Genipin derivatives, topical compositions containing same, and use as colorants

Abstract

The present application provides topical compositions comprising genipin derivatives of formula (I), which are useful, for example, as coloring agents in semi-permanent tattoos. [Formula 1] JPEG2026505978000077.jpg2937

Description

[Technical Field]

[0001] (CROSS-REFERENCE TO RELATED APPLICATIONS) This application claims priority to European Patent Application Publication Nos. 23157133.2 and 23157132.4, filed February 16, 2023, the entire contents of which are incorporated herein by reference.

[0002] The present disclosure relates to colored genipin derivatives that are adherent to skin and are useful, for example, as coloring agents in semi-permanent tattoos. [Background technology]

[0003] Temporary or semi-permanent tattoos or body inks have been used throughout human history to decorate the body. Generally, temporary or semi-permanent tattoos are transferred to the skin by directly exposing the skin to the tattoo ink for a specified latency period. The quality of the transferred image and its duration on the skin may depend on the ink distribution profile in the outer layer of the skin, called the stratum corneum. Currently used manufacturing methods for pre-made tattoo designs include the use of topical formulations in many forms, including flexographic or gravure inks, stencils, and inkjet printers.

[0004] Genipin is particularly beneficial for use in such semi-permanent tattoos because it chemically binds to skin (mammalian, particularly human, skin) in a long-lasting manner and produces an intense blue color. One model depicting the possible mechanism of chemical binding and color development on skin is shown in Figure 1. As seen in Figure 1, genipin is believed to form a colored conjugated system upon chemically binding to amino groups on skin proteins. The color of genipin when bound to skin is an intense dark blue.

[0005] However, it is also desirable to provide semi-permanent tattoos in other colors of similar intensity and / or other colors with improved intensity. In practice, designing genipin derivatives with specific colors can be challenging for several reasons. First, despite advances in calculating UV / vis absorption spectra, it is extremely difficult to precisely predict the exact color impression and intensity of a given genipin derivative. Second, while the general principles of how conjugated systems and chemical moieties affect UV / vis absorption are well established, designing genipin derivatives with desired color impressions using a trial-and-error approach can be time-consuming and laborious. Designing specific genipin colors is further burdened by the fact that the genipin core, upon binding to skin, provides the first chromophore, while other moieties on the genipin derivative provide additional chromophore systems. The resulting color impression is determined by the combined absorption of all chromophore systems. Second, achieving the desired color depends not only on providing absorption at a given wavelength, but also on providing the appropriate amount of absorption at that wavelength. In practice, achieving these two goals (absorption at a given wavelength and intensity of absorption at that wavelength) using the same chemical chromophore can be difficult.

[0006] These challenges become even more challenging when it is desired to provide a strong yellow color. The human eye generally perceives pure yellow, i.e., yellow without any greenish or orange contribution, only within a very narrow wavelength range, i.e., from about 566 to about 589 nm, depending on the sensitivity of the eye. Therefore, absorption must be tailored around this wavelength range, more specifically, within the visible range above about 589 nm and below about 566 nm. At the same time, yellow is an important color because it is a primary color and is useful for achieving a large number of mixed colors.

[0007] For these reasons, it would be desirable to have genipin derivatives that provide a suitable platform for conveniently fine-tuning color impression and intensity, especially for yellow derivatives. Summary of the Invention

[0008] In a first aspect, the present disclosure provides a compound of formula (I):

[0009] [ka] or a tautomer and / or a pharmaceutically acceptable salt thereof, During the ceremony, R 1 optionally substituted C1-C 30 represents a part, R 2 represents hydrogen or a protecting group that is hydrolyzable under physiological conditions after application of the topical composition to the skin, R 3 optionally substituted C1-C 30 represents a part, R 4 is hydrogen or optionally substituted C-C 30 represents a part,

[0010] [ka] represents a single bond, and both R 5 are, independently of each other, hydrogen or optionally substituted C-C 30 Represents a part, or

[0011] [ka] R represents a double bond, and R 5 does not exist and R 5 the other is hydrogen or an optionally substituted C-C 30 a compound, or a tautomer and / or a pharmaceutically acceptable salt thereof, representing a moiety and an excipient suitable for topical administration.

[0012] In some embodiments, R 1 Optionally substituted C1-C represented by 30 The part is C1-C 30a moiety comprising 1 to 30, more particularly 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more particularly 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms.

[0013] In some embodiments, R 1 is -COOH, R 6 , or -C(=O)-R 6 wherein R 6 is an optionally substituted C1-C 12 -Alkyl, C2-C 12 -Alkenyl, C2-C 12 -Alkynyl, C6-C 16 -aryl or C3-C 12 -heteroaryl, O-C-C 12 -Alkyl, O-C2-C 12 -Alkenyl, O-C2-C 12 -Alkynyl, O-C-C 16 -aryl or O-C3-C 12 -heteroaryl.

[0014] In some embodiments, R 1 COOH, C(=O)-O-C1-C 12 -Alkyl, or C(=O)-O-C6-C 16 -aryl, in particular COOH or C(=O)-O-C1-C4-alkyl.

[0015] In some embodiments, the compound of formula (I) is a compound of formula (II):

[0016] [ka] or a tautomer and / or a pharmaceutically acceptable salt thereof, In the formula, R 6 is hydroxyl or optionally substituted C1-C 30 R represents the part2 , R 3 , R 4 , R 5 , and

[0017] [ka] is defined as set forth above for formula (I).

[0018] In some embodiments, R 2 represents hydrogen or C1-C6 acyl, especially hydrogen.

[0019] In some embodiments, R 3 is an optionally substituted C1-C 12 -Alkyl, optionally substituted C-C 12 -Alkenyl, optionally substituted C-C 12 -alkynyl, optionally substituted C-C 16 -aryl or optionally substituted C-C 12 -represents heteroaryl.

[0020] In some embodiments, R 3 represents: a) optionally substituted C1-C 12 -alkyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; b) optionally substituted C1-C 12-alkenyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; c) optionally substituted C1-C 12 -alkynyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; d) optionally substituted C6-C 16 -aryl, wherein the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; or e) C3-C containing 1, 2, 3, or 4 heteroatoms selected from the group consisting of O, N, and S. 12 -heteroaryl, C3-C 12 -heteroaryl is optionally substituted, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms.

[0021] In some embodiments, R 3is a C-C optionally substituted with 1 to 5, more particularly 1, 2, or 3, substituent(s), especially 1, 16 -aryl, each of the above substituents independently represents: C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; O-C2-C 12 -alkenyl, more particularly O-C2-C7-alkenyl, in particular O-C2-C5-alkenyl; (C=O)-O-C1-C6-alkyl, more particularly (C=O)-O-C1-C4-alkyl; O—(C═O)—C1-C6-alkyl, more particularly O—(C═O)—C1-C4-alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 represents aryl); NH(CO)R 6 (In the formula, R 6 is C1-C6 alkyl or C6-C 12 represents aryl); (C=O)NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 aryl); and It is selected from the group consisting of S-C1-C6-alkyl, more particularly S-C1-C4-alkyl, in particular methylthio or ethylthio.

[0022] In some embodiments, R 3is a C-C optionally substituted with 1 to 5, more particularly 1, 2, or 3, substituent(s), especially 1, 16 -aryl, each of the above substituents independently represents: C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and nitro.

[0023] In some embodiments, R 3 represents phenyl substituted with 1, 2 or 3 substituent(s), each of which, independently of one another, is C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and nitro.

[0024] In some embodiments, R 3 represents phenyl substituted with 1, 2 or 3 fluorine atoms and / or 1, 2 or 3 CF groups, more particularly R 3 represents phenyl substituted with one fluorine atom or one CF3 group, in particular one fluorine atom, in the para position, or phenyl substituted with two fluorine atoms or two CF3 groups, in particular two fluorine atoms or two CF3 groups, in the meta position.

[0025] In some embodiments, R 3 represents phenyl monosubstituted in the ortho-, meta- and / or para-position by fluoro, a CF3 group or by O-C1-C4-alkyl, in particular monosubstituted in the para-position by fluoro or a CF3 group, in particular fluoro.

[0026] In some embodiments, R 3 is selected from one of the following parts:

[0027] [ka]

[0028] In some embodiments, R 4 Optionally substituted C1-C represented by 30 The part is C1-C 30 a moiety comprising 1 to 30, more particularly 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more particularly 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms.

[0029] In some embodiments, R 4 is hydrogen, C1-C6 alkyl or C6-C 16 It represents aryl; more particularly hydrogen or C1-C4 alkyl; especially hydrogen.

[0030] In some embodiments, in Formula (I) or Formula (II):

[0031] [ka] represents a single bond, and both R 5 are each independently hydrogen, C1-C6 alkyl, or C6-C 16It represents aryl; more particularly hydrogen or C1-C4 alkyl; especially hydrogen.

[0032] In some embodiments, in Formula (I) or Formula (II):

[0033] [ka] represents a double bond, and one R 5 does not exist, and the other R 5 is hydrogen, C1-C6 alkyl, or C6-C 16 It represents aryl; more particularly hydrogen or C1-C4 alkyl; especially hydrogen.

[0034] In some embodiments, the compound of formula (I) is a compound of formula (III):

[0035] [ka] where R 2 , R 4 , R 5 , and R 6 is as defined for formula (I),

[0036] [ka] is as defined for formula (I), and R n 7 is n substituents R 7 represents n is an integer of 0 to 5, more specifically 0 to 3, and particularly 1. When n is 0, R 7 means that there is no R 7 are independent of each other, C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; O-C2-C 12 -alkenyl, more particularly O-C2-C7-alkenyl, in particular O-C2-C5-alkenyl; (C=O)-O-C1-C6-alkyl, more particularly (C=O)-O-C1-C4-alkyl; O—(C═O)—C1-C6-alkyl, more particularly O—(C═O)—C1-C4-alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 represents aryl); NH(CO)R 6 (In the formula, R 6 is C1-C6 alkyl or C6-C 12 represents aryl); (C=O)NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 aryl); and It represents a moiety selected from the group consisting of S-C1-C6-alkyl, more particularly S-C1-C4-alkyl, in particular methylthio or ethylthio.

[0037] In some embodiments, in Formula (III), n is 1, 2, or 3, and R 7 The substituent(s) are in the ortho and / or para position(s). In some embodiments, n is 1 and R 7 is in the ortho or para position.

[0038] In some embodiments, in Formula (III), R 7represents, independently of one another, a moiety selected from the group consisting of O-C-C-alkyl, more particularly O-C-C-alkyl, in particular methoxy or ethoxy; halogen, more particularly chloro or fluoro, in particular fluoro; C-C-haloalkyl, more particularly C-C-fluoroalkyl, in particular trifluoromethyl; and nitro.

[0039] In some embodiments, the compound of formula (I) is a compound of formula (IV):

[0040] [ka] where R 2 and R 6 is as defined for formula (I),

[0041] [ka] is as defined for formula (I), and R n 7 is as defined above for formula (III).

[0042] In some embodiments, the compound of formula (I) is a compound of formula (V):

[0043] [ka] where R 2 and R 6 is as defined for formula (I).

[0044] In some embodiments, the composition is in the form of a solid, liquid, ink, gel, a patch for transferring the composition onto the skin, or a substrate carrier that contains the topical composition.

[0045] In some embodiments, excipients suitable for topical administration include one or more excipients selected from water, ethanol, isopropanol, n-propanol, ethylene glycol, diethylene glycol, propylene glycol, glycerol, and mixtures thereof.

[0046] In some embodiments, the composition comprises a thickening agent and / or a film-forming agent.

[0047] In some embodiments, the compound of formula (I) can be prepared by lysine conversion to the corresponding compound of formula (VI):

[0048] [ka] (In the formula, R 3 , R 4 , R 5 , and R 6 is as defined for formula (I),

[0049] [ka] is as defined for formula (I) and then absorbs light having a wavelength of about 380 nm to about 565 nm, more specifically about 380 nm to about 568 nm, and particularly about 380 nm to about 570 nm; The corresponding compound of formula (VI) optionally also absorbs light at wavelengths of from about 590 nm to about 750 nm, more particularly from about 587 nm to about 750 nm, and especially from about 585 nm to about 750 nm; and The corresponding compound of formula (VI) optionally does not absorb light at wavelengths of from about 566 nm to about 589 nm, more particularly from about 569 nm to about 586 nm, and especially from about 571 nm to about 584 nm.

[0050] In some embodiments, the composition further comprises genipin or a genipin derivative, more specifically in a relative molar amount of 0.05 to 20 relative to the amount of the compound of formula (I).

[0051] In some embodiments, the composition further comprises an antioxidant.

[0052] In a second aspect, the present disclosure relates to a storage unit comprising a topical composition according to any embodiment of the first aspect, wherein the storage unit is protected from oxygen ingress or comprises an oxygen scavenger.

[0053] In a third aspect, the present disclosure relates to a method for preparing a topical composition of any of the embodiments of the first aspect, comprising mixing a compound of formula (I) as defined above with excipients suitable for topical administration.

[0054] In a fourth aspect, the present disclosure relates to a method of combining a compound of formula (I) as defined above with genipin or a genipin derivative. [Brief explanation of the drawings]

[0055] [Figure 1] One possible mechanism of binding of genipin to skin is shown, in this case to amino groups of skin macromolecules such as collagen or keratin. [Figure 2] 1 shows a comparison of the UV / vis spectra of the compound of Example 1 before and after conversion to its lysine conjugate. DETAILED DESCRIPTION OF THE INVENTION

[0056] Provided herein are topical compositions comprising a semi-permanent colorant and / or a semi-permanent colorant precursor, including a genipin derivative. As used herein, "topical composition" refers to a composition suitable for application to skin, more specifically mammalian skin, particularly human skin (i.e., suitable for cosmetic use). As used herein, "semi-permanent colorant" refers to a colorant that penetrates one or more layers of the skin and cannot be removed from the skin without physical disruption or natural desquamation of the skin. In some embodiments, the semi-permanent colorant may include, for example, genipin, a genipin derivative colorant precursor, which develops color upon reaction with one or more other molecules on the skin. In some embodiments, the semi-permanent colorant may penetrate the stratum corneum and react with other molecules present in the stratum corneum, thereby immobilizing the semi-permanent colorant within the stratum corneum. For example, the semi-permanent colorant may react with, for example, collagen or keratin found in the stratum corneum. The semi-permanent colorant penetrates the stratum corneum, and the residence time of the colorant may depend on the natural skin exfoliation process. In some embodiments, the semi-permanent colorant cannot be washed off, for example, by water, soap, and / or isopropanol.

[0057] In a first aspect, the present disclosure provides a compound of formula (I):

[0058] [ka] or a tautomer and / or a pharmaceutically acceptable salt thereof, During the ceremony, R 1 optionally substituted C1-C 30 represents a part, R 2 represents hydrogen or a protecting group that is hydrolyzable under physiological conditions after application of the topical composition to the skin, R 3 optionally substituted C1-C 30 represents a part, R 4 is hydrogen or optionally substituted C-C 30 represents a part,

[0059] [ka] represents a single bond, and both R 5 are, independently of each other, hydrogen or optionally substituted C-C 30 Represents a part, or

[0060] [ka] R represents a double bond, and R 5 does not exist and R 5 the other is hydrogen or an optionally substituted C-C 30 a compound, or a tautomer and / or a pharmaceutically acceptable salt thereof, representing a moiety and an excipient suitable for topical administration.

[0061] The present inventors have surprisingly found that providing a carbonyl-based substituent on the conjugated core system of a genipin derivative (when attached to an amino group found on skin) provides a vivid and intense color impression to the chromophore system of the genipin derivative. As described in the experimental section, the color impression is significantly more vivid (intense, vibrant yellow compared to pale yellow) than that of a genipin derivative having an aldehyde-based substituent instead of a carbonyl-based substituent. Furthermore, although both aldehyde and carbonyl substituents can provide similar color impressions, the carbonyl-based genipin derivatives are believed to be more stable (when applied to the skin) and potentially longer-lasting than the corresponding aldehyde analogues.

[0062] In the present disclosure, the term "excipient" is understood as established in the pharmaceutical field, for example as established in the European Pharmacopoeia. In particular, "excipient" means a pharmaceutically or metabolically inactive substance that serves as a vehicle or medium for a compound of formula (I).

[0063] R 1 optionally substituted C1-C 30When referring to a moiety, it should be understood that the moiety may optionally contain other atoms, but the optional substituents do not bring the total carbon number of the moiety beyond 30. In some embodiments, an optionally substituted C-C 30 The moiety is (optionally substituted) C-C 18 Moiety or (optionally substituted) C1-C 12 It can be a part.

[0064] R 2 In this context, when referring to protecting groups that are hydrolyzable under physiological conditions after application of the topical composition to the skin, the following applies: such groups will be readily apparent to those skilled in the art and include, in particular, acyl moieties, such as optionally substituted acyl moieties containing 1 to 30, more particularly 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more particularly 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms. Specific examples include C1-C 18 The acyl moiety, more specifically C1-C 12The term "protective group hydrolyzable under physiological conditions after application of a topical composition" refers to a group that is hydrolyzed when 0.1 mol / L of the compound of formula (I) is placed in an aqueous solution having a pH of about 5 and further containing 0.1 mol / L of lysine at 37°C for 2 hours, and the group in question is qualified as "protective group hydrolyzable under physiological conditions after application of a topical composition" if a significant amount of 1,4-dihydropyridine derivative (for example, a conversion yield of more than 10 mol%) is formed. Additionally or alternatively, a compound of formula (I) contains a "protecting group hydrolyzable under physiological conditions after application of a topical composition" if the compound (or a topical composition containing the compound) cannot be comprehensively washed off the (explanted) pig skin with water, soap, and / or isopropanol after incubating the compound (or a topical composition containing the compound) on the pig skin, e.g., at 37°C for, e.g., 2 hours.

[0065] In some embodiments, R 1 Optionally substituted C1-C represented by 30 The moiety is a moiety containing 1 to 30, more specifically 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and especially 0 to 6 halogen atoms. The above numbers refer to the total number of carbon, oxygen, nitrogen, sulfur, and halogen atoms, respectively. The above optionally substituted C1-C 30It is to be understood that the moiety may optionally include other atoms and optionally further substituents, but that even in the presence of such optional further substituents the number of carbon, oxygen, nitrogen, sulfur, and halogen mentioned above may not be exceeded. It is also to be understood that halogen refers specifically to fluoro, chloro, and bromo.

[0066] In some embodiments, R 1 is -COOH, R 6 , or -C(=O)-R 6 wherein R 6 is an optionally substituted C1-C 12 -Alkyl, C2-C 12 -Alkenyl, C2-C 12 -Alkynyl, C6-C 16 -aryl or C3-C 12 -heteroaryl, O-C-C 12 -Alkyl, O-C2-C 12 -Alkenyl, O-C2-C 12 -Alkynyl, O-C-C 16 -aryl or O-C3-C 12 -heteroaryl.

[0067] In some embodiments, R 1 COOH, C(=O)-O-C1-C 12 -Alkyl, or C(=O)-O-C6-C 16 -aryl, in particular COOH or C(=O)-O-C1-C4-alkyl.

[0068] In some embodiments, the compound of formula (I) is a compound of formula (II):

[0069] [ka] or a tautomer and / or a pharmaceutically acceptable salt thereof, In the formula, R 6 is hydroxyl or optionally substituted C1-C 30 R represents the part 2 , R 3 , R4 , R 5 , and

[0070] [ka] is defined as set forth above for formula (I).

[0071] In some embodiments, R 2 represents hydrogen or C1-C6 acyl, especially hydrogen.

[0072] In some embodiments, R 3 is an optionally substituted C1-C 12 -Alkyl, optionally substituted C-C 12 -Alkenyl, optionally substituted C-C 12 -alkynyl, optionally substituted C-C 16 -aryl or optionally substituted C-C 12 -represents heteroaryl.

[0073] In some embodiments, R 3 represents: a) optionally substituted C1-C 12 -alkyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly fluoro, chloro, or bromo, especially fluoro; b) optionally substituted C1-C 12-alkenyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly fluoro, chloro, or bromo, especially fluoro; c) optionally substituted C1-C 12 -alkynyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly fluoro, chloro, or bromo, especially fluoro; d) optionally substituted C6-C 16 -aryl, wherein the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly fluoro, chloro, or bromo, especially fluoro; or e) C3-C containing 1, 2, 3, or 4 heteroatoms selected from the group consisting of O, N, and S. 12 -heteroaryl, C3-C 12-heteroaryl is optionally substituted, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly fluoro, chloro, or bromo, especially fluoro.

[0074] In some embodiments, R 3 optionally further substituted C6-C 16 It may be particularly advantageous for the optional substituents to represent -aryl, in which the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly the halogen atoms fluoro, chloro, or bromo, especially fluoro.

[0075] In some embodiments, R 3 contains 1, 2, 3, or 4 heteroatoms selected from the group consisting of O, N, and S; 12 -heteroaryl, C3-C 12Heteroaryl is optionally further substituted, where the optional substituents may particularly advantageously contain a total of 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms, more particularly fluoro, chloro, or bromo, especially fluoro. As used herein, the term "heteroaryl" refers to a stable heterocyclic or polyheterocyclic aromatic moiety having 3 to 12 carbon ring atoms. As noted above, heteroaryl groups may be substituted or unsubstituted within the above ranges. Heteroaryl may contain one or more rings. Typical examples of heteroaryl rings include 5-membered monocyclic ring groups such as thienyl, pyrrolyl, imidazolyl, pyrazolyl, furyl, isothiazolyl, furazanyl, isoxazolyl, and thiazolyl; 6-membered monocyclic ring groups such as pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, and triazinyl; and polycyclic heterocyclic ring groups such as benzo[b]thienyl, naphtho[2,3-b]thienyl, thianthrenyl, isobenzofuranyl, chromenyl, xanthenyl, phenoxathienyl, indolizinyl, and isoindo. Examples of aryl include indolyl, indolyl, indazolyl, purinyl, isoquinolyl, quinolyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, benzothiazole, benzimidazole, tetrahydroquinoline, cinnolinyl, pteridinyl, carbazolyl, beta-carbolinyl, phenanthridinyl, acridinyl, perimidinyl, phenanthrolinyl, phenazinyl, isothiazolyl, phenothiazinyl, and phenoxazinyl (see, for example, Katritzky, Handbook of Heterocyclic Chemistry, 3 rded. 2010). Further specific examples of heteroaryl rings include 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxadiazolyl, 5-oxadiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxadiazolyl, 5-oxadiazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 1-pyrrolyl, 2-pyrrolyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-pyrimidyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2 ... -pyridazinyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 5-tetrazolyl, 2-triazolyl, 5-triazolyl, 2-thienyl, 3-thienyl, carbazolyl, benzimidazolyl, benzothienyl, benzofuranyl, indolyl, quinoiinyl, benzotriazolyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, isoquinolinyl, indolyl, isoindolyl, acridinyl, or benzisoxazolyl. Heteroaryl groups also include groups in which the heteroaromatic ring is fused to one or more aromatic or non-aromatic rings, where the radical or point of attachment is on the heteroaromatic ring. Examples include tetrahydroquinoline, tetrahydroisoquinoline, and pyrido[3,4-d]pyrimidinyl, imidazo[1,2-a]pyrimidyl, imidazo[1,2-a]pyrazinyl, imidazo[1,2-a]pyiridinyl, imidazo[1,2-c]pyrimidyl, pyrazolo[1,5-a][1,3,5]triazinyl, pyrazolo[1,5-c]pyrimidyl, imidazo[1,2-b]pyridazinyl, imidazo[1,5-a]pyrimidyl, pyrazolo[1,5-b][1,2,4]triazine, quinolyl, isoquinolyl, quinoxalyl, imidazotriazinyl, pyrrolo[2,3-d]pyrimidyl, triazolopyrimidyl, pyridopyrazinyl.

[0076] In some embodiments, R 3 C-C optionally substituted by 1 to 5, more particularly 1, 2, or 3 substituent(s), especially 1 substituent 16 -aryl, each of the above substituents independently represents: C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; O-C2-C 12 -alkenyl, more particularly O-C2-C7-alkenyl, in particular O-C2-C5-alkenyl; (C=O)-O-C1-C6-alkyl, more particularly (C=O)-O-C1-C4-alkyl; O—(C═O)—C1-C6-alkyl, more particularly O—(C═O)—C1-C4-alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 represents aryl); NH(CO)R 6 (In the formula, R 6 is C1-C6 alkyl or C6-C 12 represents aryl); (C=O)NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 aryl); and It may be particularly advantageous to select from the group consisting of S-C1-C6-alkyl, more particularly S-C1-C4-alkyl, in particular methylthio or ethylthio.

[0077] In some embodiments, R 3 C-C optionally substituted by 1 to 5, more particularly 1, 2, or 3 substituent(s), especially 1 substituent 12 -aryl, each of the above substituents independently represents: C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and It may be particularly advantageous to select from the group consisting of nitro.

[0078] In some embodiments, R 3 represents phenyl substituted with 1, 2 or 3 substituent(s), each of which, independently of one another, is C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and It may be particularly advantageous to select from the group consisting of nitro.

[0079] In some embodiments, R 3 is substituted with 1, 2, 3, 4, or 5 fluorine atoms and / or fluorine-containing groups, particularly CF3.

[0080] In some embodiments, R 3 represents phenyl, naphthenyl, anthracenyl, pyrenyl, indenyl, thiophenyl, furanyl, benzoxazolyl, or indolyl substituted with 1, 2, 3, 4, or 5 fluorine atoms and / or fluorine-containing groups, in particular CF3.

[0081] In some embodiments, R 3represents phenyl substituted with 1, 2 or 3 fluorine atoms and / or 1, 2 or 3 CF groups, more particularly R 3 represents phenyl substituted with one fluorine atom or one CF3 group, in particular one fluorine atom, in the para position, or phenyl substituted with two fluorine atoms or two CF3 groups, in particular two fluorine atoms or two CF3 groups, in the meta position.

[0082] In some embodiments, R 3 represents phenyl monosubstituted in the ortho-, meta- and / or para-position by a fluoro or CF3 group or by an O-C1-C4-alkyl, in particular monosubstituted in the para-position by a fluoro or CF3 group, in particular by fluoro.

[0083] In some embodiments, R 3 is selected from one of the following parts:

[0084] [ka]

[0085] In some embodiments, R 3 is selected from one of the following parts:

[0086] [ka]

[0087] The fluoro-based substituents in the above embodiments can produce a hyperchromic effect (i.e., increased absorption) without causing a significant bathochromic or hypsochromic shift. For these reasons, the genipin derivatives of the present disclosure having such substituents are R 3 The ability to decouple the absorbance of the moiety to some extent from the absorption wavelength is particularly interesting in providing genipin derivatives with intense colors and facilitating the design of genipin derivatives with desired colors.

[0088] In some embodiments, R 4 Optionally substituted C1-C represented by 30 The part is C1-C 30 and 0 to 10, more particularly 0 to 8, particularly 0 to 6 halogen atoms. In some embodiments, an optionally substituted C1-C 30 The moiety is (optionally substituted) C-C 18 Moiety or (optionally substituted) C1-C 12 It can be a part.

[0089] In some embodiments, R 4 Optionally substituted C1-C represented by 30 The moiety is a moiety containing 1 to 30, more specifically 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and especially 0 to 6 halogen atoms. The above numbers refer to the total number of carbon, oxygen, nitrogen, sulfur, and halogen atoms, respectively. The above optionally substituted C1-C 30 It is to be understood that the moiety may optionally include other atoms and optionally further substituents, but that even in the presence of such optional further substituents the number of carbon, oxygen, nitrogen, sulfur, and halogen mentioned above may not be exceeded. It is also to be understood that halogen refers specifically to fluoro, chloro, and bromo.

[0090] In some embodiments, R 4 is hydrogen, C1-C6 alkyl or C6-C 16 It represents aryl; more particularly hydrogen or C1-C4 alkyl; especially hydrogen.

[0091] In some embodiments, R 5 Optionally substituted C1-C represented by each example of 30 The moieties are those containing (independently of each other) 1 to 30, more particularly 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more particularly 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms. The above numbers refer to the total number of carbon, oxygen, nitrogen, sulfur, and halogen atoms, respectively. The above optionally substituted C1-C 30 It is to be understood that the moiety may optionally include other atoms and optionally further substituents, but that even in the presence of such optional further substituents the number of carbon, oxygen, nitrogen, sulfur, and halogen mentioned above may not be exceeded. It is also to be understood that halogen refers specifically to fluoro, chloro, and bromo.

[0092] In some embodiments, in formula (I):

[0093] [ka] represents a single bond, and both R 5 are each independently hydrogen, C1-C6 alkyl, or C6-C 16 It represents aryl; more particularly hydrogen or C1-C4 alkyl; especially hydrogen.

[0094] In some embodiments, in formula (I):

[0095] [ka] represents a double bond, and one R 5 does not exist, and the other R 5 is hydrogen, C1-C6 alkyl, or C6-C 16 It represents aryl; more particularly hydrogen or C1-C4 alkyl; especially hydrogen.

[0096] In some embodiments, the compound of formula (I) is a compound of formula (III):

[0097] [ka] where R 2 , R 4 , R 5 , and R 6 is as defined for formula (I), more specifically, R 2 , R 4 , and R 5 represents hydrogen, and R 6 represents a methoxy group,

[0098] [ka] is as defined for formula (I), and R n 7 is n substituents R 7 represents n is an integer of 0 to 5, more specifically 0 to 3, and particularly 1. When n is 0, R 7 means that there is no R 7 are independent of each other, C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; O-C2-C 12 -alkenyl, more particularly O-C2-C7-alkenyl, in particular O-C2-C5-alkenyl; (C=O)-O-C1-C6-alkyl, more particularly (C=O)-O-C1-C4-alkyl; O—(C═O)—C1-C6-alkyl, more particularly O—(C═O)—C1-C4-alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 represents aryl); NH(CO)R 6 (In the formula, R 6 is C1-C6 alkyl or C6-C 12 represents aryl); (C=O)NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 aryl); and S-C1-C6-alkyl, more particularly S-C1-C4-alkyl, in particular a moiety selected from the group consisting of methylthio or ethylthio, more particularly n represents 1, R 7 represents fluorine or CF, more specifically fluorine, and more specifically R 7 is in para position.

[0099] In some embodiments, in Formula (III), n is 1, 2, or 3, and R 7 The substituent(s) are in the ortho and / or para position(s). In some embodiments, n is 1 and R 7 is in the ortho or para position.

[0100] In some embodiments, in Formula (III), R 7 represents, independently of one another, a moiety selected from the group consisting of O-C-C-alkyl, more particularly O-C-C-alkyl, in particular methoxy or ethoxy; halogen, more particularly chloro or fluoro, in particular fluoro; C-C-haloalkyl, more particularly C-C-fluoroalkyl, in particular trifluoromethyl; and nitro.

[0101] In some preferred embodiments, in formula (III), R 2 represents hydrogen, and R6 represents a methoxy group, and n represents 1.

[0102] [ka] is a single bond, and R 7 represents fluorine, more specifically, R 7 In an even more preferred embodiment, R 4 and R 5 represents hydrogen.

[0103] In some embodiments, the compound of formula (I) is a compound of formula (IV):

[0104] [ka] where R 2 and R 6 is as defined for formula (I),

[0105] [ka] is as defined for formula (I), more specifically, R 2 represents hydrogen, and R 6 represents a methoxy group, and R n 7 is as defined above for formula (III), more specifically, n represents 1, R 7 represents fluorine or CF, more particularly fluorine, and more particularly R 7 is in para position.

[0106] In some preferred embodiments, in formula (IV), R 2 represents hydrogen, and R 6 represents a methoxy group, and n represents 1.

[0107] [ka] is a single bond, and R 7represents fluorine, more specifically, R 7 is in para position.

[0108] In some embodiments, the compound of formula (I) is a compound of formula (V):

[0109] [ka] where R 2 and R 6 is as defined for formula (I).

[0110] In some preferred embodiments, in formula (V), R 2 represents hydrogen, and R 6 represents a methoxy group.

[0111] In some preferred embodiments, the compound of formula (III) or formula (IV) or formula (V) is the following compound:

[0112] [ka]

[0113] Generally, the above-mentioned composition can be formulated into any form known in the art for topical or cosmetic administration.Therefore, the composition can be applied in any topical form, such as aerosol spray, cream, emulsion, solid, liquid, dispersion, foam, oil, gel, hydrogel, lotion, mousse, ointment, powder, patch, pomade, solution, pump spray, stick, towelette, soap, or other forms commonly used in topical administration and / or cosmetics / sunscreen and skin care formulation fields.The composition can be water-resistant (for example, waterproof).

[0114] In some embodiments, the composition is in the form of a substrate carrier, including a solid, liquid, ink, gel, patch for transferring the composition onto the skin, or topical composition.

[0115] The compositions of the present disclosure may contain any one of the compounds described herein in the range of 0.005% to 99% by weight, with the remainder consisting of suitable excipients. Contemplated compositions may contain 0.001% to 99% by weight of any one of the compounds provided herein, in one embodiment 0.1 to 95% by weight, in another embodiment 75 to 85% by weight, and in a further embodiment 20 to 80% by weight, with the remainder consisting of any excipient described herein, or any combination of these excipients. In some preferred embodiments, the topical composition may contain 0.05% to 15% by weight, even more specifically 0.05% to 10% by weight, more specifically 0.08% to 5% by weight, and particularly 0.1% to 3% by weight, of any one of the compounds provided herein, based on the total weight of the composition.

[0116] In some embodiments, the topical composition comprises one or more additional ingredients, carriers, or diluents, including, but not limited to, absorbents, anti-irritants, anti-acne agents, preservatives, antioxidants, colorants / pigments, emollients (moisturizers), emulsifiers, film-forming / retentive agents, fragrances, leave-on exfoliants, prescription medications, preservatives, exfoliants, silicones, skin-leveling / repairing agents, slip agents, additional conventional sunscreen actives (non-limiting examples of such sunscreens include titanium dioxide and zinc oxide), surfactants / detergents, penetration enhancers, and thickeners. In particular, the composition may contain any acceptable excipient approved by the FDA or EMA for such use. Examples of acceptable inactive excipients include retinyl palmitate, parabens, PEG, fragrance, BHT, phthalates, phenoxyethanol, coconut oil, aloe vera, sunflower seed oil, calendula, almond oil, starch, gelatin, hemicellulose, arabinogalactan, agar, glycerol, lactic acid, propylene glycol, polyethylene glycol, polyvinylpyrrolidone, acrylates, acrylamide, copolymers of the above, amino acids such as arginine, alanine, or asparagine, ascorbic acid, citric acid, and mixtures thereof.

[0117] In some embodiments, excipients suitable for topical administration include one or more excipients selected from water, ethanol, isopropanol, n-propanol, ethylene glycol, diethylene glycol, propylene glycol, glycerol, and mixtures thereof.

[0118] In some preferred embodiments, excipients suitable for topical administration include water, monohydric or polyhydric alcohols, or mixtures thereof.

[0119] In some preferred embodiments, the excipient is water, C1-C4 alkyl alcohol, C1-C4 alkyloxydiglycol, C2-C8 alkanediol, glycerol, C1-C 12 These include alkylglycerols, di(C1-C6 alkyl)glycerols, saccharides, disaccharides, polysaccharides, phenoxyethanol, oils, terpenoids, phenylpropanoids, amino acids, proteins, water-soluble polymers, or mixtures thereof.

[0120] In some embodiments, it may be particularly preferred for the topical composition to have a pH of 2.5-9, more particularly 3-8, and especially 4-7.

[0121] In some embodiments, the composition comprises a thickening agent and / or a film-forming agent.

[0122] In some embodiments, the composition further comprises an antioxidant.

[0123] In some embodiments, the topical composition is contained within a container, optionally further comprising packaging surrounding the container. The term packaging should be understood to refer to its conventional meaning in the art, particularly to the enclosure or protection by a container for distribution, storage, sale, and / or use.

[0124] In some embodiments, the compound of formula (I) can be prepared by lysine conversion to the corresponding compound of formula (VI):

[0125] [ka] (In the formula, R 3 , R 4 , R 5 , and R 6 is as defined for formula (I),

[0126] [ka] is as defined for formula (I) and then absorbs light having a wavelength of about 380 nm to about 565 nm, more specifically about 380 nm to about 568 nm, and particularly about 380 nm to about 570 nm; The corresponding compound of formula (VI) optionally also absorbs light at wavelengths of from about 590 nm to about 750 nm, more particularly from about 587 nm to about 750 nm, and especially from about 585 nm to about 750 nm; and The corresponding compound of formula (VI) optionally does not absorb light at wavelengths of from about 566 nm to about 589 nm, more particularly from about 569 nm to about 586 nm, and especially from about 571 nm to about 584 nm.

[0127] With regard to the above absorption characteristics, it should be noted that the human eye is most sensitive to green light, and therefore absorption of light with wavelengths of about 380 nm to about 565 nm, more specifically about 380 nm to about 568 nm, and especially about 380 nm to about 570 nm, in particular imparts a green hue to colors and removes that portion of the visible spectrum that is most receptive to the human eye.

[0128] Optionally, the corresponding compound of formula (VI) above does not absorb light at wavelengths between about 566 nm and about 589 nm, more particularly between about 569 nm and about 586 nm, and especially between about 571 nm and about 584 nm, which correspond to wavelengths that the human eye perceives as red or reddish. Because the human eye is significantly less sensitive to these wavelengths than to "green" wavelengths, generally, lower absorption (relatively) in this wavelength region is more tolerable than in the "green" wavelength region.

[0129] Additionally, the corresponding compound of formula (VI) above optionally absorbs light at wavelengths between about 590 nm and about 750 nm, more specifically between about 587 nm and about 750 nm, and especially between about 585 nm and about 750 nm. This wavelength range is generally perceived by the human eye as yellow, and the narrowness of the bandwidth of wavelengths reflected by this characteristic is a measure of the brightness of the color (narrower wavelength distributions are perceived as brighter by humans).

[0130] The measurement conditions for determining the absorption (or lack thereof) of the corresponding compound of formula (VI) above are not particularly limited. Exemplary conditions include typical conditions for UV / vis-spectroscopic measurements, such as about 1-5×10 at about 20° C. -5 M solution. Those skilled in the art are generally able to interpret UV / vis spectra and determine whether there is absorption in a particular wavelength region. However, if a quantitative measurement is required, the corresponding compound of formula (VI) may not be considered to be such if it has a (normalized) absorption coefficient of 0.4 or less, particularly greater than 0.2, and especially greater than 0.1, in the wavelength region in question.

[0131] In some embodiments, the composition further comprises an antioxidant.

[0132] In a second aspect, the present disclosure relates to a storage unit comprising a topical composition according to any embodiment of the first aspect, wherein the storage unit is protected from oxygen ingress or comprises an oxygen scavenger. In some embodiments, the storage unit further comprises packaging surrounding the storage unit.

[0133] In a third aspect, the present disclosure relates to a method for preparing a topical composition of any of the embodiments of the first aspect, comprising mixing a compound of formula (I) as defined above with excipients suitable for topical administration.

[0134] In a fourth aspect, the present disclosure relates to a method of combining a compound of formula (I) as defined above with genipin or a genipin derivative.

[0135] The term "genipin derivative" refers to any derivative of genipin, in particular the following substituted chemical moiety of formula (VII):

[0136] [ka] wherein R independently represent H or a substituent;

[0137] [ka] represent a single bond, and each independently

[0138] [ka] both R's attached to represent hydrogen or substituents, or

[0139] [ka] represents a double bond, and

[0140] [ka] One of the Rs bonded to is absent,

[0141] [ka] The other R bonded to represents hydrogen or a substituent. In some embodiments, the genipin derivative is a compound of formula (I), more specifically, the genipin derivative is a compound of formula (II), (III), (IV), and / or (V).

[0142] In a further aspect, the present disclosure relates to a mixture of a compound of formula (I) as defined above with a dye, pigment, and / or genipin or a genipin derivative as defined above.

[0143] For clarity, the present disclosure also relates to compounds of formula (I), and more specifically to compounds of formulas (II), (III), (IV), and (V) per se.

[0144] In a still further aspect, the present disclosure relates to methods for preparing compounds of formula (I), and more particularly, compounds of formula (II), (III), (IV), or (V).

[0145] In a still further aspect, the present disclosure relates to the use of a compound of formula (I), more particularly a compound of formula (II), (III), (IV) or (V), for coloring the skin or artificial or natural fibers, in particular for coloring the skin or hair.

[0146] In some embodiments, the use comprises administering the compound to skin, particularly mammalian skin, and / or to the surface, epidermis or dermis of the skin, and / or to skin appendages such as nails. In some embodiments, the use comprises applying the compound to artificial and natural fibers. In some embodiments, the use comprises administering the compound to hair, particularly mammalian hair, especially hair still attached to the skin.

[0147] In still further aspects, the present disclosure relates to methods of coloring skin or artificial or natural fibers, particularly for skin or hair coloration using compounds of formula (I), more particularly compounds of formula (II), (III), (IV), or (V), hi some preferred embodiments, the method is a tattooing method.

[0148] The compounds provided herein also include tautomeric forms. Tautomeric forms result from the exchange of a single bond with an adjacent double bond with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers, which are isomeric protonation states with the same empirical formula and total charge. Examples of prototropic tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and cyclic forms in which protons can occupy more than one position in a heterocyclic ring system, such as 1H-imidazole and 3H-imidazole, 1H-1,2,4-triazole, 2H-1,2,4-triazole and 4H-1,2,4-triazole, 1H-isoindole and 2H-isoindole, and 1H-pyrazole and 2H-pyrazole. Tautomeric forms can be in equilibrium or can be sterically fixed into one form by appropriate substitution.

[0149] As used herein, a "salt" or "pharmaceutically acceptable salt" of a compound of any one of the formulas disclosed herein is formed between an acidic group of the compound, such as an amino functional group, and a basic group, or between a basic group of the compound, such as a carboxy functional group, and an acidic group. According to another embodiment, the compound is a pharmaceutically acceptable acid addition salt. In some embodiments, acids commonly utilized to form pharmaceutically acceptable salts of a compound of any one of the formulas include inorganic acids such as hydrogen bisulfide, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, and phosphoric acid, as well as organic acids such as para-toluenesulfonic acid, salicylic acid, tartaric acid, bitartaric acid, ascorbic acid, maleic acid, besylic acid, fumaric acid, gluconic acid, glucuronic acid, formic acid, glutamic acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, lactic acid, oxalic acid, para-bromophenylsulfonic acid, carbonic acid, succinic acid, citric acid, benzoic acid, and acetic acid, and related inorganic and organic acids. Accordingly, such pharmaceutically acceptable salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutyrate, caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne-1,4-dioate, hexyne-1,6- Included are dioate, benzoate, chlorobenzoate, methyl benzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, sulfonate, xylenesulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, β-hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene-1-sulfonate, naphthalene-2-sulfonate, mandelate, and other salts. In one embodiment, pharmaceutically acceptable acid addition salts include those formed with mineral acids such as hydrochloric acid, hydrobromic acid, and especially those formed with organic acids such as maleic acid.In some embodiments, bases commonly utilized to form pharmaceutically acceptable salts of a compound of any one of the formulas include hydroxides of alkali metals including sodium, potassium, and lithium, hydroxides of alkaline earth metals such as calcium and magnesium, hydroxides of other metals such as aluminum and zinc, ammonia, unsubstituted or hydroxyl-substituted mono-, di-, or tri-alkylamines, organic amines such as dicyclohexylamine, tributylamine, pyridine, N-methyl, N-ethylamine, diethylamine, triethylamine, mono-, bis-, or tris-(2-OH-(C1-C6)-alkylamines) such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine, N-methyl-D-glucamine, morpholine, thiomorpholine, piperidine, pyrrolidine, and amino acids such as arginine and lysine. In some embodiments, a compound of any one of the formulas disclosed herein or a salt thereof is substantially isolated.

[0150] The compounds of the present disclosure can be prepared using conventional synthetic routes known in the art or by following the reaction schemes below.

[0151] Examples and Comparative Examples All starting materials / reagents / solvents were obtained from Sigma Aldrich, Thermo Fisher, VWR, TCI Chemicals, or Oakwood chemicals and used without further purification. Genipin was supplied by Herb-Sun Biotechnology.

[0152] Comparative Example 1, methyl (4aS,7aS)-7-formyl-1-hydroxy-1,4a,5,7a-tetrahydrocyclo-penta[c]-pyran-4-carboxylate, was prepared as follows.

[0153] [ka]

[0154] To a stirred solution of genipin (50 mmol, 1 equiv.) in dichloromethane was added Dess-Martin periodinane (DMP) (55 mmol, 1.2 equiv.), and the mixture was stirred overnight. Saturated solutions of NaHCO3 and Na2SO3 were added sequentially to the reaction mixture. The resulting mixture was added to a separatory funnel and extracted with dichloromethane / water (three times), followed by brine. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The resulting crude material was 10-15% hydrated. The crude mixture was then dissolved in methanol, to which a spatula tip of Amberlite® IRA-400 resin (hydroxide form) was added. The combination was stirred at room temperature for 15 minutes. The resin was filtered, and the crude material was dry-loaded onto silica gel and purified by flash chromatography (hexane:ethyl acetate = 60:40). The NMR data were consistent with previous reports (see Tetrahedron, 1993, 49, 10555-10576; Tetrahedron Letters, 1993, 34, 2621-2624).

[0155] 1 H NMR(400MHz,CDCl3)δ 9.80(s,1H),9.69(s,1H),7.59-7.54(m,1H),7.50(s,1H),7.23(m,1H),7.16(m, 1H),6.71(d,J=10.9Hz,1H),5.24(dd,J=10.9,2.1Hz,1H),4.79(dd,J=8.4,5.9Hz ,1H),4.57(d,J=6.2Hz,1H),3.74(s,3H),3.72(s,3H),3.50(m,2H),3.36-3.18( m,2H),3.02-2.87(m,2H),2.72(dtd,J=19.8,2.8,1.7Hz,1H),2.49-2.33(m,1H).

[0156] 13C NMR(100MHz,CDCl3)δ 191.8,191.0,167.6,167.4,161.8,156.0,154.7,153.3,144.9,144.6,1 09.9,109.6,95.6,95.1,51.5,51.4,48.3,45.8,40.8,39.6,37.3,36.0; HRMS(DART+):C 11 H 13 O5 [M+H] + Calculated value: 225.07575 m / z, Measured value: 225.07637 m / z

[0157] Example 1 was prepared from Comparative Example 1 using the following general reaction scheme:

[0158] Overall reaction scheme:

[0159] [ka]

[0160] Genipin (1 equivalent) was added to a round-bottom flask and dissolved in dry methanol (0.2 M). To this was added p-toluenesulfonic acid monohydrate (0.3 equivalents), and the reaction was stirred for 68 hours, or until complete conversion was observed by TLC. The methanol was removed under vacuum, and the residue was redissolved in dichloromethane. The solution was passed through a silica plug and rinsed with dichloromethane to remove the acid catalyst. The dichloromethane was removed by rotary evaporation, and then diethyl ether / hexane was added to the residue, yielding a white precipitate. The precipitate was filtered through a Buchner funnel and washed with cold ether / hexane.

[0161] [ka]

[0162] The crude aldehyde obtained in step 1 was transferred to a 1 L Schlenk flask. To this was added THF (0.05 M) and a magnetic stir bar. The flask was cooled to 0 °C, and then the Grignard reagent (0.99 equiv.) was added dropwise at 0 °C and allowed to warm to room temperature. The reaction was monitored by TLC and was complete after 90 min. Upon completion, the reaction was cooled to 0 °C and quenched with 1 M HCl. The quenched solution was stirred for 30 min. The THF / 1 M HCl solution was poured into a separatory funnel containing ethyl acetate and water. The aqueous phase was washed three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated by rotary evaporation. The crude reaction mixture was dry-loaded onto silica and purified by flash column chromatography (EtOAc / hexane: 0:100 to 25:75). The resulting purified material may still be a mixture of diastereomers. The two diastereomers can be separated on a second column with diethyl ether / hexane (20:80→40:60).

[0163] [ka]

[0164] To a stirred solution of the alcohol (1 equivalent) in dichloromethane (0.25 M) was added DMP (1.1 equivalents) at room temperature. The reaction was monitored by TLC over 60 minutes. Upon completion, the solvent was evaporated under reduced pressure, and the residue was washed with saturated sodium bicarbonate and sodium thiosulfate (NaSO) in a separatory funnel containing diethyl ether. The organic phase was dried over sodium sulfate, concentrated, and isolated by flash column chromatography.

[0165] [ka]

[0166] The isolated material from step 3 was dissolved in a mixture of acetic acid, THF, and 3M HCl to a total concentration of 0.07M. The respective proportions were 30% AcOH, 50% THF, and 20% 3M HCl. The mixture was heated to 50°C for 5 days. Upon completion, the mixture was quenched with saturated sodium bicarbonate solution and checked with pH paper until neutral / basic. The mixture was then partitioned between ethyl acetate and water in a separatory funnel. The organic phase was collected, dried over sodium sulfate, and concentrated in vacuo. The crude material was isolated by flash column chromatography.

[0167] Characterization of the major diastereomer 1 H NMR(400MHz,CDCl3)δ 7.88-7.82(m,2H,aryl CH),7.64(1H),7.23-7.16(m,2H,aryl CH),6.89(broad t,J=2.7Hz,1H),6.43(d,J=4.0Hz,1H,OH),4.92(broad dd,J=8.5,4.0Hz,1H),3.78(s,3H),3.39(m,1H),3.29(ddd,J=19.0,8.3,3.2Hz,1H),3.04(m,1H),2.44(ddt,J=19.0,9.5,2.1Hz,1H).

[0168] 13 C NMR(101MHz, CDCl3)δ 194.7,167.7,167.3,164.7,153.4,152.0,141.6,132.3,132.2,116.1,115.8,109.7,95.9,51.5,48.3,41.4,36.3.

[0169] Genipin and the compounds of Example 1 and Comparative Example 1 were converted to their corresponding lysine conjugates according to the following procedure.

[0170] A 0.05M solution of the reactive dye precursor in MeOH was prepared and briefly stirred in a small vial equipped with a stir bar. Two equivalents of L-lysine were added, and the reaction mixture was loosely capped and stirred at room temperature for 24 hours. Upon completion, the solvent was removed under vacuum and further dried using high vacuum.

[0171] Example 1 gave a strong, bright yellow color, whereas Comparative Example 1, while yellow, was pale in comparison.

[0172] Furthermore, the UV / Vis spectra obtained for the compound of Example 1 and its conjugate with lysine are shown in FIG.

[0173] As can be seen from Figure 2, the conjugate of the compound of Example 1 with lysine is characterized by two absorption peaks centered at approximately 350 nm and 450 nm, which are not present in the compound of Example 1 prior to conversion to the lysine conjugate.

[0174] List of Embodiments The following further embodiments are also relevant to the present disclosure: 1. A compound of formula (I),

[0175] [ka] or a tautomer and / or a pharmaceutically acceptable salt thereof, During the ceremony, R 1 optionally substituted C1-C 30 represents a part, R 2 represents hydrogen or a protecting group that is hydrolyzable under physiological conditions after application of the topical composition to the skin, R 3 optionally substituted C1-C 30 represents a part, R 4 is hydrogen or optionally substituted C-C 30 represents a part,

[0176] [ka] represents a single bond, and both R 5 are, independently of each other, hydrogen or optionally substituted C-C 30 Represents a part, or

[0177] [ka] R represents a double bond, and R 5 does not exist and R 5 the other is hydrogen or an optionally substituted C-C 30 a compound, or a tautomer and / or a pharmaceutically acceptable salt thereof, representing a moiety and an excipient suitable for topical administration. 2. R 1 Optionally substituted C1-C represented by 30 The part is C1-C 30 0-8, more particularly 0-6, particularly 0-4 nitrogen atoms; 0-6, more particularly 0-4, particularly 0-3 sulfur atoms; and 0-10, more particularly 0-8, particularly 0-6 halogen atoms. 3. R 1 -COOH, R 6 , or -C(=O)-R 6 wherein R 6 optionally substituted C1-C 12 -Alkyl, C2-C 12 -Alkenyl, C2-C 12 -Alkynyl, C6-C 16 -aryl or C3-C 12 -heteroaryl, O-C-C 12 -Alkyl, O-C2-C 12 -Alkenyl, O-C2-C 12 -Alkynyl, O-C-C 16 -aryl or O-C3-C 12 -heteroaryl. 4. R 1 COOH, C(=O)-O-C1-C 12 -Alkyl or C(=O)-O-C6-C 12-aryl, in particular COOH or C(=O)-O-C1-C4-alkyl. 5. The compound of formula (I) is a compound of formula (II):

[0178] [ka] or a tautomer and / or a pharmaceutically acceptable salt thereof, In the formula, R 6 is hydroxyl or optionally substituted C1-C 30 R represents the part 2 , R 3 , R 4 , R 5 , and

[0179] [ka] The topical composition of any one of embodiments 1-4, wherein is defined as set forth in embodiment 1. 6. R 2 represents hydrogen or C1-C6 acyl, in particular hydrogen. 7. R 3 optionally substituted C1-C 12 -Alkyl, optionally substituted C-C 12 -Alkenyl, optionally substituted C-C 12 -alkynyl, optionally substituted C-C 16 -aryl or optionally substituted C-C 12 7. The topical composition according to any one of embodiments 1 to 6, wherein - represents heteroaryl. 8. R 3 represents the following: a) optionally substituted C1-C 12-alkyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; b) optionally substituted C1-C 12 -alkenyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; c) optionally substituted C1-C 12 -alkynyl, provided that the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; d) optionally substituted C6-C 16 -aryl, wherein the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; or e) C3-C containing 1, 2, 3, or 4 heteroatoms selected from the group consisting of O, N, and S. 12 -heteroaryl, C3-C 12The topical composition of any one of embodiments 1-7, wherein -heteroaryl is optionally substituted, wherein the optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms. 9. R 3 C-C optionally substituted by 1 to 5, more particularly 1, 2, or 3 substituent(s), especially 1 substituent 16 -aryl, wherein each of the above substituents, independently of one another, is C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; O-C2-C 12 -alkenyl, more particularly O-C2-C7-alkenyl, in particular O-C2-C5-alkenyl; (C=O)-O-C1-C6-alkyl, more particularly (C=O)-O-C1-C4-alkyl; O—(C═O)—C1-C6-alkyl, more particularly O—(C═O)—C1-C4-alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 represents aryl); NH(CO)R 6 (In the formula, R 6 is C1-C6 alkyl or C6-C 12 represents aryl); (C=O)NR6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 aryl); and The topical composition according to any one of embodiments 1 to 8, wherein the alkyl group is selected from the group consisting of S-C1-C6-alkyl, more particularly S-C1-C4-alkyl, in particular methylthio or ethylthio. 10. R 3 C-C optionally substituted by 1 to 5, more particularly 1, 2, or 3 substituent(s), especially 1 substituent 16 -aryl, wherein each of the above substituents, independently of one another, is C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and 10. The topical composition of any one of embodiments 1-9, wherein the compound is selected from the group consisting of nitro. 11. R 3 represents phenyl substituted by 1, 2 or 3 substituent(s), each of said substituents being, independently of one another, C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and 11. The topical composition of any one of embodiments 1-10, wherein the compound is selected from the group consisting of nitro. 12. R 3represents phenyl substituted with 1, 2 or 3 fluorine atoms and / or 1, 2 or 3 CF groups, more particularly R 3 represents phenyl substituted with one fluorine atom or one CF3 group, particularly one fluorine atom, in the para position, or phenyl substituted with two fluorine atoms or two CF3 groups, particularly two fluorine atoms or two CF3 groups, in the meta position. 13. R 3 But the following part: 13. The topical composition of any one of embodiments 1-12, representing one of:

[0180] [ka] 14. R 4 Optionally substituted C1-C represented by 30 The part is C1-C 30 14. The topical composition of any one of embodiments 1-13, wherein the moiety comprises 1 to 30, more particularly 1 to 16, and particularly 1 to 12 carbon atoms; 0 to 12, more particularly 0 to 8, and particularly 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, and particularly 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and particularly 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and particularly 0 to 6 halogen atoms. 15. R 4 is hydrogen, C1-C6 alkyl, or C6-C 16 The topical composition according to any one of embodiments 1 to 14, wherein R represents aryl; more particularly hydrogen or C1-C4 alkyl; in particular hydrogen. 16.

[0181] [ka] represents a single bond, and both R 5 are each independently hydrogen, C1-C6 alkyl, or C6-C 1216. The topical composition according to any one of embodiments 1 to 15, wherein R represents aryl; more particularly hydrogen or C1-C4 alkyl; in particular hydrogen.

[0182] 17.

[0183] [ka] represents a double bond, and one R 5 does not exist, and the other R 5 is hydrogen, C1-C6 alkyl or C6-C 16 17. The topical composition according to any one of embodiments 1 to 16, wherein R represents aryl; more particularly hydrogen or C1-C4 alkyl; in particular hydrogen. 18. The compound of formula (I) is a compound of formula (III):

[0184] [ka] where R 2 , R 4 , R 5 , and R 6 is as defined in any one of embodiments 1 to 17;

[0185] [ka] is as defined in embodiment 1, and R n 7 n substituents R 7 represents n is an integer of 0 to 5, more specifically 0 to 3, and particularly 1, and n is 0, R 7 means that there is no R 7 But independently of each other, C1-C6-alkyl, more particularly C1-C4-alkyl, in particular methyl, ethyl and tert-butyl; C1-C4-haloalkyl, more particularly C1-C4-fluoroalkyl, in particular trifluoromethyl; O-C1-C6-alkyl, more particularly O-C1-C4-alkyl, in particular methoxy or ethoxy; O-C2-C 12 -alkenyl, more particularly O-C2-C7-alkenyl, in particular O-C2-C5-alkenyl; (C=O)-O-C1-C6-alkyl, more particularly (C=O)-O-C1-C4-alkyl; O—(C═O)—C1-C6-alkyl, more particularly O—(C═O)—C1-C4-alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 represents aryl); NH(CO)R 6 (In the formula, R 6 is C1-C6 alkyl or C6-C 12 represents aryl); (C=O)NR 6 2 (wherein, R 6 are each, independently of one another, hydrogen, C1-C6 alkyl, or C6-C 12 aryl); and 18. The topical composition according to any one of embodiments 1 to 17, wherein S-C1-C6-alkyl, more particularly S-C1-C4-alkyl, represents a moiety selected from the group consisting of methylthio or ethylthio. 19. n is 1, 2, or 3, and R 7 The substituents are in the ortho and / or para position(s); particularly, n is 1 and R 7 is in the ortho or para position. 20. R 7represents, independently of one another, a moiety selected from the group consisting of O-C-C-alkyl, more particularly O-C-C-alkyl, in particular methoxy or ethoxy; halogen, more particularly chloro or fluoro, in particular fluoro; C-C-haloalkyl, more particularly C-C-fluoroalkyl, in particular trifluoromethyl; and nitro. 21. The compound of formula (I) is a compound of formula (IV):

[0186] [ka] where R 2 and R 6 is as defined in any one of embodiments 1 to 17;

[0187] [ka] is as defined in embodiment 1, and R n 7 is as defined in any one of embodiments 18-20. 22. The compound of formula (I) is a compound of formula (V):

[0188] [ka] where R 2 and R 6 is as defined in any one of embodiments 1-17. 23. A topical composition described in any one of embodiments 1 to 22, wherein the composition is in the form of a solid, liquid, ink, gel, a patch for transferring the composition onto the skin, or a substrate carrier containing the topical composition. 24. A topical composition described in any one of embodiments 1 to 23, wherein the excipient suitable for topical administration comprises one or more excipients selected from water, ethanol, isopropanol, n-propanol, ethylene glycol, diethylene glycol, propylene glycol, glycerol, and mixtures thereof. 25. A topical composition described in any one of embodiments 1 to 24, wherein the composition comprises a thickening agent and / or a film-forming agent. 26. The compound of formula (I) is lysine and the corresponding compound of formula (VI):

[0189] [ka] (In the formula, R 3 , R 4 , R 5 , and R 6 is as defined in any one of embodiments 1 to 17;

[0190] [ka] is as defined in embodiment 1) and then absorbs light having a wavelength of about 380 nm to about 565 nm, more specifically about 380 nm to about 568 nm, and particularly about 380 nm to about 570 nm; The corresponding compound of formula (VI) optionally also absorbs light at wavelengths of from about 590 nm to about 750 nm, more particularly from about 587 nm to about 750 nm, and especially from about 585 nm to about 750 nm; and 26. The topical composition of any one of embodiments 1 to 25, wherein the corresponding compound of formula (VI) optionally does not absorb light at wavelengths of from about 566 nm to about 589 nm, more particularly from about 569 nm to about 586 nm, and particularly from about 571 nm to about 584 nm. 27. The topical composition of embodiment 18, comprising: R 2 represents hydrogen, R 6 represents a methoxy group, N represents 1,

[0191] [ka] is a single bond, and R 7 represents fluorine, more specifically, R 7 is in para position, In particular, R 4 and R 5 represents hydrogen. 28. The topical composition of embodiment 21, R 2 represents hydrogen, R 6 represents a methoxy group, n represents 1,

[0192] [ka] is a single bond, and R 7 represents fluorine, more specifically, R 7 is in the para position. 29. The topical composition of embodiment 22, comprising: R 2 represents hydrogen, and R 6 represents a methoxy group. 30. The topical composition of any one of embodiments 1 to 29, wherein the composition further comprises genipin or a genipin derivative, more specifically in a relative molar amount of 0.05 to 20 relative to the amount of the compound of formula (I). 31. A topical composition according to any one of embodiments 1 to 30, wherein the composition further comprises an antioxidant. 32. A storage unit comprising the topical composition of any one of embodiments 1-31, wherein the storage unit is protected from oxygen ingress or comprises an oxygen scavenger. 33. A method for preparing a topical composition according to any one of embodiments 1 to 31, comprising mixing a compound of formula (I) as defined in any one of embodiments 1 to 30 with excipients suitable for topical administration. 34. A method, wherein a compound of formula (I) as defined in any one of embodiments 1 to 31 is mixed with genipin or a genipin derivative.

Claims

1. A compound of formula (I), 【Chemistry 1】 or a tautomer and / or a pharmaceutically acceptable salt thereof, During the ceremony, R １ is optionally substituted C １ -C ３０ represents a part, R ２ represents hydrogen or a protecting group that is hydrolyzable under physiological conditions after application of the topical composition to the skin, R ３ is optionally substituted C １ -C ３０ represents a part, R ４ is hydrogen or optionally substituted C １ -C ３０ represents a part, 【Chemistry 2】 represents a single bond, and both R ５ are each independently hydrogen or optionally substituted C １ -C ３０ Represents a part, or 【Transformation 3】 R represents a double bond, and R ５ does not exist, and R ５ The other is hydrogen or an optionally substituted C １ -C ３０ a compound, or a tautomer and / or a pharmaceutically acceptable salt thereof, representing a moiety and an excipient suitable for topical administration.

2. R １ The optionally substituted C １ -C ３０ The part is C １ -C ３０ 2. The topical composition of claim 1, which is a moiety comprising 1 to 30, more particularly 1 to 16, and especially 1 to 12 carbon atoms; 0 to 12, more particularly 0 to 8, and especially 0 to 6 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms.

3. R １ But -COOH, R ６ , or -C(=O)-R ６ wherein R ６ is optionally substituted C １ -C １２ -Alkyl, C ２ -C １２ -alkenyl, C ２ -C １２ -alkynyl, C ６ -C １６ -aryl or C ３ -C １２ -heteroaryl, O—C １ -C １２ -alkyl, O—C ２ -C １２ -alkenyl, O—C ２ -C １２ -alkynyl, O—C ６ -C １６ -aryl or O-C ３ -C １２ 3. The topical composition of claim 1 or claim 2, wherein: - is heteroaryl.

4. The compound of formula (I) is a compound of formula (II): 【Chemistry 4】 or a tautomer and / or a pharmaceutically acceptable salt thereof, In the formula, R ６ is hydroxyl or optionally substituted C １ -C ３０ represents the part, and R ２ , R ３ , R ４ , R ５ , and 【Transformation 5】 A topical composition according to any one of claims 1 to 3, wherein is defined as set forth in claim 1.

5. R ２ is hydrogen or C １ -C ６ A topical composition according to any one of claims 1 to 4, wherein acyl represents, in particular, hydrogen.

6. R ３ is optionally substituted C １ -C １２ -alkyl, optionally substituted C ２ -C １２ -alkenyl, optionally substituted C ２ -C １２ -alkynyl, optionally substituted C ６ -C １６ -aryl or optionally substituted C ３ -C １２ The topical composition according to any one of claims 1 to 5, wherein - represents heteroaryl.

7. R ３ represents the following: a) optionally substituted C １ -C １２ -alkyl, provided that said optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; b) optionally substituted C １ -C １２ -alkenyl, provided that said optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; c) optionally substituted C １ -C １２ -alkynyl, provided that said optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; d) optionally substituted C ６ -C １６ -aryl, wherein said optional substituents comprise, in total, 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms; or e) C containing 1, 2, 3, or 4 heteroatoms selected from the group consisting of O, N, and S. ３ -C １２ -heteroaryl, wherein said C ３ -C １２ 7. The topical composition of any one of claims 1 to 6, wherein the heteroaryl is optionally substituted, wherein the optional substituents comprise in total 0 to 12, more particularly 0 to 8, and especially 0 to 6 carbon atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 oxygen atoms; 0 to 8, more particularly 0 to 6, and especially 0 to 4 nitrogen atoms; 0 to 6, more particularly 0 to 4, and especially 0 to 3 sulfur atoms; and 0 to 10, more particularly 0 to 8, and especially 0 to 6 halogen atoms.

8. R ３ is optionally substituted by 1 to 5, more particularly 1, 2 or 3 substituent(s), especially 1 substituent; ６ -C １６ -aryl, wherein each of the substituents is, independently of one another, C １ -C ６ - alkyl, more specifically C １ -C ４ - alkyl, in particular methyl, ethyl and tert-butyl; C １ -C ４ -haloalkyl, more specifically C １ -C ４ fluoroalkyl, in particular trifluoromethyl; O-C １ -C ６ -alkyl, more specifically O—C １ -C ４ alkyl, in particular methoxy or ethoxy; O-C ２ -C １２ -alkenyl, more specifically O—C ２ -C ７ -alkenyl, especially O—C ２ -C ５ -alkenyl; (C═O)—O—C １ -C ６ -alkyl, more specifically (C=O)-O-C １ -C ４ - alkyl; O-(C=O)-C １ -C ６ -alkyl, more specifically O—(C═O)—C １ -C ４ - alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR ６ ２ (In the formula, R ６ are each independently hydrogen, C １ -C ６ Alkyl, or C ６ -C １２ represents aryl); NH(CO)R ６ (In the formula, R ６ is C １ -C ６ Alkyl or C ６ -C １２ represents aryl); (C=O)NR ６ ２ (In the formula, R ６ are each independently hydrogen, C １ -C ６ Alkyl, or C ６ -C １２ aryl); and SC １ -C ６ -alkyl, more specifically S—C １ -C ４ - alkyl, in particular methylthio or ethylthio.

9. R ３ is optionally substituted by 1 to 5, more particularly 1, 2 or 3 substituent(s), especially 1 substituent; ６ -C １６ -aryl, wherein each of the substituents is, independently of one another, C １ -C ６ - alkyl, more specifically C １ -C ４ - alkyl, in particular methyl, ethyl and tert-butyl; C １ -C ４ -haloalkyl, more specifically C １ -C ４ fluoroalkyl, in particular trifluoromethyl; O-C １ -C ６ -alkyl, more specifically O—C １ -C ４ alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and 9. The topical composition of any one of claims 1 to 8, wherein the compound is selected from the group consisting of nitro.

10. R ３ represents phenyl substituted by 1, 2 or 3 substituent(s), each of said substituents being, independently of one another, C １ -C ６ - alkyl, more specifically C １ -C ４ - alkyl, in particular methyl, ethyl and tert-butyl; C １ -C ４ -haloalkyl, more specifically C １ -C ４ fluoroalkyl, in particular trifluoromethyl; O-C １ -C ６ -alkyl, more specifically O—C １ -C ４ alkyl, in particular methoxy or ethoxy; Halogen, more particularly chloro or fluoro, especially fluoro; and 10. The topical composition of any one of claims 1 to 9, wherein the compound is selected from the group consisting of nitro.

11. The compound of formula (I) is a compound of formula (III): 【Transformation 6】 wherein R ２ , R ４ , R ５ , and R ６ is as defined in any one of claims 1 to 10, 【Transformation 7】 is as defined in claim 1, and R ｎ ７ is n substituents R ７ represents n is an integer from 0 to 5, more specifically from 0 to 3, and especially 1, and n being 0 is R ７ means that there is no R ７ But independently of each other, C １ -C ６ - alkyl, more specifically C １ -C ４ - alkyl, in particular methyl, ethyl and tert-butyl; C １ -C ４ -haloalkyl, more specifically C １ -C ４ fluoroalkyl, in particular trifluoromethyl; O-C １ -C ６ -alkyl, more specifically O—C １ -C ４ alkyl, in particular methoxy or ethoxy; O-C ２ -C １２ -alkenyl, more specifically O—C ２ -C ７ -alkenyl, especially O—C ２ -C ５ -alkenyl; (C═O)—O—C １ -C ６ -alkyl, more specifically (C=O)-O-C １ -C ４ - alkyl; O-(C=O)-C １ -C ６ -alkyl, more specifically O—(C═O)—C １ -C ４ - alkyl; halogen, more particularly chloro or fluoro, especially fluoro; Nitro; NR ６ ２ (In the formula, R ６ are each independently hydrogen, C １ -C ６ Alkyl, or C ６ -C １２ represents aryl); NH(CO)R ６ (In the formula, R ６ is C １ -C ６ Alkyl or C ６ -C １２ represents aryl); (C=O)NR ６ ２ (In the formula, R ６ are each independently hydrogen, C １ -C ６ Alkyl, or C ６ -C １２ aryl); and SC １ -C ６ -alkyl, more specifically S—C １ -C ４ A topical composition according to any one of claims 1 to 10, wherein - represents a moiety selected from the group consisting of alkyl, in particular methylthio or ethylthio.

12. The compound of formula (I) is a compound of formula (IV): 【Transformation 8】 wherein R ２ and R ６ is as defined in any one of claims 1 to 10, 【Chemistry 9】 is as defined in claim 1, and R ｎ ７ A topical composition according to any one of claims 1 to 11, wherein is as defined in claim 11.

13. The compound of formula (I) is a compound of formula (V): 【Chemistry 10】 wherein R ２ and R ６ A topical composition according to any one of claims 1 to 12, wherein is as defined in any one of claims 1 to 10.

14. The compound of formula (I) is lysine and the corresponding compound of formula (VI): 【Chemistry 11】 (In the formula, R ３ , R ４ , R ５ , and R ６ is as defined in any one of claims 1 to 10, 【Chemistry 12】 is as defined in claim 1) absorbs light at a wavelength of from about 380 nm to about 565 nm, more specifically from about 380 nm to about 568 nm, and especially from about 380 nm to about 570 nm, after being converted to the corresponding compound of formula (VI) optionally also absorbs light at wavelengths of from about 590 nm to about 750 nm, more particularly from about 587 nm to about 750 nm, and especially from about 585 nm to about 750 nm; and 14. The topical composition according to any one of claims 1 to 13, wherein the corresponding compound of formula (VI) optionally does not absorb light at wavelengths of from about 566 nm to about 589 nm, more particularly from about 569 nm to about 586 nm, and especially from about 571 nm to about 584 nm.

15. A method comprising mixing a compound of formula (I) as defined in any one of claims 1 to 14 with genipin or a genipin derivative.

16. Compound of formula (VIII): 【Chemistry 13】

Images