JP2019526565A - 脱色剤またはライトニング剤としての二フッ素化合物 - Google Patents
脱色剤またはライトニング剤としての二フッ素化合物 Download PDFInfo
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- JP2019526565A JP2019526565A JP2019510924A JP2019510924A JP2019526565A JP 2019526565 A JP2019526565 A JP 2019526565A JP 2019510924 A JP2019510924 A JP 2019510924A JP 2019510924 A JP2019510924 A JP 2019510924A JP 2019526565 A JP2019526565 A JP 2019526565A
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- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- GPKUICFDWYEPTK-UHFFFAOYSA-N methoxycyclohexatriene Chemical compound COC1=CC=C=C[CH]1 GPKUICFDWYEPTK-UHFFFAOYSA-N 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 239000004200 microcrystalline wax Substances 0.000 description 1
- 235000019808 microcrystalline wax Nutrition 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 231100000065 noncytotoxic Toxicity 0.000 description 1
- 230000002020 noncytotoxic effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000000574 octyl gallate Substances 0.000 description 1
- 235000010387 octyl gallate Nutrition 0.000 description 1
- NRPKURNSADTHLJ-UHFFFAOYSA-N octyl gallate Chemical compound CCCCCCCCOC(=O)C1=CC(O)=C(O)C(O)=C1 NRPKURNSADTHLJ-UHFFFAOYSA-N 0.000 description 1
- 235000019645 odor Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 239000002540 palm oil Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960005323 phenoxyethanol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000007686 potassium Nutrition 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical group 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000004051 prolonged sun exposure Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 235000019719 rose oil Nutrition 0.000 description 1
- 239000010666 rose oil Substances 0.000 description 1
- 239000008132 rose water Substances 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 208000031019 skin pigmentation disease Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229940031439 squalene Drugs 0.000 description 1
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N tetraethylene glycol Chemical compound OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 125000006000 trichloroethyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- 239000012178 vegetable wax Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000019386 wax ester Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 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
Classifications
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/235—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring and to a carbon atom of a ring other than a six-membered aromatic ring
- C07C43/253—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring and to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups
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- C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
- C07C43/29—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing halogen
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- 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
- A61K8/69—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing fluorine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P17/00—Drugs for dermatological disorders
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
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- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/74—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with rings other than six-membered aromatic rings being part of the carbon skeleton
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
- C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
- C07C217/90—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to a carbon atom of a six-membered aromatic ring, e.g. amino-diphenylethers
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Abstract
Description
R2はOH、OSiR13R14R15、OR16、OC(O)R17、OCO2R18、OC(O)NR19R20、OP(O)(OR21)2、OSO3R22、NH2、NHR33、またはNR33R34であり、
X1、X2、X3、X4およびX5は互いに独立して、水素原子、OH、OSiR23R24R25、OR26、OC(O)R27、OCO2R28、OC(O)NR29R30、OP(O)(OR31)2、またはOSO3R32であり、
R3、R4、R5、R13、R14、R15、R23、R24およびR25は、互いに独立して、(C1-C6)アルキル、アリ-ル、アリ-ル-(C1-C6)アルキルまたは(C1-C6)アルキル-アリ-ル基であり、
R6、R16およびR26は互いに独立して、O-保護基;または(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、(C3-C7)サイクロアルキル(C1-C6)アルキル、(5〜7員ヘテロサイクロアルキル)-(C1-C6)アルキル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記の基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1以上の基により場合によって置換されており、
R7、R8、R17、R18、R27およびR28は、互いに独立して、(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、(C3-C7)サイクロアルキル(C1-C6)アルキル、(5〜7員ヘテロサイクロアルキル)-(C1-C6)アルキル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記の基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1以上の基により場合によって置換されており、
R9、R10、R19、R20、R29およびR30は、互いに独立して、水素原子; N-保護基;または(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、(C3-C7)サイクロアルキル(C1-C6)アルキル、(5〜7員ヘテロサイクロアルキル)-(C1-C6)アルキル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記の基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1以上の基により場合によって置換されており、
R11、R12、R21、R22、R31およびR32は互いに独立して、水素原子または(C1-C6)アルキル基であり、
R33およびR34は互いに独立して、N-保護基;または(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、アリ-ル-(C1-C6)アルキル、ヘテロアリ-ル-(C1-C6)アルキル、(C1-C6)-アルキル-アリ-ルまたは(C1-C6)-アルキル-ヘテロアリ-ル基、前記の基がハロゲン原子、OH、COOHおよびCHOから選択される1以上の基により場合によって置換されている。)
本発明で使用される「化粧品的にまたは薬学的に許容される」は、化粧品または医薬組成物の調製に有用であるものに関し、これは一般に無毒性で安全であり、医薬および化粧品用途に許容される。
(1)塩酸、臭化水素酸、硫酸、硝酸、リン酸などの無機酸と形成される酸付加塩;あるいは、酢酸、ベンゼンスルホン酸、安息香酸、カンファ-スルホン酸、クエン酸、エタンスルホン酸、フマル酸、グルコヘプトン酸、グルコン酸、グルタミン酸、グリコ-ル酸、ヒドロキシナフトエ酸、2-ヒドロキシエタンスルホン酸、乳酸、マレイン酸、リンゴ酸、マンデル酸、メタンスルホン酸、ムコン酸、2-ナフタレンスルホン酸、プロピオン酸、サリチル酸、コハク酸、ジベンゾイル-L-酒石酸、酒石酸、p-トルエンスルホン酸、トリメチル酢酸、トリフルオロ酢酸などの有機酸で形成される酸付加塩、および
(2)親化合物中に存在する酸性プロトンが金属イオン、例えばアルカリ金属イオン(例えばNa+、K+またはLi+)、アルカリ土類金属イオン(Ca2+またはMg2+など)またはアルミニウムイオンで置換されている場合に形成される塩;または有機または無機塩基と配位結合する場合に形成され塩。許容される有機塩基としては、ジエタノ-ルアミン、エタノ-ルアミン、N-メチルグルカミン、トリエタノ-ルアミン、トロメタミンなどが挙げられる。許容される無機塩基には、水酸化アルミニウム、水酸化カルシウム、水酸化カリウム、炭酸ナトリウムおよび水酸化ナトリウムが含まれる。
式中、R1、X1、X2、X3、X4およびX5は上記または下記のとおりであり、R2bはNH2、NHR33、またはNR33R34であり、ただし、R33およびR34は上記または下記でのとおりである。したがって、R2bは、R2基であり、ただし、R2=NH2、NHR33、またはNR33R34。
R1は水素原子、OH、OR6、OC(O)R7、OCO2R8またはOC(O)NR9R10であり、
R2は、NH2、NHR33、NR33R34、OH、OR16、OC(O)R17、OCO2R18またはOC(O)NR19R20であり、特に、OH、OR16、OC(O)R17、OCO2R18またはOC(O)NR19R20である。
R1は水素原子、OHまたはOR6であり、
R2はNH2、NHR33、NR33R34、OHまたはOR16;より具体的にはNH2、OHまたはOR16であり、特にOHまたはOR16である。
ORX1、X2、X4、X5は同一で水素原子である。
ORX3はOH、OSiR23R24R25、OR26、OC(O)R27、OCO2R28、OC(O)NR29R30、OP(O)(OR31)2、またはOSO3R32であり、
R1は水素原子、OH、OSiR3R4R5、OR6、OC(O)R7、OCO2R8、OC(O)NR9R10、OP(O)(OR11)2、またはOSO3R12であり、
R2はNH2、NHR33、NR33R34、OH、OSiR13R14R15、OR16、OC(O)R17、OCO2R18、OC(O)NR19R20、OP(O)(OR21)2、またはOSO3R22であり、特に、OH、OSiR13R14R15、OR16、OC(O)R17、OCO2R18、OC(O)NR19R20、OP(O)(OR21)2、またはOSO3R22である。
X1、X2、X4、X5同一で水素原子であり、
X3はOH、OR26、OC(O)R27、OCO2R28またはOC(O)NR29R30であり、
R1は水素原子であり、OH、OR6、OC(O)R7、OCO2R8またはOC(O)NR9R10であり、
R2はNH2、NHR33、NR33R34、OH、OR16、OC(O)R17、OCO2R18またはOC(O)NR19R20;特にOH、OR16、OC(O)R17、OCO2R18またはOC(O)NR19R20である。
X1、X2、X4、X5は同一で水素原子であり、
X3はOHまたはOR26、例えばOHであり、
R1は水素原子、OHまたはOR6、例えばHまたはOHであり、
R2はNH2、NHR33、NR33R34、OHまたはOR16であり、
より具体的には、NH2、OHまたはOR16であり、特にOHまたはOR16であり、例えばOHである。
X1、X2、X4、X5は、同一で水素原子であり、
X3、R1およびR2同一でOHである。
X1、X2、X4、X5は同一で水素原子であり、
X3およびR2は同一でOHであり、
R1は水素原子である。
X1、X2、X4、X5は同一では水素原子であり、
X3はOHであり、
R2はNH2であり、
R1は水素原子である。
R6、R7、R8、R16、R17、R18、R26、R27およびR28は互いに独立して、(C1-C6)アルキル、アリ-ル、ヘテロアリ-ル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記の基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1つ以上の基により場合によって置換されている。
R9、R10、R19、R20、R29およびR30は互いに独立して、水素原子、または(C1-C6)アルキル、アリ-ル、ヘテロアリ-ル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基、この基はハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1つ以上の基により場合によって置換されている。
R33およびR34は互いに独立して、(C1-C6)アルキル、アリ-ル、ヘテロアリ-ル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記の基はハロゲン原子、OH、COOHおよびCHOから選択される1つ以上の基により場合によって置換されている。
R6、R7、R8、R16、R17、R18、R26、R27およびR28は互いに独立して、(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基であり、前記基はハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1つ以上の基により場合によって置換されている。
R9、R10、R19、R20、R29およびR30は互いに独立して、水素原子、または(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基であり、前記基はハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1つ以上の基により場合によって置換されている。
R33およびR34は互いに独立して、(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基であり、前記基がハロゲン原子、OH、COOHおよびCHOから選択される1つ以上の基により場合によって置換されている。
好ましくは、X1、X2、X3、X4、X5、R1およびR2の上記定義において、
R6、R7、R8、R16、R17、R18、R26、R27、R28、R33およびR34は互いに独立して、(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基であり、
R9、R10、R19、R20、R29およびR30は互いに独立して、水素原子、または(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基である。
例示された化合物7、8、15、16、16a、16b、21、26a、26b、28a、28b及びその化粧品的又は薬学的に許容される塩、特に例示された化合物7、8、15、16及びその化粧品的又は薬学的に許容される塩。
好ましくは、例示された化合物8、16、16a、16b、28a、28b及びその化粧品的又は薬学的に許容される塩、特に例示された化合物8、16及びその化粧品的又は薬学的に許容される塩から選択される。
フッ素化剤は、例えばDAST(ジエチルアミノサルファ-トリフルオリド)であり得る。フッ素化反応はジクロロメタン中で実施することができる。
式中、X1X、X2X、X3X、X4X、X5X、R1Xは上記のとおりであり、
Rはスルホネ-ト(例えばトリフレ-ト)などの脱離基であり、
R2Xは、上記のとおりに、場合によって保護された形のR2である。
X1X、X2X、X3X、X4X、X5X、R1X、およびR2Xのうちの少なくとも1つが保護された形である場合、1つ以上の脱保護ステップが必要であり得る。脱保護の条件は当業者に周知である(例えば、“Greene’s Protective Groups In Organic Synthesis”、 4th edition、 2007、 John Wiley & Sons、 Hoboken、 New Jersey)。
以下の略語が実施例において使用されている。
DAST:ジエチルアミノサルファ-トリフルオリド
DBU:1、8-ジアザビシクロ[5.4.0]ウンデカ-7-エン
DCM:ジクロロメタン
DMF:ジメチルホルムアミド
eq.:当量
ESI:エレクトロスプレ-イオン化
mCPBA:メタ-クロロペルオキシ安息香酸
NMR:核磁気共鳴
rt:室温
sat.aq:飽和水溶液
THF:テトラヒドロフラン
中間体化合物2の合成
19Fdec NMR (CDCl3、282.5MHz): -108.2(d、J=251Hz、1F); -113.4(d、J=251Hz、1F).
19Fdec NMR (CDCl3、282.5MHz): -102.4(d、J=274Hz、1F); -105.2(d、J=274Hz、1F).
19Fdec NMR (CDCl3、282.5MHz): -106.4(d、J=242Hz、1F); -116.3(brd、1F).
19Fdec (MeOD、282.5MHz): -104.7(brd、J=257Hz、1F); -106.8(brd、J=257Hz、1F).
19Fdec (MeOD、282.5MHz): -100.0 (d、J=246Hz、1F); -113.9(d、J=246Hz、1F).
19Fdec NMR (CDCl3、282.5MHz): -104.1 (d、J=241Hz、1F); -118.0 (brd、J=241Hz、1F).
19Fdec NMR (CDCl3、282.5MHz):-104.2 (brd、J=242Hz、1F);-118.2 (brd、J=242Hz、1F).
19Fdec NMR (CDCl3、282.5MHz):
22a:-103.8(d、J=239Hz、1F、CF2);-120.0 (d、J=240Hz、1F、CF2).
22b:-103.8 (d、J=238Hz、1F、CF2); -119.8 (d、J=238Hz、1F、CF2).
同じ条件下で22b(1当量、3.63g、14.2mmol)から粗23b(2.78g、104%)を得た。
19Fdec NMR (CDCl3、282.5MHz):-106.1 (d、J=242Hz、1F、CF2);-121.8 (d、J=242Hz、1F、CF2).
19Fdec NMR (CDCl3、285.5MHz):-105.1 (d、J=243Hz、1F、CF2); -118.2 (brd、J=243Hz、1F、CF2).
25b(4.21g、3つのステップで71%)を24b(1当量、4.74g、16.61mmol)から同じ条件下で得た。
19Fdec NMR (CDCl3、285.5MHz): -74.5 (d、J=9Hz、CF3); -102.3 (d、J1=246Hz、1F、CF2); -115、5 (d、J=246Hz、1F、CF2).
19Fdec NMR(CDCl3、285.5MHz):-101.1 (d、J=242Hz、1F、CF2);-117.0(d、J=242Hz、1F、CF2).
26b(333mg、1mmol)から同じ条件下で28b(140mg、2つのステップで58%)を得た。
19Fdec NMR (MeOD、285.5MHz): -101.4 (d、J=243Hz、1F、CF2); -117.4 (brd、J=243Hz、1F、CF2).
ヒトチロシナ-ゼ阻害剤としての化合物8のin vitro有効性
化合物8の有効性は、ヒトチロシナ-ゼのin-tuboの阻害によって評価され、先行技術の化合物デオキシアルブチンと比較された。
アッセイは、Feldan Inc(Canada)からのすぐに使えるキット:HumanLike Tyrosinase Assayキット(ref A021-a-001 Kit)を用いて実施した。
化合物8およびデオキシアルブチンは1.12mMの最終濃度で試験された。490nmで測定された吸光度を表1に示し、図1に時間の関数としてプロットした。
方法
ヒトメラニン細胞は、メラニン合成の増加を誘導するためにL-チロシンによって刺激され、ホワイトニング剤が添加されたときにこの合成の阻害を測定することができる。
試験した濃度:
メラニン合成の潜在的な阻害を評価するために使用されるべきより高い非細胞傷害性濃度を決定するために、化合物をNHEM培養物上で異なる濃度で予め試験した。決定された濃度は全ての化合物(化合物8、16および28a)について300μMであった。結果は表3に示されている。
試験した化合物28a、8および16は、メラニン合成をそれぞれ10.2μg/ml、9.3μg/mlおよび8.1μg/mlに減少させることによって高い阻害効果を示した。
Claims (22)
- 下記式Iを有する化合物、
(ただし、
R1は、水素原子、OH、OSiR3R4R5、OR6、OC(O)R7、OCO2R8、OC(O)NR9R10、OP(O)(OR11)2、またはOSO3R12であり、
R2は、OH、OSiR13R14R15、OR16、OC(O)R17、OCO2R18、OC(O)NR19R20、OP(O)(OR21)2、OSO3R22、NH2、NHR33、またはNR33R34であり、
X1、X2、X3、X4およびX5は、互いに独立して、水素原子、OH、OSiR23R24R25、OR26、OC(O)R27、OCO2R28、OC(O)NR29R30、OP(O)(OR31)2またはOSO3R32であり、
ここで、
R3、R4、R5、R13、R14、R15、R23、R24およびR25は互いに独立して、(C1-C6)アルキル、アリ-ル、アリ-ル-(C1-C6)アルキルまたは(C1-C6)アルキル-アリ-ル基であり、
R6、R16およびR26は、互いに独立して、O-保護基;または(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、(C3-C7)サイクロアルキル(C1-C6)アルキル、(5〜7員ヘテロシクロアルキル)-(C1-C6)アルキル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1つ以上の基により場合によって置換されており、
R7、R8、R17、R18、R27およびR28は、互いに独立して、(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、(C3-C7)サイクロアルキル(C1-C6)アルキル、(5〜7員ヘテロサイクロアルキル)-(C1-C6)アルキル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1以上の基により場合によって置換されており、
R9、R10、R19、R20、R29およびR30は、互いに独立して、水素原子;N-保護基;または(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、(C3-C7)サイクロアルキル(C1-C6)アルキル、(5〜7員ヘテロサイクロアルキル)-(C1-C6)アルキル、アリ-ル-(C1-C6)アルキルまたはヘテロアリ-ル-(C1-C6)アルキル基であり、前記基がハロゲン原子、(C1-C6)アルキル基および(C1-C6)アルコキシ基から選択される1以上の基により場合によって置換されており、
R11、R12、R21、R22、R31およびR32は、互いに独立して、水素原子または(C1-C6)アルキル基であり、
R33およびR34は、互いに独立して、N-保護基;または(C1-C6)アルキル、(C2-C6)アルケニル、(C2-C6)アルキニル、(C3-C7)サイクロアルキル、5〜7員ヘテロサイクロアルキル、アリ-ル、ヘテロアリ-ル、アリ-ル-(C1-C6)アルキル、ヘテロアリ-ル-(C1-C6)アルキル、(C1-C6)-アルキル-アリ-ルまたは(C1-C6)-アルキル-ヘテロアリ-ル基であり、前記基がハロゲン原子、OH、COOHおよびCHOから選択される1以上の基により場合によって置換されている。) - 下記式Iaを有する化合物である、請求項1に記載の化合物、
(ただし、
R1、X1、X2、X3、X4およびX5は、請求項1に記載のとおりであり、
R2aは、OH、OSiR13R14R15、OR16、OC(O)R17、OCO2R18、OC(O)NR19R20、OP(O)(OR21)2、またはOSO3R22であり、
R13〜R22は、請求項1に記載のとおりである。) - 下記式Ibを有する化合物である、請求項1に記載の化合物、
(ただし、
R1、X1、X2、X3、X4およびX5は、請求項1に記載のとおりであり、
R2bはNH2、NHR33、またはNR33R34であり、
R33およびR34は請求項1に記載のとおりである。) - R1は、水素原子、OH、OR6、OC(O)R7、OCO2R8またはOC(O)NR9R10である、より具体的に、水素原子、OHまたはOR6である、請求項1〜3のいずれか一項に記載される化合物。
- R2は、NH2、NHR33、NR33R34、OH、OR16、OC(O)R17、OCO2R18またはOC(O)NR19R20である、より具体的にNH2、NHR33、NR33R34、OHまたはOR16である、請求項1〜4のいずれか一項に記載される化合物。
- X1、X2、X3、X4およびX5は、互いに独立して、水素原子、OH、OR26、OC(O)R27、OCO2R28、またはOC(O)NR29R30である、好ましくは、水素原子、OHまたはOR26である、請求項1〜5のいずれか一項に記載される化合物。
- X1、X2、X3、X4およびX5のうちの少なくも一つは水素原子以外の基である、請求項1〜6のいずれか一項に記載される化合物。
- X3が水素原子以外の基である、請求項7に記載の化合物。
- X1、X2、X4およびX5はそれぞれ水素原子であり、X3は水素原子以外の基である、請求項8に記載の化合物。
- X1、X2、X4およびX5はそれぞれ水素原子であり、
X3はOHまたはOR26であり、特にOHであり、
R1はH、OHまたはOR6であり、特にHまたはOHであり、
R2はNH2、NHR33、NR33R34、OHまたはOR16であり、特にNH2またはOHである、請求項9に記載の化合物。 - R6、R7、R8、R16、R17、R18、R26、R27、R28、R33およびR34は、互いに独立して、(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基であり、
R9、R10、R19、R20、R29およびR30は、互いに独立して、水素原子、または(C1-C6)アルキル、アリ-ルまたはアリ-ル-(C1-C6)アルキル基である、請求項1〜10のいずれか一項に記載の化合物。 - 下記
- 下記
- 請求項1から13のいずれか一項に記載の少なくとも1つの化合物および少なくとも1つの化粧品的にまたは薬学的に許容される賦形剤を含む化粧品または医薬組成物。
- 脱色剤、ライトニング剤、漂白剤またはホワイトニング剤としての、特に皮膚用の、請求項1〜13のいずれか1項に記載の化合物の化粧品使用。
- 薬物として使用するための、請求項1〜13のいずれか一項に記載の化合物。
- 色素沈着障害の治療に使用するための、請求項1〜13のいずれか一項に記載の化合物。
- 色素沈着障害が、レンチゴもしくはメラズマなどの色素沈着過剰であり、特に太陽への過剰暴露、炎症、損傷、火傷、医薬品、またはホルモン変化に起因する、請求項17に記載の使用のための化合物。
- 化合物の製造方法であって、
下記式IIの化合物
(ただし、
X1X、X2X、X3X、X4X、X5X、R1XおよびR2Xはそれぞれ請求項1に記載のX1、X2、X3、X4、X5、R1およびR2であり、場合によって保護された形であり、Rは脱離基、特にトリフレ-トなどのスルホネ-トである)、
R1、R2、X1、X2、X3、X4および/またはX5の基が保護された形にある場合にそれらを脱保護するステップと、
場合によって、前記ステップで得られた式Iの化合物を塩化して、式Iの化合物の化粧品的にまたは薬学的に許容される塩を得るステップと、を含む請求項1〜13のいずれか一項に記載の化合物の製造方法。 - 下記式XIの化合物のケトン官能基をフッ素化するステップと、
式中、X1X、X2X、X3X、X4X、X5X、R1XおよびR2Xは、それぞれ請求項1に記載のX1、X2、X3、X4、X5、R1およびR2であり、場合によって、保護された形である)
R1、R2、X1、X2、X3、X4および/またはX5の基が保護された形にある場合にそれらを脱保護するステップと、
前記ステップで得られた式Iの化合物を場合によって塩化して、式Iの化合物の化粧品的にまたは薬学的に許容される塩を得るステップと、を含む請求項1〜13のいずれか一項に記載の化合物の製造方法。 - 下記式XVの化合物のアルデヒド官能基を酸化するステップと、
式中、X1X、X2X、X4X、X5X、R1XおよびR2Xは、それぞれ請求項1に記載のX1、X2、X4、X5、R1およびR2であり、場合によって保護された形である)
R1、R2、X1、X2、X4および/またはX5の基が保護された形にある場合にそれらを脱保護するステップと、
前記ステップで得られた式Iの化合物を場合によって塩化して、式Iの化合物の化粧品的にまたは薬学的に許容される塩を得るステップと、を含み、
X3=OHである、請求項1〜13のいずれか一項に記載の化合物の製造方法。 - 式XVの化合物が、下記式XVIの化合物
式中X1X、X2X、X4XおよびX5Xは前記のとおりである)
を下記式XIVの化合物
式中R1XおよびR2Xは前記のとおりである)
と反応させることによって調製される、請求項21に記載の方法。
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