JP6113171B2 - アルキルアミドチアゾール、前記アルキルアミドチアゾールを含有する化粧または皮膚科学的製剤および好ましくない皮膚色素沈着を治療もしくは予防するためのそれらの使用 - Google Patents
アルキルアミドチアゾール、前記アルキルアミドチアゾールを含有する化粧または皮膚科学的製剤および好ましくない皮膚色素沈着を治療もしくは予防するためのそれらの使用 Download PDFInfo
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- JP6113171B2 JP6113171B2 JP2014531196A JP2014531196A JP6113171B2 JP 6113171 B2 JP6113171 B2 JP 6113171B2 JP 2014531196 A JP2014531196 A JP 2014531196A JP 2014531196 A JP2014531196 A JP 2014531196A JP 6113171 B2 JP6113171 B2 JP 6113171B2
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- alkylamidothiazoles
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- 230000008859 change Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- RVOJTCZRIKWHDX-UHFFFAOYSA-N cyclohexanecarbonyl chloride Chemical compound ClC(=O)C1CCCCC1 RVOJTCZRIKWHDX-UHFFFAOYSA-N 0.000 description 1
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- VJNCICVKUHKIIV-UHFFFAOYSA-N dopachrome Chemical compound O=C1C(=O)C=C2NC(C(=O)O)CC2=C1 VJNCICVKUHKIIV-UHFFFAOYSA-N 0.000 description 1
- 229960002852 ellagic acid Drugs 0.000 description 1
- 235000004132 ellagic acid Nutrition 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- 125000001033 ether group Chemical group 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 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 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 230000036074 healthy skin Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 208000031066 hyperpigmentation of the skin Diseases 0.000 description 1
- 230000003425 hypopigmentation Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- IGGVVGHJSQSLFO-UHFFFAOYSA-N indole-5,6-quinone Chemical compound O=C1C(=O)C=C2C=CNC2=C1 IGGVVGHJSQSLFO-UHFFFAOYSA-N 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 229940100554 isononyl isononanoate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940089456 isopropyl stearate Drugs 0.000 description 1
- 229940119170 jojoba wax Drugs 0.000 description 1
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 description 1
- 229960004705 kojic acid Drugs 0.000 description 1
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- FAARLWTXUUQFSN-UHFFFAOYSA-N methylellagic acid Natural products O1C(=O)C2=CC(O)=C(O)C3=C2C2=C1C(OC)=C(O)C=C2C(=O)O3 FAARLWTXUUQFSN-UHFFFAOYSA-N 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 201000010478 microphthalmia Diseases 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- BRZJGUCWMYTOQH-UHFFFAOYSA-N n-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2,2-dimethylpropanamide Chemical compound S1C(NC(=O)C(C)(C)C)=NC(C=2C(=CC(O)=CC=2)O)=C1 BRZJGUCWMYTOQH-UHFFFAOYSA-N 0.000 description 1
- WIDNAJNXDPHROL-UHFFFAOYSA-N n-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]-2-methylpropanamide Chemical compound S1C(NC(=O)C(C)C)=NC(C=2C(=CC(O)=CC=2)O)=C1 WIDNAJNXDPHROL-UHFFFAOYSA-N 0.000 description 1
- GJAJCTJPFQCGOS-UHFFFAOYSA-N n-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]acetamide Chemical compound S1C(NC(=O)C)=NC(C=2C(=CC(O)=CC=2)O)=C1 GJAJCTJPFQCGOS-UHFFFAOYSA-N 0.000 description 1
- XOZXNIDBYLWZSE-UHFFFAOYSA-N n-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]butanamide Chemical compound S1C(NC(=O)CCC)=NC(C=2C(=CC(O)=CC=2)O)=C1 XOZXNIDBYLWZSE-UHFFFAOYSA-N 0.000 description 1
- NCEWTGCKXFLYQP-UHFFFAOYSA-N n-[4-(2,4-dihydroxyphenyl)-1,3-thiazol-2-yl]cyclohexanecarboxamide Chemical compound OC1=CC(O)=CC=C1C1=CSC(NC(=O)C2CCCCC2)=N1 NCEWTGCKXFLYQP-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- QDAGIMDDJUTAFV-UHFFFAOYSA-N n-carbamothioyl-2-methylpropanamide Chemical compound CC(C)C(=O)NC(N)=S QDAGIMDDJUTAFV-UHFFFAOYSA-N 0.000 description 1
- JHPAWUKVLIURBU-UHFFFAOYSA-N n-carbamothioylbutanamide Chemical compound CCCC(=O)NC(N)=S JHPAWUKVLIURBU-UHFFFAOYSA-N 0.000 description 1
- QBXDTNRTUPZXCO-UHFFFAOYSA-N n-carbamothioylcyclohexanecarboxamide Chemical compound NC(=S)NC(=O)C1CCCCC1 QBXDTNRTUPZXCO-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- YDPSQMGOAILWPE-UHFFFAOYSA-N octadec-2-enedioic acid Chemical compound OC(=O)CCCCCCCCCCCCCCC=CC(O)=O YDPSQMGOAILWPE-UHFFFAOYSA-N 0.000 description 1
- 229960002446 octanoic acid Drugs 0.000 description 1
- BARWIPMJPCRCTP-UHFFFAOYSA-N oleic acid oleyl ester Natural products CCCCCCCCC=CCCCCCCCCOC(=O)CCCCCCCC=CCCCCCCCC BARWIPMJPCRCTP-UHFFFAOYSA-N 0.000 description 1
- 229940120511 oleyl erucate Drugs 0.000 description 1
- BARWIPMJPCRCTP-CLFAGFIQSA-N oleyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC BARWIPMJPCRCTP-CLFAGFIQSA-N 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- BJRNKVDFDLYUGJ-UHFFFAOYSA-N p-hydroxyphenyl beta-D-alloside Natural products OC1C(O)C(O)C(CO)OC1OC1=CC=C(O)C=C1 BJRNKVDFDLYUGJ-UHFFFAOYSA-N 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- PZQSQRCNMZGWFT-QXMHVHEDSA-N propan-2-yl (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC(C)C PZQSQRCNMZGWFT-QXMHVHEDSA-N 0.000 description 1
- ZPWFUIUNWDIYCJ-UHFFFAOYSA-N propan-2-yl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(C)C ZPWFUIUNWDIYCJ-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229920002545 silicone oil Polymers 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 210000000434 stratum corneum Anatomy 0.000 description 1
- 230000035882 stress Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 150000007979 thiazole derivatives Chemical class 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/46—Acylated amino or imino radicals by carboxylic acids, or sulfur or nitrogen analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/16—Emollients or protectives, e.g. against radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/44—Acylated amino or imino radicals
- C07D277/48—Acylated amino or imino radicals by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof, e.g. carbonylguanidines
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Toxicology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cosmetics (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
R1、R2、XおよびYは、異なるか、ある程度同じか或は完全に同じであってもよく、互いに独立して、下記を意味してもよく:
R1=−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖および分枝)、−C1−C8−シクロアルキル、−C1−C8−シクロアルキル−アルキルヒドロキシ、−C1−C24−アルキルヒドロキシ(直鎖および分枝)、−C1−C24 アルキルアミン(直鎖および分枝)、−C1−C24−アルキルアリール(直鎖および分枝)、−C1−C24−アルキルアリール−アルキル−ヒドロキシ(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、−C1−C24−アルキル−O−C1−C24−アルキル(直鎖および分枝)、−C1−C24 アルキ−モルホリノ、−C1−C24 アルキ−ピペリジノ、−C1−C24 アルキ−ピペラジノ、−C1−C24 アルキ−ピペラジノ−N−アルキル、
R2=H、−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖
および分枝)、−C1−C8−シクロアルキル、−C1−C24−ヒドロキシアルキル(直鎖および分枝)、−C1−C24−アルキルアリール(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、
X=−H、−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖および分枝)、−C1−C8−シクロアルキル、C1−C24−アリール(場合により−OH、−F、−Cl、−Br、−I、−OMe、−NH2、−CNで一置換もしくは多置換されてもよい)、−C1−C24−ヘテロアリール(場合により−OH、−F、−Cl、−Br、−I、−OMe、−NH2、−CNで一置換もしくは多置換されてもよい)、−C1−C24−アルキルアリール(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、−アリール(場合により−OH、−F、−Cl、−Br、−I、−OMe、−NH2、−CNで一置換もしくは多置換されてもよい)、−フェニル、−2,4−ジヒドロキシフェニル、−2,3−ジヒドロキシフェニル、−2,4−ジメトキシフェニル、−2,3−ジメトキシフェニル、
Y=H、−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖および分枝)、−C1−C8−シクロアルキル、−C1−C24−アリール、−C1−C24−ヘテロアリール、−C1−C24−アルキルアリール(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、−アリール、−フェニル、−2,4−ジヒドロキシフェニル、−2,3−ジヒドロキシフェニル、−2,4−ジメトキシフェニル、−2,3−ジメトキシフェニル、−COO−アルキル、−COO−アルケニル、−COO−シクロアルキル、−COO−アリール、−COO−ヘテロアリール、かつ
X、Yは場合によりまた縮合芳香族を意味してもよく、かつ
XおよびYは互いに一緒になって環形成原子数がn以下の芳香もしくは脂肪族単素もしくは複素環系を形成していてもよく、かつ数nは5から8の値を取ってもよくかつ個々の環系はn−1個以下のアルキル基、ヒドロキシル基、カルボキシル基、アミノ基、ニトリル官能基、硫黄含有置換基、エステル基および/またはエーテル基で置換されていてもよい]
で表されるアルキルアミドチアゾールにある。
X=
R1=−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖および分枝)、−C1−C8−シクロアルキル、−C1−C8−シクロアルキル−アルキルヒドロキシ、−C1−C24 アルキルヒドロキシ(直鎖および分枝)、−C1−C24 アルキルアミン(直鎖および分枝)、−C1−C24−アルキルアリール(直鎖および分枝)、−C1−C24−アルキルアリール−アルキル−ヒドロキシ(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、−C1−C24−アルキル−O−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルキ−モルホリノ、−C1−C24 アルキ−ピペリジノ、−C1−C24 アルキ−ピペラジノ、−C1−C24 アルキ−ピペラジノ−N−アルキル、
R2=H、−C1−C24−アルキル(直鎖および分枝)、
Z=−H、−OH、−F、−Cl、−Br、−I、−OMe、−NH2、−CN、アセチル、
である化合物である。
X=
R1=−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖および分枝)、−C1−C8−シクロアルキル、−C1−C8−シクロアルキル−アルキルヒドロキシ、−C1−C24−アルキルヒドロキシ(直鎖および分枝)、−C1−C24 アルキルアミン(直鎖および分枝)、−C1−C24−アルキルアリール(直鎖および分枝)、−C1−C24−アルキル−アリール−アルキル−ヒドロキシ(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、−C1−C24−アルキル−O−C1−C24−アルキル(直鎖および分枝)、−C1−C24 アルキ−モルホリノ、−C1−C24 アルキ−ピペリジノ、−C1−C24 アルキ−ピペラジノ、−C1−C24 アルキ−ピペラジノ−N−アルキル、
R2=H、
である化合物が好適である。
アミンおよびアミドを製剤に組み込む目的でそれらをブチレングリコールに場合により加熱しながら溶解させそして乳液に添加した後、最初の均一化を約65℃で実施した。あらゆる有効成分を実験バッチ中0.1%の濃度になるように混合した。
測定を受けさせるべきサンプルをメタノール/水混合物[70:30]に入れて抽出を実施した後、HPLC−DADで測定を実施した。その測定を外部標準較正を用いて実施した[参照章]。評価を296nmで実施した。
チアゾールが示す効果を酵素試験を用いて実証したが、この試験ではヒトチロシナーゼによるL−ドーパからL−ドーパキノンへの変換を測定した。この文献で公知の方法(Winder、A.J.およびHarris、H.、New assays for the tyrosine hydroxlase and dopaoxidase activities of tyrosinase、Eur.J.Biochem.(1991)、198、317−26)では、反応生成物であるL−ドーパキノンをMBTH(3−メチル−2−ベンゾチアゾリンヒドラゾン)と反応させてピンク色の物質を生じさせるが、その色の増加を経時的に490nmの所の吸収で測定する。表1に例として請求する物質のいくつかが示した効果データを示す。これによって本発明に従う物質は極めて有効な色素沈着抑制物質であると結論付けることができる。
2−ブロモ−2’,4’−ビスメトキシカルボニルオキシアセトフェノン:
)のNaOHを250mlの水に入れたものと混合した。撹拌を室温で30分間実施した後の反応溶液を300mlの水で取り上げた後、2NのHClで中和した。その結果として生じた沈澱物を濾過で取り出した後、エタノール/水を用いた再結晶化を実施した。80gのチアゾールを得た。1HNMR(DMSO−D6):11.77(bs、1H)、11.02(bs、1H)、9.47(bs、2H)、7.65(d、1H)、7.39(s、1H)、6.30(s、1H)、6.28(d、1H)、1.27(s、9H)ppm;融点257−259℃。
BANYU Pharmaceutical Co.Ltd.、EP2072519A1、2009
収量:96%.1H NMR(DMSO−D6):12.03(bs、1H)、3.85、3.82(2×d、2H)、2.50、2.47(2×m、1H)、2.00(s、3H)、0.95−1.90(m、9H)ppm
(br、2H)、7.64(d、1H)、7.39(s、1H)、6.29(m、2H)、4.40(br、1H)、3.32、3.23(2×d、2H)、2.65、2.44(2×m、1H)、1.90(m、1H)、1.78(m、2H)、1.50(m、5H)、0.94(m、1H)ppm;融点152−160℃。
BANYU Pharmaceutical Co.Ltd.、EP2072519A1、2009
収率:76%.1H NMR(DMSO−D6):12.31(bs、1H)、7.26(m、4H)、5.05(s、2H)、3.57(s、2H)、2.05(s、3H)ppm
しくない皮膚色素沈着の治療および/または予防で用いることも同様に本発明の有利な態様である。
−鉱油、鉱ろう
−油、例えばカプリン酸またはカプリル酸のトリグリセリドなど、また天然の油、例えばヒマシ油など、
−脂肪、ろうおよび他の天然および合成脂肪体、好適には脂肪酸と低炭素数のアルコール、例えばイソプロパノール、プロピレングリコールまたはグリセロールなどのエステル、または脂肪アルコールと低炭素数のアルカン酸もしくは脂肪酸のエステル、
−安息香酸アルキル、
−シリコーン油、例えばジメチルポリシロキサン、ジエチルポリシロキサン、ジフェニルポリシロキサンおよびこれらの混合物。
る如き乳化剤を含有して成る。
Claims (7)
- 遊離塩基または化粧的および皮膚科学的に使用可能な塩のいずれかとしての一般式
R1は−C1−C24−アルキル(直鎖および分枝)、−C1−C24−アルケニル(直鎖および分枝)、−C3−C8−シクロアルキル、−C3−C8−シクロアルキル−アルキルヒドロキシ、−C1−C24−アルキルヒドロキシ(直鎖および分枝)、−C1−C24アルキルアミン(直鎖および分枝)、−C1−C24−アルキルアリール−アルキル−ヒドロキシ(直鎖および分枝)、−C1−C24−アルキルヘテロアリール(直鎖および分枝)、−C1−C24−アルキル−O−C1−C24−アルキル(直鎖および分枝)、−C1−C24アルキル−モルホリノ、−C1−C24アルキル−ピペリジノ、−C1−C24アルキル−ピペラジノ、−C1−C24アルキル−ピペラジノ−N−アルキルであり、
R2はHであり、
Xは−2,4−ジヒドロキシフェニルであり、
YはHである。]
で表されるアルキルアミドチアゾール。 - ハロゲン化物、炭酸塩、アスコルビン酸塩、硫酸塩、酢酸塩または燐酸塩の形態で存在する請求項1記載のアルキルアミドチアゾール。
- 化粧もしくは皮膚科学製剤であって、請求項1記載の1種以上のアルキルアミドチアゾールを含有する製剤。
- 請求項1記載の1種以上のアルキルアミドチアゾールを製剤の総重量を基準にして0.000001から10重量%含有する請求項4記載の製剤。
- 請求項1記載の1種以上のアルキルアミドチアゾールを製剤の総重量を基準にして0.0001から3重量%含有する請求項5記載の製剤。
- 請求項1記載の1種以上のアルキルアミドチアゾールを製剤の総重量を基準にして0.001から1重量%含有する請求項5記載の製剤。
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DE102011083259.9 | 2011-09-23 | ||
PCT/EP2012/068362 WO2013041526A1 (de) | 2011-09-23 | 2012-09-18 | Alkylamidothiazole, sie enthaltende kosmetische oder dermatologische zubereitungen und deren verwendung zur bekämpfung und prophylaxe unerwünschter pigmentierung der haut |
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DE102013204081A1 (de) * | 2013-03-11 | 2014-09-11 | Beiersdorf Ag | Wirkstoffkombinationen aus Alkylamidothiazolen und einen oder mehreren kosmetisch oder dermatologisch unbedenklichen Konservierungsmitteln |
RU2552529C1 (ru) * | 2013-11-29 | 2015-06-10 | Федеральное государственное бюджетное учреждение "Медицинский радиологический научный центр" Министерства здравоохранения Российской Федерации (ФГБУ МРНЦ Минздрава России) | Вазопрессорное средство |
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KR101700946B1 (ko) | 2014-11-11 | 2017-02-02 | 연세대학교 산학협력단 | Cxcr4 길항제를 포함하는 피부 색소침착의 예방 또는 개선용 조성물 |
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DE202018004125U1 (de) | 2018-09-05 | 2018-10-11 | Beiersdorf Ag | Alkylamidothiazole in Polypropylen-haltigen Packmitteln |
MX2022015522A (es) | 2020-06-15 | 2023-01-16 | Dsm Ip Assets Bv | Proceso para la elaboracion de alquilamidotiazoles. |
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