CN102985415B - 用于治疗色素沉着和皮肤衰老疾病的呫吨二酮衍生物 - Google Patents
用于治疗色素沉着和皮肤衰老疾病的呫吨二酮衍生物 Download PDFInfo
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- CN102985415B CN102985415B CN201180034125.0A CN201180034125A CN102985415B CN 102985415 B CN102985415 B CN 102985415B CN 201180034125 A CN201180034125 A CN 201180034125A CN 102985415 B CN102985415 B CN 102985415B
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- xanthene
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Abstract
本发明涉及通式（I）的化合物及其药学上或化妆品上可接受的盐，其中：R1和R2代表：OH、氢原子、C1-C6烷基基团、C1-C6烷氧基基团、卤素或OCOR3；R3代表：C1-C24烷基基团、包含至少一个不饱和度的C12-C24烯基基团；R4代表：COR5、被一个或多个乙酰基基团取代或未取代的糖基；R5代表：C10-C24烷基基团或包含至少一个不饱和度的C12-C24烯基基团；R6和R7代表：-同时为氢原子或甲基基团，或者-当R6代表氢原子时，R7代表C1-C6烷基基团或者被一个或多个C1-C3烷氧基基团或一个或多个卤素取代或未取代的苯基，或者-R6和R7连接在一起并形成C3-C6环烷基。
Description
技术领域
本发明涉及呫吨二酮衍生物和包括其的药物或化妆品组合物，其制备方法及其用途，特别是作为药物或作为化妆品的活性成分的用途。
背景技术
根据本发明的新化合物以呫吨二酮前体的形式得到。这些前体的用途在于能够使皮肤介质中的呫吨二酮官能团缓慢地释放。
一方面，它们可以是糖苷类，其源于葡萄糖和呫吨二酮官能团的缩合。
在这种情况下，本发明的原理与葡糖脑苷脂酶的用途有关，所述葡糖脑苷脂是存在于所有细胞中并因此天然存在于皮肤中的溶酶体酶(Yutaka Takagi,ErnstKriehuber,Genji Imokawa,Peter M.Elias,and Walter M.Holleran,β-Glucocerebrosidase activity in mammalian stratum corneum,The Journal of LipidResearch,Vol.40,861-869,(1999)。葡糖脑苷脂酶水解活性前体，从而释放生物学活性物质(参见方案1)，即呫吨二酮官能团。
通过葡糖脑苷脂酶的酶水解缓慢地释放呫吨二酮官能团。这种缓慢的释放能够避免活性成分的浓度过大。因此，活性成分的缓慢释放确保其在皮肤介质中更好的生物利用度，并因此确保更有效的保护。
另一方面，它们可以是呫吨二酮的烷基酯或烯基酯。所述酯也能够很容易地被存在于皮肤中的酯酶裂解(Redoules,D.,Tarroux,R.,Assalit,M.F.and Perié,J.J.Characterization and assay of five enzymatic activities in the stratum corneum usingtape-stripping,Skin Pharmacol.Appl.Skin Physiol.,12,182-192(1999))。所述酯被存在于皮肤中的酯酶裂解，然后该裂解使活性成分缓慢地扩散(参见方案1)，这对应于“药物递送”的概念。
方案1：通过皮肤的酯酶或葡糖脑苷脂酶的通式(I)的化合物的裂解。
发明内容
因此，本发明的目的在于下列通式(I)的化合物及其化妆品上或药学上可接受的盐：
其中：
·R1和R2同时或独自代表：OH、氢原子、C1-C6烷基基团、C1-C6烷氧基基团、卤素或OCOR3；
·R3代表：C1-C24烷基基团、包含至少一个不饱和度的C12-C24烯基基团，有利地所述不饱和度为从1到6并且优选从1到4；
·R4代表：COR5、被一个或多个乙酰基基团取代或未取代的糖基(glucide)；
·R5代表：C10-C24烷基基团，或包含至少一个不饱和度的C12-C24烯基基团，有利地所述不饱和度为从1到6并且优选从1到4；
·R6和R7代表：
-同时为氢原子或甲基基团，
或者
-当R6代表氢原子时，R7代表C1-C6烷基基团或者被一个或多个C1-C3烷氧基基团或一个或多个卤素取代或未取代的苯基，
或者
-R6和R7彼此连接并形成C3-C6环烷基。
定义：
根据本发明，“烷基基团”意指饱和的直链或支链脂肪族烃链并且其包含规定数目的碳原子。例如，可以引用的有甲基、乙基和丙基。特别地，所述烷基基团可以代表C1-C24的烃链，特别是C10-C24的饱和脂肪酸。
所述饱和脂肪酸可以是癸酸(10:0)、十一烷酸(11:0)、月桂酸(12:0)、十三烷酸(13:0)、肉豆蔻酸(14:0)、十五烷酸(15:0)、棕榈酸(16:0)、十七烷酸(17:0)、硬脂酸(18:0)、十九烷酸(19:0)、花生酸(20:0)、二十一烷酸(21:0)、山嵛酸(22:0)、二十三烷酸(23:0)、二十四烷酸(24:0)。特别地，所述饱和脂肪酸可以是棕榈酸和硬脂酸。
根据本发明，“烷氧基基团”意指包含指定数目的碳原子和氧原子的直链或支链烃链，例如甲氧基基团、乙氧基基团、丙氧基基团或丁氧基基团。
根据本发明，“烯基基团”意指包含指定数目的碳原子并且包含至少一个不饱和度(有利地为1至6并且优选1至4)的直链或支链烃链。根据本发明，“不饱和度”意指C＝C双键。
特别地，所述烯基基团可以代表源于包含至少一个不饱和度(有利地为1至6并且优选1至4)的C12-C24不饱和脂肪酸的烃链。
所述不饱和脂肪酸可以是月桂烯酸(C12:1)、肉豆蔻烯酸(C14:1)、棕榈烯酸(C16:1)、油酸(C18:1)、蓖麻油酸(C18:1)、鳕油酸(C20:1)、芥子酸(C22:1)、α-亚麻酸(C18:3)、十八碳四烯酸(C18:4)、二十碳三烯酸(C20:3)、二十碳四烯酸(C20:4)、二十碳五烯酸(C20:5)、二十二碳五烯酸(C22:5)、二十二碳六烯酸(C22:6)、二十四碳五烯酸(C24:5)、二十四碳六烯酸(C24:6)、亚油酸(C18:2)、γ-亚麻酸(C18:3)、二十碳二烯酸(C20:2)、二高-γ-亚麻酸(C20:3)、花生四烯酸(C20:4)、二十二碳二烯酸(C22:2)、二十二碳五烯酸(C22:5)、二十二碳四烯酸(C22:4)和十八碳三烯酸(C18:3)。特别地，所述不饱和脂肪酸可以是：α-亚麻酸(C18:3)、油酸(C18:1)、亚油酸(C18:2)、γ-亚麻酸(C18:3)和二高-γ-亚麻酸(C20:3)。
“乙酰基”意指乙酸的盐或酯。
卤素意指氯原子、氟原子、溴原子和碘原子。
根据本发明，“糖基”意指包括一个羰基基团(醛或酮)和多个羟基(-OH)基团的一类有机分子。
术语糖基、单糖、糖类(saccharide)、碳水化合物、糖类(sugars)在本发明中是等同的。
有利地，通式(I)的糖基选自单糖。
更有利地，通式(I)的糖基选自D系列(series D)的单糖。
甚至更有利地，通式(I)的糖基选自D系列的C3-C6单糖，如甘油醛、赤藓糖、苏阿糖、核糖、阿拉伯糖、木糖、来苏糖、阿洛糖、阿卓糖、古洛糖、艾杜糖、塔罗糖、葡萄糖、半乳糖、甘露糖、果糖及其衍生物，当它们存在时，如其环状形式，例如吡喃糖或呋喃糖型。本发明中优选的单糖是D-吡喃葡萄糖。如果α或β糖苷型键在糖基的异头碳上，那么所述糖基可以通过所述糖苷型键连接至呫吨二酮糖衍生物。如果在糖基的非异头碳的氧上形成简单的醚键，那么所述糖基也可以通过所述醚键连接至呫吨二酮衍生物。
根据本发明的实施方案，通式(I)的化合物是如下化合物：其中R1和R2同时或独自代表氢原子或C1-C6烷氧基基团。
根据本发明，通式(I)的化合物是如下化合物：其中R4代表COR5。
本发明还涉及通式(I)的化合物，其中R5代表C14-C18烷基基团或包含1至3个不饱和度的C14-C18烯基基团。
根据本发明的实施方案，通式(I)的化合物是如下化合物：其中R4代表被一个或多个乙酰基取代或未取代的糖类，特别地，所述糖基是吡喃糖基团，如果合适，其是部分或完全乙酰化的。
根据本发明，通式(I)的化合物是如下化合物：其中R6和R7同时代表甲基基团。
通式(I)的化合物可以选自下列的化合物：
-2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯基棕榈酸酯
-(9Z,12Z)-2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯基十八碳-9,12-二烯酸酯
-(3R,4S,5S)-2-(乙酰氧基甲基)-6-(2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
-9-(3-甲氧基-4-((3S,4S,5S)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
-(3S,4S,5S,6S)-2-(乙酰氧基甲基)-6-(2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
-9-(3-甲氧基-4-((2S,3S,4S,5R)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-l,8(2H)-二酮
-(3R,4S,5S,6S)-2-(乙酰氧基甲基)-6-(4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
-3,3,6,6-四甲基-9-(4-((2S,3S,4S,5S)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,4,5,6,7,9-六氢-lH-呫吨-1,8(2H)-二酮。
本发明还延伸至通式(I’)的化合物及其药学上或化妆品上可接受的盐，其用作药物或用作化妆品的活性成分：
其中基团R1、R2、R3、R4、R5、R6和R7具有与前述给定的基团相同的含义，但是其中R4可以另外代表氢原子或乙酰基基团。
本发明还涉及如上所定义的通式(I’)的化合物，其用于皮肤和/或头发和/或体毛的色素脱除，用于治疗和/或预防皮肤衰老，或者用于治疗和/或预防皮肤炎症。
本发明还涉及如上所定义的通式(I’)的化合物，其中R4代表氢原子，其用于皮肤和/或头发和/或体毛的色素脱除，用于治疗和/或预防皮肤衰老，或者用于治疗和/或预防皮肤炎症。
本发明涉及通式(I’)的化合物，其用作色素脱除活性成分、抗氧化活性成分或抗炎活性成分。
色素脱除活性可以通过根据本发明的不同类型的行为来显现，其通常在于减少和/或抑制负责色素沉着的黑色素的产生，或者在于减少树突中黑色素的运输：
减少和/或消除色素斑，如归因于促炎应激的色素过度沉着斑(例如，呈褐色的紫外线诱导的色素斑)和黄褐斑，或者；
漂白和/或亮化皮肤和/或体毛和/或头发，优先为了：
均衡肤色，其特征在于，获得均衡的、更明亮的、更透明的、更容光焕发的皮肤肤色。肤色光泽从而得到改善。所获得的优点特别有益于敏感皮肤而无论其性质(干性、中性、油性)，并且更加特别有益于晦暗和无光泽的敏感皮肤特别沉闷，和/或；
治疗归因于表皮色素过度沉着的某些难看的色素斑，尤其是如皮肤的老化斑点。然后，根据本发明的色素脱除活性导致色素斑的强度和尺寸的明显减少和/或预防出现另外的斑点。
本发明涉及通式(I’)的化合物，其中R4代表氢原子，其用作色素脱除活性成分、抗氧化活性成分或抗炎活性成分。
本发明还涉及包含通式(I’)的化合物的化妆品组合物的用途，其用于皮肤和/或头发和/或体毛的色素脱除，用于治疗和/或预防皮肤衰老，或者用于治疗和/或预防皮肤炎症。
本发明涉及漂白和/或亮化人类皮肤和/或体毛和/或头发的方法，所述方法包括将含有至少一种通式(I’)的化合物的化妆品组合物应用在皮肤和/或体毛和/或头发上。
本发明涉及治疗和/或预防皮肤衰老的美容方法，所述方法包括将含有至少一种通式(I’)的化合物的化妆品组合物应用在皮肤上。
本发明涉及治疗和/或预防皮肤炎症反应的美容方法，所述方法包括将含有至少一种通式(I’)的化合物的化妆品组合物应用在皮肤上。
本发明还延伸至合成通式(I)的化合物的方法，其特征在于，在酸性或碱性催化剂的存在下使两分子的1,3-二酮与醛反应：
其中R1、R2、R3、R4、R5、R6和R7具有与通式(I)中给定的基团相同的含义。
对于R4＝COR5的通式(I)的产品的合成而言，使苯酚与R5COCl活化的羧酸反应
其中R1、R2、R3、R5、R6和R7具有与通式(I)中给定的基团相同的含义。
对于R4＝被一个或多个乙酰基基团取代的糖基的通式(I)的产品的合成而言，使苯酚与被一个或多个乙酰基基团取代的糖基基团反应。
其中R1、R2、R3、R5、R6和R7具有与通式(I)中给定的基团相同的含义，如果合适，在所述反应之后可以进行皂化步骤。
具体实施方式
1)用于合成根据本发明的化合物的通用方案
实施例1：
-9-(4-羟基-3-甲氧基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
通用方案A
文献中描述了在酸催化或碱催化剂的存在下，起始于1,3-二酮和醛的一个或两个步骤中的呫吨二酮官能团的合成(S.Kantevari等人,Arkivoc 2006,136-148)(B.Das等人,Catalysis Communications 8(2007)535-538)。
向1.40g的5,5-二甲基-1,3-环己二酮(双甲酮，10mmol)和0.76g的香草醛(5mmol)在10mL乙腈中的混悬液中，加入0.63mL氯化三甲基硅烷(5mmol)。将混合物于110℃的温度下回流，观察到混悬液中颗粒的增溶而形成澄清的黄色溶液。反应6小时后，将溶液冷却至环境温度10分钟，然后在冰浴中放置10分钟。然后加入水，以沉淀由此获得的呫吨二酮。然后将混合物在烧结体上过滤，采用蒸馏水，然后是正戊烷淋洗。将固体在真空烘箱中于50mbar和40℃干燥至少一夜，以获得收率为79％的白色固体。
1H NMR(400MHz,CDC13):δ:1.00(s,6H)；1.10(s,6H)；2.20(dd,4H)；2.45(s,4H)；3.87(s,3H)；4.66(s,1H)；5.60(s,1H)；6.58(dd,1H)；6.72(d,1H)；6.99(d,1H).
13C NMR 100MHz,CDC13):δ:27.2；29.2；31.2；32.1；40.8；50.7；55.8；112.2；113.9；115.7；145.8；162.0；196.5.
MS(ESI+):397.1[M+H]+
Rf(庚烷/EtOAc；1/1):0.57
实施例2：
-9-(3,4-二羟基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,DMSO d6):δ:0.91(s,6H)；1.02(s,6H)；2.07(d,AB系统,2H)；2.23(d,AB系统,2H)；2.52(m,4H)；4.37(s,1H)；6.36(d,1H)；6.53(d,1H)；6.60(s,1H)；8,58(s,OH,1H)；8.7(s,OH,1H).
13C NMR(100MHz,DMSO d6):δ:26.4；28.6；30.0；31.7；50.0；114.8；114.9；115.8；118.4；135.3；143.4；144.4；162.3；195.9.
MS(APCI):383.2[M+H]+
Rf(1/1；庚烷/EtOAc):0.75
实施例3：
9-(4-羟基-3,5-二甲氧基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,DMSO d6):δ:0.93(s,6H)；1.03(s,6H)；2.10(d,AB系统,2H)；2.27(d,AB系统,2H)；2.52(m,4H)；3.66(s,6H)；4.44(s,1H)；6.36(s,2H)；8.1(s,OH,1H).
13C NMR(100MHz,DMSO d6):δ:26.1；28.7；30.6；31.7；49.9；55.8；105.6；114.4；124.9；134.1；134.4；147.4；162.6；196.0.
MS(ESI+):427.2[M+H]+
实施例4：
9-(3,4-二羟基苯基)-3,6-二苯基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDC13):δ:2.64(m,4H)；2.83(m,4H)；3.35(m,1H)；3.46(m,1H)；4.81(s,1H)；6.38-7.04(m,3H)；7.3(m,10H).
MS(APCI+):479.1[M+H]+
Rf(环己烷/EtOAc；1/1):0.38
实施例5：
9-(3,5-二叔丁基-4-羟基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:0.99(s,6H)；1.10(s,6H)；1.37(s,18H)；2.20(dd,4H)；2.45(dd,4H)；4.67(s,1H)；4.98(d,1H)；7.02(s,2H).
13C NMR(100MHz,CDCl3):δ:26.9；29.4；30.3；31.0；32.2；34.1；40.9；50.7；116.2；124.8；134.8；134.9；152.0；162.0；196.3.
MS(ESI+):479.3[M+H]+
Rf(庚烷/EtOAc；7/3):0.26
实施例6：
9-(4-羟基-3-甲氧基苯基)-3,6-二苯基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:2.66(m,4H)；2.87(m,4H)；3.30(m,1H)；3.48(m,1H)；3.84(s,3H)；4.81(s,1H)；5.57(s,1H)；6.43-6.83(m,3H)；7.09-7.36(m,10H).
MS(ESI+):515.0[M+Na]+
Rf(环己烷/EtOAc；1/1):0.51
实施例7：
-(9Z,12Z)-2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨9-基)苯基十八碳-9,12-二烯酸酯
在N2下，向0.99g的呫吨二酮(实施例1)(2.5mmol)在12.5mL无水DCM中的溶液中，加入417μL三乙胺(3mmol)。通过冰浴，将混合物冷却至0℃，然后逐滴加入0.88mL亚油酰氯。于0℃搅拌5分钟后，移除冰浴，并使所述反应在环境温度下持续过夜。采用蒸馏水萃取混合物，并采用饱和的NaCl溶液洗涤所述混合物，之后采用MgSO4干燥有机相，所述MgSO4随后被滤除。将溶液蒸发至干，以获得黄色油状物并进行闪式分离法(combiflash)。使用梯度为95:5至50:50的庚烷/乙酸乙酯。回收并蒸发纯净的级分。
将固体在烘箱中于50mbar干燥至少30分钟，以获得收率为76.5％的1.26g米色产物。
1H NMR(400MHz,CDCl3):δ:0.88(t,3H)；1.01(s,6H)；1.10(s,6H)；1.30(m,14H)；1.72(m,2H)；2.05(m,4H)；2.17(m,4H)；2.45(s,4H)；2.53(m,2H)；2.77(t,2H)；3.81(s,3H)；4.76(s,1H)；5.30(m,4H)；6.70(dd,1H)；6.74(d,1H)；7.04(d,1H).
13C NMR(100MHz,CDCl3):δ:14.03；22.51；24.94；25.56；27.14；27.35；28.94；29.09；29.13；29.17；29.28；29.55；31.35；31.45；31.97；32.15；32.30；33.96；40.81；50.66；55.78；76.68；77.00；77.32.
MS(ESI+):659.4[M+H]+
Rf(环己烷/EtOAc；2/1):0.52
实施例8：
2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯基棕榈酸酯
与实施例7相同的方案，由棕榈酰氯合成。
1H NMR(400MHz,CDC13):δ:0.89(t,3H)；1.00(s,6H)；1.10(s,6H)；1.31(m,22H)；1.39(m,2H)；1.72(m,4H)；2.22(m,4H)；2.45(m,4H)；3.81(s,3H)；4.66(s,1H)；6.69(dd,1H)；6.84(d,1H)；7.04(d,1H).
MS(ESI+):652.5[M+NH4]+
Rf(庚烷/EtOAc；1/1):0.54
实施例9：
9-(4-羟基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:0.99(s,6H)；1.09(s,6H)；2.20(m,4H)；2.46(s,4H)；4.66(s,1H)；5.83(s,1H)；6.54(d,2H)；7.07(d,2H).
13C NMR(100MHz,CDCl3):δ:27.33；29.09；30.89；32.21；40.79；50.70；115.22；115.82；129.26；135.41；154.74；162.43；197.28.
MS(ESI+):367.2[M+H]+
Rf(环己烷/EtOAc；1/1):0.58
实施例10：
-9-(4-羟基-3,5-二甲基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:0.99(s,6H)；1.09(s,6H)；2.05(s,6H)；2.20(s,4H)；2.46(s,4H)；4.60(s,1H)；5.00(s,1H)；6.83(s,2H).
13C NMR(100MHz,CDCl3):δ:15.95；27.31；29.15；30.85；32.19；40.82；50.77；115.90；122.56；128.43；135.49；150.79；161.96；196.72.
MS(ESI+):395.2[M+H]+
Rf(环己烷/EtOAc；1/1):0.64
实施例11：
-9-(4-羟基-3-甲氧基苯基)-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:2.00(m,4H)；2.33(m,4H)；2.60(m,4H)；3.87(s,3H)；4.73(s,1H)；5.49(s,1H)；6.53(dd,1H)；6.73(d,1H)；7.07(d,1H).
MS(ESI+):358.2[M+NH4]+
Rf(环己烷/EtOAc；3/7):0.39
实施例12：
-9-(4-羟基-3-甲氧基苯基)-3,6-二异丙基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDC13):δ:0.92(m,12H)；1.60(m,2H)；1.70(m,2H)；2.10(m 2H)；2.30(m,2H)；2.45(m,2H)；2.65(m,2H)；3.88(s,3H)；4.70(s,1H)；5.62(s 1H)；6.51(m,1H)；6.72(m,1H)；7.07(m,1H).
MS(ESI+):425.2[M+H]+
Rf(环己烷/EtOAc；1/1):0.65
实施例13：
-3,6-双(4-氟苯基)-9-(4-羟基-3-甲氧基苯基)-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:2.30(m,4H)；2.78(m,4H)；3.00(m,1H)；3.40(m,1H)；3.54(s,1H)；3.84(m,3H)；5.50(s,1H)；6.40(m,1H)；6.68(m,1H)；6.90(m,1H)；7.08(m,4H)；7.25(m,4H).
MS(ESI+):547.2[M+NH4]+
Rf(环己烷/EtOAc；1/1):0.50
实施例14：
-3,6-双(3,4-二甲氧基苯基)-9-(4-羟基-3-甲氧基苯基)-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:2.65(m,4H)；2.87(m,4H)；3.31(m,1H)；3.47(m,1H)；3.85(m,15H)；4.80(m,1H)；5.53(s,1H)；6.50(m,1H)；6.70(m,6H)；7.10(m,1H)；7.30(m,1H).
MS(ESI+):630.3[M+NH4]+
Rf(环己烷/EtOAc；3/7):0.42
实施例15：
-9-(3-乙氧基-4-羟基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDC13):δ:0.99(s,6H)；1.09(s,6H)；1.40(t,3H)；2.20(m,4H)；2.46(s,4H)；4.13(s,2H)；4.64(s,1H)；5.56(s,1H)；6.56(dd,1H)；6.73(d,1H)；6.98(d,1H).
13C NMR(100MHz,CDC13):δ:14.79；27.21；29.22；31.21；32.11；40.76；50.69；64.22；113.05；113.78；115.71；119.82；136.26；144.02；145.07；162.00；196.52.
MS(ESI+):411.2[M+H]+
Rf(环己烷/EtOAc；1/1):0.50
实施例16：
-9-(3-氯-4-羟基-5-甲氧基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:1.00(s,6H)；1.10(s,6H)；2.20(m,4H)；2.47(s,4H)；3.90(s,3H)；4.64(s,1H)；5.73(s,1H)；6.61(d,1H)；6.97(d,1H).
13C NMR(100MHz,CDCl3):δ:27.34；29.18；31.33；32.20；40.80；50.71；56.29；111.18；115.21；118.82；120.41；136.59；140.44；146.72；162.37；196.55.
MS(ESI+):431.1[M+H]+
Rf(环己烷/EtOAc；1/1):0.48
实施例17：
-9-(3-溴-4-羟基-5-甲氧基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:1.00(s,6H)；1.10(s,6H)；2.20(m,4H)；2.47(s,4H)；3.90(s,3H)；4.64(s,1H)；5.80(s,1H)；6.74(d,1H)；7.01(d,1H).
13C NMR(100MHz,CDCl3):δ:27.31；29.17；31.25；32.19；40.78；50.69；56.26；107.57；111.84；115.19；123.17；137.19；141.50；146.50；162.36；196.55.
MS(ESI+):475.0[M+H]+
Rf(环己烷/EtOAc；1/1):0.37
实施例18：
-9-(4-羟基-3-碘-5-甲氧基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:1.00(s,6H)；1.10(s,6H)；2.20(m,4H)；2.47(s,4H)；3.89(s,3H)；4.61(s,1H)；6.00(s,1H)；6.92(d,1H)；7.04(d,1H).
13C NMR 100MHz,CDCl3):δ:27.25；29.19；31.03；32.18；40.76；50.67；56.15；80.60；112.78；115.20；128.93；138.05；144.07；145.35；162.30；196.54.
MS(ESI+):523.1[M+H]+
Rf(环己烷/EtOAc；1/1):0.47
实施例19：
-9-(3,4-二羟基-5-甲氧基苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
1H NMR(400MHz,CDCl3):δ:1.00(s,6H)；1.10(s,6H)；2.17(m,4H)；2.45(s,4H)；3.85(s,3H)；4.64(s,1H)；5.47(s,2H)；6.31(d,1H)；6.65(d,1H).
13C NMR(100MHz,CDCl3):δ:27.40；29.06；31.33；32.10；40.73；50.66；55.97；104.89；107.54；115.55；131.04；135.94；143.68；146.35；162.23；196.84.
MS(ESI+):413.2[M+H]+
Rf(环己烷/EtOAc；3/7):0.66
实施例20：
-(3R,4S,5S)-2-(乙酰氧基甲基)-6-(2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
根据通用方案A，由葡萄糖基化香草醛获得该产物，文献中描述葡萄糖基化香草醛的合成(Chemical and pharmaceutical bulletin,51(11),1268-1272；2003)。
经过硅胶上的纯化之后，获得白色固体形式的产物。
1H NMR(400MHz,CDCl3):δ:0.97(s,3H)；1.02(s,3H)；1.10(s,3H)；1.11(s,3H)；2.02(s,3H)；2.03(s,3H)；2.05(s,3H)；2.06(s,3H)；2.21(m,4H)；2.45(m,4H)；3.71(m,1H)；3.81(s,3H)；4.11(dd,1H)；4.25(dd,1H)；4.69(s,1H)；4.88(d,1H)；5.13(dd,1H)；5.24(m,2H)；6.64(dd,1H)；6.92(d,1H)；6.99(d,1H).
13C NMR(100MHz,CDCl3):δ:20.56；20.61；20.68；26.85；27.13；27.30；29.25；31.47；32.12；32.15；40.79；50.67；50.70；55.94；61.86；68.40；71.14；71.69；72.60；100.69；113.85；115.33；115.54；119.74；120.05；140.99；144.29；150.09；162.13；162.46；169.38；169.39；170.23；170.61；196.42；196.64.
MS(APCI+):727.2[M+H]+
实施例21：
-9-(3-甲氧基-4-((3S,4S,5S)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
根据下列参考文献中描述的方案，采用甲醇钠溶液处理实施例20的无水甲醇溶液。然后，获得白色固体形式的产物。(European Journal of Medicinal Chemistry43(2008)2549-2556)
1H NMR(300MHz,CD3OD):δ:1.00(s,6H)；1.12(s,6H)；2.17(d,2H)；2.33(d,2H)；2.58(2d,4H)；3.36(m,2H)；3.39(m,2H)；3.70(m,1H)；3.85(m,1H)；3.87(s,3H)；4.60(s,1H)；4.82(d,1H)；6.73(d,1H)；6.97(s,1H)；7.03(d,1H).
MS(ESI+):581.1[M+Na]+
实施例22：
-(3S,4S,5S,6S)-2-(乙酰氧基甲基)-6-(2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
根据如实施例20所述的方案，由半乳糖基化香草醛获得该产物，文献中描述半乳糖基化香草醛的合成(European Journal of Medicinal Chemistry,43(2008)166-173)
经过硅胶上的纯化之后，获得白色固体形式的产物。
1H NMR(400MHz,CDCl3):δ:0.97(s,3H)；1.02(s,3H)；1.10(s,3H)；1.11(s,3H)；2.00(s,3H)；2.02(s,3H)；2.07(s,3H)；2.15(s,3H)；2.21(m,4H)；2.45(m,4H)；3.81(m,1H)；3.92(t,1H)；4.12(m,1H)；4.69(s,1H)；4.83(d,1H)；5.06(dd,1H)；5.43(m,2H)；6.63(dd,1H)；6.92(d,1H)；6.99(d,1H)..
MS(APCI+):727.4[M+H]+,744.4[M+NH4]+.
实施例23：
-9-(3-甲氧基-4-((2S,3S,4S,5R)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
根据下列参考文献中描述的方案，采用甲醇钠溶液处理实施例22的无水甲醇溶液。然后，获得白色固体形式的产物。(European Journal of Medicinal Chemistry,43(2008)2549-2556)
1H NMR(400MHz,CDCl3):δ:0.92(s,6H)；1.15(s,6H)；2.09(dd,2H)；2.11(dd,2H)；2.54(m,4H)；3.57(m,3H)；3.68(s,3H)；4.47(m,2H)；4.62(t,1H)；4.80(dd,2H)；4.98(d,1H)；6.63(dd,1H)；6.72(d,1H)；6.91(d,1H).
实施例24：
-(3R,4S,5S,6S)-2-(乙酰氧基甲基)-6-(4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
根据通用过程，由葡萄糖基化香草醛获得该产物，文献中描述葡萄糖基化香草醛合成(Chemical and pharmaceutical bulletin,51(11),1268-1272；2003)。
经过硅胶上的纯化之后，获得白色固体形式的产物。
1H NMR(400MHz,CDCl3):δ:0.98(s,6H)；1.10(s,6H)；2.02(s,3H)；2.03(s,3H)；2.05(s,3H)；2.06(s,3H)；2.20(m,4H)；2.45(m,4H)；3.81(m,1H)；4.13(dd,1H)；4.28(dd,1H)；4.70(s,1H)；5.01(d,1H)；5.14(dd,1H)；5.24(m,2H)；6.83(d,2H)；7.21(d,2H).
MS(ESI+):697.3[M+H]+；714.3[M+NH4]+.
实施例25:
-3,3,6,6-四甲基-9-(4-((2S,3S,4S,5S)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
根据下列参考文献中描述的方案，采用甲醇钠溶液处理实施例24的无水甲醇溶液。然后，获得白色固体形式的产物。(European Journal of Medicinal Chemistry,43(2008)2549-2556)
1H NMR(300MHz,CD3OD):δ:0.88(s,6H)；1.0(s,6H)；2.20(d,2H)；2.42(d,2H)；2.52(2d,4H)；3.20(m,2H)；3.28(m,4H)；3.57(dd,1H)；3.76(d,1H)；4.49(s,1H)；4.73(d,1H)；6.84(d,2H)；7.06(d,1H).
13C NMR(75MHz,CD3OD):δ:27.7；27.8；29.8；29.9；32.7；33.6；41.8；51.9；62.9；71.7；75.3；78.3；78.4；102.7；117.0；117.6；130.9；140.0；158.0；165.4；199.7.
MS(ESI+):529.3[M+H]+；546.3[M+NH4]+；551.2[M+Na]+.
实施例26:
4-(1,8-二氧代-3.6-二苯基-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)-1,2-苯二酚二乙酸酯
由3,4-二乙酰氧基苯甲醛制备。
1H NMR(400MHz,CDCl3):δ:2.27(s,6H)；2.30(m,4H)；2.83(m,4H)；3.4(m,1H)；3.5(m,1H)；4.93(s,1H)；7.04(m,3H)；7.3(m,10H).
MS(ESI+):563.2[M+H]+
Rf(环己烷/EtOAc；1/1):0.40
实施例27:
-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)-1,2-苯二酚二乙酸酯
由3,4-二乙酰氧基苯甲醛制备。
1H NMR(400MHz,CDCl3):δ:0.99(s,6H)；1.09(s,6H)；1.88(s,3H)；2.22(m,4H)；2.46(s,4H)；4.77(s,1H)；7.04(dd,1H)；7.20(d,1H)；7.22(d,1H).
13C NMR(100MHz,CDCl3):δ:20.62；27.46；29.04；31.08；32.17；40.77；50.59；115.03；122.62；122.88；126.55；140.34；141.61；142.58；162.50；167.91；168.16；196.50.
MS(ESI+):467.1[M+H]+
Rf(环己烷/EtOAc；3/7):0.38
2)实验测试方案
A)B16-F10细胞中的黑色素分析测试
原理：
这涉及到通过在小鼠黑色素瘤细胞系(B16-F10系)上进行比色分析法来测量黑色素合成的测试。该测试能够使活性成分的色素脱除活性得以评价。
将B16-F10细胞在96孔板中在补充有FCS(胎牛血清)的DMEM培养基中培养，并在37℃，5％CO2下孵育24小时。然后将所述细胞采用0.1μΜα-MSH刺激(以刺激黑色素的合成，观察到的刺激为150％左右)并采用待测的活性成分处理72小时。至少一式三份地测试每个浓度下的活性成分。然后，通过405nm处的吸光度读数来测定总黑色素的含量，随后将细胞内黑色素溶解于裂解缓冲液中。测量裂解物中总蛋白质的含量，并且结果以mg黑色素/mg蛋白质来表示。活性百分比计算如下：
负值表示抑制黑色素的合成，而正值表示诱导黑色素的合成。
-通用实验条件：
-设备：
-CO2细胞培养箱(Heraeus)、烘箱、离心机(Heraeus)、空气层流通风柜、透明底的96孔板-Falcon、无菌锥形容器-Treff Lab、Polylabo、Mithras LB940(Berthold Technologies)-154/MIP A/003
-生物学设备：
-介于P10和P20之间的B16-F10细胞系(小鼠黑色素细胞)(ATCC、CRL-6475)
-试剂
-不含酚红的DMEM(GIBCOBRL，31053-028)；200mM Glutamax-I补充剂(GIBCOBRL，35050-038)；D-PBS(GIBCOBRL，14190-094)；胎牛血清(Invitrogen，10270-098)；胰蛋白酶-EDTA(GIBCOBRL，25300-054)；NaOH(Sigma，S8045-500G)；DMSO(Sigma，471267-1L)；亮氨酸，苯丙氨酸-黑色素细胞刺激激素(Sigma，M-8764)；黑色素(Sigma，M-0418)；BCA-COPPER(SIGMA，B9643和C2284)；BSA(SlGMA，P0914)
B)通过化学发光法研究抗氧化能力的测试(Photochem Analytik Jena)
-原理：
本测试用于确定分子的抗氧化能力。这是一种通过光化学信号来产生自由基的方法。该方法的氧化强度比正常条件下获得的强度高1000倍。
通过化学发光法进行检测。这能够评价水溶性和脂溶性抗氧化剂分子或提取物。
结果分别表示为维生素C或Trolox(6-羟基-2,5,7,8-四甲基色满-2-羧酸)的当量。灵敏度为纳摩尔级。
在该测试中研究的抗氧化活性代表通过化学发光法来特异性捕获超氧化物阴离子的能力。
定量结果表示为Trolox(标准物)的当量，即“相当于1μg Trolox的产品μg数”，这意味着需要x量的样品以获得与1μg标准物所检测的活性相当的活性。这是一种相对于参照物的抗氧化活性，能够独立地确定测试浓度。
-含氧自由基的产生：
通过光化学反应产生超氧化物基团：O2°-：
L+hv(UV)+O2→L*O2→L°++O2°-
L*:激发状态的鲁米诺
L°+:鲁米诺基团
-信号检测：
通过抗氧化物来淬灭一部分超氧化物阴离子。通过化学发光法来量化剩余的自由基。
L°++O2°-→N2+AP*2-→AP2-+hv(发冷光)
AP*2-:激发状态的氨基邻苯二甲酸根
| 名称 | 条件 | 感光性 | 抗氧化剂 |
| 空白组 | 产生100％O2°- | + | - |
| 标准组 | 标准范围：从1至3nmol | + | 维生素C或Trolox |
| 测试组 | 产生+/-O2°- | + | 待测分子x |
3)实验测试结果。
A)B16-F10细胞中的黑色素分析测试：
结果如下列总结表1所示。
-结果阐释：
IC50代表观察到50％的黑色素合成抑制的浓度。
可以观察到，大多数的测试化合物具有良好的黑色素合成抑制能力。根据本发明的化合物具有良好的色素脱除活性。
B)通过化学发光法研究抗氧化能力的测试(Photochem Analytik Jena)
结果也在下列总结表1中给出。
大多数的化合物具有良好的抗氧化活性。用于阐释结果的标度如下：
| 产品 | 相当于1μg Trolox的样品μg数 | 活性 |
| 维生素C | 0.1至3.0 | 非常好 |
| BHT | 3.01至50 | 好 |
| 半胱氨酸 | 50.1至1000 | 中等 |
| 白蛋白 | >1000 | 低 |
| 硫辛酸 | 负值 | 无 |
大多数化合物具有与维生素C相当的结果。所有化合物均显示出低于1000μgTrolox的结果(74μg是由实施例30获得的最低结果)；因此，它们均具有有价值的抗氧化活性。
作为本发明目的的化合物的这种抗氧化活性(通过自由基的捕获来体现)也有可能实现其在治疗和/或预防皮肤炎症中的用途(“Free radicals in inflammation:second messengers and mediators of tissue destruction”,V.R.Winrow等人.http://bmb.oxfordjournals.org/cgi/content/abstract/49/3/506)。
表1：实验测试的结果
C)用于研究色素脱除活性的重建表皮测试
根据组合物A的实例，将浓度为0.5％的实施例8和21的化合物配制在单一(Simplex)配方中。使用黑色皮肤的人(Melanoderm)-B(黑人)或黑色皮肤的人A(亚洲人)(MatTek，美国)重建的表皮模型。选定的参考化合物是在水溶液中滴定至2％的曲酸。每天更换培养基。每两天通过局部模式将所述产品施用在表皮上。对于所述施用而言，采用PBS漂洗表皮，然后施用待测产品。
初步毒性研究有可能确定用于每一次治疗的施用剂量为25μL。
通过施用所述产品不会改变组织中黑色素细胞的形态和数量。
由3名独立的专家于D3、D7、D10、D14(黑色皮肤的人B)或D6、D10、D14和D21(黑色皮肤的人A)观察所述组织。
单一组合物A配方：
在黑色皮肤的人B模型上观察到的结果在下列表2中给出：
表2：对比于阴性对照(水)的表皮评级(rating)(3名独立的观察员)
Dx：给药或观察的天数
C：与绝对对照相比，表皮颜色较浅(色素脱除)
F：与绝对对照相比，表皮颜色较深(促进色素沉着)
I：与绝对对照相比，表皮颜色相同
(X/X)：用于观察效果的观测次数
表皮的着色对比于阴性对照(水)的着色。单一对照配方不显示任何宏观的色素脱除效果(除了于D7)：因此，该配方相对于阴性对照不具有任何特定的效果。另一方面，含有根据实施例8或实施例21的化合物的配方于D3、D7、D10和D14在黑色皮肤的人B(黑人)表皮模型上显示出宏观的色素脱除效果。这些结果确实显示出针对配制的实施例8和21的特定的色素脱除效果。
在黑色皮肤的人A模型上观察到的结果被记录在下列表3中：
表3：对比于单一对照配方的表皮评级(3名独立的观察员)
Dx：给药或观察的天数
C：与相应对照相比，表皮颜色较浅(色素脱除)
F：与相应对照相比，表皮颜色较深(促进色素沉着)
I：与相应对照相比，表皮颜色相同
(X/X)：用于观察效果的观测次数
同样在黑色皮肤的人-A(亚洲人)模型中测试含有实施例8的配方。表皮的着色相比于单一对照配方的着色。含有实施例8的配方于D6、D10、D14、D21显示出宏观的色素脱除效果。根据由S.Bessous-Touya描述的技术(J.Invest.Dermatol.111:1103-1109(1998))而进行的黑色素测试显示出相对于由单一对照配方处理的表皮的4.1μg的黑色素降低。
4)组合物
本发明还涉及一种药物或化妆品组合物，其特征在于，其包含作为活性成分的至少一种通式(I’)的化合物与药学上或化妆品上可接受的赋形剂：
其中基团R1、R2、R3、R4、R5、R6和R7具有与前述给定的基团相同的含义，但是其中R4可以另外代表氢原子或乙酰化基团。
根据本发明的药物或化妆品组合物的特征在于，通式(I’)的化合物的量在相对于所述组合物总重量的0.01重量％和10重量％之间，并且优选从0.1重量％至5重量％变化。
根据本发明的药物或化妆品组合物的特征在于，其用于皮肤和/或头发和/或体毛的色素脱除，用于治疗和/或预防皮肤衰老，或者用于治疗和/或预防皮肤炎症。
此外，根据本发明的组合物可以包含常规的化妆品佐剂，所述化妆品佐剂尤其选自脂肪相、有机溶剂、增稠剂、软化剂、遮光剂、稳定剂、润肤剂、消泡剂、保湿剂、芳香剂、湿润剂、胶凝剂、防腐剂如尼泊金类、聚合物、填充剂、螯合剂、杀菌剂、臭味吸收剂、碱化或酸化试剂、表面活性剂、pH调节剂、抗自由基剂、抗氧化剂、维生素E和C、α-羟基酸，或温泉水如雅漾(Avène)温泉水，或者化妆品中常用(特别是用于生产该类型组合物)的任何其他成分。
此外，根据本发明的组合物可以包含脂肪相。所述脂肪相可以由油或蜡或其混合物构成，还可以包含脂肪酸、脂肪醇和脂肪酸酯。所述油可以选自动物油、植物油、矿物油或合成油，并且尤其选自凡士林油、石蜡油、硅油、挥发性或非挥发性油如二甲硅油；异石蜡烃、聚烯烃、氟化或全氟化油。类似地，所述蜡可以选自动物蜡、矿物蜡、植物蜡或合成蜡，如蜂蜡、小烛树蜡、巴西棕榈蜡、乳木果油、石油蜡(或微晶蜡)、石蜡及其混合物。
此外，根据本发明的组合物可以包含在环境温度(25℃左右)下于水中易混溶的多元醇，尤其选自特别具有从2至20个碳原子，优选具有从2至10个碳原子，并且更优选具有从2至6个碳原子的多元醇，如甘油；二醇的衍生物如丙二醇、丁二醇、戊二醇、己二醇、二丙二醇、二乙二醇；二醇醚如单-、二-或三-丙二醇的C1-C4烷基醚、单-、二-或三-乙二醇的C1-C4烷基醚；及其混合物。
根据本发明的组合物还可以包含增稠剂或流变改性剂，如(例如)非离子型乙氧基化疏水改性的乌拉坦，聚羧酸增稠剂如丙烯酸酯/硬脂醇聚醚-20甲基丙烯酸酯的共聚物、卡波姆、丙烯酸酯共聚物及其混合物。
根据本发明的组合物还可以包含酸和碱，使其有可能调节所述组合物的pH范围。所述碱可以是无机碱(氢氧化钠、氢氧化钾、氨水等)或有机碱如单-、二-或三-乙醇胺、氨甲基丙二醇、N-甲基葡萄糖胺、碱性氨基酸如精氨酸和赖氨酸，及其混合物。
根据本发明的组合物还可以包含皮肤调理剂。皮肤调理剂的实例包括(但不限于)乳化剂，阴离子、阳离子和非离子型乳化剂如月桂基硫酸钠、二辛基磺基琥珀酸钠、硬脂酸钠、山梨坦酯；乙氧基化脂肪酸；乙氧基化脂肪醇如十三烷醇聚醚-9和PEG-5的乙基己酸酯；硬脂酸；本领域技术人员已知的任何其他乳化剂和调理剂；及其混合物。
此外，根据本发明的组合物可以含有导致互补效果的其他活性成分。
根据本发明的组合物可以是适用于局部施用(特别是在皮肤和/或头发上)的任何形式。特别地，它们能够是通过油相在水相中的分散而获得的乳剂形式(例如水包油或油包水或多重乳剂)，或凝胶剂形式，或可注射的填充剂形式，或液体、糊状或固体无水产物，或存在小球体(spherule)的分散剂形式。根据本发明的组合物还可以是流动性较差的流体并且是白色或彩色霜剂、软膏剂、奶剂、洗剂、浆液、糊剂、面膜、粉末剂、固体棒的形式，或者是(如果合适)气雾剂、泡沫剂或喷雾剂。
组合物的实例：
在该组合物中，活性成分的百分比能够在相对于所述组合物总重量的介于0.01重量％至10重量％之间并且优选从0.1重量％至5重量％的范围内变化。
Claims (18)
1.通式(I)的化合物及其药学上或化妆品上可接受的盐：
其中：
R1和R2同时或独自代表：OH、氢原子、C1-C6烷基基团、C1-C6烷氧基基团、卤素或OCOR3；
R3代表：C1-C24烷基基团、包含至少一个不饱和度的C12-C24烯基基团；
R4代表：COR5、被一个或多个乙酰基基团取代或未取代的吡喃糖基团；
R5代表：C10-C24烷基基团或包含至少一个不饱和度的C12-C24烯基基团；
R6和R7代表：
-同时为氢原子或甲基基团，
或者
-当R6代表氢原子时，R7代表C1-C6烷基基团或者被一个或多个C1-C3烷氧基基团或一个或多个卤素取代或未取代的苯基，
或者
-R6和R7彼此连接并形成C3-C6环烷基。
2.根据权利要求1所述的通式(I)的化合物，其特征在于，R1和R2同时或独自代表氢原子或C1-C6烷氧基基团。
3.根据权利要求1至2中任一项所述的通式(I)的化合物，其特征在于，R4代表COR5。
4.根据权利要求1所述的通式(I)的化合物，其特征在于，R5代表C14-C18烷基基团或包含1至3个不饱和度的C14-C18烯基基团。
5.根据权利要求1所述的通式(I)的化合物，其特征在于，R6和R7同时代表甲基基团。
6.根据权利要求1所述的通式(I)的化合物，其特征在于，所述不饱和度为从1到6。
7.根据权利要求1所述的通式(I)的化合物，其特征在于，所述不饱和度为从1到4。
8.根据权利要求1所述的通式(I)的化合物，其特征在于，所述化合物选自下列化合物之一：
-2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯基棕榈酸酯
-(9Z,12Z)-2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯基十八碳-9,12-二烯酸酯
-(3R,4S,5S)-2-(乙酰氧基甲基)-6-(2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
-9-(3-甲氧基-4-((3S,4S,5S)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-1,8(2H)-二酮
-(3S,4S,5S,6S)-2-(乙酰氧基甲基)-6-(2-甲氧基-4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
-9-(3-甲氧基-4-((2S,3S,4S,5R)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,3,6,6-四甲基-3,4,5,6,7,9-六氢-1H-呫吨-l,8(2H)-二酮
-(3R,4S,5S,6S)-2-(乙酰氧基甲基)-6-(4-(3,3,6,6-四甲基-1,8-二氧代-2,3,4,5,6,7,8,9-八氢-1H-呫吨-9-基)苯氧基)四氢-2H-吡喃-3,4,5-三基三乙酸酯
-3,3,6,6-四甲基-9-(4-((2S,3S,4S,5S)-3,4,5-三羟基-6-(羟甲基)四氢-2H-吡喃-2-基氧基)苯基)-3,4,5,6,7,9-六氢-lH-呫吨-1,8(2H)-二酮。
9.通式(I’)的化合物及其化妆品上或药学上可接受的盐，其用作药物或用作化妆品的活性成分：
其中基团R1、R2、R3、R4、R5、R6和R7具有与权利要求1至7中给定的基团相同的含义，但是其中R4可以另外代表氢原子或乙酰基基团。
10.根据权利要求9所述的通式(I’)的化合物，其特征在于，R4代表氢原子，其用作药物或用作化妆品的活性成分。
11.根据权利要求9或10中任一项所述的通式(I’)的化合物在制备药物中的用途，其中所述药物用于皮肤和/或头发和/或体毛的色素脱除，用于治疗和/或预防皮肤衰老，或者用于治疗和/或预防皮肤炎症。
12.药物或化妆品组合物，其特征在于，其包含作为活性成分的至少一种如权利要求9至10所定义的通式(I’)的化合物以及药学上或化妆品上可接受的赋形剂。
13.根据权利要求12所述的药物或化妆品组合物，其特征在于，通式(I’)的化合物的量在相对于所述组合物总重量的0.01重量％和10重量％之间变化。
14.根据权利要求12所述的药物或化妆品组合物，其特征在于，通式(I’)的化合物的量在相对于所述组合物总重量的从0.1重量％至5重量％变化。
15.根据权利要求12至14中任一项所述的药物或化妆品组合物在制备药物中的用途，其中所述药物用于皮肤和/或头发和/或体毛的色素脱除，用于治疗和/或预防皮肤衰老，或者用于治疗和/或预防皮肤炎症。
16.用于合成根据权利要求1至8中任一项所述的通式(I)的化合物的方法，其特征在于，在酸性或碱性催化剂的存在下使两分子的1,3-二酮与醛反应：
其中R1、R2、R3、R4、R5、R6和R7具有与权利要求1至7中相同的含义。
17.用于合成根据权利要求1至7中任一项所述的通式(I)的化合物的方法，其特征在于，在碱的存在下使苯酚与R5COCl活化的羧酸反应：
其中R1、R2、R3、R5、R6和R7具有与权利要求1至7中相同的含义，并且R4代表COR5。
18.用于合成根据权利要求1至2和5至7中任一项所述的通式(I)的化合物的方法，其特征在于，在路易斯酸和二氯甲烷的存在下使苯酚与被一个或多个乙酰基基团取代的糖基基团反应：
其中R1、R2、R3、R5、R6和R7具有与权利要求1至7中相同的含义，并且R4代表被一个或多个乙酰基基团取代的吡喃糖基团，在所述反应之后可以进行皂化步骤，所述路易斯酸为BF3，Et2O。
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| FR1055595A FR2962436B1 (fr) | 2010-07-09 | 2010-07-09 | Derives de xanthedediones pour le traitement des troubles de la pigmentation et du vieillissement cutane |
| FR1055595 | 2010-07-09 | ||
| PCT/EP2011/061637 WO2012004390A1 (en) | 2010-07-09 | 2011-07-08 | Xanthenedione derivatives for the treatment of pigmentation and skin ageing disorders |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178789A (zh) * | 1996-08-07 | 1998-04-15 | 弗·哈夫曼-拉罗切有限公司 | 呫吨和吖啶衍生物及其用途 |
| CN1372467A (zh) * | 1999-08-13 | 2002-10-02 | 福托金公司 | 改进的局部用药物和疾病的光动力学治疗方法 |
| CN1423557A (zh) * | 2000-03-24 | 2003-06-11 | 福托金公司 | 用于疾病的光动疗法的体内药物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| SU895985A1 (ru) * | 1980-03-27 | 1982-01-07 | Ордена Трудового Красного Знамени Институт Органического Синтеза Ан Латвсср | 9-Ароил-3,3,6,6-тетраметил-1,2,3,4,5,6,7,8-октагидроксантен-1,8-дионы в качестве промежуточных продуктов дл синтеза соединений,обладающих антиоксидантной активностью |
| JP3498857B2 (ja) * | 1994-01-28 | 2004-02-23 | 株式会社ノエビア | 皮膚外用剤 |
| FR2756183B1 (fr) * | 1996-11-25 | 1999-08-27 | Fabre Pierre Dermo Cosmetique | Association d'huile et de peptides d'argan utile pour le traitement des troubles lies au vieillissement cutane |
| EP1213025A1 (de) * | 2000-12-06 | 2002-06-12 | Laboratoires Serobiologiques(Societe Anonyme) | Kosmetische und/oder dermopharmazeutische Zubereitungen enthaltend Extrakte aus den Blättern der Pflanze Argania spinosa |
| GB0215534D0 (en) * | 2002-07-04 | 2002-08-14 | Ecole Polytech | Selective photochemotherapy using oligonucleotide targeting agents |
| EP1824442A4 (en) * | 2004-11-16 | 2009-11-11 | Renaissance Herbs Inc | PHARMACEUTICAL AND THERAPEUTIC COMPOSITIONS DERIVED FROM GARCINIA MANGOSTANA L. |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1178789A (zh) * | 1996-08-07 | 1998-04-15 | 弗·哈夫曼-拉罗切有限公司 | 呫吨和吖啶衍生物及其用途 |
| CN1372467A (zh) * | 1999-08-13 | 2002-10-02 | 福托金公司 | 改进的局部用药物和疾病的光动力学治疗方法 |
| CN1423557A (zh) * | 2000-03-24 | 2003-06-11 | 福托金公司 | 用于疾病的光动疗法的体内药物 |
Non-Patent Citations (3)
| Title |
|---|
| Glycerol as a promoting medium for electrophilic activation of aldehydes: catalyst-free synthesis of di(indolyl)methanes, xanthene-1,8(2H)-diones and 1-oxo-hexahydroxanthenes;Fei He等;《Green Chemistry》;20090907;第11卷;第1767–1773页 * |
| REACTION OF LONG-CHAIN VANILLYL ESTERS WITH CH-ACIDS AND 2-NAPHTHYLAMINE;N. G. Kozlov等;《Chemistry of Natural Compounds》;20041231;第40卷(第1期);第79-82页 * |
| Vanilline Alkanoates in the Synthesis of Hexahydrobenzacridine and Octahydroxanthene Derivatives;N. G. Kozlov等;《Russian Journal of General Chemistry》;20050401;第75卷(第4期);第617-621页 * |
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| Publication number | Publication date |
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| JP5829272B2 (ja) | 2015-12-09 |
| HK1178521A1 (zh) | 2013-09-13 |
| BR112013000431A2 (pt) | 2016-05-17 |
| FR2962436A1 (fr) | 2012-01-13 |
| FR2962436B1 (fr) | 2012-12-14 |
| US20130108568A1 (en) | 2013-05-02 |
| TW201206488A (en) | 2012-02-16 |
| WO2012004390A1 (en) | 2012-01-12 |
| RU2013103030A (ru) | 2014-08-20 |
| EP2590959A1 (en) | 2013-05-15 |
| RU2598374C2 (ru) | 2016-09-27 |
| AU2011275686A1 (en) | 2013-01-31 |
| MA34390B1 (fr) | 2013-07-03 |
| US8906416B2 (en) | 2014-12-09 |
| NZ605750A (en) | 2015-12-24 |
| MX2013000077A (es) | 2013-03-18 |
| AU2011275686B2 (en) | 2014-11-27 |
| SG186941A1 (en) | 2013-02-28 |
| TWI538693B (zh) | 2016-06-21 |
| AR082141A1 (es) | 2012-11-14 |
| CN102985415A (zh) | 2013-03-20 |
| ZA201300413B (en) | 2013-09-25 |
| IL224123A (en) | 2016-06-30 |
| JP2013530203A (ja) | 2013-07-25 |
| KR20130043181A (ko) | 2013-04-29 |
| CA2804334A1 (en) | 2012-01-12 |
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