- 239000002537 cosmetic Substances 0.000 claims description 20
- 230000002087 whitening effect Effects 0.000 claims description 19
- 229940125904 compound 1 Drugs 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 11
- 229940126214 compound 3 Drugs 0.000 claims description 9
- 229940125782 compound 2 Drugs 0.000 claims description 7
- 229940125898 compound 5 Drugs 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- QNYCWAPCVWRQHB-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-7-methoxy-3-methyl-5-propyl-1-benzofuran Chemical compound CC=1C2=CC(CCC)=CC(OC)=C2OC=1C1=CC=C(OC)C(OC)=C1 QNYCWAPCVWRQHB-UHFFFAOYSA-N 0.000 claims description 5
- AATWXJWGOIWOPY-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-7-methoxy-3-methyl-5-propyl-2,3-dihydro-1-benzofuran Chemical compound O1C=2C(OC)=CC(CCC)=CC=2C(C)C1C1=CC=C(OC)C(OC)=C1 AATWXJWGOIWOPY-UHFFFAOYSA-N 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- LXRVZJFJYYQBCU-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-7-methoxy-3-methyl-5-prop-1-enyl-1-benzofuran Chemical compound C1=C(OC)C(OC)=CC=C1C1=C(C)C2=CC(C=CC)=CC(OC)=C2O1 LXRVZJFJYYQBCU-UHFFFAOYSA-N 0.000 claims description 3
- ITFKWUHXYCXXFF-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-7-methoxy-3-methyl-5-prop-1-enyl-2,3-dihydro-1-benzofuran Chemical compound O1C=2C(OC)=CC(C=CC)=CC=2C(C)C1C1=CC=C(OC)C(OC)=C1 ITFKWUHXYCXXFF-UHFFFAOYSA-N 0.000 claims description 3
- 210000003491 skin Anatomy 0.000 description 59
- 239000000203 mixture Substances 0.000 description 43
- -1 methylenedioxyphenyl Chemical group 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 28
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 238000012360 testing method Methods 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 239000008213 purified water Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- 235000014113 dietary fatty acids Nutrition 0.000 description 12
- 239000000194 fatty acid Substances 0.000 description 12
- 229930195729 fatty acid Natural products 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 11
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- DNIAPMSPPWPWGF-UHFFFAOYSA-N monopropylene glycol Natural products CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 208000012641 Pigmentation disease Diseases 0.000 description 9
- 125000003342 alkenyl group Chemical group 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 229920001296 polysiloxane Polymers 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- FULZLIGZKMKICU-UHFFFAOYSA-N N-phenylthiourea Chemical compound NC(=S)NC1=CC=CC=C1 FULZLIGZKMKICU-UHFFFAOYSA-N 0.000 description 7
- 239000006096 absorbing agent Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000004359 castor oil Substances 0.000 description 7
- 235000019438 castor oil Nutrition 0.000 description 7
- 235000011187 glycerol Nutrition 0.000 description 7
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 7
- 230000002401 inhibitory effect Effects 0.000 description 7
- 230000008099 melanin synthesis Effects 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical class C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 5
- BJIOGJUNALELMI-ARJAWSKDSA-N cis-isoeugenol Chemical class COC1=CC(\C=C/C)=CC=C1O BJIOGJUNALELMI-ARJAWSKDSA-N 0.000 description 5
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 5
- 239000008309 hydrophilic cream Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000006210 lotion Substances 0.000 description 5
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 230000019612 pigmentation Effects 0.000 description 5
- 229920001451 polypropylene glycol Polymers 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 4
- 239000004166 Lanolin Substances 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 4
- 229910001873 dinitrogen Inorganic materials 0.000 description 4
- 239000000839 emulsion Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 150000004665 fatty acids Chemical class 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 235000010382 gamma-tocopherol Nutrition 0.000 description 4
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 235000019388 lanolin Nutrition 0.000 description 4
- 229940039717 lanolin Drugs 0.000 description 4
- 230000001590 oxidative effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 229960004063 propylene glycol Drugs 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N squalane Chemical compound CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- 239000002478 γ-tocopherol Substances 0.000 description 4
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 4
- ITDOFWOJEDZPCF-UHFFFAOYSA-N 2-methoxy-4-(7-methoxy-3-methyl-5-prop-1-enyl-2,3-dihydro-1-benzofuran-2-yl)phenol Chemical compound O1C=2C(OC)=CC(C=CC)=CC=2C(C)C1C1=CC=C(O)C(OC)=C1 ITDOFWOJEDZPCF-UHFFFAOYSA-N 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
- DWSUJONSJJTODA-UHFFFAOYSA-N 5-(chloromethyl)-1,3-benzodioxole Chemical compound ClCC1=CC=C2OCOC2=C1 DWSUJONSJJTODA-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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- BJIOGJUNALELMI-ONEGZZNKSA-N Isoeugenol Natural products COC1=CC(\C=C\C)=CC=C1O BJIOGJUNALELMI-ONEGZZNKSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
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- 150000001298 alcohols Chemical class 0.000 description 3
- 150000004347 all-trans-retinol derivatives Chemical class 0.000 description 3
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- 229960000541 cetyl alcohol Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 3
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- BJIOGJUNALELMI-UHFFFAOYSA-N trans-isoeugenol Natural products COC1=CC(C=CC)=CC=C1O BJIOGJUNALELMI-UHFFFAOYSA-N 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- DSEKYWAQQVUQTP-XEWMWGOFSA-N (2r,4r,4as,6as,6as,6br,8ar,12ar,14as,14bs)-2-hydroxy-4,4a,6a,6b,8a,11,11,14a-octamethyl-2,4,5,6,6a,7,8,9,10,12,12a,13,14,14b-tetradecahydro-1h-picen-3-one Chemical compound C([C@H]1[C@]2(C)CC[C@@]34C)C(C)(C)CC[C@]1(C)CC[C@]2(C)[C@H]4CC[C@@]1(C)[C@H]3C[C@@H](O)C(=O)[C@@H]1C DSEKYWAQQVUQTP-XEWMWGOFSA-N 0.000 description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 2
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- 125000006017 1-propenyl group Chemical group 0.000 description 2
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical compound CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 2
- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 description 2
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- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
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- 239000002253 acid Substances 0.000 description 2
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- 150000001350 alkyl halides Chemical class 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
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- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 2
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- 239000002585 base Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 239000007844 bleaching agent Substances 0.000 description 2
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
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- 238000006482 condensation reaction Methods 0.000 description 2
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- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 2
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- TUNFSRHWOTWDNC-HKGQFRNVSA-N tetradecanoic acid Chemical compound CCCCCCCCCCCCC[14C](O)=O TUNFSRHWOTWDNC-HKGQFRNVSA-N 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
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- 230000001052 transient effect Effects 0.000 description 1
- UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
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- 235000010447 xylitol Nutrition 0.000 description 1
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- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000011787 zinc oxide 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
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Cosmetics (AREA)
Description
本発明は、ベンゾフラン誘導体及びベンゾフラン誘導体を含有する皮膚外用剤に関する。 The present invention relates to a benzofuran derivative and an external preparation for skin containing a benzofuran derivative.
皮膚におけるシミ、ソバカスや日焼け後の色素沈着は、皮膚内に存在する色素細胞(メラノサイト)の活性化によりメラニン生成が著しく亢進した状態である。これらの皮膚色素トラブルを防止または改善する目的の皮膚外用剤として、アスコルビン酸類、過酸化水素、コロイド硫黄、グルタチオン、ハイドロキノン、またはカテコールなどを配合した皮膚外用剤(特に美白剤)が知られている(例えば、非特許文献1参照)。しかしながら、これらの美白剤は何れも、有効に作用する場合があると同時に、作用しない場合があることが知られている。さらにその原因については、詳細に知られていないのが現状である。 Spots, buckwheat, and pigmentation after sunburn in the skin are a state in which melanin production is remarkably enhanced by activation of pigment cells (melanocytes) existing in the skin. Skin external preparations (especially whitening agents) containing ascorbic acids, hydrogen peroxide, colloidal sulfur, glutathione, hydroquinone, or catechol are known as skin external preparations for the purpose of preventing or improving these skin pigment troubles. (For example, refer nonpatent literature 1). However, it is known that any of these whitening agents may work effectively and may not work at the same time. Furthermore, the cause is not known in detail.
さらに、前記美白剤は、安定性や安全性などの面からも問題のある場合があった。すなわち、色素沈着症の予防または改善に関し、アスコルビン酸は、含水化粧料の如き水分を多く含む系においては酸化されやすく不安定なことがあり、皮膚外用剤(美白剤)を変色させる原因となり得る。また、過酸化水素水は保存上の安定性ならびに安全性上の問題があり、グルタチオンやコロイド硫黄は著しい異臭を放つため美白剤の成分として使用することは制約される。更に、ハイドロキノン、カテコールなどは、皮膚刺激性、アレルギー性などの安全性に問題がある場合がある。 Furthermore, the whitening agent sometimes has problems in terms of stability and safety. That is, ascorbic acid can be easily oxidized and unstable in a system containing a large amount of water such as water-containing cosmetics, and can cause discoloration of a topical skin preparation (whitening agent). . In addition, hydrogen peroxide solution has problems in terms of storage stability and safety, and glutathione and colloidal sulfur give off a remarkable off-flavor, so use as a whitening agent component is restricted. Furthermore, hydroquinone, catechol, and the like may have problems with safety such as skin irritation and allergy.
一方、特定の構造を有するベンゾフラン類が、メラニン産生を抑制すること(特許文献1)、色素沈着を軽減化すること(特許文献2)、または皮膚の漂白作用があること(特許文献3)が知られている。しかしながら、これらのベンゾフラン類は天然物からの抽出物であるため入手が容易でなかったり、ヒトでの効果が充分でなかったりなど、いまだ充分に満足すべき前記皮膚色素トラブルを防止または改善する皮膚外用剤は得られていない。言い換えれば、現在知られている美白のための素材には、何れも少なからぬ配合上の問題があり、新たな美白素材の開発が望まれている。 On the other hand, benzofurans having a specific structure suppress melanin production (Patent Document 1), reduce pigmentation (Patent Document 2), or have skin bleaching action (Patent Document 3). Are known. However, since these benzofurans are extracts from natural products, they are not readily available, and skin that prevents or ameliorates the above-mentioned skin pigment troubles that are still satisfactory, such as insufficient effects in humans. An external preparation has not been obtained. In other words, all of the currently known whitening materials have many formulation problems, and the development of new whitening materials is desired.
また、別の特定の構造を有するベンゾフラン類は、紫外線吸収作用や免疫賦活作用などを有し、該ベンゾフラン類を含有する化粧料などの皮膚外用剤は、抗日光化粧品または皮膚免疫賦活剤などとして知られている(例えば、特許文献4〜6を参照)。 In addition, benzofurans having another specific structure have an ultraviolet absorption action and an immunostimulatory action, and skin external preparations such as cosmetics containing the benzofurans are used as anti-sunlight cosmetics or skin immunostimulants. It is known (see, for example, Patent Documents 4 to 6).
本発明は、上記した状況に鑑みてなされたものであり、1)新規の美白素材を提供すること、および2)これを利用して、皮膚色素沈着症の予防、改善に対して優れた効果を発揮するばかりでなく、皮膚に対する安全性上の懸念がなく、安全に使用することができる
皮膚外用剤を提供することを課題とする。
The present invention has been made in view of the above-described circumstances, and 1) to provide a novel whitening material, and 2) to use this, an excellent effect for the prevention and improvement of skin pigmentation. It is an object of the present invention to provide an external preparation for skin that can be used safely as well as exhibiting the above.
本発明者らは、上記課題を解決するために鋭意研究を重ねた結果、特定のベンゾフラン誘導体(具体的には一般式(I)で表される化合物またはその塩)が、色素細胞のメラニン生成に対して強力な抑制効果を有することを見出した。さらに一般式(I)で表される化合物のうち、一般式(II)で表される化合物を新たに合成し、それらについても上記抑制効果を有することを見出した。
更に、上記ベンゾフラン誘導体を皮膚外用剤基材中に配合せしめた場合に、皮膚に対する優れた色素沈着症の予防及び改善効果を発現することを見いだした。
上記知見に基づき本発明は完成された。即ち、本発明は以下の通りである。
As a result of intensive studies to solve the above problems, the present inventors have found that a specific benzofuran derivative (specifically, a compound represented by the general formula (I) or a salt thereof) produces melanin in pigment cells. It has been found that it has a strong inhibitory effect. Furthermore, among the compounds represented by the general formula (I), the compounds represented by the general formula (II) were newly synthesized, and they were found to have the above-described inhibitory effect.
Furthermore, when the said benzofuran derivative was mix | blended in the skin external preparation base material, it discovered that the prevention and improvement effect of the excellent pigmentation disease with respect to skin was expressed.
The present invention has been completed based on the above findings. That is, the present invention is as follows.
(1) 下記一般式(I)で表される化合物及びその塩より選ばれる1種または2種以上を含む皮膚外用剤。 (1) A skin external preparation containing one or more selected from compounds represented by the following general formula (I) and salts thereof.
(2) 一般式(I)で表される化合物が、
2,3−ジヒドロ−2−(3’,4’−ジメトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物1)
(2,3-dihydro-2-(3',4'-dimethoxyphenyl)-7-methoxy-3-methyl-5-(1-propenyl)-benzofuran)
(2) The compound represented by the general formula (I) is
2,3-dihydro-2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (compound 1)
(2,3-dihydro-2- (3 ', 4'-dimethoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) -benzofuran)
2−(3’,4’−ジメトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物2)
(2-(3',4'-dimethoxyphenyl)-7-methoxy-3-methyl-5-(1-propenyl)-benzofuran)
2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (compound 2)
(2- (3 ', 4'-dimethoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) -benzofuran)
2,3−ジヒドロ−2−(3’,4’−ジメトキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物3)
(2,3-dihydro-2-(3',4'-dimethoxyphenyl)-7-methoxy-3-methyl-5-propyl-benzofuran)
2,3-dihydro-2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 3)
(2,3-dihydro-2- (3 ', 4'-dimethoxyphenyl) -7-methoxy-3-methyl-5-propyl-benzofuran)
2−(3’,4’−ジメトキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物4)(2-(3',4'-dimethoxyphenyl)-7-methoxy-3-methyl-5-propyl-benzofuran) 2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 4) (2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl- 5-propyl-benzofuran)
2−(3’,4’−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−プロピル)ベンゾフラン(化合物5)(2-(3',4'-methylenedioxyphenyl)-7-methoxy-3-methyl-5-propyl-benzofuran) 2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5-propyl) benzofuran (Compound 5) (2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3 -methyl-5-propyl-benzofuran)
2,3−ジヒドロ−2−(3’,4’−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物6)
(2,3-dihydro-2-(3',4'-methylenedioxyphenyl)-7-methoxy-3-methyl-5-propyl-benzofuran)
2,3-Dihydro-2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (Compound 6)
(2,3-dihydro-2- (3 ', 4'-methylenedioxyphenyl) -7-methoxy-3-methyl-5-propyl-benzofuran)
2−(3’,4’−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物7)
(2-(3',4'-methylenedioxyphenyl)-7-methoxy-3-methyl-5-(1-propenyl)-benzofuran)
2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (Compound 7)
(2- (3 ', 4'-methylenedioxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) -benzofuran)
2,3−ジヒドロ−2−(3’,4’−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物8)
(2,3-dihydro-2-(3',4'-methylenedioxyphenyl)-7-methoxy-3-methyl-5-(1-propenyl)-benzofuran)
2,3-Dihydro-2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (Compound 8)
(2,3-dihydro-2- (3 ', 4'-methylenedioxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) -benzofuran)
から選ばれる少なくとも1つである、(1)に記載の皮膚外用剤。 The external preparation for skin according to (1), which is at least one selected from:
(3) 前記一般式(I)で表される化合物の含有率が、外用剤全体に対して0.0001〜10質量%である、(1)又は(2)に記載の皮膚外用剤。
(4) 「医薬部外品」である旨の表示を付されていることを特徴とする(1)〜(3)のいずれかに記載の皮膚外用剤。
(5) 美白化粧料であることを特徴とする、(1)〜(4)のいずれかに記載の皮膚外用剤。
(6) 下記一般式(II)で表される化合物。
(3) The skin external preparation as described in (1) or (2) whose content rate of the compound represented by the said general formula (I) is 0.0001-10 mass% with respect to the whole external preparation.
(4) The external preparation for skin according to any one of (1) to (3), which is labeled as “quasi-drug”.
(5) The skin external preparation according to any one of (1) to (4), which is a whitening cosmetic.
(6) A compound represented by the following general formula (II).
(7) 2,3−ジヒドロ−2−(3’,4’−ジメトキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物3)、または
2,3−ジヒドロ−2−(3’,4’−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物6)
であることを特徴とする、(6)に記載の化合物。
(7) 2,3-dihydro-2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 3), or 2,3-dihydro-2- (3 ', 4'-Methylenedioxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (Compound 6)
The compound according to (6), wherein
本発明により、新規の美白素材(新規のベンゾフラン誘導体であり得る)が提供され、さらにこれを利用して、皮膚色素沈着症の予防、改善に対して優れた効果を発揮するばかりでなく、皮膚に対する安全性上の懸念がなく、安全に使用することができる皮膚外用剤が提供される。 According to the present invention, a novel whitening material (which may be a novel benzofuran derivative) is provided, and further using this, not only exhibits an excellent effect on the prevention and improvement of skin pigmentation, but also the skin There is provided a skin external preparation that can be used safely without any safety concerns.
<本発明のベンゾフラン誘導体、又は本発明の化粧料に含まれるベンゾフラン誘導体>
本発明の皮膚外用剤の必須構成成分であるベンゾフラン誘導体は、一般式(I)で表される化合物である(以下、「化合物(I)」とも称する)。
一般式(I)において破線で表される結合は、存在して二重結合を形成しても良いし、存在せずに単結合を形成していても良い。すなわち、化合物(I)はベンゾフラン誘導体及びジヒドロベンゾフラン誘導体のいずれでもよい。
<The benzofuran derivative of this invention or the benzofuran derivative contained in the cosmetics of this invention>
The benzofuran derivative, which is an essential component of the external preparation for skin of the present invention, is a compound represented by the general formula (I) (hereinafter also referred to as “compound (I)”).
The bond represented by the broken line in the general formula (I) may be present to form a double bond, or may not be present to form a single bond. That is, compound (I) may be either a benzofuran derivative or a dihydrobenzofuran derivative.
化合物(I)を表す一般式(I)において、R3は任意の基でありうるが、好ましくは置換基を有していてもよいアルキル基、またはアルケニル基であり、さらに好ましくは炭素数1〜4のアルキル基、または炭素数2〜4のアルケニル基である。具体的には、前記アルキル基としてはメチル基、エチル基、n−プロピル基、イソプロピル基、ブチル基、sec−ブチル基などが例示でき、これらの内ではn−プロピル基が特に好ましい。また、前記アルケニル基としては、ビニル基、1−プロペニル基、2−プロペニル基、1−ブテニル基、2−ブテニル基、3−ブテニル基などが例示でき、これらの内では1−プロペニル基が特に好ましい。 In the general formula (I) representing the compound (I), R 3 may be any group, but is preferably an alkyl group or alkenyl group which may have a substituent, and more preferably 1 carbon atom. An alkyl group having 4 to 4 carbon atoms, or an alkenyl group having 2 to 4 carbon atoms. Specifically, examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, a butyl group, and a sec-butyl group, and among these, an n-propyl group is particularly preferable. Examples of the alkenyl group include vinyl group, 1-propenyl group, 2-propenyl group, 1-butenyl group, 2-butenyl group, and 3-butenyl group. Among these, 1-propenyl group is particularly preferable. preferable.
一般式(I)において、R4は任意の基でありうるが、好ましくは置換基を有していてもよいアルキル基またはアルケニル基であり、さらに好ましくは炭素数1〜4のアルキル基、または炭素数2〜4のアルケニル基である。より好ましくは炭素数1〜4のアルキル基である。前記アルキル基としてはメチル基が特に好ましく、前記アルケニル基としては、2−プロペニル基が特に好ましい。 In the general formula (I), R 4 may be an arbitrary group, but is preferably an alkyl group or an alkenyl group which may have a substituent, more preferably an alkyl group having 1 to 4 carbon atoms, or An alkenyl group having 2 to 4 carbon atoms. More preferably, it is a C1-C4 alkyl group. The alkyl group is particularly preferably a methyl group, and the alkenyl group is particularly preferably a 2-propenyl group.
一般式(I)において、R5は任意の基でありうるが、好ましくは置換基を有していてもよいアルキル基、またはアルケニル基であり、さらに好ましくは炭素数1〜4のアルキル基、または炭素数2〜4のアルケニル基である。より好ましくは炭素数1〜4のアルキル基である。前記アルキル基としてはメチル基が特に好ましく、前記アルケニル基としては、2−プロペニル基が特に好ましい。 In general formula (I), R 5 may be any group, but is preferably an alkyl group which may have a substituent or an alkenyl group, more preferably an alkyl group having 1 to 4 carbon atoms, Or it is a C2-C4 alkenyl group. More preferably, it is a C1-C4 alkyl group. The alkyl group is particularly preferably a methyl group, and the alkenyl group is particularly preferably a 2-propenyl group.
一般式(I)においてR1及びR2はそれぞれ任意の基または原子でありうるが、好ましくはそれぞれ独立に水素原子、水酸基又は炭素数1〜4のアルキルオキシ基である。前記アルキルオキシ基としては、メトキシ基、エトキシ基、プロポキシ基などを例示できる。
また、R1及びR2が結合して、炭素鎖数1〜2のアルキレンジオキシ基を形成していてもよい。前記アルキレン基は、置換基を有していてもよいメチレン基、エチレン基でありうるが、好ましくはメチレン基である。すなわち、好ましくはベンゾジオキソール環(メチレンジオキシフェニル環)を形成している。
In the general formula (I), R 1 and R 2 may each be any group or atom, but preferably each independently a hydrogen atom, a hydroxyl group, or an alkyloxy group having 1 to 4 carbon atoms. Examples of the alkyloxy group include a methoxy group, an ethoxy group, and a propoxy group.
R 1 and R 2 may be bonded to form an alkylenedioxy group having 1 to 2 carbon chains. The alkylene group may be a methylene group or an ethylene group which may have a substituent, but is preferably a methylene group. That is, a benzodioxole ring (methylenedioxyphenyl ring) is preferably formed.
化合物(I)はフリー体で本発明の化粧料に使用することもできるが、アルカリなどを用いて塩と為し、塩として使用することも可能である。このような塩としては、たとえばナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩、マグネシウム塩等のアルカリ土類金属塩、アンモニウム塩、トリエタノールアミン塩、トリエチルアミン塩等の有機アミン塩、リジン塩、アルギニン塩等の塩基性アミノ酸塩等が好ましく例示できる。 Compound (I) can be used in the free form of the cosmetic of the present invention, but it can be converted into a salt using an alkali or the like and used as a salt. Examples of such salts include alkali metal salts such as sodium salts and potassium salts, alkaline earth metal salts such as calcium salts and magnesium salts, organic amine salts such as ammonium salts, triethanolamine salts and triethylamine salts, and lysine salts. Preferred examples include basic amino acid salts such as arginine salt.
化合物(I)はジアステレオマーまたはエナンチオマーを有しうる。例えば、破線で表される結合が存在しない場合(ジヒドロベンゾフラン誘導体の場合)は、2つのキラル炭素を有するので、ジアステレオマー及びエナンチオマーが存在する。化合物(I)はそれらのいずれかの異性体でもよく、それらの混合物でもよい。 Compound (I) may have diastereomers or enantiomers. For example, when there is no bond represented by a broken line (in the case of a dihydrobenzofuran derivative), since there are two chiral carbons, diastereomers and enantiomers exist. Compound (I) may be any isomer thereof or a mixture thereof.
本発明は特に、一般式(I)で表される化合物(化合物(I))のうち、上記一般式(II)で表される化合物に関する。一般式(II)で表される化合物(以下、「化合物(II)」とも称する)は新規の化合物である。 The present invention particularly relates to a compound represented by the above general formula (II) among the compounds represented by the general formula (I) (compound (I)). The compound represented by the general formula (II) (hereinafter also referred to as “compound (II)”) is a novel compound.
一般式(II)においてR6で表されるアルキル基としては、置換基を有していてもよい炭素数2〜4のアルキル基が好ましく、プロピル基(さらにはn−プロピル基)が特に好ましい。
一般式(II)におけるR7,R8,R9,R10は、それぞれ一般式(I)におけるR1,R2,R4,R5と同様に定義される。
In the general formula (II), the alkyl group represented by R 6 is preferably an alkyl group having 2 to 4 carbon atoms which may have a substituent, and particularly preferably a propyl group (more preferably an n-propyl group). .
R 7 , R 8 , R 9 and R 10 in the general formula (II) are defined in the same manner as R 1 , R 2 , R 4 and R 5 in the general formula (I), respectively.
化合物(I)及び(II)は、任意の方法で製造することができるが、例えばスキーム1及び2で概略される方法に従って製造することができる。また当業者は、以下の方法を適宜変更して目的とする化合物を製造することができることを理解する。
また、スキーム1及び2では、化合物(I)の合成法として説明されているが、同様に化合物(II)が製造できることは言うまでもない。
Compounds (I) and (II) can be produced by any method, for example, according to the methods outlined in Schemes 1 and 2. Further, those skilled in the art understand that the target compound can be produced by appropriately changing the following method.
In Schemes 1 and 2, although described as a synthesis method of compound (I), it goes without saying that compound (II) can be produced in the same manner.
スキーム1に従って、一般式(I)においてR1が水酸基またはORc;R2がORa;R3がCH2CH2RbまたはCH=CHRb;R4がRa;R5がRbである化合物(I)を合成することができる。好ましくは、Ra=Rb=Rc=CH3とすることにより、(C)において化合物1:(D)において化合物2:(E)において化合物3:(F)において化合物4を合成することができる。 According to scheme 1, in general formula (I), R 1 is a hydroxyl group or OR c ; R 2 is OR a ; R 3 is CH 2 CH 2 R b or CH═CHR b ; R 4 is R a ; R 5 is R b Compound (I) can be synthesized. Preferably, compound 4 is synthesized in compound 1: (F) in compound 1: (D) in compound 2: (E) in compound 3: (F) by setting R a = R b = R c = CH 3. Can do.
スキーム1における各反応について簡単に説明する。
反応1:イソオイゲノール誘導体(A)の酸化的縮合反応にて(B)が合成される。該反応において塩化第二鉄、塩化第二銅などを用いることができる。好ましくは、イソオイゲノール(Ra=Rb=CH3)を酸化的縮合反応することにより、2,3−ジヒドロ−2−(4’−ヒドロキシ−3’−メトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)−ベンゾフランを合成することができる。また、(A)のRbはシス、トランスのいずれでもよいが、好ましくはトランスである。
反応2:(B)の4’位の(フェニル環上の)水酸基を、種々のアルキル化剤(例えばハロゲン化アルキル、ジアルキル硫酸など)と反応させてアルコキシ基に変換することにより、(C)が合成される。好ましくは2,3−ジヒドロ−2−(4’−ヒドロキシ−3’−メトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)−ベンゾフランをメチル化剤と反応させて化合物1(Ra=Rb=Rc=CH3)を合成する。
なお、別途、(B)または(C)の3’位の(フェニル環上の)ORaを選択的に加水分解して水酸基とし、これを種々のアルキル化剤(例えばハロゲン化アルキル)と反応させてアルコキシ基に変換することも可能である。
反応3:(C)のジヒドロベンゾフラン環を酸化することによりベンゾフラン体(D)を合成する。該酸化は任意の方法により行うことができるが、5位のアルケニル基(CH=CHRb)を臭素によりジブロモ化して保護し、さらにフラン環上のベンジル位をN―ブロモサクシイミドなどでブロモ化したのち、亜鉛などの脱ハロゲン化剤で処理することにより行うことができる。(C)が化合物1であれば、化合物2を合成することができる
。
反応4:(C)を還元することにより(E)を合成する。該還元は例えば接触還元反応により行う。(C)が化合物1であれば化合物3を合成することができる。
反応5:(E)のジヒドロベンゾフラン環を酸化することによりベンゾフラン体(F)を合成する。該酸化は、例えばDDQ(2,3-Dichloro-5,6-dicyano-1,4-benzoquinone)を用いて行う。(E)が化合物3であれば化合物4を合成することができる。
Each reaction in Scheme 1 will be briefly described.
Reaction 1: (B) is synthesized by an oxidative condensation reaction of the isoeugenol derivative (A). In the reaction, ferric chloride, cupric chloride and the like can be used. Preferably, 2,3-dihydro-2- (4′-hydroxy-3′-methoxyphenyl) -7-methoxy-3 is obtained by subjecting isoeugenol (R a ═R b ═CH 3 ) to an oxidative condensation reaction. -Methyl-5- (1-propenyl) -benzofuran can be synthesized. In addition, R b in (A) may be either cis or trans, but is preferably trans.
Reaction 2: By converting the hydroxyl group (on the phenyl ring) at the 4 ′ position of (B) to an alkoxy group by reacting with various alkylating agents (eg, alkyl halide, dialkyl sulfuric acid, etc.), (C) Is synthesized. Preferably, 2,3-dihydro-2- (4′-hydroxy-3′-methoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) -benzofuran is reacted with a methylating agent to give compound 1 (R a = R b = R c = CH 3 ) is synthesized.
Separately, OR a (on the phenyl ring) at the 3 ′ position of (B) or (C) is selectively hydrolyzed to a hydroxyl group, which is reacted with various alkylating agents (for example, alkyl halides). It is also possible to convert it into an alkoxy group.
Reaction 3: A benzofuran body (D) is synthesized by oxidizing the dihydrobenzofuran ring of (C). The oxidation can be carried out by any method, but the alkenyl group at the 5-position (CH═CHR b ) is protected by dibromination with bromine, and the benzyl position on the furan ring is brominated with N-bromosuccinimide or the like. Then, it can carry out by processing with dehalogenating agents, such as zinc. If (C) is compound 1, compound 2 can be synthesized.
Reaction 4: (E) is synthesized by reducing (C). The reduction is performed by, for example, a catalytic reduction reaction. If (C) is compound 1, compound 3 can be synthesized.
Reaction 5: A benzofuran body (F) is synthesized by oxidizing the dihydrobenzofuran ring of (E). The oxidation is performed using, for example, DDQ (2,3-Dichloro-5,6-dicyano-1,4-benzoquinone). If (E) is compound 3, compound 4 can be synthesized.
スキーム2に従って、化合物(I)を合成することができる。スキーム2におけるベンゾイルクロリド(J)を適宜選択することで、上述のスキーム1では合成が困難であるR1及びR2が閉環構造を形成している化合物をも合成することできる。好ましくは、スキーム2における(J)をピペロニルクロリドにすることで、R1及びR2がメチレンジオキシフェニル(ベンゾジオキソール)を形成している化合物(例えば化合物5〜8)を合成しうる。 Compound (I) can be synthesized according to Scheme 2. By appropriately selecting benzoyl chloride (J) in Scheme 2, a compound in which R 1 and R 2 , which are difficult to synthesize in Scheme 1 above, form a closed ring structure, can also be synthesized. Preferably, compounds in which R 1 and R 2 form methylenedioxyphenyl (benzodioxole) (for example, compounds 5 to 8) are synthesized by changing (J) in Scheme 2 to piperonyl chloride. Yes.
スキーム2における各反応について簡単に説明する。
反応6:イソオイゲノール誘導体(G)をカルボン酸と反応させてアシル化することで(H)を合成する。該アシル化はFriedel-Crafts アシル化法、その他の変法を用いて行うことができる。R3=n−プロピルである(G)を用いることが好ましい。
反応7:(H)とベンゾイルハライド(J)(好ましくはピペロニルクロリド)とを反応させて(K)を合成する。
反応8:(K)のCOR5のカルボニルを還元して2級アルコールとし、さらにアルコールを臭素化することで(L)を合成する。カルボニルの還元は例えばNaBH4などを用いて行うことができ、臭素化は好ましくはトリフェニルホスフィンを用いてアルコキシホスホニウム塩を中間体として、さらに臭素を用いて行うことが好ましい。
反応9:(L)からリンイリドを生成させ、さらに分子内Wittig 反応させることにより(M)を合成する。中間体のリンイリドは単離してもしなくてもよい。
反応10:(M)のベンゾフラン環の2,3位の二重結合を還元することで(N)を合成する。該還元は例えば接触還元により行うことができる。
反応11:(M)においてR3=CH2CH2Rである場合に、R3のベンジル位をハロゲン化(好ましくはブロモ化)し、さらに塩基を用いて脱ハロゲン化水素反応させることで(O)を合成する。該ハロゲン化はラジカル反応により行うことが好ましく、過酸化ベンゾイルなどのラジカル開始剤を用いることができる。好ましくはR3=n−プロピル(R=CH3)である。
反応12:(O)のベンゾフラン環の2,3位の二重結合を還元することで(P)を合成する。該還元は任意の方法で行うことができるが、当モルの量の臭素で選択的にR−CH=CH−(例えばプロペニル基)をジブロモ化し、次いでフラン環の二重結合を還元したのち、亜鉛などの脱ハロゲン化剤で処理してR−CH=CH−(例えばプロペニル基)を再生させることにより行うことができる。
Each reaction in Scheme 2 will be briefly described.
Reaction 6: Isoeugenol derivative (G) is reacted with a carboxylic acid and acylated to synthesize (H). The acylation can be carried out by using Friedel-Crafts acylation method and other modified methods. It is preferable to use (G) where R 3 = n-propyl.
Reaction 7: (K) is synthesized by reacting (H) with benzoyl halide (J) (preferably piperonyl chloride).
Reaction 8: The carbonyl of COR 5 in (K) is reduced to a secondary alcohol, and the alcohol is further brominated to synthesize (L). The reduction of carbonyl can be performed using, for example, NaBH 4 and the like, and bromination is preferably performed using triphenylphosphine as an alkoxyphosphonium salt as an intermediate and further using bromine.
Reaction 9: Phosphoryl ylide is produced from (L), and (M) is synthesized by further intramolecular Wittig reaction. The intermediate phosphorus ylide may or may not be isolated.
Reaction 10: (N) is synthesized by reducing the double bond at the 2- and 3-positions of the benzofuran ring in (M). The reduction can be performed by, for example, catalytic reduction.
Reaction 11: When R 3 = CH 2 CH 2 R in (M), the benzyl position of R 3 is halogenated (preferably brominated), and further dehydrohalogenated using a base ( O) is synthesized. The halogenation is preferably performed by radical reaction, and a radical initiator such as benzoyl peroxide can be used. R 3 = n-propyl (R═CH 3 ) is preferred.
Reaction 12: (P) is synthesized by reducing the double bond at the 2- and 3-positions of the benzofuran ring of (O). The reduction can be carried out by any method, but after selectively dibrominating R—CH═CH— (eg propenyl group) with an equimolar amount of bromine and then reducing the furan ring double bond, It can be carried out by regenerating R—CH═CH— (for example, propenyl group) by treatment with a dehalogenating agent such as zinc.
化合物(I)または(II)は上記のようにして合成することができるが、合成された化合物の同定は、通常の有機化合物の同定法、例えばプロトンNMRスペクトルを測定及び分析することにより行うことができる。 Compound (I) or (II) can be synthesized as described above, but identification of the synthesized compound should be performed by ordinary methods for identifying organic compounds, for example, by measuring and analyzing proton NMR spectra. Can do.
化合物(I)及び化合物(II)は、下記する試験例にも示されているように、メラニン生成抑制作用を有する。したがって、皮膚外用剤に含有されることにより、該外用剤が皮膚に塗布された場合に、メラニン生成抑制作用に基づく優れた色素沈着症の予防及び改善、いわゆる美白効果を発揮する。したがって、化合物(I)及び(II)は、皮膚外用剤の含有成分として用いることができる。 Compound (I) and Compound (II) have a melanin production inhibitory effect as shown in the following test examples. Therefore, when contained in a skin external preparation, when the external preparation is applied to the skin, it exhibits an excellent prevention and improvement of pigmentation based on a melanin production inhibitory action, a so-called whitening effect. Therefore, the compounds (I) and (II) can be used as components for external preparations for skin.
<本発明の皮膚外用剤>
本発明の皮膚外用剤は、上記一般式(I)で表される化合物(化合物(I))、もしくは一般式(II)で表される化合物(化合物(II))、またはそれらの塩を必須成分として含む。化合物(I)もしくは(II)またはそれらの塩は、前述の説明の通りである。含まれる化合物(I)もしくは(II)またはそれらの塩は、一種類だけでもよく、二種類以上の組み合わせでもよい。なお、以下において、化合物(I)もしくは(II)またはそれらの塩を、「化合物(I)または(II)」と略記することがある。
<Skin external preparation of the present invention>
The skin external preparation of the present invention essentially comprises the compound represented by the above general formula (I) (compound (I)), the compound represented by the general formula (II) (compound (II)), or a salt thereof. Contains as an ingredient. Compound (I) or (II) or a salt thereof is as described above. The compound (I) or (II) or a salt thereof contained may be only one type or a combination of two or more types. Hereinafter, the compound (I) or (II) or a salt thereof may be abbreviated as “compound (I) or (II)”.
本発明の皮膚外用剤は、化合物(I)または(II)の他に、医薬品、化粧品等に一般的に用いられる各種成分、すなわち、油脂、ロウ類、炭化水素類、脂肪酸、高級アルコール、エステル類、油剤、水性成分、粉末成分、界面活性剤、保湿剤、増粘剤、色剤、香料、抗酸化剤、pH調整剤、キレート剤、防腐剤、あるいは紫外線防御剤、抗炎症剤等を含みうる。 In addition to compound (I) or (II), the external preparation for skin of the present invention comprises various components generally used in pharmaceuticals, cosmetics, etc., that is, fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, esters Oils, aqueous components, powder components, surfactants, moisturizers, thickeners, colorants, fragrances, antioxidants, pH adjusters, chelating agents, preservatives, UV protection agents, anti-inflammatory agents, etc. May be included.
本発明の皮膚外用剤に含まれる油脂またはロウ類としては、具体的には、例えばマカデミアナッツ油、アボガド油、トウモロコシ油、オリーブ油、ナタネ油、ゴマ油、ヒマシ油、サフラワー油、綿実油、ホホバ油、ヤシ油、パーム油、液状ラノリン、硬化ヤシ油、硬化油、モクロウ、硬化ヒマシ油、ミツロウ、キャンデリラロウ、カルナウバロウ、イボタロウ、ラノリン、還元ラノリン、硬質ラノリン、ホホバロウ等のオイル、ワックス類、流
動パラフィン、スクワラン、プリスタン、オゾケライト、パラフィン、セレシン、ワセリン、マイクロクリスタリンワックス等の炭化水素類が挙げられ、
脂肪酸としては、オレイン酸、イソステアリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、ベヘン酸、ウンデシレン酸等の高級脂肪酸類が挙げられ、
高級アルコールとしては、セチルアルコール、ステアリルアルコール、イソステアリルアルコール、ベヘニルアルコール、オクチルドデカノール、ミリスチルアルコール、セトステアリルアルコール等が挙げられ、
エステル類としては、イソオクタン酸セチル、ミリスチン酸イソプロピル、イソステアリン酸ヘキシルデシル、アジピン酸ジイソプロピル、セバチン酸ジ−2−エチルヘキシル、乳酸セチル、リンゴ酸ジイソステアリル、ジ−2−エチルヘキサン酸エチレングリコール、ジカプリン酸ネオペンチルグリコール、ジ−2−ヘプチルウンデカン酸グリセリン、トリ−2−エチルヘキサン酸グリセリン、トリ−2−エチルヘキサン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ−2−エチルヘキサン酸ペンタンエリトリット等の合成エステル油類が挙げられ、
油剤としては、ジメチルポリシロキサン、メチルフェニルポリシロキサン、ジフェニルポリシロキサン等の鎖状ポリシロキサン、オクタメチルシクロテトラシロキサン、デカメチルシクロペンタシロキサン、ドデカメチルシクロヘキサンシロキサン等の環状ポリシロキサン、アミノ変性ポリシロキサン、ポリエーテル変性ポリシロキサン、アルキル変性ポリシロキサン、フッ素変性ポリシロキサン等の変性ポリシロキサン等のシリコーン油等が挙げられる。
Specific examples of the oil or wax contained in the external preparation for skin of the present invention include, for example, macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, Oils such as coconut oil, palm oil, liquid lanolin, hydrogenated palm oil, hydrogenated oil, molefish, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, ibotarou, lanolin, reduced lanolin, hard lanolin, jojoba wax, waxes, liquid paraffin , Hydrocarbons such as squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax, etc.
Examples of fatty acids include higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid,
Examples of higher alcohols include cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol,
Esters include cetyl isooctanoate, isopropyl myristate, hexyl decyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, diisostearyl malate, ethylene glycol di-2-ethylhexanoate, dicaprin Acid neopentyl glycol, di-2-heptylundecanoic acid glycerin, tri-2-ethylhexanoic acid glycerin, tri-2-ethylhexanoic acid trimethylolpropane, triisostearic acid trimethylolpropane, tetra-2-ethylhexanoic acid pentane ester Synthetic ester oils such as trit
As the oil agent, chain polysiloxane such as dimethylpolysiloxane, methylphenylpolysiloxane, diphenylpolysiloxane, cyclic polysiloxane such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexanesiloxane, amino-modified polysiloxane, Examples thereof include silicone oils such as polyether-modified polysiloxane, alkyl-modified polysiloxane, and modified polysiloxane such as fluorine-modified polysiloxane.
本発明の皮膚外用剤に含まれる界面活性剤としては、脂肪酸セッケン(ラウリン酸ナトリウム、パルミチン酸ナトリウム等)、ラウリル硫酸カリウム、アルキル硫酸トリエタノールアミンエーテル等のアニオン界面活性剤類、塩化ステアリルトリメチルアンモニウム、塩化ベンザルコニウム、ラウリルアミンオキサイド等のカチオン界面活性剤類、イミダゾリン系両性界面活性剤(2−ココイル−2−イミダゾリニウムヒドロキサイド−1−カルボキシエチロキシ2ナトリウム塩等)、ベタイン系界面活性剤(アルキルベタイン、アミドベタイン、スルホベタイン等)、アシルメチルタウリン等の両性界面活性剤類、ソルビタン脂肪酸エステル類(ソルビタンモノステアレート、セスキオレイン酸ソルビタン等)、グリセリン脂肪酸類(モノステアリン酸グリセリン等)、プロピレングリコール脂肪酸エステル類(モノステアリン酸プロピレングリコール等)、硬化ヒマシ油誘導体、グリセリンアルキルエーテル、POEソルビタン脂肪酸エステル類(POEソルビタンモノオレエート、モノステアリン酸ポリオキエチレンソルビタン等)、POEソルビット脂肪酸エステル類(POE−ソルビットモノラウレート等)、POEグリセリン脂肪酸エステル類(POE−グリセリンモノイソステアレート等)、POE脂肪酸エステル類(ポリエチレングリコールモノオレート、POEジステアレート等)、POEアルキルエーテル類(POE2−オクチルドデシルエーテル等)、POEアルキルフェニルエーテル類(POEノニルフェニルエーテル等)、プルロニック型類、POE・POPアルキルエーテル類(POE・POP2−デシルテトラデシルエーテル等)、テトロニック類、POEヒマシ油・硬化ヒマシ油誘導体(POEヒマシ油、POE硬化ヒマシ油等)、ショ糖脂肪酸エステル、アルキルグルコシド等の非イオン界面活性剤類が挙げられる。 Surfactants contained in the external preparation for skin of the present invention include fatty acid soap (sodium laurate, sodium palmitate, etc.), anionic surfactants such as potassium lauryl sulfate, triethanolamine ether alkyl sulfate, stearyltrimethylammonium chloride , Cationic surfactants such as benzalkonium chloride, laurylamine oxide, imidazoline-based amphoteric surfactants (such as 2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt), betaine-based interfaces Activators (alkylbetaines, amidebetaines, sulfobetaines, etc.), amphoteric surfactants such as acylmethyltaurine, sorbitan fatty acid esters (sorbitan monostearate, sorbitan sesquioleate, etc.), glycerin fatty acids (mono Glyceryl thetearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hydrogenated castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (POE sorbitan monooleate, polyoxyethylene sorbitan monostearate, etc.) POE sorbite fatty acid esters (such as POE-sorbitol monolaurate), POE glycerin fatty acid esters (such as POE-glycerin monoisostearate), POE fatty acid esters (such as polyethylene glycol monooleate and POE distearate), POE alkyl ether (POE2-octyldodecyl ether, etc.), POE alkylphenyl ethers (POE nonylphenyl ether, etc.), Pluronic type, POE OP alkyl ethers (POE / POP2-decyltetradecyl ether, etc.), Tetronics, POE castor oil / hardened castor oil derivatives (POE castor oil, POE hardened castor oil, etc.), non-sucrose fatty acid esters, alkyl glucosides, etc. Examples include ionic surfactants.
本発明の皮膚外用剤に含まれる保湿剤としては、ポリエチレングリコール、グリセリン、1,3−ブチレングリコール、エリスリトール、ソルビトール、キシリトール、マルチトール、プロピレングリコール、ジプロピレングリコール、ジグリセリン、イソプレングリコール、1,2−ペンタンジオール、2,4−ヘキシレングリコール、1,2−ヘキサンジオール、1,2−オクタンジオール等の多価アルコール類、ピロリドンカルボン酸ナトリウム、乳酸、乳酸ナトリウム等が挙げられ、
増粘剤としては、グアガム、クインスシード、カラギーナン、ガラクタン、アラビアガム、ペクチン、マンナン、デンプン、キサンタンガム、カードラン、メチルセルロース、
ヒドロキシエチルセルロース、カルボキシメチルセルロース、メチルヒドロキシプロピルセルロース、コンドロイチン硫酸、デルマタン硫酸、グリコーゲン、ヘパラン硫酸、ヒアルロン酸、ヒアルロン酸ナトリウム、トラガントガム、ケラタン硫酸、コンドロイチン、ムコイチン硫酸、ヒドロキシエチルグアガム、カルボキシメチルグアガム、デキストラン、ケラト硫酸、ローカストビーンガム、サクシノグルカン、カロニン酸、キチン、キトサン、カルボキシメチルキチン、寒天、ポリビニルアルコール、ポリビニルピロリドン、カルボキシビニルポリマー、ポリアクリル酸ナトリウム、ポリエチレングリコール、ベントナイト等が挙げられる。
As the moisturizing agent contained in the external preparation for skin of the present invention, polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, maltitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1, Polyhydric alcohols such as 2-pentanediol, 2,4-hexylene glycol, 1,2-hexanediol, 1,2-octanediol, sodium pyrrolidonecarboxylate, lactic acid, sodium lactate, etc.
Thickeners include guar gum, quince seed, carrageenan, galactan, gum arabic, pectin, mannan, starch, xanthan gum, curdlan, methylcellulose,
Hydroxyethylcellulose, carboxymethylcellulose, methylhydroxypropylcellulose, chondroitin sulfate, dermatan sulfate, glycogen, heparan sulfate, hyaluronic acid, sodium hyaluronate, tragacanth gum, keratan sulfate, chondroitin, mucoitin sulfate, hydroxyethyl guar gum, carboxymethyl guar gum, dextran, kerato Examples include sulfuric acid, locust bean gum, succinoglucan, caronic acid, chitin, chitosan, carboxymethylchitin, agar, polyvinyl alcohol, polyvinylpyrrolidone, carboxyvinyl polymer, sodium polyacrylate, polyethylene glycol, bentonite and the like.
本発明の皮膚外用剤に含まれる粉体類としては、表面を処理されていても良い、マイカ、タルク、カオリン、合成雲母、炭酸カルシウム、炭酸マグネシウム、無水ケイ酸(シリカ)、酸化アルミニウム、硫酸バリウム等が挙げられ、
無機顔料としては、表面を処理されていても良い、ベンガラ、黄酸化鉄、黒酸化鉄、酸化コバルト、群青、紺青、酸化チタン、酸化亜鉛等が挙げられ、
パール剤類としては、表面を処理されていても良い、雲母チタン、魚燐箔、オキシ塩化ビスマス等が挙げられ、
有機色素類としては、レーキ化されていても良い赤色202号、赤色228号、赤色226号、黄色4号、青色404号、黄色5号、赤色505号、赤色230号、赤色223号、橙色201号、赤色213号、黄色204号、黄色203号、青色1号、緑色201号、紫色201号、赤色204号等が挙げられ、
有機粉体類としては、ポリエチレン末、ポリメタクリル酸メチル、ナイロン粉末、オルガノポリシロキサンエラストマー等が挙げられる。
The powders included in the external preparation for skin of the present invention may be treated with mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, sulfuric acid Barium, etc.
Examples of the inorganic pigment include a bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, and zinc oxide whose surface may be treated.
Examples of the pearl agents include mica titanium, fish phosphorus foil, bismuth oxychloride, etc., whose surface may be treated,
Organic dyes that may be raked Red 202, Red 228, Red 226, Yellow 4, Blue 404, Yellow 5, Red 505, Red 230, Red 223, Orange 201, red 213, yellow 204, yellow 203, blue 1, green 201, purple 201, red 204, etc.
Examples of organic powders include polyethylene powder, polymethyl methacrylate, nylon powder, and organopolysiloxane elastomer.
本発明の皮膚外用剤に含まれる紫外線吸収剤類としては、パラアミノ安息香酸系紫外線吸収剤、アントラニル酸系紫外線吸収剤、サリチル酸系紫外線吸収剤、桂皮酸系紫外線吸収剤、ベンゾフェノン系紫外線吸収剤、糖系紫外線吸収剤、2−(2’−ヒドロキシ−5’−t−オクチルフェニル)ベンゾトリアゾール、4−メトキシ−4’−t−ブチルジベンゾイルメタン等が挙げられる。 Examples of the ultraviolet absorbers contained in the external preparation for skin of the present invention include paraaminobenzoic acid ultraviolet absorbers, anthranilic acid ultraviolet absorbers, salicylic acid ultraviolet absorbers, cinnamic acid ultraviolet absorbers, benzophenone ultraviolet absorbers, Examples thereof include sugar-based ultraviolet absorbers, 2- (2′-hydroxy-5′-t-octylphenyl) benzotriazole, 4-methoxy-4′-t-butyldibenzoylmethane, and the like.
さらに本発明の皮膚外用剤は、低級アルコール類(エタノール、イソプロパノール等)、またはビタミンA又はその誘導体、ビタミンB6塩酸塩、ビタミンB6トリパルミテート、ビタミンB6ジオクタノエート、ビタミンB2又はその誘導体、ビタミンB12、ビタミンB15又はその誘導体等のビタミンB類、α−トコフェロール,β−トコフェロール,γ−トコフェロール,ビタミンEアセテート等のビタミンE類、ビタミンD類、ビタミンH、パントテン酸、パンテチン、ピロロキノリンキノン等のビタミン類などを含みうる。 Furthermore, the topical skin preparation of the present invention comprises lower alcohols (ethanol, isopropanol, etc.), vitamin A or a derivative thereof, vitamin B6 hydrochloride, vitamin B6 tripalmitate, vitamin B6 dioctanoate, vitamin B2 or a derivative thereof, vitamin B12, Vitamin B such as vitamin B15 or a derivative thereof, vitamin E such as α-tocopherol, β-tocopherol, γ-tocopherol, vitamin E acetate, vitamin D, vitamin H, pantothenic acid, panthetin, pyrroloquinoline quinone May be included.
また、本発明の皮膚外用剤は化合物(I)または(II)以外の美白成分または美白剤をさらに配合されても良い。そのような美白成分または美白剤としては例えば、パンテテイン−S−スルホン酸、イソフェルラ酸、アスコルビン酸リン酸塩、ルシノール、アルブチン、コウジ酸、リノール酸、リノール酸メチル等が挙げられる。 Moreover, the skin external preparation of this invention may further mix | blend the whitening component or whitening agent other than compound (I) or (II). Examples of such a whitening component or whitening agent include pantethein-S-sulfonic acid, isoferulic acid, ascorbic acid phosphate, lucinol, arbutin, kojic acid, linoleic acid, methyl linoleate and the like.
本発明の皮膚外用剤は前述の通り、1種類または2種類以上の、化合物(I)または(II)を含む。該外用剤における化合物(I)または(II)の総含有率は、皮膚外用剤全体に対して0.0001質量%以上、好ましくは0.001質量%以上、さらに好ましくは0.1質量%以上である。一方、上限は10質量%以下、好ましくは5質量%以下、さらに好ましくは3質量%以下である。 As described above, the external preparation for skin of the present invention contains one or more compounds (I) or (II). The total content of the compound (I) or (II) in the external preparation is 0.0001% by mass or more, preferably 0.001% by mass or more, more preferably 0.1% by mass or more, based on the whole external preparation for skin. It is. On the other hand, the upper limit is 10% by mass or less, preferably 5% by mass or less, and more preferably 3% by mass or less.
本発明の皮膚外用剤に含まれる化合物(I)または(II)は、メラニン生成抑制作用を発揮し、該外用剤に優れた色白効果を発揮させうる。皮膚外用剤中の化合物(I)また
は(II)の含有率が、0.0001質量%以上であれば、該外用剤に十分な色白効果を発揮させることができる。
The compound (I) or (II) contained in the external preparation for skin of the present invention exhibits a melanin production inhibitory action, and can exhibit an excellent fairness effect in the external preparation. When the content of compound (I) or (II) in the external preparation for skin is 0.0001% by mass or more, the external preparation can exhibit a sufficient fairness effect.
さらに、本発明の皮膚外用剤における化合物(I)または(II)の好ましい含有率は、該皮膚外用剤の用途、または塗布される部位によって異なりうる。具体的に述べれば、本発明の皮膚外用剤を、日焼けによるシミ、ソバカス、色黒を予防することを目的とした化粧料の如き皮膚外用剤として用いる場合には、0.0001質量%以上であることが好ましい。また、本発明の皮膚外用剤を、色素沈着症の改善を目的とした医薬部外品や皮膚外用医薬品として用いる場合には、0.001質量%以上が有効含有率として望ましい。つまり、含有率が0.0001質量%より少なくなると、後記試験例においても示されているように、メラニン生成抑制作用がかなり低下する傾向がある。一方、含有率を10質量%超としても効果が頭打ちになる。よって、本発明の皮膚化粧料は、化合物(I)または(II)を上記範囲で含有することが望ましい。 Furthermore, the preferred content of compound (I) or (II) in the external preparation for skin of the present invention may vary depending on the use of the external preparation for skin or the site to be applied. Specifically, when the skin external preparation of the present invention is used as a skin external preparation such as a cosmetic for the purpose of preventing spots, freckles and darkness due to sunburn, it is 0.0001% by mass or more. Preferably there is. In addition, when the external preparation for skin of the present invention is used as a quasi-drug or external preparation for the purpose of improving pigmentation, 0.001% by mass or more is desirable as an effective content. In other words, when the content is less than 0.0001% by mass, the melanin production inhibitory action tends to be considerably reduced as shown in the test examples described later. On the other hand, even if the content rate exceeds 10% by mass, the effect reaches its peak. Therefore, it is desirable that the skin cosmetic of the present invention contains compound (I) or (II) in the above range.
本発明の皮膚外用剤の剤型は任意であり、通常この種の皮膚外用剤に用いられる剤型であれば何れでも良く、例えば化粧水、乳液、軟膏、クリーム、ローション、パック等の剤型が挙げられる。 The dosage form of the external preparation for skin of the present invention is arbitrary, and any dosage form may be used as long as it is usually used for this type of external preparation for skin. For example, the dosage forms of lotions, emulsions, ointments, creams, lotions, packs, etc. Is mentioned.
本発明の皮膚外用剤は、皮膚に連続して貯留する形態で使用される形態、例えば化粧水、乳液、軟膏、クリーム、ローションであることが望ましい。また、パック料等は連続する作用時間が短いが、閉塞による効果があるので好ましい形態の一つである。一方、洗浄剤などの一過性の処置において使用されるものは好ましくない形態である可能性がある。これは本発明の皮膚外用剤に含まれる化合物(I)または(II)が、皮膚内に浸透していってメラニン生成抑制作用を示すからである。 It is desirable that the external preparation for skin of the present invention is a form used in a form that continuously accumulates in the skin, for example, lotion, emulsion, ointment, cream, lotion. In addition, a pack material or the like is a preferred form because it has a short action time but has an effect of blocking. On the other hand, those used in transient treatments such as cleaning agents may be in an undesirable form. This is because the compound (I) or (II) contained in the external preparation for skin of the present invention penetrates into the skin and exhibits a melanin production inhibitory action.
本発明の皮膚外用剤は、医療用、非医療用(化粧用を含む)のいずれの皮膚外用剤であってもよいが、好ましくは非医療用である。したがって、本発明の皮膚外用剤は医薬部外品に分類されることが望ましく、パッケージに「医薬部外品」である旨の表示が付されていることが好ましい。 The external preparation for skin of the present invention may be any of external preparations for medical use or non-medical use (including cosmetics), but is preferably non-medical use. Therefore, it is desirable that the external preparation for skin of the present invention is classified as a quasi-drug, and the package is preferably labeled as “quasi-drug”.
本発明の皮膚外用剤は、化合物(I)または(II)を含むこと以外は、通常の皮膚外用剤の製造と同様にして製造することができる。 The external preparation for skin of the present invention can be produced in the same manner as the production of an external preparation for skin, except that it contains compound (I) or (II).
以下に実施例及び試験例を参照して、本発明について更に詳細に説明を加えるが、本発明がこれらの実施例及び試験例によって限定を受けないことは言うまでもない。 Hereinafter, the present invention will be described in more detail with reference to Examples and Test Examples, but it goes without saying that the present invention is not limited by these Examples and Test Examples.
<実施例>
ベンゾフラン誘導体の合成(実施例1〜8)
<実施例1>
化合物1の合成
トランス体のイソオイゲノール(75g)をエタノール(640ml)に溶解し、水(335ml)を加え、これに塩化鉄・6水和物(175g)を水(230ml)に溶解した溶液を加え、5℃にて一晩放置し、析出物を濾取し、エタノールより再結晶化することにより、2,3−ジヒドロ−2−(4’−ヒドロキシ−3’−メトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)−ベンゾフラン(2,3-dihydro-2-(4'-hydroxy-3'-methoxyphenyl)-7-methoxy-3-methyl-5-(1-propenyl)-benzofuran)(22.5g)を得た。
このベンゾフラン体(5g)をアセトン(60ml)に溶解し、ジメチル硫酸(2.2g)、炭酸カリウム(3.2g)を加え16時間加熱還流した。水、酢酸エチルを加えて液−液抽出を行い、酢酸エチル層をあわせて濃縮し、酢酸エチル−ジエチルエーテル系よ
り再結晶化し、化合物1を得た。
1H-NMR(in CDCl3)δ1.37(3H,d), 1.86(3H,d), 3.43(1H,m), 3.83(3H,s), 3.85(3H,s),
3.88(3H,s), 5.15(1H,d), 6.12(1H,m), 6.35(1H,m), 6.74-7.00(5H,m)
<Example>
Synthesis of benzofuran derivatives (Examples 1 to 8)
<Example 1>
Synthesis of Compound 1 A trans isomer isoeugenol (75 g) was dissolved in ethanol (640 ml), water (335 ml) was added, and a solution of iron chloride hexahydrate (175 g) dissolved in water (230 ml) was added thereto. In addition, the mixture was allowed to stand at 5 ° C. overnight, and the precipitate was collected by filtration and recrystallized from ethanol, whereby 2,3-dihydro-2- (4′-hydroxy-3′-methoxyphenyl) -7- Methoxy-3-methyl-5- (1-propenyl) -benzofuran (2,3-dihydro-2- (4'-hydroxy-3'-methoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl ) -benzofuran) (22.5 g).
This benzofuran compound (5 g) was dissolved in acetone (60 ml), dimethyl sulfate (2.2 g) and potassium carbonate (3.2 g) were added, and the mixture was heated to reflux for 16 hours. Liquid-liquid extraction was performed by adding water and ethyl acetate, the ethyl acetate layers were combined and concentrated, and recrystallized from an ethyl acetate-diethyl ether system to obtain Compound 1.
1 H-NMR (in CDCl 3 ) δ 1.37 (3H, d), 1.86 (3H, d), 3.43 (1H, m), 3.83 (3H, s), 3.85 (3H, s),
3.88 (3H, s), 5.15 (1H, d), 6.12 (1H, m), 6.35 (1H, m), 6.74-7.00 (5H, m)
<実施例2>
化合物2の合成
化合物1(2.81g)をクロロホルム(200ml)に溶解し、臭素(1.5g)を滴下し、次いでN-ブロモサクシイミド(1.87g)を添加し1時間加熱還流し、冷却後、亜鉛末(0.7g)を加えて2時間、加熱還流した。反応溶液を濾過後、濾液を濃縮し、シリカゲルカラム(溶出溶媒:n―ヘキサン/酢酸エチル=8/2)にて精製し、化合物2を油状物として得た。
1H-NMR(in CDCl3)δ1.30(3H,d), 1.40(3H,s), 3.83(3H,s), 3.85(3H,s), 3.88(3H,s),
6.12(1H,m), 6.35(1H,m), 6.74-7.00(5H,m)
<Example 2>
Synthesis of Compound 2 Compound 1 (2.81 g) was dissolved in chloroform (200 ml), bromine (1.5 g) was added dropwise, then N-bromosuccinimide (1.87 g) was added, and the mixture was heated to reflux for 1 hour. After cooling, zinc dust (0.7 g) was added and heated to reflux for 2 hours. After the reaction solution was filtered, the filtrate was concentrated and purified with a silica gel column (eluent: n-hexane / ethyl acetate = 8/2) to obtain Compound 2 as an oil.
1 H-NMR (in CDCl3) δ 1.30 (3H, d), 1.40 (3H, s), 3.83 (3H, s), 3.85 (3H, s), 3.88 (3H, s),
6.12 (1H, m), 6.35 (1H, m), 6.74-7.00 (5H, m)
<実施例3>
化合物3の合成
化合物1(1.3g)を酢酸エチル(50ml)に溶解し、パラジウム炭素(0.2g)を添加し、反応容器を密封した。反応系を窒素ガスにて置換し、減圧後、水素ガスを導入し、20時間撹拌した。濾過後、濾液を濃縮し、酢酸エチルより再結晶化し、化合物3を白色針状結晶として得た。
1H-NMR(in CDCl3)δ0.97(3H,t), 1.37(3H,d), 1.65(2H,m), 2.55(2H,t), 3.46(1H,m),
3.87(9H,s), 5.10(1H,d), 6.6-7.0(5H,m)
<Example 3>
Synthesis of Compound 3 Compound 1 (1.3 g) was dissolved in ethyl acetate (50 ml), palladium carbon (0.2 g) was added, and the reaction vessel was sealed. The reaction system was replaced with nitrogen gas, and after decompression, hydrogen gas was introduced and stirred for 20 hours. After filtration, the filtrate was concentrated and recrystallized from ethyl acetate to obtain Compound 3 as white needle crystals.
1 H-NMR (in CDCl3) δ 0.97 (3H, t), 1.37 (3H, d), 1.65 (2H, m), 2.55 (2H, t), 3.46 (1H, m),
3.87 (9H, s), 5.10 (1H, d), 6.6-7.0 (5H, m)
<実施例4>
化合物4の合成
化合物3(1.0g)をジクロロメタン(100ml)に溶解し、2,3−ジクロロ−5,6−ジシアノ−ベンゾキノン(DDQ ; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone)(700mg)を加え、室温で2時間撹拌し、反応液を濃縮後、シリカゲルカラム(溶出液:n―ヘキサン/酢酸エチル=85/15)にて精製し、化合物4を得た。
1H-NMR(in CDCl3)δ0.97(3H,t), 1.72(2H,m), 2.42(3H,s), 2.70(2H,t), 3.93(3H,s),
3.98(3H,s), 4.04(3H,s), 6.6-7.35(5H,m)
<Example 4>
Synthesis of Compound 4 Compound 3 (1.0 g) was dissolved in dichloromethane (100 ml), and 2,3-dichloro-5,6-dicyano-benzoquinone (DDQ; 2,3-dichloro-5,6-dicyano-1, 4-benzoquinone) (700 mg) was added, and the mixture was stirred at room temperature for 2 hours. The reaction solution was concentrated and purified by a silica gel column (eluent: n-hexane / ethyl acetate = 85/15) to obtain Compound 4. .
1 H-NMR (in CDCl3) δ 0.97 (3H, t), 1.72 (2H, m), 2.42 (3H, s), 2.70 (2H, t), 3.93 (3H, s),
3.98 (3H, s), 4.04 (3H, s), 6.6-7.35 (5H, m)
<実施例5>
化合物5の合成
イソオイゲノール(25g)を酢酸エチル(200ml)に溶解し、反応系を密封し、パラジウム炭素(0.7g)を添加し、窒素ガスを導入後、さらに脱気した。これに水素ガスを導入し、24時間撹拌後、パラジウム炭素を濾別、濾液を濃縮し、フェノール体を淡黄色液状物として得た。このフェノール体(23.04g)に酢酸(20ml)、三フッ化ホウ素エチルエーテルコンプレックス(16ml)を添加し、150℃で2時間加熱した。飽和重曹水を加え、ジエチルエーテルで抽出、濃縮後、シリカゲルカラム(溶出液:n―ヘキサン/酢酸エチル=9/1)にて精製し、アセトフェノン体(14.72g)を淡黄色液状物として得た。このアセトフェノン体(14.72g)、ピペロニルクロリド(16.2g)をピリジン(200ml)に溶解し、室温下、一晩撹拌した。濃縮後、シリカゲルカラム(溶出液:n―ヘキサン/酢酸エチル=8/2)にて精製し、エステル体(9.72g)を無色の液状物として得た。
<Example 5>
Synthesis of Compound 5 Isoeugenol (25 g) was dissolved in ethyl acetate (200 ml), the reaction system was sealed, palladium carbon (0.7 g) was added, nitrogen gas was introduced, and further degassed. Hydrogen gas was introduced into this, and after stirring for 24 hours, palladium carbon was filtered off and the filtrate was concentrated to obtain a phenol compound as a pale yellow liquid. Acetic acid (20 ml) and boron trifluoride ethyl ether complex (16 ml) were added to this phenol compound (23.04 g), and the mixture was heated at 150 ° C. for 2 hours. Saturated aqueous sodium bicarbonate was added, extracted with diethyl ether, concentrated, and then purified on a silica gel column (eluent: n-hexane / ethyl acetate = 9/1) to obtain an acetophenone (14.72 g) as a pale yellow liquid. It was. The acetophenone compound (14.72 g) and piperonyl chloride (16.2 g) were dissolved in pyridine (200 ml) and stirred overnight at room temperature. After concentration, the residue was purified with a silica gel column (eluent: n-hexane / ethyl acetate = 8/2) to obtain an ester (9.72 g) as a colorless liquid.
上記エステル体(9.72g)をテトラヒドロフラン(200ml)に溶解し、イソプロピルアルコール(40ml)を添加した。これに水素化ホウ素ナトリウム(480mg)を添加して、室温下、2時間撹拌した。反応液に少量の希塩酸を加えて水素化ホウ素ナトリウムをクエンチし、次いで飽和重曹水をいれ、酢酸エチルにて抽出した。濃縮後、エ
タノールより再結晶し、アルコール体(4.8g)を得た。
The above ester (9.72 g) was dissolved in tetrahydrofuran (200 ml), and isopropyl alcohol (40 ml) was added. To this was added sodium borohydride (480 mg), and the mixture was stirred at room temperature for 2 hours. A small amount of dilute hydrochloric acid was added to the reaction solution to quench sodium borohydride, then saturated aqueous sodium bicarbonate was added, and the mixture was extracted with ethyl acetate. After concentration, recrystallization from ethanol gave an alcohol form (4.8 g).
トリフェニルフォスフィン(4.2g)をアセトニトリル120mlに溶解し、臭素(2.8g)、上記アルコール体(4.8g)をアセトニトリル(240ml)に溶解したものを加え、1時間加熱還流した。濃縮後シリカゲルカラム(溶出液:n―ヘキサン/クロロホルム=1/1)にて精製し、臭化物(4.2g)を無色液状物として得た。 Triphenylphosphine (4.2 g) was dissolved in 120 ml of acetonitrile, bromine (2.8 g) and a solution of the above alcohol (4.8 g) in acetonitrile (240 ml) were added, and the mixture was heated to reflux for 1 hour. After concentration, the residue was purified by a silica gel column (eluent: n-hexane / chloroform = 1/1) to obtain bromide (4.2 g) as a colorless liquid.
上記臭化物(4.2g)をアセトニトリル(160ml)に溶解し、トリフェニルフォスフィン(3.12g)を加えて加熱還流した。減圧下で濃縮し、これにトルエン(400ml)、トリエチルアミン(32ml)を加えて、150時間加熱還流した。濃縮後、シリカゲルカラム精製し、化合物5(1.41g)を得た。
1H-NMR(in CDCl3)δ0.95(3H,t), 1.75(2H,m), 2.4(3H,s), 2.65(2H,t), 4.05(3H,s),
6.0(2H,s), 6.6-7.3(5H,m)
The bromide (4.2 g) was dissolved in acetonitrile (160 ml), triphenylphosphine (3.12 g) was added, and the mixture was heated to reflux. The mixture was concentrated under reduced pressure, toluene (400 ml) and triethylamine (32 ml) were added thereto, and the mixture was heated to reflux for 150 hours. After concentration, purification on a silica gel column gave compound 5 (1.41 g).
1 H-NMR (in CDCl3) δ 0.95 (3H, t), 1.75 (2H, m), 2.4 (3H, s), 2.65 (2H, t), 4.05 (3H, s),
6.0 (2H, s), 6.6-7.3 (5H, m)
<実施例6>
化合物6の合成
化合物5(0.4g)を酢酸エチル(25ml)に溶解し、パラジウム炭素(0.25g)を加え、反応容器を密封した。反応系を窒素ガスにて置換し、次いで水素ガスを導入し、20時間撹拌した。反応終了後、濾過し、さらに濾液を濃縮し、エタノールより再結晶化し、化合物6(0.38g)を白色結晶として得た。
1H-NMR(in CDCl3)δ0.95(3H,t), 1.40(3H,d), 1.65(2H,m), 2.55(2H,d), 3.4(1H,m),
4.0(3H,S) 5.10(1H,d), 5.95(2H,s), 6.6-7.3(5H,m)
<Example 6>
Synthesis of Compound 6 Compound 5 (0.4 g) was dissolved in ethyl acetate (25 ml), palladium carbon (0.25 g) was added, and the reaction vessel was sealed. The reaction system was replaced with nitrogen gas, and then hydrogen gas was introduced and stirred for 20 hours. After completion of the reaction, the mixture was filtered, and the filtrate was further concentrated and recrystallized from ethanol to obtain Compound 6 (0.38 g) as white crystals.
1 H-NMR (in CDCl3) δ 0.95 (3H, t), 1.40 (3H, d), 1.65 (2H, m), 2.55 (2H, d), 3.4 (1H, m),
4.0 (3H, S) 5.10 (1H, d), 5.95 (2H, s), 6.6-7.3 (5H, m)
<実施例7>
化合物7の合成
化合物5(1.0g)をクロロホルム(60ml)に溶解し、クロロホルム(40ml)に溶解した臭素(0.53g)を滴下し、さらにN−ブロモサクシイミド(0.79g)と過酸化ベンゾイル(55mg)を加え、3時間加熱還流した。冷却後、濾過、濃縮し、再度クロロホルム(100ml)に溶解し、亜鉛末(0.8g)を添加して2時間加熱還流した。これを濾過、濃縮後、t−ブタノール(80ml)に溶解し、ポタシウムt−ブトキシド(0.4g)を加えて2時間加熱還流した。反応溶液を濾過、濃縮後、シリカゲルカラムにて精製し、化合物7(0.64g)を得た。
1H-NMR(in CDCl3)δ1.30(3H,d), 1.40(3H,s), 3.85(3H,s), 5.95(2H,s), 6.12(1H,m),
6.35(1H,m), 6.74-7.00(5H,m)
<Example 7>
Synthesis of Compound 7 Compound 5 (1.0 g) was dissolved in chloroform (60 ml), bromine (0.53 g) dissolved in chloroform (40 ml) was added dropwise, and N-bromosuccinimide (0.79 g) and excess were added. Benzoyl oxide (55 mg) was added and heated to reflux for 3 hours. After cooling, the mixture was filtered, concentrated, dissolved again in chloroform (100 ml), zinc dust (0.8 g) was added, and the mixture was heated to reflux for 2 hours. This was filtered, concentrated, dissolved in t-butanol (80 ml), potassium t-butoxide (0.4 g) was added, and the mixture was heated to reflux for 2 hours. The reaction solution was filtered and concentrated, and then purified on a silica gel column to obtain Compound 7 (0.64 g).
1 H-NMR (in CDCl3) δ 1.30 (3H, d), 1.40 (3H, s), 3.85 (3H, s), 5.95 (2H, s), 6.12 (1H, m),
6.35 (1H, m), 6.74-7.00 (5H, m)
<実施例8>
化合物8の合成
化合物7(0.32g)を四塩化炭素(40ml)に溶解し、四塩化炭素(100ml)に溶解した臭素(170mg)を滴下し、室温で30分間撹拌した。次いでパラジウム炭素(0.22g)を加え、窒素ガスにて反応系を置換し、さらに水素ガスを導入して、15時間撹拌した。濾過、濃縮後、クロロホルム(100ml)に溶解し、亜鉛末(0.4g)を加えて2時間、加熱還流した。反応溶液を濾過、濃縮後、シリカゲルカラム(溶出溶媒:n―ヘキサン/酢酸エチル=8/2)にて精製した後、酢酸エチルより再結晶化し、化合物8を白色結晶として得た。
1H-NMR (in CDCl3)δ1.37(3H,d), 1.86(3H,d), 3.43(1H,m), 3.85(3H,s), 5.15(1H,d), 5.95(2H,s), 6.12(1H,m), 6.35(1H,m), 6.74-7.00(5H,m)
<Example 8>
Synthesis of Compound 8 Compound 7 (0.32 g) was dissolved in carbon tetrachloride (40 ml), bromine (170 mg) dissolved in carbon tetrachloride (100 ml) was added dropwise, and the mixture was stirred at room temperature for 30 minutes. Next, palladium carbon (0.22 g) was added, the reaction system was replaced with nitrogen gas, hydrogen gas was further introduced, and the mixture was stirred for 15 hours. After filtration and concentration, the residue was dissolved in chloroform (100 ml), zinc dust (0.4 g) was added, and the mixture was heated to reflux for 2 hours. The reaction solution was filtered and concentrated, then purified with a silica gel column (eluent: n-hexane / ethyl acetate = 8/2) and recrystallized from ethyl acetate to obtain Compound 8 as white crystals.
1 H-NMR (in CDCl3) δ 1.37 (3H, d), 1.86 (3H, d), 3.43 (1H, m), 3.85 (3H, s), 5.15 (1H, d), 5.95 (2H, s ), 6.12 (1H, m), 6.35 (1H, m), 6.74-7.00 (5H, m)
本発明の化粧料の製造(実施例9〜16)
以下、処方における各成分の数値の単位は質量部である。
<実施例9>
下記に示す処方に従って水中油クリームを作製した。すなわち、(A)の各成分を混合し、80℃に加熱した。一方、(B)の各成分を混合し80℃に加熱した。(A)の混合物に、(B)の混合物を加えて撹拌して乳化させ、その後35℃にまで冷却した。
(A)POE(30)セチルエーテル 2.0
グリセリンモノステアレート 10.0
流動パラフィン 10.0
ワセリン 4.0
セタノール 5.0
γ−トコフェロール 0.05
BTH 0.01
ブチルパラベン 0.1
化合物1 1.0
(B)1,3−ブタンジオール 10.0
精製水 57.84
Production of cosmetics of the present invention (Examples 9 to 16)
Hereinafter, the unit of the numerical value of each component in the prescription is part by mass.
<Example 9>
An oil-in-water cream was prepared according to the formulation shown below. That is, each component of (A) was mixed and heated to 80 ° C. On the other hand, each component of (B) was mixed and heated to 80 ° C. The mixture of (A) was added to the mixture of (B), stirred and emulsified, and then cooled to 35 ° C.
(A) POE (30) cetyl ether 2.0
Glycerol monostearate 10.0
Liquid paraffin 10.0
Vaseline 4.0
Cetanol 5.0
γ-tocopherol 0.05
BTH 0.01
Butylparaben 0.1
Compound 1 1.0
(B) 1,3-butanediol 10.0
Purified water 57.84
<実施例10>
下記に示す処方に従って乳液を作製した。すなわち、(A)の各成分を混合し、70℃に加熱した。一方、(B)の各成分を混合し70℃に加熱した。(B)の混合物に、(A)の混合物を加えて予備乳化を行い、さらにホモミキサーで均一に乳化し、乳化後かき混ぜながら30℃にまで冷却して、乳液を得た。
(A)合成ゲイロウ 2.5
セタノール 1.0
スクワラン 4.0
ステアリン酸 1.0
モノステアリン酸ポリエチレングリコール
(25EO) 2.2
モノステアリン酸グリセリン 0.5
γ−トコフェロール 0.05
BHT 0.01
ブチルパラベン 0.1
化合物2 0.5
(B)1,3−ブタンジオール 3.0
プロピレングリコール 7.0
キサンタンガム 0.1
カルボキシビニルポリマー 0.2
水酸化カリウム 0.2
精製水 77.64
<Example 10>
An emulsion was prepared according to the formulation shown below. That is, each component of (A) was mixed and heated to 70 ° C. On the other hand, each component of (B) was mixed and heated to 70 ° C. To the mixture of (B), the mixture of (A) was added and pre-emulsified, and then uniformly emulsified with a homomixer. After emulsification, the mixture was cooled to 30 ° C. with stirring to obtain an emulsion.
(A) Synthetic Geyrow 2.5
Cetanol 1.0
Squalane 4.0
Stearic acid 1.0
Polyethylene glycol monostearate
(25EO) 2.2
Glycerol monostearate 0.5
γ-tocopherol 0.05
BHT 0.01
Butylparaben 0.1
Compound 2 0.5
(B) 1,3-butanediol 3.0
Propylene glycol 7.0
Xanthan gum 0.1
Carboxyvinyl polymer 0.2
Potassium hydroxide 0.2
Purified water 77.64
<実施例11>
下記に示す処方に従って化粧水を作製した。(A)の各成分を混合し、室温下で溶解させた。一方(B)の各成分を室温下で混合し、溶解させた。(B)の混合物に、(A)の混合物を加えて可溶化させた。
(A)POE(20)ソルビタン
モノラウリン酸エステル 1.5
POE(20)ラウリルエステル 0.5
エタノール 10.0
γ−トコフェロール 0.02
化合物3 0.25
(B)グリセリン 5.0
プロピレングリコール 4.0
イソフェルラ酸ナトリウム 0.05
クエン酸 0.15
クエン酸ナトリウム 0.1
精製水 78.43
<Example 11>
A lotion was prepared according to the formulation shown below. Each component of (A) was mixed and dissolved at room temperature. On the other hand, each component of (B) was mixed and dissolved at room temperature. To the mixture of (B), the mixture of (A) was added and solubilized.
(A) POE (20) Sorbitan
Monolaurate 1.5
POE (20) lauryl ester 0.5
Ethanol 10.0
γ-tocopherol 0.02
Compound 3 0.25
(B) Glycerin 5.0
Propylene glycol 4.0
Sodium isofellrate 0.05
Citric acid 0.15
Sodium citrate 0.1
Purified water 78.43
<実施例12>
下記に示す処方に従ってパック料を作製した。(A)の各成分を室温にて分散溶解させ、これに(B)の混合物を加えて均一に溶解させた。
(A)ポリビニルアルコール 15
精製水 40
(B)ビザボロール 0.5
γ−ココフェロール 0.02
エタノール 4
化合物4 3
POE(8)ポリオキシプロピレングリコール 3
精製水 34.48
<Example 12>
A pack charge was prepared according to the formulation shown below. Each component of (A) was dispersed and dissolved at room temperature, and the mixture of (B) was added thereto and dissolved uniformly.
(A) Polyvinyl alcohol 15
Purified water 40
(B) Visaborol 0.5
γ-Cocopherol 0.02
Ethanol 4
Compound 4 3
POE (8) polyoxypropylene glycol 3
Purified water 34.48
<実施例13>
下記に示す処方に従ってパック料を作製した。(A)の各成分を室温にて分散溶解させ、これに(B)の混合物を加えて均一に溶解させた。
(A)ポリビニルアルコール 15
精製水 40
(B)ビザボロール 0.5
γ−ココフェロール 0.02
エタノール 4
化合物5 3
POE(8)ポリオキシプロピレングリコール 3
精製水 34.48
<Example 13>
A pack charge was prepared according to the formulation shown below. Each component of (A) was dispersed and dissolved at room temperature, and the mixture of (B) was added thereto and dissolved uniformly.
(A) Polyvinyl alcohol 15
Purified water 40
(B) Visaborol 0.5
γ-Cocopherol 0.02
Ethanol 4
Compound 5 3
POE (8) polyoxypropylene glycol 3
Purified water 34.48
<実施例14>
下記に示す処方に従ってパック料を作製した。(A)の各成分を室温にて分散溶解させ、これに(B)の混合物を加えて均一に溶解させた。
(A)ポリビニルアルコール 15
精製水 40
(B)ビザボロール 0.5
γ−ココフェロール 0.02
エタノール 4
化合物6 3
POE(8)ポリオキシプロピレングリコール 3
精製水 34.48
<Example 14>
A pack charge was prepared according to the formulation shown below. Each component of (A) was dispersed and dissolved at room temperature, and the mixture of (B) was added thereto and dissolved uniformly.
(A) Polyvinyl alcohol 15
Purified water 40
(B) Visaborol 0.5
γ-Cocopherol 0.02
Ethanol 4
Compound 6 3
POE (8) polyoxypropylene glycol 3
Purified water 34.48
<実施例15>
下記に示す処方に従ってパック料を作製した。すなわち、(A)の各成分を室温にて分散溶解させ、これに(B)の混合物を加えて均一に溶解させた。
(A)ポリビニルアルコール 15
精製水 40
(B)ビザボロール 0.5
γ−ココフェロール 0.02
エタノール 4
化合物7 3
POE(8)ポリオキシプロピレングリコール 3
精製水 34.48
<Example 15>
A pack charge was prepared according to the formulation shown below. That is, each component of (A) was dispersed and dissolved at room temperature, and the mixture of (B) was added thereto and dissolved uniformly.
(A) Polyvinyl alcohol 15
Purified water 40
(B) Visaborol 0.5
γ-Cocopherol 0.02
Ethanol 4
Compound 7 3
POE (8) polyoxypropylene glycol 3
Purified water 34.48
<実施例16>
下記に示す処方に従ってパック料を作製した。(A)の各成分を室温にて分散溶解させ、これに(B)の混合物を加えて均一に溶解させた。
(A)ポリビニルアルコール 15
精製水 40
(B)ビザボロール 0.5
γ−ココフェロール 0.02
エタノール 4
化合物8 3
POE(8)ポリオキシプロピレングリコール 3
精製水 34.48
<Example 16>
A pack charge was prepared according to the formulation shown below. Each component of (A) was dispersed and dissolved at room temperature, and the mixture of (B) was added thereto and dissolved uniformly.
(A) Polyvinyl alcohol 15
Purified water 40
(B) Visaborol 0.5
γ-Cocopherol 0.02
Ethanol 4
Compound 8 3
POE (8) polyoxypropylene glycol 3
Purified water 34.48
<試験例>
本発明のベンゾフラン誘導体の色素細胞の淡色化試験(試験例1〜2)
<試験例1>
プラスチック培養フラスコ(25cm2)24本それぞれに、10%牛胎児血清を含むイーグルMEM培地を5ml入れ、このフラスコ内の培地にそれぞれ培地1ml当たり1.8×104個のマウスメラノーマ細胞(B−16細胞)を播種し、5%二酸化炭素雰囲気下、37℃で一昼夜培養を行った。その後、前記、フラスコを3本ずつ8組に分け、そのうち4組には化合物1のDMSO(ジメチルスルフォキシド)溶液を、培地中における化合物1の濃度が2,5,10,20μMとなるように添加し、また別の3組にはチロシナーゼ阻害剤として知られるフェニルチオウレアのDMSO溶液を、培地中におけるフェニルチオウレアの濃度がそれぞれ20,50,100μMとなるように添加し、さらに残りの1組にはDMSO溶液のみを添加し、上記培養と同様の条件(37℃、5%CO2)でさらに2日間培養した。なお、化合物1の濃度2μMは0.000068質量%に該当する。
<Test example>
Lightening test of pigment cells of benzofuran derivative of the present invention (Test Examples 1-2)
<Test Example 1>
In each of 24 plastic culture flasks (25 cm 2 ), 5 ml of Eagle's MEM medium containing 10% fetal calf serum was placed, and 1.8 × 10 4 mouse melanoma cells (B− 16 cells) was seeded and cultured overnight at 37 ° C. in a 5% carbon dioxide atmosphere. Thereafter, the flasks are divided into 8 groups of 3 flasks, 4 groups of which have a DMSO (dimethyl sulfoxide) solution of Compound 1 so that the concentration of Compound 1 in the medium is 2, 5, 10, 20 μM. In another three groups, a DMSO solution of phenylthiourea known as a tyrosinase inhibitor was added so that the concentrations of phenylthiourea in the medium were 20, 50 and 100 μM, respectively, and the remaining one group Was added with DMSO solution alone, and further cultured for 2 days under the same conditions (37 ° C., 5% CO 2) as above. The concentration of Compound 1 of 2 μM corresponds to 0.000068% by mass.
培養終了後、上記各培養フラスコから培養液を除去し、PBS(リン酸緩衝生理食塩水溶液)で洗浄後、トリプシン及びEDTA含有溶液を使用してフラスコ壁面より細胞を剥離し細胞懸濁液とし、遠心分離にて細胞を回収した。この際、各フラスコ毎に、回収した細胞の量を肉眼観察で測定した。 After completion of the culture, the culture solution is removed from each of the above culture flasks, washed with PBS (phosphate buffered saline solution), and then cells are detached from the flask wall using a trypsin and EDTA-containing solution to obtain a cell suspension. Cells were collected by centrifugation. Under the present circumstances, the quantity of the collect | recovered cell was measured by visual observation for every flask.
DMSO溶液のみを添加した場合の細胞量に対する、化合物1を添加したフラスコにおける細胞量の百分率をそれぞれ求め、さらに各濃度においてフラスコ3本の平均値を求めた。得られた値を以下の評価基準によって評価した。結果を表1に示す。 The percentage of the amount of cells in the flask to which Compound 1 was added relative to the amount of cells when only the DMSO solution was added was determined, and the average value of the three flasks was determined at each concentration. The obtained value was evaluated according to the following evaluation criteria. The results are shown in Table 1.
(評価基準)
→ :100%(コントロールと同等)
↓ :80%以上100%未満
↓↓:50%以上80%未満
↓↓↓:50%未満
死滅 :細胞が確認できない
(Evaluation criteria)
→: 100% (equivalent to control)
↓: 80% or more and less than 100%
↓↓: 50% or more and less than 80% ↓↓↓: Less than 50% killed: cells cannot be confirmed
また、上記回収された化合物1添加の各フラスコにおける細胞について、その色調を、コントロール及びフェニルチオウレア添加のフラスコにおける回収細胞の各添加濃度毎の平均的な色調と比較して、以下の評価基準により評価した。この結果も表1に示す。
(評価基準)
− :コントロールの細胞と同等の色調
± :フェニルチオウレア20.0μM添加の細胞と同等の色調
+ :フェニルチオウレア50.0μM添加の細胞と同等の色調
++:フェニルチオウレア100.0μM添加の細胞と同等の色調
In addition, the color tone of the cells in each flask to which the compound 1 was added was compared with the average color tone for each added concentration of the recovered cells in the flask to which the control and phenylthiourea had been added. evaluated. The results are also shown in Table 1.
(Evaluation criteria)
−: Color tone equivalent to control cell ±: Color tone equivalent to cell added with phenylthiourea 20.0 μM +: Color tone equivalent to cell added with phenylthiourea 50.0 μM ++: Same color as cell added with phenylthiourea 100.0 μM Color
ここで、マウスメラノーマ培養細胞の色調は、培養の際に添加されたフェニルチオウレアの量が多いほど、淡色化の度合いが大きい。 Here, the color tone of the mouse melanoma cultured cells increases as the amount of phenylthiourea added at the time of culture increases.
<試験例2>
試験例1と同様の試験を、試験例1における化合物1を、化合物2〜化合物8にそれぞれ置換して行った。その結果を表2から8に示す。
<Test Example 2>
A test similar to Test Example 1 was conducted by replacing Compound 1 in Test Example 1 with Compound 2 to Compound 8, respectively. The results are shown in Tables 2 to 8.
本発明の化粧料の実使用テスト(試験例3)
<試験例3>
次に、上記の結果を踏まえ、本発明の皮膚外用剤の、皮膚色素沈着症の予防及び改善に対する効果を調べた。実施例9で製造した水中油型クリームを用いて、長期連続使用による実使用テストを行い、その効力を確認した。比較品としては、実施例9における化合物1を精製水に置き換えて調製した水中油型クリームを用いた。
Actual use test of cosmetics of the present invention (Test Example 3)
<Test Example 3>
Next, based on the above results, the effect of the external preparation for skin of the present invention on the prevention and improvement of skin pigmentation was examined. Using the oil-in-water cream produced in Example 9, a long-term continuous use test was conducted to confirm its efficacy. As a comparative product, an oil-in-water cream prepared by replacing Compound 1 in Example 9 with purified water was used.
即ち、色黒、シミ、ソバカスに悩む女性ボランティア40名を、統計的に同等な2群に分け、A群の顔面には、本発明品である後記実施例3の水中油型クリームを、B群の顔面
には比較品の水中油型クリームをそれぞれ3ヶ月間使用してもらった。3ヶ月後の色素沈着に対する改善効果を肉眼観察により評価し、群間比較を行った。その結果を表9に示す。尚、有効率はやや有効以上の効果が認められた場合を有効とした。
That is, 40 female volunteers suffering from darkness, stains, and freckles are divided into two statistically equivalent groups, and the oil-in-water cream of Example 3 below, which is the product of the present invention, is applied to the face of Group A, B The group's face was each used a comparative oil-in-water cream for 3 months. The improvement effect on pigmentation after 3 months was evaluated by visual observation, and comparison between groups was performed. The results are shown in Table 9. The effective rate was determined to be effective when an effect slightly higher than the effective rate was recognized.
表9の結果に示されるように、本発明の皮膚外用剤の有効率は80%であり、比較品の皮膚外用剤の有効率15%に比べて、格段に有効な色素沈着症の予防及び改善効果を有することが証明された。なお、本発明品の塗布部位において好ましくない反応は観察されず、本発明品の外用剤は、安全性の高いことも併せて確認された。 As shown in the results of Table 9, the effective rate of the external preparation for skin of the present invention is 80%, which is much more effective in preventing pigmentation and the effective rate of 15% for the external preparation for comparison. It was proved to have an improvement effect. In addition, the reaction which is not preferable in the application | coating site | part of this invention product was not observed, and it was also confirmed that the external preparation of this invention product has high safety | security.
本発明は、美白用の化粧料などの皮膚外用剤に応用できる。 The present invention can be applied to skin external preparations such as whitening cosmetics.
Claims (4)
2,3−ジヒドロ−2−(3',4'−ジメトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物1)、
2−(3',4'−ジメトキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物2)、
2,3−ジヒドロ−2−(3',4'−ジメトキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物3)、
2−(3',4'−ジメトキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物4)、
2−(3',4'−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物5)、
2,3−ジヒドロ−2−(3',4'−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−プロピルベンゾフラン(化合物6)、
2−(3',4'−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−(1
−プロペニル)ベンゾフラン(化合物7)、および
2,3−ジヒドロ−2−(3',4'−メチレンジオキシフェニル)−7−メトキシ−3−メチル−5−(1−プロペニル)ベンゾフラン(化合物8)
から選ばれる少なくとも1つである、請求項1に記載の美白化粧料。
2,3-dihydro-2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (compound 1),
2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (compound 2),
2,3-dihydro-2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 3),
2- (3 ′, 4′-dimethoxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 4),
2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 5),
2,3-dihydro-2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5-propylbenzofuran (compound 6),
2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5- (1
-Propenyl) benzofuran (compound 7), and 2,3-dihydro-2- (3 ′, 4′-methylenedioxyphenyl) -7-methoxy-3-methyl-5- (1-propenyl) benzofuran (compound 8) )
The whitening cosmetic according to claim 1, wherein the whitening cosmetic is at least one selected from the group consisting of:
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Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS54138530A (en) * | 1978-03-22 | 1979-10-27 | Pharmaceutical Licences Co | Dilignol and dilignol analogur compound as hepatitis therapeutically active substance |
JPH03263481A (en) * | 1990-03-13 | 1991-11-22 | Kanebo Ltd | Eliminating agent of active oxygen |
JPH05306214A (en) * | 1992-04-24 | 1993-11-19 | Mikimoto Pharmaceut Co Ltd | Cosmetic |
JPH06271454A (en) * | 1993-03-23 | 1994-09-27 | Kanebo Ltd | Skin cosmetic |
JPH0892053A (en) * | 1994-09-20 | 1996-04-09 | Tsuneo Nanba | External preparation for skin |
JP2001223725A (en) * | 2000-02-10 | 2001-08-17 | Nec Eng Ltd | Ring system constituting device |
JP2003055184A (en) * | 2001-08-08 | 2003-02-26 | Nonogawa Shoji Kk | Skin care preparation |
JP2003081749A (en) * | 2001-09-13 | 2003-03-19 | Nonogawa Shoji Kk | Skin care preparation |
JP2003095857A (en) * | 2001-09-26 | 2003-04-03 | Nonogawa Shoji Kk | Skin care preparation |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9716244D0 (en) * | 1997-07-31 | 1997-10-08 | Electrophoretics International | Pharmaceutical compounds |
KR20040074994A (en) * | 2001-12-05 | 2004-08-26 | 가부시키가이샤 사카모토 바이오 | Melanogenesis inhibitors and whitening agents comprising egonol derivatives and compositions containing egonol derivatives |
-
2004
- 2004-04-22 JP JP2004127055A patent/JP4568527B2/en not_active Expired - Lifetime
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS54138530A (en) * | 1978-03-22 | 1979-10-27 | Pharmaceutical Licences Co | Dilignol and dilignol analogur compound as hepatitis therapeutically active substance |
JPH03263481A (en) * | 1990-03-13 | 1991-11-22 | Kanebo Ltd | Eliminating agent of active oxygen |
JPH05306214A (en) * | 1992-04-24 | 1993-11-19 | Mikimoto Pharmaceut Co Ltd | Cosmetic |
JPH06271454A (en) * | 1993-03-23 | 1994-09-27 | Kanebo Ltd | Skin cosmetic |
JPH0892053A (en) * | 1994-09-20 | 1996-04-09 | Tsuneo Nanba | External preparation for skin |
JP2001223725A (en) * | 2000-02-10 | 2001-08-17 | Nec Eng Ltd | Ring system constituting device |
JP2003055184A (en) * | 2001-08-08 | 2003-02-26 | Nonogawa Shoji Kk | Skin care preparation |
JP2003081749A (en) * | 2001-09-13 | 2003-03-19 | Nonogawa Shoji Kk | Skin care preparation |
JP2003095857A (en) * | 2001-09-26 | 2003-04-03 | Nonogawa Shoji Kk | Skin care preparation |
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