1,5-dicarbonylic compounds attachable to keratinous tissues

Abstract

Compounds of formula (I) and their use for covalently binding to substrates comprising amino groups, such as collagen or keratin in skin or hair, are disclosed. The 3,4-dihydro-2H-pyran moieties in compounds (I) react via their 1,5-diketonic or mixed ketoaldehydic tautomers with the amino groups to form stable 1,4-dihydropyridine moieties, or their oxidized pyridine derivatives. Once covalently bound, some compounds (I) can provide color to the substrates. In some embodiments, compounds (I) are in the form of conjugates to provide active agents such as moisturizers, pharmaceuticals and pesticides to the substrates.

Description

[0001] 1,5-Dicarbonylic compounds attachable to keratinous tissues

[0002] CROSS REFERENCE TO RELATED APPLICATIONS

[0003] This application claims benefit from the European Patent Applications Nos. EP24219629.3, 24219630.1, 24219631.9, and 24219632.7, all titled: “Compounds attachable to keratinous tissues” and all filed on December 12, 2024, their content being incorporated herein in their entirety by reference thereto; as well as the benefit of the European Patent Applications EP25177118.4, and EP25194313.0, both titled: “Compounds attachable to keratinous tissues”, filed on May 16, 2025, their content also being incorporated herein in their entirety by reference thereto. The contents of disclosure of the PCT applications filed by the present applicant on the same day with the Canadian Patent Office having the titles “Bicyclic compounds attachable to keratinous tissues”, “Dimeric compounds attachable to keratinous tissues”, “Derivatives of elenolic acid attachable to keratinous tissues”, “Insect repellants attachable to keratinous tissues” and “Retinal derivatives attachable to keratinous tissues” are also being incorporated herein in their entirety by reference thereto.

[0004] TECHNICAL FIELD

[0005] This disclosure relates to compounds which can be reliably and efficiently grafted onto keratinous tissues such as skin or hair. More specifically, the present disclosure relates to conjugated molecules comprising an active ingredient (or a precursor thereof) and a specifically selected anchoring moiety which binds to keratinous tissues in a fast and irreversible manner. In many instances, the anchoring moiety does not noticeably add a color of its own, i.e. the active ingredient can be unobtrusively linked to skin and hair. The active ingredient may provide its effect while being bound to the keratinous tissues, or it can provide its effect after a precursor of the active ingredient has been e.g. hydrolytically or enzymatically cleaved from the e.g. anchored compound. The disclosure also relates to compounds as such, to topical compositions comprising these compounds and to various methods and applications for these compounds. BACKGROUND

[0006] Genipin is the naturally occurring compound methyl (!R,4aS,7aS)-l-hydroxy-7- (hydroxymethyl)-l,4a,5,7a-tetrahydrocyclopenta[c]pyran-4-carboxylate (CAS RN. 6902-77- 8). It has the following structure, and for the purposes of the present disclosure, the following ring atom numbering will be used:

[0007] Genipin can be coupled to keratinous tissues such as skin and hair. For instance, keratin in skin comprises lysine amino acids having aliphatic amino side chains. These amino side chains react with genipin according to the below representative reaction scheme:

[0008] When bound to skin, genipin develops an intense blue color. For this reason, genipin is used as a colorant in semi-permanent inks.

[0009] WO 2023 / 102652 Al discloses that genipin and related iridoids can be hydrogenated to provide compounds which bind to skin without adding color of their own. WO 2023 / 102652 Al leverages this finding to provide compounds which unobtrusively attach UV-absorbers to skin and to provide novel skin-attachable colorants.

[0010] In their extensive research regarding genipin chemistry, the present inventors have surprisingly found that a broad range of 3,4-saturated 2H-pyran derivatives can be reliably and efficiently coupled to keratinous tissues such as skin and hair. This robust coupling chemistry can be attributed to the 3,4-saturated 2H-pyran moiety of genipin and is largely unaffected by the further substitution of the 3,4-saturated 2H-pyran moiety. This finding is further supported in the literature which describes that e.g. oleuropein and aucubin activated by P-glucosidase have very strong protein-denaturing, protein-crosslinking, and amino acid-alkylating activities, see Konno et al., PNAS, 1999, 96 (16) 9159-9164. Deglycosylated oleuropein (also called oleuropein aglycone) and deglycosylated aucubin have the following structures, all comprising 3,4-saturated 2H-pyran moieties:

[0011] Regarded in isolation, the aforementioned 3,4-saturated 2H-pyran moiety is a derivative of, in IUPAC nomenclature, a 3,4-dihydro-2H-pyran moiety. When referring to the atoms of the 3,4- saturated 2H-pyran moieties, the following ring numbering will be used throughout the present disclosure.

[0012] The present inventors have found that it is the 2-hydroxy-3,4-saturated 2H-pyran moiety itself which provides the robust coupling to keratinous tissues. This finding can be rationalized when considering the coupling mechanism of the 2-hydroxy-3,4-saturated 2H-pyran moiety. This coupling mechanism will in the following be explained using genipin as an example.

[0013] Genipin exists in a number of tautomers, including the ring-opened 1,5-dialdehydic tautomer which has some similarity to the well-known cross-linking agent glutaraldehyde:

[0014] Ring-open dialdehydic tautomer Glutaraldehyde

[0015] Like glutaraldehyde, genipin can be coupled to keratinous tissues. For instance, keratin in skin comprises lysines having aliphatic amino side chains. These amino side chains react with genipin according to the below representative reaction scheme:

[0016] The crosslinking reaction of genipin can theoretically proceed by a number of reaction pathways. A mechanistic study by Adamo et al., RSC Adv., 2014, 4, 11029, concluded that the predominant reaction pathway proceeds via the more reactive ring-opened 1,5-dialdehydic tautomer of genipin:

[0017] The coupling to keratinous tissues is also irreversible due to the high stability of the generated 1,4-dihydropyridine moiety and due to fact that its formation involves the elimination of two equivalents of water. Other 3,4-saturated 2H -pyran derivatives are also subject to the aforementioned ring-opening tautomerism and the reactive ring-opened 1,5-dialdehydic tautomers readily undergo the same coupling reaction as genipin. This explains why structurally very diverse 3,4-saturated 2H- pyran derivatives can bind to keratinous tissues.

[0018] Utilizing the robustness of this coupling chemistry via ring-opened 1,5-dialdehydic tautomers, the present inventors have prepared and made available a reliable and effective platform of compounds for topically coupling a very diverse range of active ingredients including, for instance, humectants, insect repellents and pharmaceuticals to keratinous tissues such as skin or hair. This is the subject-matter of the patent applications WO 2024 / 250111 Al and WO 2024 / 250112 Al which are incorporated herein in their entirety by reference thereto.

[0019] However, 3,4-saturated 2H-pyran derivatives which are ring-opening to 1,5-dialdehydic tautomers are not readily commercially available and are largely limited to naturally occurring iridoids and seco-iridoids such as genipin, oleuropein, and others. These natural compounds are difficult to source in larger quantities and in consistent quality.

[0020] SUMMARY OF THE INVENTION

[0021] In a first aspect, the present disclosure relates to the use of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, Ae and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0022] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0023] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0024] A4 and As are, independently from each other, defined as indicated for Ai;

[0025] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0026] In a second aspect, the present disclosure relates to a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair; wherein the compound of formula (I) is capable of covalently binding to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Ls and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0027] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0028] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0029] A4 and As are, independently from each other, defined as indicated for Ai;

[0030] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Ls-As and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0031] In a third aspect, the present disclosure relates to a topical composition comprising one or more of the compounds recited in the second aspect of the present disclosure. In a fourth aspect, the present disclosure relates to the compounds recited in the second aspect of the present disclosure for use in medicine. More specifically, according to the fourth aspect, the present disclosure relates to a compound of formula (I) the present disclosure relates to a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair; wherein the compound of formula (I) is capable of covalently binding to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, Aa, A4, As, Ag and A7 not representing one of the one or more active ingredients and precursors is defined as follows: Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0032] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0033] A4 and As are, independently from each other, defined as indicated for Ai;

[0034] Ae and A 7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate; and, in particular, wherein at least one of the one or more active ingredients and precursors thereof is a pharmaceutical, a UVA- and / or UVB- absorbing moiety, or a precursor thereof; for use in medicine.

[0035] In particular, the aforementioned compounds are for use in treating a skin-associated disease, an allergic condition, pain, or inflammation.

[0036] In a fifth aspect, the present disclosure relates to a method of preparing a topical composition comprising a compound of formula (I) as defined in the second aspect of the present disclosure.

[0037] DESCRIPTION OF DRAWINGS

[0038] Fig. 1 shows a reaction scheme for the synthesis of a platform compound which can be utilized to synthesize genipin-like compounds of formula (I) of the present disclosure.

[0039] Fig. 2 shows a reaction scheme for the synthesis of a platform compound which can be utilized to synthesize elenolic acid-like compounds of formula (I) of the present disclosure.

[0040] Fig. 3 and 4 show the UV-vis spectrum of compounds of the present disclosure.

[0041] DETAILED DESCRIPTION

[0042] The present inventors set out to find alternatives to the naturally occurring 3,4-saturated 2H- pyran derivatives which are ring-opening to 1,5-dialdehydic tautomers and have realized that not only these 3,4-saturated 2H-pyran derivatives are effective and reliable in coupling to skin and hair, but that 3,4-saturated 2H-pyran derivatives which are ring-opening to 1,5-diketonic tautomers and mixed ketoal dehy die tautomers (i.e. to l-keto-5-aldehyde tautomers or 1- aldehyde-5-keto tautomers) are also effective in coupling to skin and hair. The coupling is also reliable and robust, which is explainable considering that these 3,4-saturated 2H-pyran derivatives, after the initial reaction with an amine of the keratinous tissue, also undergo the sequence of reactions towards the aforementioned very stable 1,4-dihydropyridine moiety.

[0043] In fact, the present inventors have found that the 3,4-saturated 2H-pyran derivatives are not only effectively and irreversibly coupling to skin and hair, but also to numerous other substrates comprising amino groups, such as plant materials, amino-functionalized polymers and various textile fabrics. This further broadens the utility of the 3,4-saturated 2H-pyran derivatives of the present disclosure to a greater range of substrates comprising amino groups.

[0044] In addition, the present inventors have also realized that colored embodiments of the compounds of the present disclosure, i.e. compounds having more extended conjugated systems after having reacted with the substrate’s amino group, are equally accessible and can be used as colorants in e.g. semi-permanent tattoos, in hair dyes or as colored markers in e.g. the farming industry to monitor the residual presence of an active ingredient (e.g. an insect repellent or a pesticide) on the skin and / or hair of farm animals. These uses are not mutually exclusive, i.e. the present disclosure also relates to compounds being both colored after having bound to the substrate and comprising an active ingredient.

[0045] Moreover, 3,4-saturated 2H-pyran derivatives which are ring-opening to 1,5-diketonic tautomers and mixed ketoaldehydic tautomers are conveniently accessible by standard total synthesis.

[0046] Therefore, the present inventors have found that 3,4-saturated 2H-pyran derivatives which ringopen to 1,5-diketonic tautomers and mixed ketoaldehydic tautomers (or, more generally, to 1,5- dicarbonyl tautomers) are representing an attractive and more accessible platform of compounds which are suitable for (topically) coupling a very diverse range of active ingredients to substrates comprising amino groups, in particular keratinous tissues such as skin or hair. Finally, the present inventors have realized that this new platform does not only allow to covalently bind an active ingredient to substrates comprising amino groups, in particular skin or hair, but that the irreversibly bound 3,4-saturated 2H-pyran derivative can be provided with linkers or functional groups which are cleavable to release the active ingredient over time, for instance by hydrolysis or enzymatic cleavage. Suitable functional groups providing such sustained release properties are well-known in the art and readily available to the skilled person, see for instance V. Redasani, and S. Bariwidely, Prodrug Design - Perspectives, Approaches and Applications in Medicinal Chemistry, 1sted., 2015, ISBN: 9780128035191, which is incorporated herein in its entirety by reference thereto.

[0047] Accordingly, in a first aspect, the present disclosure relates to the use of a compound of formula (I), for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair. The compound of formula (I) may also be present as a tautomer and / or a pharmaceutically acceptable salt thereof.

[0048] The type of substrate is not particularly limited as long as it comprises amino groups which can be brought into reactive contact with the compound of formula (I). In some embodiments, the substrate is a keratinous tissue, in particular skin and / or hair. In some embodiments, the substrate is a textile fabric such as wool, amino-functionalized cotton, or an aminofunctionalized synthetic fiber including polyester fibers and in particular a polyethylene terephthalate fiber, or a polyamide fiber, in particular a nylon-6 fiber or a nylon-6.6 fiber. In some embodiments, it may be particularly advantageous that the substrate is a mammalian keratinous tissue, more specifically human skin and / or hair, and in particular human skin. The compound of formula (I) is capable of covalently binding to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with an amino group of the substrate. For clarification, formula (I) comprises a 3,4-saturated 2H-pyran moiety which is a cyclic hemiacetal moiety in case R1represents H and a cyclic acetal moiety in case R1represents any other moiety. The principal reaction pathway for the compounds of formula (I) is analogous to the reaction pathway discussed above in the background section for hydrogenated genipin, i.e. via the cyclic hemiacetal. Accordingly, the 3,4-saturated 2H-pyran moiety is converted to a 1,4-dihydro- pyridine derivative (or tautomer thereof) which, in many cases, will be readily oxidized under ambient conditions to an aromatic pyridinium derivative (as e.g. well-established for genipin). These moieties can form more extensive conjugated systems with the remainder of the substituents L1-A1 to L7-A7 and / or interact with auxochromic groups provided by these substituents. Therefore, in some embodiments, the compound of formula (I), after having covalently bound to the substrate, provides color to the substrate. Additionally or alternatively, the compound of formula (I) comprises one or more active ingredients.

[0049] The term “active ingredient” is to be given its ordinary meaning in the art and is i.a. meant to include any ingredient which provides a direct effect to the substrate that goes beyond any changes caused by the reaction of the 3,4-saturated 2H-pyran moiety with the substrate. To give an example, the conversion of the 3,4-saturated 2H-pyran moiety to a 1,4-dihydropyridine moiety upon binding to the substrate, typically provides some UV-absorption capability to the substrate that is inherent to the 1,4-dihydropyridine moiety. This does not mean that the compound comprises a UV-absorbing moiety as an active ingredient according to the aforementioned definition, since there is no direct effect to the substrate that goes beyond any changes caused by the reaction of the cyclic (hemi)acetal moiety with the substrate. However, once one of the Ai to A7 represents a UV-absorbing moiety such as salicylic acid that provides additional UV-absorbing capabilities to the substrate, the compound of the present disclosure comprises an active ingredient since the provided additional UV-protective effect goes beyond the UV-protective effect provided by the 1,4-dihydropyridine moiety. Additionally or alternatively, an active ingredient is meant to refer to any ingredient that provides a biological, cosmetic or pharmaceutical effect or activity to the substrate, in particular in case the substrate is a keratinous tissue such as skin and / or hair. The one or more active ingredients are not particularly limited, but are advantageously selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, a UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair.

[0050] In some embodiments, the compound of formula (I) is topically applied to skin and / or hair. It comprises a 3,4-saturated 2H-pyran moiety which, once the compound of formula (I) has been topically applied to skin and / or hair, can covalently bind to the skin and / or the hair by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups which are present on the skin and / or the hair.

[0051] In some embodiments, the compound of formula (I) comprises one or more active ingredients which are, independently from each other, present in the compound a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate.

[0052] It should be understood that the compound of formula (I) comprising the active ingredient as the active ingredient according to the above option a) means that the moiety representing the active ingredient is capable of providing its effect or activity while being bound to the substrate (more precisely while being attached to the remainder of the compound of formula (I) in the form as it is covalently bound to the substrate). As an example, a polyhydroxy-based skin moisturizer is able to provide its moisturizing effect while being bound to the skin since its hydroxyl groups provide their water-retaining effect irrespective of whether the moisturizer is bound to the skin or not. However, this should not be understood as excluding the possibility that the active ingredient is chemically modified while being bound to skin. For instance, a polyhydroxy-based skin moisturizer may be acetylated at a terminal hydroxyl group to make it more lipophilic and allow a deeper penetration into the epidermis before the compound of formula (I) binds to the skin. The acetylated hydroxyl group may be subsequently hydrolyzed or cleaved by esterase enzymes which are natively present on skin such that the polyhydroxybased skin moisturizer provides, over time, its moisturizing effect as a chemically modified active ingredient. The term “precursor” in the above option b) is to be given its ordinary meaning in the art as a moiety that participates in a chemical reaction that produces another compound (namely the active ingredient) that is no longer part of the compound of formula (I) in the form as it is covalently bound to the substrate. Alternative terms include e.g. the term “prodrug” in case the active ingredient is a pharmaceutical. It should also be understood that a precursor will be cleaved to the corresponding active ingredient. For brevity, the precursor corresponding to an active ingredient will in the following also be referred to as “the corresponding precursor thereof’ or simply “precursor”. However, it should be understood that, unless specified otherwise, the term “precursor” is meant to refer to the precursor corresponding to the active ingredient which is mentioned in the respective context. It should also be understood that an active ingredient may have multiple precursors, i.e. the term “precursor” will often refer to a group of moieties.

[0053] Moreover, it should be understood that the compound of formula (I) comprising a precursor of an active ingredient means that the active ingredient is providing its effect or activity after its corresponding active ingredient has been cleaved from the remainder of the compound of formula (I) in the form as it is covalently bound to the substrate. As an example, a precursor of a fragrance will provide its olfactory effect only after being released from the substrate. However, this should not be construed as excluding the possibility that a precursor may already provide a reduced effect or activity or an otherwise altered effect or activity before being cleaved from the remainder of the compound of formula (I) in the form as it is covalently bound to the substrate. For instance, the precursor of an insect repellent may already act as contact repellent while being bound as a precursor, but may provide as a more potent olfactory repellent effect after being cleaved from the remainder of the compound of formula (I) in the form as it is covalently bound to the substrate.

[0054] In the compound of formula (I), the substituents are defined as follows:

[0055] In embodiments in which the compound of formula (I) comprises one or more active ingredients, each of the one or more active ingredients and precursor moieties is represented by one of Ai, A2, A3, A4, As, As and A7. In other words: In case the compound of formula (I) comprises one active ingredient, one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient. In case the compound of formula (I) comprises one precursor, one of Ai, A2, A3, A4, As, Ae and A 7 represents said precursor. In case the compound of formula (I) comprises two active ingredients, one of Ai, A2, A3, A4, As, As and A7 represents the first active ingredient and another one of Ai, A2, A3, A4, As, As and A 7 represents the second active ingredient. In case the compound of formula (I) comprises one active ingredient and one precursor of another active ingredient, one of Ai, A2, A3, A4, As, As and A7 represents the active ingredient and another one of Ai, A2, A3, A4, As, As and A7 represents the precursor, and so on.

[0056] Irrespective of the presence or absence of an active ingredient, Li, L2, L3, L4, Ls, Ls and L7 represent, independently from each other, a linker group or are absent. These linker groups Li to L7 connect the corresponding substituents Ai to A7 to the 3,4-saturated 2H-pyran moiety. In case the linker group is absent, the corresponding substituent (the respective Ai to A7 in formula (I)) is directly attached to the 3,4-saturated 2H-pyran moiety. In case the linker group is present, it serves to connect the corresponding substituent (the respective Ai to A7 in formula (I)) to the cyclic (hemi)acetal moiety. In these instances, the linker is attached to the 3,4-saturated 2H- pyran moiety and the corresponding substituent is attached to linker, i.e. said corresponding substituent is merely indirectly connected to the 3,4-saturated 2H-pyran moiety.

[0057] Each of Ai, A2, A3, A4, As, Ae and A 7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0058] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen.

[0059] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo.

[0060] A4 and As are, independently from each other, defined as indicated for AL

[0061] Ae and A 7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen.

[0062] The proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen means that the compound of formula (I) is only comprising 3,4-saturated 2H-pyran derivatives which are capable of ring-opening to 1,5-diketonic tautomers or to aforementioned mixed ketoaldehydic tautomers. Accordingly, formula (I) excludes 3,4-saturated 2H-pyran derivatives which are capable of ring-opening to 1,5-dialdehydic tautomers. R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate. The primary purpose of providing a hydrolysable protective group is to increase the storage stability of the compound, at least in a neutral or slightly alkaline formulation, more specifically in a formulation having a pH of 7.0 or higher, of 7.5 or higher, of 8.0 or higher or of 8.5 or higher. However, once applied to the substrate with its typically lower pH environment, more specifically a pH of 6.9 or lower, of 6.5 or lower, of 6.0 or lower, or of 5.5 or lower, R1should be hydrolyzed to the more reactive hemi-acetal which then binds to the substrate.

[0063] In some embodiments, R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (I) to the skin and / or the hair. The primary purpose of providing a protective group hydrolysable under physiological conditions is to increase the storage stability of the compound of formula (I), at least in a neutral or slightly alkaline formulation, more specifically in a formulation having a pH of 7.0 or higher, of 7.5 or higher, of 8.0 or higher or of 8.5 or higher. However, once applied to skin or hair with their lower pH environment, R1should be hydrolyzed to the more reactive hemi-acetal which then binds to the skin and / or the hair. When referring in this context to “physiological conditions” it should be understood that this refers to the pH conditions encountered at the locus where the compound of formula (I) is supposed to bind to in the subject to be treated (skin or hair). Moreover, it should be understood that the hydrolysis under physiological conditions takes place in an amino-acid rich environment such as collagen which is the predominant skin protein. Collagen comprises a complex mixture of the following amino acids: alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, threonine, tyrosine, and valine. These aminoacids, and in particular those with nucleophilic side chains such as lysine, will further facilitate hydrolysis.

[0064] Accordingly, a group qualifies as “protective group hydrolysable under physiological conditions after application of the compound of formula (I) to the skin and / or the hair”, if the compound of formula (I) comprising the group in question as R1hydrolyses to the corresponding hemi-acetal (and its tautomers) by more than 10 mol-%, more specifically by more than 50 mol%, and in particular by more than 80 mol%, when incubating 0.1 mmol / mL of the compound of formula (I) for 24 hours at 37°C in any one of the following three solutions: a) a phosphate buffer solution, pH 5.5; an aqueous solution of bovine collagen type I (1 mg / mL, adjusted to pH 5.5); and c) an aqueous solution of lysine (1 mg / mL, adjusted to pH 5.5 using a phosphate buffer solution). The conversion can be monitored by any suitable means, including nuclear magnetic resonance spectroscopy (NMR), high-performance liquid chromatography (HPLC), optionally coupled to mass spectrometer (MS) or a UV / vis. The aforementioned conversion ratio in mol% can also be determined using any suitable means, including the aforementioned methods. Additionally or alternatively, a group qualifies as “protective group hydrolysable under physiological conditions after application of the compound of formula (I) to the skin and / or the hair” if the compound cannot be comprehensively washed off from a sample of (explanted) porcine skin or from a hair sample by water, soap, and / or isopropanol after incubating the compound (or a topical composition comprising the compound) on the porcine skin sample or on a hair sample at 37°C for 24 hours.

[0065] As said, the compound of formula (I) may be topically applied to skin and / or hair. As used herein, the term “skin” refers to skin, including lips and the oral cavity, and skin appendages. Skin appendages are epidermal and dermal-derived components of the skin and include nails, sweat glands, and sebaceous glands. As used herein, the term “hair” refers to hair and other fibrous keratinous materials such as eyebrows and eye lashes. In some embodiments, the skin is mammalian skin and in particular human skin. In some embodiments, the hair is mammalian hair and in particular human hair.

[0066] In some embodiments, the compound of formula (I), once it has been topically applied to skin and / or hair, can covalently bind to the skin and / or the hair by the reaction of its 3,4-saturated 2H-pyran moiety, with amino groups which are present on the skin and / or the hair. Whether the compound of formula (I) has covalently bound to the skin and / or the hair by reaction of its 3,4- saturated 2H-pyran moiety can be determined by any suitable means. For instance, if the compound cannot be comprehensively washed off from an (explanted) sample of porcine skin or from a hair sample by water, soap, and / or isopropanol after incubating the compound of formula (I) (or atopical composition comprising said compound) on the respective porcine skin or hair sample at 37°C for 24 hours, the compound of formula (I) can be considered to have covalently bound by reaction of its 3,4-saturated 2H-pyran moiety to skin or hair. Additionally or alternatively, the compound can be considered to realize this feature if it passes a suitable in-vitro test, in particular placing 0.1 mol / L of the compound of formula (I) in an aqueous or methanolic solution having a pH of about 5.5 and further containing 0.1 mmol / mL lysine at 37°C for 24 hours, wherein the compound of formula (I) passes the test if it is converted by more than 10 mol%, more specifically by more than 50 mol%, and in particular by more than 75 mol%, to its corresponding 1,4-dihydropyridine derivative. The conversion can be monitored by any suitable means, including nuclear magnetic resonance spectroscopy (NMR), high- performance liquid chromatography (HPLC), optionally coupled to mass spectrometer (MS) or a UV / vis detector. The aforementioned conversion ratio in mol% can also be determined using any suitable means, including the aforementioned methods. It should further be understood that the reaction of the compound of formula (I) proceeds via its 3,4-saturated 2H-pyran moiety in its hemiacetal form, i.e. when R1represents hydrogen. Accordingly, the aforementioned in-vitro test may, for those compounds of formula (I) in which R1does not represent hydrogen, also alternatively be performed with the corresponding derivative of formula (I) in which R1represents hydrogen.

[0067] The term “moisturizer” refers to a compound / moiety which is capable of directly binding water (via hydrogen bonding) in the respective keratinous tissue (skin or hair) or of reducing evaporation of water from the skin. Accordingly, the term encompasses moisturizes, emollients and occlusives as these terms are used and understood in the art.

[0068] The term “pesticide” refers to its common meaning in the art and in particular refers compounds capable of killing, incapacitating, repelling or in any other way ameliorating a risk to mammalian (human) health, comfort or well-being posed by invertebrates, in particular insects.

[0069] The term “skin whitening agent” refers to the common meaning in the art and in particular refers to a compound which is chemically and / or metabolically able to lighten the color tone of the skin. The term “skin whitening agent” does not refer to pigments or dyes or optical brighteners.

[0070] The term “fragrance” refers to the common meaning in the art and in particular refers to a volatile compound which is capable of providing an olfactory impression, in particular an olfactory impression comprising one or more of the seven fundamental odors (floral, fruity, minty, nutty, pungent, sweet, and woody). The term “pharmaceutical” refers to the common meaning in the art and in particular refers to a compound capable / intended for use in the diagnosis, cure, mitigation, treatment, therapy, or prevention of a disease in mammals, in particular humans and domestic and farm animals.

[0071] The term “UVA- and / or UVB-absorbing moiety” refers to the common meaning in the art and in particular refers to a moiety which reduces the amount of UVA- and / or UVB-radiation that can pass through the compound of formula (I).

[0072] The term “color-imparting moiety” refers to the common meaning in the art and in particular refers to moiety which imparts a color-impression perceivable by the human eye.

[0073] The term “cosmetic hair coating” refers to a compound / moiety which is capable of providing a coating onto hair which provides a cosmetic benefit to the subject. Accordingly, the term encompasses coatings imparting a hair conditioning effect, gloss or shine, an anti-frizz effect, or a reinforcing (styling) effect.

[0074] The term “primer for attaching dyes to the hair” refers to a compound / moiety which provides a functional group to the hair which is suitable for anchoring a colorant (dye or pigment) and / or compounds which can be developed into dyes or pigments. Said anchoring is preferably, but not necessarily, a covalent binding. In other words, the term “primer for attaching dyes to the hair” refers to a compound / moiety comprising a functional group which is suitable for reacting with and in particular suitable to covalently bind to a colorant, or a compound / moiety which can be converted into a colorant by reacting with a color developer.

[0075] The usefulness of the compounds of the present disclosure will be exemplarily illustrated by the following examples. Of course, other applications will be readily apparent and routinely available to the skilled person on the basis of the guidance given in the present disclosure.

[0076] The first example concerns a compound intended to provide a moisturizing effect. Skin moisturizers are well-established in cosmetics and include a large variety of compounds capable of binding water in the stratum comeum. Examples include polyols such as glycerol, pentaerythritol and sorbitol but also other hydrogen-bonding compounds such as urea. A compound according to the present disclosure carrying a pentaerythritol as the skin moisturizing is shown below:

[0077] Due to the large number of hydroxyl groups, the above compound according to the present disclosure can be expected to provide a long-lasting moisturizing effect to the skin. The moisturizing effect will be given even if the pentaerythritol moiety is still attached to the skin via the 3,4-saturated 2H-pyran moiety. The above compound will also unobtrusively bind to the skin since it’s a C5-methyl derivative of hydrogenated genipin for which the present inventors have previously shown that it binds in colorless form to the skin.

[0078] An outline of the chemical synthesis to a platform compound suitable for preparing the above compound is shown in Fig. 1.

[0079] The second example concerns a compound intended to provide a pesticidal effect, more specifically an insect repellant effect. para-Menthane-3,8-diol (PMD) is an insect repellent which can be used directly on skin or clothing, ft has broad efficacy against various arthropods such as mosquitos, ticks, gnats, flies and fleas, and is colorless. The chemical structure of PMD is reproduced below: PMD’s insect repelling potency rivals that of AA-diethyl-m-methylbenzamide (DEET). However, like DEET, it provides only a briefly lasting effect of up to 6-8 hours. This is mostly due to the relatively high volatility of PMD.

[0080] Efforts have been ongoing to increase the residence time of PMD on skin. Of particular interest, a recent study has revealed that PMD can be retained in the stratum comeum for up to 5 days by chemically binding PMD to an acrylic copolymer which is topically applied to the skin (Shah, S.I. et al., Pharmaceutics 2021, 13, 403). More specifically, the authors demonstrated that acryloyl chloride could be conjugated with the secondary alcohol of PMD via an ester bond, and that the resulting conjugated monomer could be crosslinked to a copolymer carrying PMD conjugates. The authors further demonstrated that esterases could release PMD from the copolymer in in-vitro tests and also when the copolymer was applied to porcine skin in ex-vivo tests.

[0081] Therefore, compounds of the present disclosure comprising PMD which is bound to the remainder of the molecule via an ester group are suitable candidates for releasing PMD to skin in a sustained release. A concrete exemplary compound is shown below:

[0082] The compound is readily accessible by using the synthesis to the platform compound shown in Fig. 1.

[0083] As supported by the article of Shah, S.I. et al., Pharmaceutics 2021, 13, 403, the ester group linking PMD to the remainder of the compound can be expected to be cleaved by esterases of the skin and PMD is released over time to the stratum comeum to provide its insect repellent effect. Minoxidil and its derivatives, such as kopexil, are topically applied to treat alopecia. Minoxidil is typically applied twice per day to the scalp in an alcoholic solution (ethanol and propylene glycol). The compound is generally well tolerated, but common side effects include dandruff and contact dermatitis which are caused by the frequent exposure to ethanol and propylene glycol which dry the scalp. Hence, to minimize the side effects and to improve the patient compliance, a topical delivery system which requires less frequent application of minoxidil would be desirable.

[0084] Minoxidil has the following chemical structure:

[0085] The article by Stoica et al. in Bioorganic & Medicinal Chemistry Letters, 2016, 26(4), 1145- 1150, provides a convenient method of coupling minoxidil to alcohols via activation of the compound with V, V-carbonyldiimidazol (CDI). This synthetical pathway allows easy access to the following compound of the present disclosure:

[0086] The starting alcohol is readily accessible by using the synthesis to the platform compound shown in Fig. 2. The above compound will also unobtrusively bind to skin since it’s a C5- methyl derivative of hydrogenated oleuropein / elenolic acid for which the present inventors have previously shown that it binds in colorless form to the skin. Monosubstituted carbamate groups are frequently used in prodrugs and can be cleaved by esterases (see review by Gosh et al., J. Med. Chem, 2015, 58, 7, 2895-2940). Thus, the above compound is a promising candidate to provide sustained release of minoxidil to the skin.

[0087] The fourth example also concerns a compound intended to provide a pharmaceutical effect, more specifically the treatment of an allergic condition.

[0088] Desloratadine, the metabolically active form of loratadine, is a very potent antihistamine that is administered orally once per day at a dosage of 5 mg. Topical formulations of desloratadine are currently investigated. Mohamed et al., Pharmaceuticals 2023, 16(4), 578, describe desloratadine as having good permeation through the skin when applied as a transdermal gel formulation. They found that the gel formulation had higher bioavailability, and eliminated slowly compared to the tablet formulation. The bioavailability of the gel formulation was 2.4- 3.2 fold of the tablet formulation. This implies that a very low daily dosage of about 2 mg of desloratadine may be sufficient to provide an adequate anti-allergic effect which makes desloratadine even more attractive as a pharmaceutical moiety for the compounds of the present disclosure since systemic side-effects associated with oral administration of desloratadine can be mitigated. Desloratadine has the following chemical structure:

[0089] It can be coupled to e.g. the platform compound shown in Figure 2 via a V, V-disubstituted carbamate group: AA-disubstituted carbamate groups as utilized in the above compound are frequently used in prodrugs (e.g. in bambuterol) and can be cleaved by esterases with a relatively long sustained release (see review by Gosh et al., J. Med. Chem, 2015, 58, 7, 2895-2940). Thus, the above compound is a promising candidate to provide a long-term release of desloratadine to the skin. Thus, a long-lasting depot effect can be expected, possibly allowing less frequent administration, in particular such as a once weekly administration. In practice, this may be done by applying a transdermal patch overnight which transfers and anchors the desloratadinecontaining compound to the skin. From there it is released by the skin’s enzymatic activity over the period of e.g. one week.

[0090] As can be seen from the above examples, the compounds of the present disclosure provide broad utility and versatility in topically applying active ingredients to keratinous tissue.

[0091] The fifth example concerns a compound intended to provide a color to the substrate. An exemplary synthetical approach is shown below, starting from a readily available lawsone derivative and the compound 3-benzylidene camphor (3-BC) which is a well-known and mass- produced UV-protecting agent in cosmetics:

[0092] In the above reaction, the lawsone derivative acts as the Michael donor and 3-BC as the Michael acceptor. The reaction with a substrate comprising an amino group yields a 1 ,4-dihydropyridine derivative which colors the substrate. Further (forced) oxidation will yield a pyridinium derivative with an extensive conjugated system which can be expected to be intensely colored. The wavy bond in the reaction scheme below represents the covalent bond to the substrate:

[0093] Such compounds may also be particularly beneficial in those applications in which coloring is desirable, for instance in marking or treating farm animals where the compounds’ inherent color may also be used as an indicator of the presence of residual active ingredients bound to the animal’s skin and / or fur. In view of the inexpensive starting materials, and the polar nature of the covalently bound compounds, such compounds are also of interest as dyes for fabrics based on e.g. amino-functionalized polyester or cotton or polyamide.

[0094] Further examples will be discussed in the experimental section below.

[0095] In the following, further specific embodiments of the first aspect will be described.

[0096] The terms “at least one of the one or more active ingredients or of the corresponding precursors thereof’ and “at least one of the one or more active ingredients or of the precursors thereof’ will be used interchangeably. Moreover, for reasons of conciseness, many embodiments will specify a feature for “at least one of the one or more active ingredients or of the (corresponding) precursors thereof’. However, it should be understood that, in case that the compound of formula (I) comprises multiple active ingredients and / or precursors, and unless expressly stated otherwise, this is meant to also disclose the embodiment in which more than one and in particular all, active ingredients and / or precursors are provided with that feature.

[0097] In some embodiments, at least one of the one or more active ingredients or of the corresponding precursors thereof is a Ci-Ceo moiety. In some embodiments, the Ci-Ceo moiety comprises 1 to 60, more specifically 1 to 48, and in particular 1 to 36 carbon atoms; 0 to 24, more specifically 0 to 16, and in particular 0 to 12 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 12, more specifically 0 to 10, and in particular 0 to 8 halogen atoms. In some embodiments, the Ci-Ceo moiety is a Cio-Ceo moiety, a C15-C60 moiety or a C20-C60 moiety, all of which may optionally comprise the same aforementioned heteroatoms.

[0098] In some embodiments, at least one of the one or more active ingredients or of the corresponding precursors thereof is a polymeric moiety. As used herein, the term “polymeric moiety” is not particularly limited beyond its common understanding in the art and refers to any oligomeric (herein defined as more than 3 and up to 8 repeat units) or polymeric moiety (herein defined as having more than 8 repeat units). The polymeric moiety will typically comprise carbon and / or silicon, but the presence of further heteroatoms, i.e. atoms not being C or Si, is not excluded, i.e. atoms such aH, O, N and others may be contained in the polymeric moiety.

[0099] In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent either Ci-Ceo moieties or polymeric moieties. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent Ci-Ceo moieties. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent polymeric moieties.

[0100] In some embodiments, the compound of formula (I) comprises more than one of the active ingredients or of the precursor thereof. In some embodiments, and in fact in the most preferred embodiment from a standpoint of synthetical simplicity, the compound of formula (I) comprises only one of the active ingredients or of only the precursor thereof. However, below, there may also be cases where it is advantageous that the compound of formula (I) comprises a plurality of active ingredients, a plurality of precursors, or a mixture of one or more active ingredients and one or more precursors.

[0101] Specifically, in some embodiments, the compound of formula (I) comprises: one or more of the active ingredients or of the corresponding precursors thereof; two or more of the active ingredients or of the corresponding precursors thereof; three or more of the active ingredients or of the corresponding precursors thereof; in total, one, two or three of the active ingredients or of the corresponding precursors thereof; in total, one or two of the active ingredients or of the corresponding precursors thereof; in total, one of the active ingredients or of the corresponding precursors thereof; in total, one of the active ingredients and none of the precursors; in total, two of the active ingredients and none of the precursors; in total, one of the active ingredients and one of the precursors; or, in total, two of the precursors and none of the active ingredients.

[0102] In some embodiments, it may be particularly advantageous that the compound of formula (I) comprises a UVA- and / or UVB-absorbing moiety as one of the active ingredients and a further one of the active ingredients or of the precursors thereof, which is not a UVA and / or UVB- absorbing moiety. Providing a UVA- and / or UVB-absorbing moiety in combination with a further active ingredient or precursor thereof may provide particularly efficient UV-protection to further active ingredient or precursor thereof and reduce photodegradation.

[0103] In some embodiments, it may be particularly advantageous that the compound of formula (I) comprises a moisturizer as one of the active ingredients or of the precursors thereof, and a further one of the active ingredients or of the precursors thereof, which is not a moisturizer. Providing a moisturizer in combination with a further active ingredient or precursor thereof may reduce skin irritation caused by the further active ingredient, or the corresponding precursor thereof.

[0104] In some embodiments, it may be particularly advantageous that the compound of formula (I) comprises a UVA- and / or UVB-absorbing moiety as one of the active ingredients, a moisturizer as one of the active ingredients or of precursors thereof, and a further one of the active ingredients or of the precursors thereof, which is not a UVA and / or UVB-absorbing moiety and not a moisturizer.

[0105] In some embodiments, specifically those uses in which the compound of formula (I) is used for covalently binding the one or more active ingredients to skin, at least one of the one or more active ingredients or of the precursors thereof is selected from the group consisting of skin moisturizers, pesticides, skin whitening agents, fragrances, pharmaceuticals, UVA- and / or UVB-absorbing moieties, and color-imparting moieties; and in particular at least one of the one or more active ingredients or of the precursors thereof is selected from the group consisting of skin moisturizers, pesticides, skin whitening agents, fragrances, and pharmaceuticals. In some embodiments, specifically those uses in which the compound of formula (I) is used for covalently binding the one or more active ingredients to hair, at least one of the one or more active ingredients or of the precursors thereof is selected from the group consisting of hair moisturizers, fragrances, cosmetic hair coating agents, primers for attaching dyes to hair, UVA- and / or UVB-absorbing moieties, and color-imparting moieties; and in particular at least one of the one or more active ingredients or of the precursors thereof is selected from the group consisting of hair moisturizers, fragrances, cosmetic hair coating agents, and primers for attaching dyes to hair.

[0106] In some embodiments, L7-A7 represents hydrogen or the C1-C30 moiety. In some embodiments, Lg-Ag represents hydrogen or the C1-C30 moiety. In some embodiments, L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety. In some embodiments, L7-A7 represents the C1-C30 moiety and Lg-Ag represents hydrogen. In some embodiments, L7-A7 represents the Ci- C30 moiety and Lg-Ag represents the C1-C30 moiety. It may be particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety or that L7-A7 represents the C1-C30 moiety and Lg-Ag represents hydrogen since this substitution pattern retains the initial high reactivity of an aldehyde group. It may be further particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety since this substitution pattern is conveniently synthetically accessible, as discussed below in the experimental section.

[0107] In some embodiments, at least one of Ai, A2, A3 and A4 represents one of the one or more active ingredients or of the precursors thereof. This substitution pattern may be particularly beneficial since it reduces the propensity of the active ingredient(s) or precursor(s) to sterically interfere with the reaction of the 3,4-saturated 2H-pyran moiety (or its ring-opened tautomers) with the amino groups on skin and / or hair.

[0108] In some embodiments, at least one of A2, A3 and A4 represents one of the one or more active ingredients or of the corresponding precursors thereof. This substitution pattern may be particularly beneficial since it mimics the substitution pattern observed in genipin and oleuropein which are known to be well-tolerated.

[0109] Cleavable and non-cleavable functional groups linking the active ingredients When referring to a compound of formula (I) which is cleavable to release the active ingredient from the precursor, it should be understood that “cleavable” in this context in particular means that, after the compound of formula (I) has covalently bound to the substrate (in particular skin and / or the hair), that one or more bonds of the compound of formula (I), in the form as it is present on the substrate, can be broken such that the active ingredient is released.

[0110] Accordingly, in some embodiments, the compound of formula (I) comprises a functional group which couples one of the one or more active ingredients or of the precursors thereof to the remainder of the compound of formula (I) and wherein the functional group comprises a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, a boron atom, or a combination thereof; more specifically a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof; and in particular a carbon atom and / or an oxygen atom.

[0111] It should be understood that the aforementioned functional group serves to join the active ingredient or precursor to the linker or directly to the 3,4-saturated 2H-pyran moiety (in case the linker is absent). Accordingly, said functional group can be considered to be part of the active ingredient or the precursor and of the linker or, if the linker is absent, of the 3,4-saturated 2H-pyran moiety. Accordingly, in some embodiments, the at least one of the L1-A1, L2-A2, L3- A3, L4-A4, L5-A5, Lg-As and L7-A7 comprising one of the one or more active ingredients or of the precursor thereof, further comprises a functional group, wherein said functional group comprises a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, a boron atom, or a combination thereof; more specifically a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof; and in particular a carbon atom and / or an oxygen atom.

[0112] In some embodiments, the functional group comprises one or more of, two or more of, three or more of, four or more of, five or more, or all of:

[0113] 1 to 12 carbon atoms, more specifically 1 to 8 carbon atoms, and in particular 1 to 4 carbon atoms;

[0114] 1 to 4 oxygen atoms, more specifically 1 to 3 oxygen atoms, and in particular 1 or 2 oxygen atoms;

[0115] 1 to 4 nitrogen atoms, more specifically 1 to 3 nitrogen atoms, and in particular lor 2 nitrogen atoms; 1 to 3 sulfur atoms, more specifically 1 or 2 sulfur atoms, and in particular 1 sulfur atom;

[0116] 1 to 3 phosphorus atoms, more specifically 1 or 2 phosphorus atoms, and in particular 1 phosphorus atom;

[0117] 1 or 2 boron atoms, and in particular 1 boron atom.

[0118] In some embodiments, after the compound of formula (I) has bound to the skin and / or the hair, the functional group is biostable. When referring in this context to “biostable”, it should be understood that the functional group is not subject to biodegradation under physiological conditions encountered after application of the compound to the skin and / or the hair for 14 days which is a typical time span before the natural desquamation of the skin removes any bound compounds from the skin. It should be understood that, when referring in this context or another context to “physiological conditions”, it is in particular referred to the ambient conditions, in particular pH, enzymatic and temperature conditions, encountered at the locus where the compound of formula (I) is supposed to bind to keratinous tissues in e.g. the hair of the (mammalian, in particular human) subject to be treated.

[0119] In some embodiments, after the compound of formula (I) has bound to the skin and / or the hair, the functional group is cleavable, more specifically cleavable under physiological conditions encountered after its application to the skin and / or the hair. In some embodiments, it may be particularly advantageous that the functional group can be cleaved under physiological conditions to provide the active ingredient from the corresponding precursor over a plurality of hours or days. In some embodiments, the plurality of hours is 8 hours or more, more specifically 12 hours or more, and in particular 24 hours or more. In some embodiments, the plurality of days is 2 days or more, more specifically 3 days or more, and in particular 7 days or more.

[0120] In some embodiments, after the compound of formula (I) has bound to the skin and / or the hair, the functional group is cleavable under conditions preselected for said use. The term “cleavable under conditions preselected for said use” should be understood as referring to conditions not normally encountered in said specific use and, thus, are suitable for defining conditions for a triggering event which results in the functional group being cleaved or starting to being cleaved. In particular, such preselected conditions include: cleavable upon elevation of temperature to higher than 37 °C (i.e. higher than body surface temperature); cleavable upon exposure to daylight; cleavable upon exposure to UVA- and / or UVB-light; cleavable upon exposure to acids; cleavable upon exposure to an oxidizing agent suitable for oxidizing said functional group; cleavable upon exposure to a reducing agent suitable for reducing said functional group; cleavable upon applying an enzyme; and cleavable upon exposure to salts. To give an example, in the use of compound of formula (I) for applying a fragrance to hair, the functional group may be an ester group which starts to be hydrolyzed in the presence of moisture (originating from the wet hair) and at temperatures of greater than 40°C (as encountered when hair is dried with a hair dryer). Another example is the use of compound of formula (I) for applying a pharmaceutical to skin, wherein the functional group is a coumarin moiety which photodegrades to liberate the pharmaceutical from its prodrug moiety upon exposure to daylight. The use of coumarin-based linkers for light-triggered drug release is reviewed in e.g. Johan et al., Pharmaceuticals (Basel), 2022, 15(6):655, which is incorporated herein in its entirety by reference thereto.

[0121] In some embodiments, the functional group is hydrolysable at the physiological pH of mammalian skin, more specifically of human skin, and in particular at a pH of between about 5 to about 6. A suitable in-vitro test is incubating 0.1 mmol / mL of the compound of formula (I) for 24 hours at 37°C in any of the following three solutions: a) a phosphate buffer solution, pH 5.5; an aqueous solution of bovine collagen type I (1 mg / mL, adjusted to pH 5.5); and c) an aqueous solution of lysine (1 mg / mL, adjusted to pH 5.5 using a phosphate buffer solution), wherein the group in question qualifies as hydrolysable if a notable amount of the group is hydrolysed (e.g. more than 5 mol%, or more than 10 mol%). The conversion can be monitored by any suitable means, including nuclear magnetic resonance spectroscopy (NMR), high- performance liquid chromatography (HPLC), optionally coupled to mass spectrometer (MS) or a UV / vis detector. The aforementioned conversion ratio in mol% can also be determined using any suitable means, including the aforementioned methods.

[0122] In some embodiments, the functional group is enzymatically cleavable under physiological conditions after the compound of formula (I) is topically applied onto mammalian, more specifically human skin, in particular enzymatically cleavable by enzymes present in the mammalian, more specifically human skin. A suitable in-vitro test is placing 0.1 mol / L of the compound of formula (I) in an aqueous solution having a pH of about 5.5 at 37°C for 24 hours and further containing 50 U of esterase activity, wherein the group in question qualifies as enzymatically cleavable if a notable amount of the group is cleaved (e.g. more than 5 mol-%, or more than 10 mol-%). The conversion can be monitored by any suitable means, including nuclear magnetic resonance spectroscopy (NMR), high-performance liquid chromatography (HPLC), optionally coupled to mass spectrometer (MS) or a UV / vis detector. The aforementioned conversion ratio in mol% can also be determined using any suitable means, including the aforementioned methods.

[0123] In some embodiments, the functional group can be cleaved to provide a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime; or salts thereof.

[0124] In some embodiments, the functional group can be cleaved to provide a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime; or salts thereof; to the active ingredient.

[0125] In some embodiments, the functional group can be cleaved to provide a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime to the active ingredient; and to provide a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime, to the remainder of the compound of formula (I) (in the form as bound to skin or hair).

[0126] In some embodiments, the functional group comprises a carbon ester, in particular a monoester, 1,1-diester, a carbonate, or a carbamate; an ether or thioether, in particular an acetal, a hemiacetal, a glycosidic group or a thioacetal; a disulfide; a carbon amide, in particular a peptide or a N-Mannich base; an enol; an enamine; an imine; an oxime; a sulfate ester; a sulfonic acid ester; a sulfonic acid amide; a phosphoric acid ester; a phosphonic acid ester; a phosphoric acid amide; a phosphonic acid amide; a boronic ester, a borinic ester, a boric ester; an oxazol, a triazole, a benzothiazole, or a coumarin. In some embodiments, the functional group may be a functional group mentioned in chapter 6 of the textbook Prodrug Design Perspectives, Approaches and Applications in Medicinal Chemistry, 1sted., 2015, ISBN: 9780128035191, which is incorporated herein (for the aforementioned purpose and in its entirety) by reference thereto.

[0127] Specific compounds

[0128] In some embodiments, the compound of formula (I) is a compound of formula (II), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Ae, A7, Li, L2, L3, L4, Le, and L7 are defined as indicated for any of the above embodiments.

[0129] In some embodiments, it may be particularly advantageous that, in the above formula (II), Li- Ai and L4-A4 do not represent hydrogen. Like glutardialdehyde, 3,4-saturated 2H-pyran derivatives may undergo side-reactions which result in oligomerized or polymerized sideproducts which are undesirable in view of a potential skin irritation or skin sensitization. One major pathway for the generation of these side products is that, once the ring-opened form of the 3,4-saturated 2H-pyran derivatives has reacted to an imine, its tautomeric enamine can bind - via the nucleophilic carbon atom of the enamine - to other 3,4-saturated 2H-pyran derivatives. However, if both C-3 and C-5 (i.e. the carbon atoms to which L1-A1 and L4-A4 are attached) are not carrying a hydrogen atom, the subsequent elimination of hydrogen to a stable intermediate is no longer possible and this reaction pathway to oligomerized and polymerized side products is effectively suppressed. In some embodiments, in the above formula (II), it may further be particularly advantageous that L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety or that L7-A7 represents the C1-C30 moiety and Lg-Ag represents hydrogen since this substitution pattern retains the initial high reactivity of an aldehyde group. It may be further particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety since this substitution pattern is conveniently synthetically accessible, as discussed below in the experimental section.

[0130] In some embodiments, in the above formula (II), at least one of A2, A3 and A4 represents one of the one or more active ingredients or of the precursors thereof. This substitution pattern may be particularly beneficial since it reduces the propensity of the active ingredient(s) or precursor(s) to sterically interfere with the reaction of the 3,4-saturated 2H-pyran moiety (or its ring-opened tautomers) with the amino groups on skin and hair. Moreover, this substitution pattern may be particularly beneficial since it mimics the substitution pattern observed in genipin and oleuropein which are known to be well-tolerated.

[0131] In some embodiments, Ai represents one of the one or more active ingredients or of the corresponding precursors thereof and A2, As and A4 represent independently from each other hydrogen or the C1-C30 moiety.

[0132] In some embodiments, Ai represents the C1-C30 moiety and A2, A3 or A4 represents one of the one or more active ingredients or of the corresponding precursors thereof. In some embodiments, it may further be particularly advantageous that A2 represents one of the one or more active ingredients or of the corresponding precursors thereof, wherein A3 represents the C1-C30 moiety, and A4 represents the C1-C30 moiety.

[0133] In some embodiments, A4 represents one of the one or more active ingredients or of the corresponding precursors thereof, and: A2 represents hydrogen and A3 represents hydrogen; or A2 represents the C1-C30 moiety and A3 represents hydrogen; or A2 represents hydrogen and A3 represents the C1-C30 moiety; or A2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety.

[0134] Linkers Li to Ls In some embodiments, Li, L2, L3, L4, Ls, Le, L7 and Ls (referenced below) independently from each other are absent or represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms.

[0135] In some embodiments, it may be particularly advantageous that, independently from each other:

[0136] Li is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0137] L2 is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0138] L3 is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0139] L4 is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0140] Ls is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0141] Le is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0142] L7 is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0143] Ls is absent or present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, and in particular 1 to 8 carbon atoms. In some embodiments, Li may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to Li. Alternatively or additionally, in some embodiments, L2 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L2. Alternatively or additionally, in some embodiments, L3 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L3. It should be understood that the term “optionally substituted hydrocarbon moiety”, here and elsewhere in the specification, is not meant to exclude the presence of heteroatoms (i.e. atoms besides C and H).

[0144] Alternatively or additionally, in some embodiments, L4 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L4. Alternatively or additionally, in some embodiments, Ls may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to Ls. Alternatively or additionally, in some embodiments, Lg may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to Lg. Alternatively or additionally, in some embodiments, L7 may be present and represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 8 carbon atoms and the functional group may be attached to L7.

[0145] In some embodiments, each of Li, L2, L3, L4, Ls, Lg, L7 and Ls comprises, optionally and independently from each other further, 1 to 8, more specifically 1 to 6, and in particular 1 to 4 oxygen atoms; 1 to 8, more specifically 1 to 6, and in particular 1 to 4 nitrogen atoms; 1 to 6, more specifically 1 to 4, and in particular 1 to 3 sulfur atoms; 1 to 6, more specifically 1 to 4, and in particular 1 to 3 phosphorus atoms, 1 to 4, more specifically 1 to 3, and in particular 1 or 2 boron atoms; and 1 to 10, more specifically 1 to 8, and in particular 1 to 6 halogen atoms. In some embodiments, independently from each other further, each of Li, L2, L3, L4, Ls, Lg, L7 and Ls does not comprise any further atoms species besides carbon, the (optional) aforementioned atom species and hydrogen.

[0146] In some embodiments, each of Li, L2, L3, L4, Ls, Le, L7 and Ls is attached to its respective ring carbon atom by a carbon atom, by an oxygen atom, or by a nitrogen atom, more specifically by a carbon atom, or by an oxygen atom, and in particular by a carbon atom.

[0147] In some embodiments, two linkers may also jointly form a ring. In some embodiments, Li and Lg are present and form a ring; Alternatively or additionally, Li and L2 are present and form a ring. Alternatively or additionally, L2 and L4 are present and form a ring. Alternatively or additionally, L4 and L7 are present and form a ring. Alternatively or additionally, L4 and R1are present and form a ring. The presence of such rings, more specifically of rings formed by Li and L2, by L2 and L4, and by L4 and L7, and in particular of rings formed by L2 and L4, restrict the conformational freedom of the ring-opened 1,5-dicarbonyl tautomer and favors the close proximity of the 1,5-dicarbony positions, thus, may facilitate the ring-closing reaction to form the 1,4-dihydropyridine.

[0148] In some embodiments, in case Ai, A3, As, As and A7 do not represent one of the one or more active ingredients or of the precursors thereof, Li, L3, Ls,Ls and L7 are absent.

[0149] In some embodiments, the ring is a 5-, 6-, 7- or 8-membered ring, more specifically a 5-, 6-, or 7-membered ring, and in in particular a 5- or 6-membered ring.

[0150] In some embodiments, the ring is an optionally substituted cyclopentyl ring, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring.

[0151] In some embodiments, L3 and L4 are present and form an optionally substituted 5-, 6-, 7- or 8- membered ring comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, in particular an optionally substituted cyclopentyl, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring. These substitution patterns may be particularly advantageous in view of skin irritation potential since they mimic the well-tolerated genipin structure. In some embodiments, it may be particularly advantageous that L3 and L4 are present and represent an optionally substituted 5-or 6-membered ring, in particular cyclopentyl, cyclopentenyl, tetrahydrofuranyl, cyclohexyl, or cyclohexenyl, to which A3 and A4 are attached, optionally via a group selected from: -O-, -S-, -C(O)-, -CO2-, -O-C(O)- , -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-, -(CH2)I-4-O- and -O-(CH2)I-4-, or combinations thereof.

[0152] It should also be understood that one or more of the linker groups can, independently from each other, be a polymeric moiety or comprise a polymeric moiety. In some embodiments, none of Li to Ls represents a polymeric moiety.

[0153] C1-C30 moiety

[0154] In any of the embodiments of the present disclosure, and independently from each other for each occurrence of the C1-C30 moiety in the present disclosure, it may be particularly advantageous that: the C1-C30 moiety comprises 1 to 30, more specifically 1 to 16, and in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, Ls, Le, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Le, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0155] In some embodiments, it may further be advantageous that, again independently from each other, for each occurrence of the C1-C30 moiety in the present disclosure: the C1-C30 moiety is selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl or (hetero)aryl, each comprising 1 to 30, more specifically 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0156] In some further embodiments, it may be particularly advantageous that, again independently from each other, for each occurrence of the C1-C30 moiety in the present disclosure: the C1-C30 moiety is selected from a saturated or unsaturated (hetero)alkyl comprising 1 to 12, more specifically 1 to 8, and in particular 1 to 4, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and the C1-C30 moiety is bound: a) to the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0157] Hydrolysable protective group R1

[0158] In some embodiments, R1represents Ci-g acyl, in particular C1-3 acyl or trifluoracetyl; Ci-g alkyl, in particular methyl or ethyl; or a silyl group, in particular trimethoxysilyl triethoxysilyl, and fert-butyldimethylsilyl. In some embodiments, it is most advantageous that R1represents hydrogen. In some embodiments, R1may also represent the protective group hydrolysable under physiological conditions. The choice of said protective group is not particularly limited. Of note, glucoside moieties such as pyranosyl were found to not be suitable as protective groups since the glucosidic bond between the glucoside moiety and the 3,4-saturated 2H-pyran moiety (which is part of two acetals) is not readily hydrolyzed. However, suitable leaving groups can be readily determined by following one or more of the following principles:

[0159] Small protective groups which do not hinder the accessibility of the acetal group (of which R1is a part) by water and nucleophiles which are natively present on the skin and / or the hair, and in particular the accessibility by the n-butyl amino group of lysine, will favor the rate of hydrolysis.

[0160] Protective groups which represent good leaving groups, in particular protective groups which are able to delocalize or stabilize a positive or negative charge, such as an acyl moiety, will favor the rate of hydrolysis.

[0161] Protective groups which themselves can be hydrolysed or decompose under conversion of the ether bond to the 3,4-saturated 2H-pyran moiety can also be utilized. Examples include silylgroups.

[0162] In some embodiments, R1represents Ci-6 acyl, in particular C1-3 acyl or trifluoracetyl; C1-6 alkyl, in particular methyl or ethyl; or a silylgroup, in particular trimethoxysilyl triethoxysilyl, and / c / v-butyldimethylsil l.

[0163] Further specific compounds

[0164] In some embodiments, the compound of formula (I) is a compound of formula (III), or a tautomer and / or a salt thereof; wherein R1, Ai, A2, As, A4, Ae, A7, L2, L3, L4, Le and L7 are defined as in any preceding embodiment; wherein X represents O or S, and in particular O; and wherein Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms, and wherein the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom. Compounds of formula (III) may be particularly advantageous since the (thio-)carbonyl group facilitates the ring-opening to the more reactive 1,5-di carbonyl tautomer. Moreover, it blocks the C-5 position as previously mentioned and allows to delocalize charge in the cascade of reactions towards the 1,4-dihydropyridine derivative, both of which may be beneficial in suppressing the formation of oligomers and polymers as previously mentioned.

[0165] In some embodiments, Ai represents the C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0166] In some embodiments, Lx-Ai represents a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. Compounds of this embodiment may be particularly beneficial since they mimic genipin, oleuropein and elenolic acid which are generally regarded as safe.

[0167] No or low color compounds

[0168] The compounds of the present disclosure do not necessarily have to be colorless when bound to the substrate, in particular to skin or to hair. For instance, if the compounds are used to bind active ingredients to farm animals, color does not play a prominent role. However, in particular in uses for humans, it may be beneficial that the compounds of formula (I), in the form as they are bound to skin or hair, are colorless (or nearly colorless and, thus, not visually perceivable on the skin and hair) or do not add more color than already provided by the active ingredient and / or the precursor comprised in the compound.

[0169] Accordingly, in some embodiments, the compound of formula (I), after having covalently bound to the skin and / or the hair, is not observable to the human eye on the skin and / or the hair. This may, for instance, be tested with a test sample of explanted porcine skin to which the compound has been covalently bound.

[0170] Suitable test conditions include a visual inspection, optionally by a test panel of 5 of more panelists, in a dark room under artificial light conditions of 3000 Kelvin and an intensity of 1000 Lux. The test sample may be prepared by applying a methanolic solution of the compound of formula (I) onto explanted porcine skin at a concentration of 1 pmol / in2(=0.156 pmol / cm2), followed by incubation at 25°C and at 50% relative humidity for 24 hours. At the concentration of 1 pmol / in2, hydrogenated genipin and oleuropein aglycone bind to skin without being visually perceivable whereas skin-bound genipin is still perceivable at about 0.07 pmol / in2. For compounds of formula (I) comprising oligomeric or polymeric active ingredients or precursors, the number-average molecular weight of the compound can be determined by any suitable means, for instance high-pressure liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), MALDI mass spectrometry, size exclusion chromatography (SEC), gel permeation chromatography (GPC),1H- or13C-NMR, or diffusion-ordered NMR spectroscopy (DO SY). Alternatively, for compounds of formula (I) comprising oligomeric or polymeric active ingredients or precursors, the test sample may also be prepared by applying the equivalent of 3 mg of the compound of formula (I) in a methanolic solution onto an area of 1 in2(= 6.45 cm2) of explanted porcine skin, followed by incubation at 25°C and at 50% relative humidity for 24 hours.

[0171] Alternatively or additionally, a comparative test can be performed: The compound of formula (I) can be considered to have bound to the skin and / or the hair as not observable to the human eye, if the compound of formula (I) is not observable at such a high concentration that oleuropein aglycone is starting to be observable. Suitable test conditions again include a visual inspection, optionally by a test panel of 5 of more panelists, in a dark room under artificial light conditions of 3000 Kelvin and an intensity of 1000 Lux. The test samples may be prepared by applying a methanolic solution of the compounds onto samples of explanted porcine skin at a series of diluted concentrations, optionally including concentrations of 5 and 10 pmol / in2(=0.780 pmol / cm2and 1.56 pmol / cm2), followed by incubation of each sample at 25°C and at 50% relative humidity for 24 hours.

[0172] In some embodiments, the compound of formula (I), after having covalently bound to lysine, does not show UV / vis absorption peaks having an extinction of more than 0.5 within the wavelength range of 380 to 790 nm in a 2 mM methanolic solution.

[0173] In some embodiments, the compound of formula (I), after having covalently bound to lysine, does not show UV / vis absorption peaks having an extinction higher than oleuropein aglycone in the wavelength range of 380 to 790 nm when both compounds are tested at the same concentration.

[0174] In some embodiments, L2-A2, L3-A3 and L4-A4 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0175] The present inventors have also found that a large variety of 3,4-saturated 2H-pyran derivatives will unobtrusively bind to skin or hair as long as the 3,4-saturated 2H-pyran derivatives are selected such that the formation of larger conjugated 7i-electron systems involving the skinbound 1,4-dihydropyridine moiety is avoided.

[0176] Accordingly, in some embodiments, L1-A1 and Lg-Ag do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0177] In some embodiments, L4-A4 and L7-A7 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0178] In some embodiments, L1-A1 and L2-A2 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alpha-position to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0179] In some embodiments, the 3,4-saturated 2H-pyran moiety of the compound of formula (I) covalently binds to the skin and / or the hair forming a compound of formulae (la) and / or (lb), or a tautomer and / or a salt thereof; wherein the broken bond represents the covalent bond to the skin and / or the hair; and wherein Ai, A2, As, A4, Ae, A7, Li, L2, L3, L4, Lg and L7 are defined as indicated in any of the preceding embodiments. Moreover, it may be particularly advantageous that, after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formulae (la) and / or (lb), no more than one, and in particular none, of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I) forms a conjugated 71-electron system comprising more than 6 double bonds, more specifically more than 5 double bonds, and in particular more than 4 double bonds, with the heterocycle marked by letters a to e in the formula (la) and more than 7 double bonds, more specifically more than 6 double bonds, and in particular more than 5 double bonds, with the heterocycle marked by letters a to e in the formula (lb).

[0180] In some embodiments, the combination of all of Li-Ai, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I), after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or the hair forming a compound of formula (la) and / or (lb) does not form a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (la) and (lb). In some embodiments, the combination of all of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I), after the 3,4-saturated 2H -pyran moiety has covalently bound to the skin and / or hair forming a compound of formula (la) and / or (lb) forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (la) which comprises less than 7 double bonds, more specifically less than 6 double bonds, and in particular less than 5 double bonds, and forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (lb) which comprises less than 8 double bonds, more specifically less than 7 double bonds, and in particular less than 6 double bonds.

[0181] It may also be particularly advantageous that no more than three, more specifically no more than two, and in particular no more than one, of L1-A1, L2-A2, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I) comprise a carbonyl group which forms or is part of a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (la) and (lb).

[0182] It may also be particularly advantageous that L1-A1, L2-A2, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I) are selected such that - after the compound has bound to skin or hair - they do not provide a combination of electron-withdrawing and electron-donating groups to the conjugated 71-electron system formed with the respective heterocycles marked by letters a to e in the formulae (la) and (lb).

[0183] Further specific compounds

[0184] In some embodiments, the compound of formula (I) is a compound of formula (IV), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Li, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; wherein R2represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; and wherein R3represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms.

[0185] In some embodiments, in the above formula (IV), it may be advantageous that R2represents Ci-Ce alkyl or C6-C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms; and R3represents hydrogen or Ci-Ce alkyl or Ce- C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R3does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms. In some embodiments, R2represents a Ci-Ce alkyl which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 12 carbon atoms, 4 oxygen atoms, 3 nitrogen atoms, 2 sulfur atoms, and 3 halogen atoms; and R3represents hydrogen or C1-C4 alkyl.

[0186] In some embodiments, R2represents an aliphatic C1-C4 moiety, optionally comprising a carboxylic acid or a salt thereof, a carboxylic acid ester, a ketone, an alcohol, an ether, or combinations thereof; and wherein R3represents hydrogen.

[0187] In some embodiments, the compound of formula (I) is a compound of formula (V), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, A2, A3, A4, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; and wherein R4represents hydrogen or a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone or an amide; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(0)-NH2, -C(O)NHRa, and -C(0)NRa2; wherein each instance of Rarepresents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0188] In some embodiments, in the above formula (V), it may be advantageous that R4represents - COOH or a salt thereof, -COORb, -C(O)-Rb, C(O)-NH2, -C(O)NHRb, -C(O)NRb2, wherein Rbrepresents a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, more specifically a moiety comprising 1 to 4 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, and 1 to 3 halogen atoms. It may be particular advantageous that Rbrepresents -Ci-C4-alkyl, more specifically methyl or ethyl and in particular methyl.

[0189] In some embodiments, the compound of formula (I) is a compound of formula (Via) or (VIb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, and R4are defined as indicated in any of the preceding embodiments; wherein each of R5, independently from each other, represents hydrogen or a Ci-Ce moiety which optionally further comprises 1- 3 oxygen atoms, 1-3 nitrogen atoms, and 1-2 sulfur atoms; wherein for formula (Via) Ls and As are defined as L2 and A2 in any of the preceding embodiments; and wherein for formula (VIb) Ls and As are defined as L4 and A4 in any of the preceding embodiments.

[0190] In some embodiments, in formulae (Via) or (VIb), it may be advantageous that Ls represents a saturated Ci-Ce-alkyl moiety which is optionally substituted with a group selected from: -O-, - C(O)-, -CO2-, -O-C(O)-, -NH-, -N(Ci-C4-alkyl)-, -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-, -(CH2)i- 4-O-, -O-(CH2)I-4-, -S(O)-, -SO2-, or combinations thereof. It may be particularly advantageous that each of R5, independently from each other, represents hydrogen or a C1-C4 alkyl. In some embodiments, the compound of formula (I) is a compound of formula (Vila) or (Vllb), (Vllb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, and R5are defined as indicated in any of the preceding embodiments; wherein the dashed line represents a bond or is absent; wherein n is an integer between 0 and 6, more specifically between 0 and 4, and in particular between 0 and 3; and m is an integer between 0 and 8, more specifically between 0 and 4, and in particular between 0 and 3; and wherein Ls and As are defined as L4 and A4 in any of the preceding embodiments.

[0191] In some embodiments, in formulae (Vila) or (Vllb), it may be advantageous that R2represents H or C1-C4 alkyl, R3represents H or C1-C4 alkyl, R4represents -COOH or a salt thereof, - COORa, -C(O)-Ra, C(0)-NH2, -C(O)NHRa, -C(0)NRa2, wherein Ra and NRa2 are defined as in any preceding embodiment.

[0192] In the following, the active components linked to the remainder of the compounds according to the present disclosure will be discussed. For reasons of simplicity of language, in some instances, reference to the active ingredient will be made as if the active ingredient is an individual compound instead of a moiety attached to the remainder of the compound of formula (I). It should be understood that this is to be interpreted as a reference to a moiety that is attached to the remainder of the compound of formula (I), by e.g. elimination of a hydrogen atom from the active ingredient.

[0193] It should further be understood that the below-mentioned disclosure regarding the active components is freely combinable with the above disclosure relating to the compounds according to formulae (I) to (Vllb). Indeed, these combinations represent preferred embodiments of the present disclosure, although it should also be understood that the present disclosure is not limited thereto. Humectants, Emollients, Occlusives

[0194] In some embodiments, at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents the active ingredient or the precursor of the active ingredient, and the active ingredient is the moisturizer, the skin moisturizer or the hair moisturizer, respectively. In some embodiments, the active ingredient comprises a plurality of hydrogen bonding groups selected from the group consisting of hydroxyl groups, ether groups, carboxylic acids, amines and amides; and their salts. In some embodiments, the plurality of hydrogen bonding groups comprises three or more, more specifically 4 or more, and in particular 6 or more hydrogen bonding groups. In some embodiments, the ratio of C-atoms to the sum of hydrogen bonding groups comprised in the active ingredient is between about 4:1 to 1:1, more specifically between about 3:1 to about 1: 1 and in particular between about 2:1 to about 1:1. In some embodiments, the active ingredient has a molecular weight of at least 60 g / mol, more specifically at least 90 g / mol, and in particular at least 120 g / mol. In some embodiments, the active ingredient has a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol. In some embodiments, the ratio of C-atoms to the sum of heteroatoms comprised in the active ingredient is between about 4:1 to 1:2, more specifically between about 3:1 to about 1:1.5, and in particular between about 2:1 to about 1:1, wherein the heteroatoms are selected from nitrogen and oxygen. In some embodiments, the active ingredient comprises: a polyol, more specifically a polyol having n hydroxyl groups with n being 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, or 16 or more; a mono- or polyvalent carboxylic acid comprising one or more hydroxyl groups, more specifically glycolic acid, lactic acid, malic acid, tartaric acid or citric acid; a sugar, more specifically a triose, a tetrose, a pentose a hexose, a monosaccharide, a disaccharide, a trisaccharide, or an oligosaccharide; a sugar alcohol, more specifically a sugar alcohol comprising between 2 and 24 carbon atoms, in particular ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; or a sugar acid, more specifically an aldonic acid, an ulosonic acid, an uronic acid or an aldaric acid; or a salt thereof; or an ester thereof, in particular a Ci-C4-alkylester thereof; or an amide thereof; or a polysaccharide; more specifically a glycosaminoglycan, such as chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid; and in particular hyaluronic acid; and copolymers thereof, in particular copolymers comprising polyethylene glycol.

[0195] In some embodiments, it may be particularly advantageous that the active ingredient is a hyaluronic acid, more specifically a hyaluronic acid having a weight-average or a numberaverage, and in particular a number-average, molecular weight of between 3000 and 3 million kDa, more specifically between 5000 and 2 million kDa, and in particular between 10,000 and 1.5 million kDa.

[0196] In some embodiments, the active ingredient is an emollient or an occlusive.

[0197] In some embodiments, the active ingredient comprises: a Cio-Ceo moiety, more specifically a C15-C60 moiety and in particular a C20-C60 moiety; or an oligo- or poly siloxane, in particular a poly(di-Ci-C4-alkyl)siloxane. In some embodiments, the active ingredient is the Ci-Ceo moiety and has a molecular weight of 140 g / mol to 2000 g / mol, more specifically 160 g / mol to 1600 g / mol, and in particular 180 g / mol to 1200 g / mol. In some embodiments, the active ingredient has more than 30 carbon atoms. In some embodiments, the active ingredient comprises a saturated or unsaturated Cio-Ceo aliphatic moiety, more specifically a Cis-Ceo aliphatic moiety, and in particular a C20-C60 aliphatic moiety. In some embodiments, the ratio of C-atoms to the sum of heteroatoms comprised in the active ingredient is between about 60: 1 to 5:1, more specifically between about 50:1 to about 10:1, and in particular between about 40:1 to about 20:1, wherein the heteroatoms are selected from nitrogen and oxygen. In some embodiments, the Ci-Ceo moiety is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin.

[0198] In some embodiments, at least one of Ai, A2, As, A4, As, and Ae represents the moisturizer, the skin moisturizer or the hair moisturizer, respectively. In some embodiments, at least one of Ai, A2, A3, A4, As, and As represents the precursor of the moisturizer, the skin moisturizer or the hair moisturizer, respectively.

[0199] Pesticides

[0200] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents the active ingredient or the precursor of the active ingredient, and the active ingredient is the pesticide.

[0201] In some embodiments, the pesticide may be an insect repellant. For the purposes of the present disclosure, an insect repellent is a chemical used to control insects without killing or incapacitating them, in particular by making the host (i.e. the subject to which the insect repellant is applied) less attractive to the insect.

[0202] In some embodiments, the pesticide may be an insecticide. For the purposes of the present disclosure, an insecticide is a chemical used to control insects by killing or incapacitating them.

[0203] In some embodiments, the insect repellant or insecticide may act against an ectoparasite and / or a hematophagous insect, in particular a hematophagous insect selected from the group consisting of mosquitoes, ticks, mites, gnats, fleas, chiggers, leeches and bugs. Ectoparasites are organisms that live on the skin of a host, from which they derive their sustenance.

[0204] In some embodiments, the pesticide may be an insect repellant which may be selected from isoprenoids, tertiary amides, and phenylpropanoids.

[0205] In some embodiments, the insect repellant may be an isoprenoid, more specifically a monoterpenoid, a diterpenoid or a triterpenoid, and in particular a terpineol or derivative thereof, a monoterpenoid aldehyde or a derivative thereof, a limonoid or a derivative thereof; or a pyrethrin or a derivative thereof. In some embodiments, the isoprenoid may be selected from citronellal, hydroxy citronellal, citronellol, citral A, citral B, or a derivative thereof; a necrodane, in particular a-necrodol, or a derivative thereof; a limonoid, in particular azadirachtine, or a derivative thereof; or a pyrethrin, in particular a jasmolin, a cinerin, or a derivative thereof. In some embodiments, the insect repellant may comprise a tertiary amide. In some embodiments, the tertiary amide may be selected from picaridine, an N,N-di(Ci-Ce-alkyl)- toluamide, in particular N,N-diethyl-meta-toluamide, ethyl 3-( / V-butylacetamido)propanoate; and derivatives thereof.

[0206] In some embodiments, the insect repellant may be selected from one of the following compounds and moieties / derivatives thereof: N,N-diethyl-meta-toluamide, diethyl phenyl acetamide, N-butylacetanilide, ethyl butylacetylaminopropionate, picaridine, N-(2- methylpiperidin- 1 -yl)cy clohex-3-ene- 1 -carboxamide, and 1 - [3 -cy clo-hexen- 1 -ylcarbonyl] -2- methylpiperidine or l-[3-cyclohexen-l -ylcarbonyl] piperidine.

[0207] In some embodiments, the insect repellant may be a phenylpropanoid, in particular eugenol or a derivative thereof.

[0208] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents a moiety of formula (Villa) or formula (Vlllb),

[0209] (Villa) (Vlllb).

[0210] In some embodiments, the insect repellant comprises a tertiary amide. It may be particularly advantages that the tertiary amide is selected from picaridine, an N,N-di(Ci-Cs-alkyl)- toluamide, in particular N,N-diethyl-meta-toluamide, p-menthane-3,8-diol, ethyl 3-(N- butylacetamido)propanoate; and derivatives thereof.

[0211] In some embodiments, the insect repellant is selected from one of the following compounds and moieties / derivatives thereof: N,N-diethyl-meta-toluamide, diethyl phenyl acetamide, N- butylacetanilide, ethyl butylacetylaminopropionate, picaridine, N-(2-methylpiperidin-l- yl)cyclohex-3-ene-l-carboxamide, and l-[3-cyclo-hexen-l-ylcarbonyl]-2-methylpiperidine or l-[3-cyclohexen-l-ylcarbonyl] piperidine. In some embodiments, at least one of Ai, A2, Aa, A4, As, As, A7 and As represents a moiety of formula (IX),

[0212] (IX).

[0213] In some embodiments, at least one of Ai, A2, As, A4, As, As, A7 and As represents a moiety of formula (X),

[0214] In some embodiments, the pesticide is a topical insecticide, in particular a topical insecticide which is selected from permethrine; cypermethrin; deltamethrin; ivermectin; amidines, in particular amitraz; bendiocarb; malathion; carbaryl; diazinon; DDT; fenthion; fipronil; imidacloprid; nitenpyram; and propoxur.

[0215] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents the pesticide, in particular the insect repellant.

[0216] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents the precursor of the pesticide, in particular the insect repellant. Skin whitening agents

[0217] In some embodiments, relating to uses of the compounds of the present disclosure for covalently binding the one or more active ingredients to the skin, at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents the active ingredient of the active ingredient, and the active ingredient is the skin whitening agent.

[0218] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents the precursor of the active ingredient, and the active ingredient is the skin whitening agent.

[0219] In some embodiments, the skin whitening agent acts by chemically or metabolically whitening the skin, in particular by providing a bleaching effect or decreasing melanin production.

[0220] In some embodiments, the skin whitening agent is selected from corticosteroids, in particular clobetasol derivatives, fluocinolone derivative, or betamethasone; a vitamin A derivative, in particular tretinoin, isotretinoin, alitretinoin, retinol or retinal; a hydroxyphenol derivative, in particular hydroquinone; an aliphatic dicarboxylic acid, in particular azelaine; alpha-hydroxyacids, in particular lactic and glycolic acid; and vitamin C.

[0221] Fragrances

[0222] In some embodiments, at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents the precursor of the active ingredient, and the active ingredient is the fragrance. In some embodiments, the precursor is a Ci-Ceo moiety comprising a functional group which couples the Ci-Ceo moiety to the corresponding Li, L2, L3, L4, Ls, Le, L7, or Ls moiety or, if the corresponding Li, L2, L3, L4, Ls, Lg or L7 moiety is absent, to the 3,4-saturated-2H-pyran moiety, or, if the corresponding Ls moiety is absent, to the respective cycloalkane moiety. In some embodiments, the Ci-Cso moiety is cleaved under physiological conditions on skin and / or hair to an aldehyde, a ketone, a thiol, a hydroxy, a carboxy, or an amine. In some embodiments, the functional group is an imine, an acetal, a 1,1 -diester, an enolether, an ester, an amide, a thioester, or a thioacetal. In some embodiments, the Ci-Cso moiety has a molecular weight after being cleaved off of less than 400 g / mol, more specifically less than 300 g / mol, and in particular less than 200 g / mol. In some embodiments, the fragrance is not benzyl alcohol or hexanol. Pharmaceuticals

[0223] In some embodiments, at least one of Ai, A2, As, A4, As, As, A7 and As represents one of the one or more active ingredients or of the precursors thereof, and the active ingredient is the pharmaceutical.

[0224] In some embodiments, the pharmaceutical is suitable for treating a skin-associated disease and / or a hair-associated disease. In some embodiments, the skin-associated disease is selected from acneiform eruptions, autoinflammatory syndromes, chronic blistering, conditions of the mucus membranes, conditions of the skin appendages, conditions of the subcutaneous fat, congenital anomalies, connective tissue diseases, abnormalities of dermal fibrous and elastic tissue, dermal and subcutaneous growths, dermatitis, eczema, seborrheic dermatitis, disturbances of pigmentation, endocrine-related skin conditions, eosinophilic cutaneous conditions, skin lesions, skin cancer, erythemas, genodermatoses, infection-related cutaneous conditions, lichenoid eruptions, lymphoid-related cutaneous condition, melanocytic nevi and neoplasms, monocyte- and macrophage-related cutaneous conditions, mucinoses, neurocutaneous conditions, Noninfectious immunodeficiency-related cutaneous conditions, Nutrition-related cutaneous conditions, Papulosquamous hyperkeratotic cutaneous conditions, Palmoplantar keratodermas, pruritus, psoriasis, reactive neutrophilic cutaneous conditions, skin conditions resulting from errors in metabolism, skin conditions resulting from physical factors, urticaria, dandruff, desquamation disorders, and vascular-related cutaneous conditions; and / or the hair-associated disease is selected from dandruff and alopecia.

[0225] In some embodiments, the active ingredient is an agonist of a retinoid receptor, more specifically a retinoic acid receptor, a retinoid X receptor and / or a RAR-related orphan receptor. In some embodiments, the active ingredient comprises a vitamin A vitamer, more specifically a vitamer selected from the group of retinol, tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, adapalene and / or bexarotene, in particular retinol, retinal and / or adapalene.

[0226] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents a moiety of formula (XI), (XI), wherein R6represents H, OH, Ci-C4-alkyl, NH2, N(Ci-C4-alkyl)2, N-morpholino-l-yl, or piperi din-1 -yl; wherein Lyrepresents group selected from -C(O)-, -C(O)-(CH2)I-4-, -C(O)-O-, - C(O)-O-(CH2)I-4-, -C(O)-NRYC(O)-, -C(O)-NRYC(O)-(CH2)I-4-, -S(O)2-O-, and -S(O)2-O- (CH2)I-4; wherein RYrepresents H or C1-C4 alkyl; and wherein Lyis part of the linker group Li, L2, L3, L4, Ls, Le, L7, or Ls corresponding to the Ai, A2, A3, A4, As, Ae, A7, or As which represents the moiety of formula (XI).

[0227] In some embodiments, R6represents H (i.e. kopexil) or piperidin-l-yl (i.e. minoxidil).

[0228] In some embodiments, the pharmaceutical may be suitable for treating an allergic condition. In some embodiments, the pharmaceutical may be an antihistamine. In some embodiments, at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents a moiety of formula (XU), (XII), wherein Lxrepresents group selected from -C(O)-, -C(O)-(CH2)I-4-, -C(O)-O-, -C(O)-O-(CH2)I-4-, -C(O)-NRYC(O)-, -C(O)-NRYC(O)-(CH2)I-4-, -S(O)2-O-, and -S(O)2-O-(CH2)I-4; wherein RYrepresents H or C1-C4 alkyl; and wherein Lxis part of the linker group Li, L2, L3, L4, Ls, Le, L7, or Ls corresponding to the Ai, A2, A3, A4, As, Ae, A7, or As which represents the moiety of formula (XII). In some embodiments, the pharmaceutical or the corresponding precursor thereof may not be a compound or moiety for the prevention of sunburn, skin cancer and / or other skin diseases associated with UV-A / UV-B exposure. In some embodiments, the Ci-Ceo moiety of group b) may not comprise or be derived from salicylic acid and its derivatives. In some embodiments, the compound according to formula (I) does not comprise an ester of salicylic acid. This includes both esters formed with the hydroxy group of salicylic acid and esters formed by the carboxylic acid of salicylic acid.

[0229] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents the pharmaceutical.

[0230] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents the precursor of the pharmaceutical.

[0231] Cosmetic hair coating agents

[0232] In some embodiments, relating to uses of the compounds of the present disclosure for covalently binding the one or more active ingredients to hair, at least one of Ai, A2, Aa, A4, As, As, A7 and As represents one of the one or more active ingredients or of the precursors thereof, and the active ingredient is the cosmetic hair coating agent.

[0233] In some embodiments, the cosmetic hair coating agent provides a conditioning effect to the hair. Compounds / moieties providing a hair-conditioning effect are well-known in the art. Suitable examples include compounds / polymers having long hydrocarbon or siloxane backbones which help to lubricate the surface of the hair, thereby reducing the sensation of roughness and assisting combing. Conventional conditioners often also contain quaternary cationic groups. These groups have a dual purpose: First, they help in attaching conventional conditioners to the hair. The outermost layer of a hair is rich in cysteine groups which are mildly acidic. When the hair is washed these groups can deprotonate, giving the hair a negative charge. Positively charged quaternary ammonium species can then become attached to the hair via electrostatic interactions. This functionality is of lesser importance for the present disclosure since the compounds attach to hair in a different manner. However, the surface coating of cationic groups also results in the hair being repelled from each other electrostatically which reduces clumping. Accordingly, while not essential, the active ingredient may also benefit from the presence of the quaternary cationic groups.

[0234] In some embodiments, the cosmetic hair coating agent provides a gloss effect (or shine) to the hair. Compounds / moieties providing a gloss-effect or shine effect are well-known in the art. Typical examples include polymer having a high refractive index and examples (copolymers comprising poly ether blocks and polysiloxane blocks) are, for instance, disclosed in European Patent Application EP 3 162 408 Al which is incorporated herein in its entirety by reference thereto.

[0235] In some embodiments, the cosmetic hair coating agent provides a reinforcing effect to the hair. When referring to a reinforcing effect, it is meant that the hair is physically coated with e.g. a polymer to make it thicker and that the hair is provided with a coating that improves the styling performance of the hair (much like e.g. a styling gel would). Compounds providing such reinforcing effects are well-known in the art and include vinyl (co-)polymers such as polyvinyl pyrrolidone or a copolymer of dimethylamino-ethylmethacrylate and polyvinyl pyrrolidone. Such (co-)polymers are capable of forming hydrogen bonds along the entire polymer chain which provides the styling effect. Other suitable polymers include derivatives of polyethylene glycol. A reinforcing (styling) effect such as curling can also be provided by enriching the surface with moieties provided with one or more thiols. Examples of such moieties include cysteine and cysteine derivatives. These thiols can be oxidized to dithiols (just as in a conventional perm) with an oxidizing agent (such as an peroxide) to provide the hair with a desired shape.

[0236] In some embodiments, the cosmetic hair coating agent provides an anti-frizz effect to the hair. When referring to an anti-frizz effect, it is meant that the frizziness of the hair is reduced. Compounds / moieties providing an anti-frizz effect are also well-known in the art and include compounds that can act as antistatic agents. Suitable compounds are well-known in the art and in particular encompass compounds / polymers which contain quaternary cationic groups and poly carboxylic acids or poly carboxylates, in particular a polyitaconate.

[0237] Accordingly, in some embodiments, the cosmetic hair coating agent may in particular be further characterized as follows: In some embodiments, the cosmetic hair coating agent provides a conditioning effect to the hair. In some embodiments, the cosmetic hair coating agent provides a gloss effect to the hair. In some embodiments, the cosmetic hair coating agent provides an anti-frizz effect to the hair. In some embodiments, the cosmetic hair coating agent provides a reinforcing effect to the hair.

[0238] In some embodiments, the cosmetic hair coating agent represents a Ci-Ceo moiety, in particular a Ci-Ceo moiety having a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol; or a polymeric moiety.

[0239] In some embodiments, the cosmetic hair coating agent is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin. In some embodiments, the cosmetic hair coating agent is positively charged and / or comprises a cation, in particular a quaternary cation. In some embodiments, the cosmetic hair coating agent is negatively charged and / or comprises an anion, in particular a sulfate ion or a carboxylate ion. In some embodiments, the cosmetic hair coating agent is a polymeric moiety, in particular a polymeric moiety that is positively charged and / or comprises a cation, in particular a quaternary cation. In some embodiments, the cosmetic hair coating agent is a polyquatemium, in particular polyquatemium-16, polyquatemium-46, polyquatemium-11, polyquatemium-28, polyquatemium-6, polyquatemium-7, polyquatemium-22, polyquatemium-39, polyquatemium-2, polyquatemium- 17, or polyquatemium-18. In some embodiments, the cosmetic hair coating agent is a poly carboxylic acid or a polycarboxylate, in particular a polyitaconate. In some embodiments, the cosmetic hair coating agent comprises a poly ether, more specifically a poly-(Ci-C6)ether, and in particular polymers of ethylene oxide and / or propylene oxide. In some embodiments, the cosmetic hair coating agent comprises a polysiloxane, more specifically a poly(di-Ci-C4- alkyl)siloxane and derivatives thereof. In some embodiments, the cosmetic hair coating agent comprises a copolymer comprising polyether blocks and polysiloxane blocks.

[0240] Primers for attaching dyes to hair

[0241] Hair dyes and also reactive hair dyes are well-known in the art. The compounds of the present disclosure can be utilized to provide functional groups to the hair surface and / or its interior which subsequently allow the (covalent) attachment of dyes and pigments to the hair which are otherwise not attachable to hair, or only under aggressive conditions which may damage the hair.

[0242] Moreover, the compounds of the present disclosure can also be utilized to provide a more gentle hair dying method. Conventional hair dyes require a rather aggressive treatment of the hair to open the hair cuticle such that dye precursors can access the core of the hair. The dye precursors deposited in the core of the hair are then developed into a color using oxidative or reductive developers, followed by a treatment with a conditioner to restore the cuticle layer to encapsulate the dye in the core of the hair. However, this process is far from perfect and permanently damages the hair. The compounds of the present disclosure can be utilized to covalently bind such dye precursors to the hair surface and / or its interior under milder conditions, and the bound dye precursors can then be developed into dyes using the established developers.

[0243] To summarize, the compounds of the present disclosure may be used for priming the hair by covalently binding functional groups to the hair which are subsequently utilized to attach colorants (dyes or pigments) to the hair or by covalently binding dye precursors to the hair which are subsequently converted into (the desired) color by applying a color developer. Both of these concepts are to be understood as concepts for attaching dyes to the hair, in accordance with the present disclosure.

[0244] Utilizing the compounds of the present disclosure for attaching two types of primer are of particular relevance, namely a) enriching the hair with functional groups which are naturally occurring in hair (hydroxyl, amines, sulfides, etc.) but not in sufficient number to adequately attach colorants to the hair; and, additionally or alternatively, b) providing functional groups not naturally occurring in hair (e.g. aromatic diamines, aminophenols and resorcinol derivatives) to use their functionality to attach colorants to the hair or to develop them to dyes using a developer.

[0245] The above concept of hair dyeing may be particularly gentle to the hair, in particular since the core of the hair does not need to be made accessible to entrap the dye in the core of the hair.

[0246] Accordingly, in some embodiments, relating to uses of the compounds of the present disclosure for covalently binding the one or more active ingredients to hair, at least one of Ai, A2, A3, A4, As, As, A? and As represents the active ingredient which is the primer for attaching dyes to the hair.

[0247] In some embodiments, the primer comprises one or more functional groups, in particular thiol or amino groups, and the use comprises treating the hair with a second composition comprising a colorant (a dye or a pigment) which is capable of covalently binding to said one or more functional groups, optionally in the presence of a coupling agent, in particular an oxidizing agent or a reducing agent. In some embodiments, the coupling agent is comprised in the second composition. In some embodiments, the coupling agent is comprised in a third composition.

[0248] In some embodiments, the primer comprises a thiol group, the second composition comprises a colorant comprising a thiol group which is capable of covalently binding with the thiol group of the primer under formation of a disulfide bond, optionally in the presence of a coupling agent, in particular an oxidizing agent.

[0249] In some embodiments, the primer comprises one or more ionic functional groups, and the use comprises treating the hair with a second composition comprising a colorant (a dye or a pigment) which is capable of binding to said one or more ionic functional groups by ion-ion interactions and / or by forming a chelate.

[0250] In some embodiments, the primer comprises one or more dye precursors, and the use comprises treating the hair with a second composition comprising a developer which is reacting with the one or more dye precursors to provide a colorant, optionally in the presence of a coupling agent, in particular an oxidizing agent or a reducing agent. In some embodiments, the developer is said oxidizing agent or said reducing agent. In some embodiments, the coupling agent is comprised in the second composition. In some embodiments, the coupling agent is comprised in a third composition.

[0251] In some embodiments, the primer is a Ci-Cso moiety, in particular a Ci-Cso moiety having a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol. In some embodiments, the primer is an aromatic moiety comprising two or more functional groups selected from hydroxyls, primary, secondary or tertiary amines, and ethers.

[0252] In some embodiments, the primer is selected from resorcinol, m-aminophenol, 2-methyl-5- aminophenol, p-phenylenediamine, 2,4-diaminoanisole, 1,5-dihydroxynaphthalene, 4- methoxy-3-aminophenol, 2,4-diaminophenoxyethanol, m-diethylaminophenol and p-amino-o- cresol; and derivatives thereof.

[0253] In some embodiments, the dye precursor is selected from para-phenylenediamine and paraaminophenol.

[0254] In some embodiments, the dye precursor is a precursor (or a derivative thereof) as disclosed in the review article by Morel et al., in Chem. Rev. 2011, 111, 4, 2537-2561, which is incorporated herein in its entirety by reference thereto.

[0255] In some embodiments, the oxidizing agent is a peroxide, in particular hydrogen peroxide.

[0256] In some embodiments, the reducing agent is a thiol-based reducing agent, and in particular a thiol-based reducing agent selected from the group consisting of thioglycolic acid, cysteine, thiolactate, and salts thereof.

[0257] In some embodiments, the compound of formula (I) is less than 14 Angstrom, more specifically less than 12 Angstrom, and in particular less than 9 Angstrom, in size. The small size of the molecules may help in penetrating the hair which has been likened to a molecular sieve with a sieve hole size of 14.8 Angstrom in the literature.

[0258] UVA and / or UVB-absorbing moieties and a color-imparting moieties

[0259] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents one of the one or more active ingredients, and the active ingredient is the color-imparting moiety or the UVA and / or UVB-absorbing moiety. In some embodiments, the color-imparting moiety has at least one absorption peak within the wavelength range of 380 to 790 nm, more specifically at least one absorption peak within the wavelength range of 380 to 790 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0260] In some embodiments, the UVA- and / or UVB-absorbing moiety has at least one absorption peak within the wavelength range of 280 to 379 nm, more specifically at least one absorption peak within the wavelength range of 280 to 379 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0261] In some embodiments, at least one of Ai, A2, As, A4, As, As, A7 and As represents the colorimparting moiety, and said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 40 carbon atoms; or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 6 to 40 carbon atoms and at least 3 conjugated C-C double bonds.

[0262] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents a UVA and / or UVB absorbing moiety, wherein said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms; or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms, and at least 2 conjugated C-C double bonds.

[0263] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents a chromophore (dye moiety) selected from an azo group; a diazo group; a diphenylamine group; a nitroarylamine group; an azine group; an oxazine group; an acridine group; an indoline group; a sulfur dye group, in particular a thiazine group, a thiazole group, a thiazone group, a thianthrene group, or a phenothiazonethioanthrone group; a quinoid or quinone group; an anthraquinoid or anthraquinone group; a xanthene group; a naphthostyryl group; a diaryl methyl or triarylmethyl group; a benzodifuranone-based group; a formazan group; a phthalocyanine group; or a metal complex.

[0264] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents a UVA- and / or UVB-absorbing moiety as one of the active ingredients or of the precursors thereof which is selected / derived from: a benzophenone group, a benzotriazole group, a benzone group, salicylic acid or a salicylic acid derivative, a benzocaine group, an esculin or an esculin derivative, a ferulic acid or a ferulic acid derivative, octinoxate or an octinoxate derivative, or octocrylene or an octocrylene derivative.

[0265] In some embodiments, at least one of Ai, A2, A3, A4, As, As, A7 and As represents a moiety which is selected from the following group of moi eties:

[0266]

[0267] In some embodiments, the compound of formula (I) does not include an active ingredient that is a color-imparting moiety; or a color-imparting moiety having at least one absorption peak within the wavelength range of 380 to 790 nm; or a color-imparting moiety having at least one absorption peak within the wavelength range of 380 to 790 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0268] In some embodiments, the compound of formula (I) does not include an active ingredient that is a UV-absorbing moiety; or UVA- and / or UVB-absorbing moiety; or a UVA- and / or UVB- absorbing moiety having at least one absorption peak within the wavelength range of 280 to 379 nm; or a UVA- and / or UVB-absorbing moiety having at least one absorption peak within the wavelength range of 280 to 379 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0269] In some embodiments, the compound of formula (I) is a compound of formula (XIII),

[0270] or a tautomer and / or a pharmaceutically acceptable salt thereof, wherein R1, Ai, A3, A4, Ae, A7, Le and L7 are defined as in any preceding embodiment. X represents O or S, and in particular O.

[0271] Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms. Said hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom.

[0272] One moiety selected from L3, and L4 represents an optionally substituted (hetero) aromatic C3- C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0273] The other moiety amongst L3 and L4 represents a C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0274] Compounds of formula (XIII) may be particularly advantageous since the (thio-)carbonyl group facilitates the ring-opening to the more reactive 1,5-dicarbonyl tautomer. Moreover, the C-5 position is blocked and a delocalization of ionic charges in the cascade of reactions towards the 1,4-dihydropyridine derivative is facilitated, both of which are beneficial in suppressing the formation of potentially cytotoxic oligomers and polymers as previously mentioned.

[0275] In some embodiments, L3 represents the optionally substituted (hetero)aromatic C3-C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0276] In some embodiments, L3 represents an optionally substituted phenyl moiety comprising, in combination with its optional substituents, 6 to 12, more specifically 6 to 10, and in particular 6 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. In some embodiments, the phenyl moiety is optionally substituted with - OH; -O-Ci-C4-alkyl; -N(Ci-C4-alkyl)2; one or more halogen atoms, each independently from each other selected from Cl, Br, and F; -NO2; and -CF3.

[0277] In some embodiments, L4 represents an optionally substituted aliphatic moiety comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms. In some embodiments, the aliphatic moiety is a Ci-Ce-alkyl, more specifically a linear or branched Ci-C4-alkyl; and in particular a linear Ci-C4-alkyl. In some embodiments, Ai represents the C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0278] In some embodiments, Lx-Ai represents a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Ra represents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0279] Topical application in the uses of the present disclosure

[0280] In some embodiments, the use further comprises applying the compounds of the present disclosure to the skin and / or hair as atopical composition which comprises one or more of said compounds. In some embodiments, the topical composition is left in contact with the skin and / or the hair for at least 30 minutes. In some embodiments, the use includes cleaning, optionally with an acidic cleaning solution, or chemically peeling the skin and / or the hair prior to applying the topical composition onto the skin.

[0281] Treating domestic and farm animals In some embodiments, the use comprises applying the compounds of the present disclosure to the skin and / or fur of domestic or farm animals, in particular wherein said compound comprises an active ingredient or precursor thereof which is selected from pesticides and UVA- and / or UVB-absorbing moieties. In some embodiments, it may be further advantageous that the compounds of the present disclosure further provide color to the skin and / or fur of domestic or farm animals since this may provide an indication of the (residual) amount of active ingredient being present on the skin and / or fur.

[0282] Cosmetic and non-therapeutic uses

[0283] In some embodiments, the use according to the first aspect of the present disclosure is a non- therapeutic use. In some embodiments, said use is for preventing insect bites, in particular mosquito bites. In some embodiments, said use is for preventing sunbum. In some embodiments, the use according to the first aspect of the present disclosure is a cosmetic use.

[0284] Second aspect of the present disclosure

[0285] In a second aspect, the present disclosure relates to the compounds recited in the first aspect of the present disclosure per se, i.e. independent from the use.

[0286] More specifically, according to the second aspect, the present disclosure relates to a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Ls and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, Aa, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0287] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0288] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0289] A4 and As are, independently from each other, defined as indicated for Ai;

[0290] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Ls-As and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0291] Any of the specific compounds which are disclosed for the first aspect of the present disclosure also represent specific embodiments according to this second aspect of the present disclosure.

[0292] Third aspect of the present disclosure In a third aspect, the present disclosure relates to the topical composition comprising one or more of the compounds recited in the second aspect of the present disclosure.

[0293] Any of the specific compounds which are disclosed for the first and second aspect of the present disclosure also represent specific embodiments according to this third aspect of the present disclosure.

[0294] The topical composition is not particularly limited and includes any such composition for topical administration. Topical administration in the sense of the present disclosure refers to any local (i.e. not systemic) administration, whether through ointments, gels, creams, lotions, or other similar formulations, of the compounds or compositions of the present disclosure, including administration directly to the external epidermis or dermis of a subject, including administration to skin appendages such as hair but excluding oral, rectal, intrapulmonary and intranasal administration.

[0295] As one form of topical composition, the present disclosure further pertains in some embodiments to the compounds or compositions of the present disclosure for use as a cosmetic.

[0296] In the present application, a cosmetic or a cosmetic use means that the composition is suitable for external use (i.e. extracorporeal use, e.g. not ingested) and is in particular suitable for application to the skin or hair. In some embodiments, the term “cosmetic” is referring to an article intended to be applied to the human body for cleansing, beautifying, promoting attractiveness, or altering the appearance. In some embodiments, the reference to a cosmetic use is excluding a medical use. In some embodiments, the reference to a cosmetic use means that the compounds of the present disclosure, and / or the composition comprising them, complies with with Regulation (EC) N° 1223 / 2009 of the European Union and / or The Modernization of Cosmetics Regulation Act of 2022 of the USA.

[0297] Generally, the aforementioned compositions can be formulated in any form known in the art for cosmetic (topical) administration. Hence, the composition can be applied in any topical form, such as in the form of 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 employed in the art of topical administration and / or cosmetic / sunscreen and skin care formulation. The composition can also be water-resistant (e.g. waterproof).

[0298] The topical composition may also be present in the form of a patch or a carrier comprising the topical composition. Examples of a patch include an adhesive label or thin foil on which the composition is coated or printed. Examples of a carrier include a non-woven material or a hydrogel in which the composition is impregnated.

[0299] The compositions of this disclosure may contain one or more of the compounds of the present disclosure described herein in the range of 0.005 wt.-% to 99 wt.-% with the balance made up from the suitable excipients. The contemplated compositions may contain 0.01 wt.-% to 99 wt.- % of any one of the compounds provided herein, in one embodiment 0.1 to 95 wt.-%, in another embodiment 75 to 85 wt.-%, in a further embodiment 20 to 80 wt.-%, wherein the balance may be made up of any excipient described herein, or any combination of these excipients.

[0300] The topical composition according to the present disclosure further comprises an excipient suitable for topical administration. The excipient is not particularly limited. In some embodiments, the excipient suitable for topical administration comprises one or more excipients selected from water, ethanol, isopropanol, n-propanol, ethylene glycol, diethylene glycol, a propylene glycol, pentylene glycol, diethylene glycol monoethyl ether, DMSO, and glycerol.

[0301] In some embodiments, the topical composition can also be a pre-dispersed composition comprising the compound of this disclosure and a liquid carrier. These compositions can be a solution (e.g., free of any undissolved solid particles), a dispersion (e.g., containing a liquid phase and a solid precipitant phase), or an emulsion.

[0302] In some embodiments, the topical composition may contain water and / or organic solvents as suitable carriers and excipients. In one example, the liquid composition can be sterile and / or prepared from a sterile aqueous solution for infusion. In some embodiments, the composition may also include a surface-active agent, such as an alkylbenzene sulfonate, an alkyl sulfate, an alkyl ether sulfate, a soap, an ethoxylate, an alkyl alcohol, a lignosulfonate, or a triglyceride. The composition may also include a solid matrix. Suitable examples of a matrix component include a sugar, a sugar alcohol (e.g., sorbitol, mannitol, xylitol, isomalt, hydrogenated starch hydrolysates), a polymer, or a combination of two or more thereof.

[0303] In some embodiments, the composition may also include a skin penetration enhancer. A “skin penetration enhancer” as used herein refers to a substance that penetrates into skin (penetrant) to reversibly decrease its barrier resistance. In some embodiments, a skin penetration enhancer can also enhance the solubility of the penetrant to increase loading, which may, for example, enhance the flux of the penetrant across the skin. Non-limiting examples of a skin penetration enhancer include an alcohol, an amide, an ester, an ether alcohol, a fatty acid, a glycol, a pyrrolidone, a sulphoxide, and a terpene.

[0304] In some embodiments, it may be particularly beneficial that the topical composition comprises trehalose. Trehalose is a disaccharide otherwise known as a-D-glucopyranosyl-a-D- glucopyranoside. Unlike other disaccharides or sugar analogs that have been used in moisturizers for the skin, the present inventors have found that trehalose, besides providing a moisturizing effect, also facilitates the penetration of compounds of the present disclosure into the deeper layers of the skin, thereby enhancing the attachment and long-lasting effect of the compounds of the present disclosure.

[0305] In some embodiments, the composition may also include a preservative, a thickening agent, a film-forming agent and / or a humectant.

[0306] As used herein, a “preservative” refers to an agent that protects the topical composition against decay, discoloration, and / or spoilage. Non-limiting examples of a preservative include ascorbic acid, an ascorbate, a palmitate, citric acid, a benzoate, a benzoic acid, a sorbate, sorbic acid, methylisothiazolinone, phenoxyisopropanol, chlorhexidine and its derivatives, ethylenediaminetetraacetic acid (EDTA), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), a sulfite, a bisulfite, a metabisulfite, propylparaben, an isothiazoline, a paraben, phenoxyethanol, tocopherol, or combinations thereof. As used herein, a “thickening agent” refers to an agent that increases the viscosity of a liquid. In some embodiments, the thickening agent increases the viscosity of the liquid without substantially changing other properties of the topical composition. Non-limiting examples of thickening agents include starches; gums (e.g., natural and synthetic gums); in particular xanthan gum; cellulosics; and arabinogalactan; and combinations thereof.

[0307] As used herein in context of the formulation of a topical composition, a “humectant” refers to a substance that attracts water. For example, a humectant may attract water to bring moisture to the skin and / or to bind moisture to the skin. Non-limiting examples of humectants include polyhydric alcohols, for example, polyalkylene glycols (e.g., alkylene polyols and their derivatives), alpha hydroxy acids, sugars, Aloe vera gel, vegetable oil, lithium chloride, allantoin, urea, and dicyanamide, and combinations thereof.

[0308] As used herein, a “film-forming agent” refers to a compound that can produce a continuous fdm on skin, more specifically a continuous film on skin upon drying of the topical composition. Non-limiting examples of film-forming agents include (volatile) silicone resins, polyvinylpyrrolidone, (meth)acrylates, acrylamides, copolymers of (meth)acrylates and / or acrylamides, isododecane resins, and combinations thereof. Non-limiting examples of (volatile) silicone resins include polymethylsilsesquioxane, trimethylsiloxysilicate, polypropylsilsesquioxane, dimethicone, cyclopentasiloxane, dimethiconol crosspolymer, polysilicone-6, polysilicone-8, polysilicone-11, and polysilicone-14. Non-limiting examples of copolymers include acrylates copolymer, styrene / acrylates copolymer, acrylates / C 12-22 alkyl methacrylate copolymer, acrylates / polytrimethylsiloxymethacrylate copolymer, polyvinylpyrrolidone / vinyl acetate (VP / VA) copolymer, VP / dimethiconylacrylate / polycarbamyl / polyglycol ester, VP / dimethylaminoethylmethacrylate copolymer, VP / dimethyl amino ethylmethacrylate / polycarbamyl polyglycol ester, VP / eicosene copolymer, VP / hexadecene copolymer, VP / methacrylamide / vinyl imidazole copolymer, VP / polycarbamyl polyglycol ester, VP / VA copolymer, polyester-1, polyester-2, polyester-3, polyester-4, polyester-5, polyester-7, polyester-8, and polyester-10.

[0309] In some embodiments, it may be particularly advantageous to use more than one film-forming agent, more specifically two or more film-forming agents, and in particular three or more film- forming agents. Using a plurality of film-forming agents may be particularly advantageous to provide a reliable and strong film-forming property under the diverse conditions of use and in view of the diverse skin types. The formation of a film slows drying of the topical composition and wet or moist conditions facilitate the coupling of the compounds of the present disclosure to the keratinous tissue such as skin or hair.

[0310] The topical compositions can be applied to the skin of the subject using inkjet printing directly onto a skin transfer substrate such as a patch. The composition in this case is applied to the transfer substrate using printer nozzles.

[0311] In some embodiments, the composition may also be contained in a pen-like applicator since this may allow more selective localized delivery. It may be particularly advantageous that the pen-like applicator comprises one or more features disclosed in WO 2023 / 023851 Al, the content of which are incorporated herein in its entirety by reference thereto. More specifically, in some embodiments, the pen-like applicator is an ink applicator having one or more of the device features as disclosed in any of claims 1 to 50 of WO 2023 / 023851 Al, the respective content of said claims is incorporated herein in its entirety by reference thereto for the purposes of further defining the aforementioned pen-like applicator.

[0312] In some embodiments, the topical formulation comprising the compound of formula (I) is storage stable (i.e., the compound of formula (I) retains its original chemical structure at greater than 95 mol.-%) for a period of time from greater than 1 month, more specifically greater than 3 months, and in particular greater than 6 months, when stored at 21 °C and 25% RH. In some embodiments, aqueous solubility of the compound of formula (I) is from about 1 g / L to about 100 g / L, from about 5 g / L to about 50 g / L, or from about 10 g / L to about 100 g / L.

[0313] In some embodiments, it may be particularly advantageous that the topical composition is not too “runny” in order to facilitate that the topical formulation is retained locally on the skin at the site of administration. Accordingly, it may be particularly advantageous that the topical composition is having a dynamic viscosity, measured at 37°C, of more than 2 mPa s, more specifically more than 10 mPa s, and in particular more than 50 mPa s, for instance, in the range of 2 mPa s to 50,000 mPa s, more specifically in the range of 10 mPa s to 20,000 mPa s, and in particular in the range of 50 mPa s to 10,000 mPa s. Suitable measuring methods are well- known in the art and include ASTM D-2196-20, using test method A at 30 rpm, or DIN EN ISO 2555:2018-09, at 30 rpm, on a rotational viscosimeter, for instance ViscoQC 100, optionally equipped with a PTD 100 Cone-Plate for smaller sample sizes, obtainable from Anton Paar GmbH, Germany.

[0314] In some embodiments, the topical composition is a skin care composition. In some embodiments, the topical composition is a hair care composition. In some embodiments, said skin care composition or hair care composition is enclosed in a container. In some embodiments, the container is sealed and / or releasable after opening. In some embodiments, the container comprises a label and / or is provided with packaging.

[0315] Fourth aspect of the present disclosure

[0316] In a fourth aspect, the present disclosure relates to the compounds recited in the second aspect of the present disclosure for use in medicine. More specifically, according to the fourth aspect, the present disclosure relates to a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, Ag and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0317] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0318] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0319] A4 and As are, independently from each other, defined as indicated for Ai;

[0320] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate; in particular wherein at least one of the one or more active ingredients and precursors thereof is a pharmaceutical, a UVA- and / or UVB-absorbing moiety, or a precursor thereof; for use in medicine.

[0321] Any of the specific compounds which are disclosed for the first and second aspect of the present disclosure also represent specific embodiments according to this fourth aspect of the present disclosure.

[0322] In particular, any of the specific compounds disclosed for the first and second aspect of the present disclosure are herewith disclosed for use in treating a skin-associated disease, an allergic condition, pain, or inflammation. In some embodiments, the skin-associated disease may be selected from acneiform eruptions, autoinflammatory syndromes, chronic blistering, conditions of the mucus membranes, conditions of the skin appendages, conditions of the subcutaneous fat, congenital anomalies, connective tissue diseases, abnormalities of dermal fibrous and elastic tissue, dermal and subcutaneous growths, dermatitis, eczema, seborrheic dermatitis, disturbances of pigmentation, endocrine-related skin conditions, eosinophilic cutaneous conditions, skin lesions, skin cancer, erythemas, genodermatoses, infection-related cutaneous conditions, lichenoid eruptions, lymphoid-related cutaneous condition, melanocytic nevi and neoplasms, monocyte- and macrophage-related cutaneous conditions, mucinoses, neurocutaneous conditions, noninfectious immunodeficiency-related cutaneous conditions, nutrition-related cutaneous conditions, papulosquamous hyperkeratotic cutaneous conditions, palmoplantar keratodermas, pruritus, psoriasis, reactive neutrophilic cutaneous conditions, skin conditions resulting from errors in metabolism, skin conditions resulting from physical factors, urticaria, dandruff, desquamation disorders, and vascular-related cutaneous conditions.

[0323] In some embodiments, the skin-associated disease is selected from alopecia, psoriasis, desquamation disorders, and seborrheic dermatitis.

[0324] In some embodiments, the compound of formula (I) comprises the pharmaceutical as a precursor and wherein, after the application of the compound of formula (I) to the skin and / or the hair, the precursor is cleaved on the skin and / or the hair to release the pharmaceutical as the active ingredient over a plurality of hours or days. In some embodiments, the plurality of hours is 8 hours or more, more specifically 12 hours or more, and in particular 24 hours or more. In some embodiments, the plurality of days is 2 days or more, more specifically 3 days or more, and in particular 7 days or more.

[0325] Fifth aspect of the present disclosure

[0326] In a fifth aspect, the present disclosure relates to a method of preparing a topical composition comprising a compound of formula (I) as defined in the second aspect of the present disclosure. Any of the specific compounds which are disclosed for the first and second aspect of the present disclosure also represent specific embodiments according to this fifth aspect of the present disclosure.

[0327] Methods of preparing the compounds of the present disclosure

[0328] The methods of preparing the compounds of the present disclosure are not particularly limited.

[0329] Particularly suitable is using the platform compound shown in Figure 1 which can be prepared starting from compound 3 -cyclopentene- 1 -carboxylic acid which is a readily available key intermediate in the synthesis of the drug Dolasetron.

[0330] Particularly suitable is also using the platform compound shown in Figure 2 which can be prepared using 3-formyl crotyl acetate which is a readily available key intermediate in the synthesis of vitamin A.

[0331] Further examples are provided in the experimental section.

[0332] Further Definitions

[0333] As used herein, the term "about" means "approximately" (e.g., plus or minus approximately 10% of the indicated value). For example, "about 20" means or includes amounts from 18 to and including 22.

[0334] At various places in the present specification, substituents of compounds of the invention are disclosed in groups or in ranges. It is specifically intended that the invention includes each and every individual sub-combination of the members of such groups and ranges. For example, the term “Ci-6 alkyl” is specifically intended to individually disclose methyl, ethyl, C3 alkyl, C4 alkyl, C5 alkyl, and Ce alkyl.

[0335] As used herein, the term “carboxy” refers to a -C(O)OH group. Throughout the definitions, the term “Cn-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include Ci-4, Ci-6, and the like.

[0336] As used herein, the term “Cn-Cmmoiety”, as it is used in e.g. C1-C30 moiety, C1-C16 moiety, Ci- Ceo moiety etc., refers to any carbon-containing moiety having the referenced number of carbon atoms. It should be understood that the reference to a “Cn-Cmmoiety” is a closed definition and defines a finite moiety, i.e. a “Cn-Cmmoiety” is a moiety which, with respect to the number of carbon atoms, contains between n and m carbon atoms, but not more or less carbon atoms. However, it should be further understood that a “Cn-Cmmoiety” may optionally comprise further atom species not being C, i.e. atom species such a H, O, S, and N and others may be contained in the Ci-Ceo moiety.

[0337] As used herein, any reference to a moiety comprising a specified number or a specified range of an atom species, such as e.g. “a C1-C30 moiety comprising 1 to 12 oxygen atoms”, should be understood as defining a finite moiety, i.e. a moiety which, with respect to said atom species, contains said atom species in said specified amount. So, the aforementioned “C1-C30 moiety comprising 1 to 12 oxygen atoms” refers to a C1-C30 moiety containing between 1 to 12 oxygen atoms. However, it should be further understood that said moiety may optionally comprise further atom species besides the specified atom species, i.e. the aforementioned “C1-C30 moiety containing between 1 to 12 oxygen atoms” may optionally comprise further atom species not being C and not being O, i.e. atom species such H, S, and N and others. In case a specified range of a specified atom species starts with zero (“0”), the presence of the referenced atom species is optional. To give an example, a “C1-C30 moiety comprising 0 to 12 oxygen atoms and 0 to 4 nitrogen atoms” is to be understood a s reference to a C1-C30 moiety optionally containing 1 to 12 oxygen atoms and optionally containing 1 to 4 nitrogen atoms.

[0338] As used herein, the term “Cn-m alkyl”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chained or branched, having n to m carbons. Examples of alkyl moi eties include, but are not limited to, chemical groups such as methyl, ethyl, / 7-prop l. isopropyl, / 7-but l. / c / 7-butyl. isobutyl, se -butyl; higher homologs such as 2-methyl-l -butyl, w-pentyl, 3-pentyl, / 7-hexyl. 1,2,2-trimethylpropyl, and the like. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, more specifically from 1 to 4 carbon atoms, even more specifically from 1 to 3 carbon atoms, and in particular 1 to 2 carbon atoms.

[0339] As used herein, the term “Cn-m acyl”, employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chained or branched, having n to m carbons.

[0340] As used herein, the term “Cn-mhaloalkyl”, employed alone or in combination with other terms, refers to an alkyl group having from one halogen atom to 2s+l halogen atoms which may be the same or different, where “s” is the number of carbon atoms in the alkyl group, wherein the alkyl group has n to m carbon atoms. In some embodiments, the haloalkyl group is fluorinated only. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0341] As used herein, “Cn-malkenyl” refers to an alkyl group having one or more double carboncarbon bonds and having n to m carbons. Example alkenyl groups include, but are not limited to, ethenyl, w-propenyl, isopropenyl, / 7-butenyl. scc-butenyl. and the like. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0342] As used herein, “Cn-m alkynyl” refers to an alkyl group having one or more triple carbon-carbon bonds and having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-l-yl, propyn-2-yl, and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0343] As used herein, the term “Cn-m alkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group having n to m carbons. Examples of alkylene groups include, but are not limited to, ethan- 1,1 -diyl, ethan-l,2-diyl, propan-1,1, -diyl, propan-1, 3-diyl, propan- 1,2-diyl, butan-l,4-diyl, butan-1, 3-diyl, butan-l,2-diyl, 2-methyl-propan-l, 3-diyl, and the like. In some embodiments, the alkylene moiety contains 2 to 6, 2 to 4, 2 to 3, 1 to 6, 1 to 4, or 1 to 2 carbon atoms.

[0344] As used herein, the term “amino” refers to a group of formula -NH2.

[0345] As used herein, the term “halogen” refers in particular to F, Cl, Br and I. The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C=N double bonds, N=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms. In some embodiments, the compound has the ^-configuration. In some embodiments, the compound has the (^-configuration.

[0346] The term “compound” as used herein is meant to include all stereoisomers, geometric isomers, tautomers, and isotopes of the structures depicted. Compounds herein identified by name or structure as one particular tautomeric form are intended to include other tautomeric forms unless otherwise specified.

[0347] As used herein, the term “tautomer” is attributed its ordinary meaning in the art and, in particular, comprises the corresponding ring-opened 1,5-di carbonyls (i.e. keto / keto, keto / aldehyde and aldehyde / keto). Moreover, the term is also meant to encompass those constitutional isomers of the compound of formula (I) which are accessible by an intramolecular nucleophilic ring-closure of the said 1,5-dicarbonyls, as well as their respective tautomers.

[0348] As used herein, a “salt” or “pharmaceutically acceptable salt” of a compound of any one of the formulae disclosed herein is formed between an acid and a basic group of the compound, such as an amino functional group, or a base and an acidic group of the compound, such as a carboxyl functional group. According to another embodiment, the compound is a pharmaceutically acceptable acid addition salt. In some embodiments, acids commonly employed to form pharmaceutically acceptable salts of the compounds of any one of the formulae 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, as well as related inorganic and organic acids. Such pharmaceutically acceptable salts thus 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, mal onate, succinate, suberate, sebacate, fumarate, maleate, butyne- 1,4-dioate, hexyne- 1,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, sulfonate, xylene sulfonate, phenylacetate, phenylpropionate, phenylbutyrate, citrate, lactate, P-hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthalene- 1 -sulfonate, naphthal ene-2- sulfonate, mandelate and other salts. In one embodiment, pharmaceutically acceptable acid addition salts include those formed with mineral acids such as hydrochloric acid and hydrobromic acid, and especially those formed with organic acids such as maleic acid. In some embodiments, bases commonly employed to form pharmaceutically acceptable salts of the compounds of any one of the formulae disclosed herein 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, organic amines such as unsubstituted or hydroxyl-substituted mono-, di-, or tri-alkylamines, dicyclohexylamine; tributyl amine; pyridine; N-methyl, N-ethylamine; diethylamine; tri ethylamine; mono-, bis-, or tris-(2-OH-(Ci-C6)-alkylamine), 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, lysine, and the like. In some embodiments, the compounds of any one of the formulae disclosed herein, or salts thereof, are substantially isolated.

[0349] The terms “protecting group” and “protective group” refer to a moiety that reversibly chemically modifies a functional group in order to obtain chemoselectivity or in order to reduce degradation in one or more subsequent chemical reactions. Suitable protecting groups are well known in the art (see, e.g., Greene and Wuts, Protective Groups in Organic Synthesis, 3rd Ed., John Wiley & Sons, New York, N.Y, 1999, which is incorporated herein by reference in its entirety). As used herein, “color” refers to wavelengths of electromagnetic radiation visible to the human eye and “colorless” and like expressions such as “not perceivable by the human eye”, “not visually perceivable” or “not observable” refers to the absence of wavelengths of electromagnetic radiation visible to the human eye.

[0350] EXPERIMENTAL SECTION

[0351] Starting materials were obtained from commercial vendors such as Sigma- Aldrich Canada Ltd. (Oakville, Canada).

[0352] 1. Synthesis of compound 6

[0353] Compound 6 was synthesized as shown in the reaction scheme below:

[0354] Step 1 :

[0355] To a solution of 1 (5.0 g, 37 mmol) in piperidine (1.1 mL), acetic acid (3.0 mL) was added. Afterwards, 2 (8.6 g, 74 mmol) was added to the reaction mixture. The yellow reaction mixture was stirred vigorously overnight at room temperature. After 20 h, it was a light-yellow solution, which was quenched with saturated NaHCO3 (100 mL). The reaction mixture was then extracted with ethyl acetate (3 x 20 mL). The combined organic extract was washed with brine (50 mL) and then dried over sodium sulfate. All solvents were evaporated to obtain a crude yellow oil, which was subjected to column chromatography (hexane / ethyl acetate) to obtain 3 (4.2 g, 49%).

[0356] Step 2:

[0357] In a reaction flask, 3 (500 mg, 2.1 mmol), 5 (140 mg, 0.43 mmol) and acetic acid (0.13 mL) were taken in water and were cooled to 0 °C in an ice-bath. Afterwards, 4 (310 mg, 4.3 mmol) was added to the reaction mixture. The reaction was stirred at 0 °C for 1 h and was then warmed to room temperature and stirred overnight. After 48 h, the reaction was quenched with sat. NaHCO3 (100 mL), extracted with ethyl acetate (3 x 30 mL). The combined organic extract was washed with brine (50 mL) and then dried over sodium sulfate. All solvents were evaporated to obtain a crude yellow oil, which was subjected to column chromatography (DCM / EtOAc) to obtain pure 6 (370 mg, 57%) as a colorless oil.

[0358] NMR (400 MHz, CDCh) 5 7.18 - 7.01 (m, 2H), 6.95 - 6.74 (m, 2H), 5.30 - 4.97 (m, 1H), 3.77 (s, 3H), 3.52 - 3.46 (m, 3H), 2.42 - 2.28 (m, 3H), 1.81 - 1.34 (m, 3H), 1.22 - 1.09 (m, 1H), 1.06 - 0.99 (m, 3H).

[0359] HRMS (DART ) m / z calculated for CI7H23O5+[M+H]+: 307.15400, found : 307.15406

[0360] 2. Reaction of compound 6 with n-hexylamine

[0361] Compound 6 was reacted with n-hexylamine as a model compound for a substrate comprising an amino group. reflux

[0362] 6

[0363] Areaction mixture of 6 (55 mg, 0. 18 mmol) and n-hexylamine (150 mg, 1.5 mmol) was refluxed in toluene at 114 °C. After 20 h, it was then cooled to room temperature. After evaporating all solvents, the crude yellow oil was subjected to column chromatography (hexanes / ethyl acetate) to obtain the pure product (20 mg, 30%). 8 7.13 (d, J= 8.6 Hz, 2H), 6.77 (d, J= 8.6 Hz, 2H), 5.73 (s, 1H), 4.37 (s, 1H), 3.76 (s, 3H), 3.61 - 3.44 (m, 4H), 3.24 (dt, J = 14.8, 7.5 Hz, 1H), 2.42 (s, 3H), 1.99 - 1.78 (m, 2H), 1.61 (d, J= 7.5 Hz, 3H), 1.33 (d, J = 2.7 Hz. 5H), 0.97 (t, J= 7.4 Hz, 3H), 0.94 - 0.82 (m, 3H).

[0364] HRMS (DART ) m / z calculated for C23H34NO3+[M+H]+: 372.25332, found : 372.25400

[0365] The resulting UV / vis spectroscopy at concentration 0.04 mM is shown in Figure 4. It is apparent from the absorption peaks that the compound is not visible (or barely visible) to the human eye.

[0366] 3. Synthesis of compound 9

[0367] Compound 9 was synthesized as shown in the reaction scheme below:

[0368] Step 1 :

[0369] In ethanol (38 mL), 7 (5.0 g, 38 mmol) and 2 (4.4 g, 38 mmol) were taken. Afterwards, piperidine (1.9 mL) followed by acetic acid (1.0 mL) were added to the reaction mixture. The reaction mixture was stirred at room temperature. After half an hour, it was a clear yellow solution. After 3h, white precipitate started to come out of the reaction mixture. The reaction mixture was stirred at room temperature overnight. After 20 h, white precipitate was separated from the reaction mixture. The precipitate was washed with EtOH (5 x 100 mL). Yield = 5.3 g (61%) Step 2:

[0370] In a reaction flask, 8 (500 mg, 2.1 mmol), 5 (140 mg, 0.43 mmol) and acetic acid (0.13 mL) were taken in water and were cooled to 0 °C in an ice-bath. Afterwards, 4 (320 mg, 4.4 mmol) was added to the reaction mixture. The reaction was stirred at 0 °C for Ih and was then warmed to room temperature and stirred overnight. After 48 h, the reaction was quenched with sat. NaHCO3 (100 mL), extracted with ethyl acetate (3 x 30 mL). The combined organic extract was washed with brine (50 mL) and then dried over sodium sulfate. All solvents were evaporated to obtain a crude yellow oil, which was subjected to column chromatography (DCM) to obtain pure 9 (190 mg, 29%).

[0371] 'H NMR (400 MHz, CDCh) 57.58 - 7.53 (m, 2H), 7.32 - 7.26 (m, 2H), 5.24 - 5.22 (m, IH), 3.82 - 3.79 (m, IH), 3.49 - 3.42 (m, 3H), 2.35 - 2.32 (m, 3H), 2.07 - 1.11 (m, 7H).

[0372] HRMS (DART ) m / z calculated for C17H20NOZ [M+H]+: 302.13868, found : 302.13925

[0373] 4. Reaction of compound 9 with n-hexylamine

[0374] Compound 9 was reacted with n-hexylamine as a model compound for a substrate comprising an amino group.

[0375] Areaction mixture of 9 (55 mg, 0.18 mmol) and n-hexylamine (150 mg, 1.5 mmol) was refluxed in toluene at 114 °C. After 20 h, it was then cooled to room temperature. After evaporating all solvents, the crude yellow oil was subjected to column chromatography (hexanes / ethyl acetate) to obtain the pure product.

[0376] HRMS (DART ) m / z calculated for C23H3IN2O2+[M+H]+: 367.23800, found : 367.23913 The resulting UV / vis spectroscopy at concentration 0.04 mM is shown in Figure 5. It is apparent from the absorption peaks that the compound is not visible (or barely visible) to the human eye and that the UV absorption is blue-shifted in comparison to Compound 6, presumably due to the electron-withdrawing effect of the -CN.

[0377] 5. Synthesis of compound 12

[0378] Compound 12 was synthesized as shown in the reaction scheme below:

[0379] Step 1 :

[0380] 10 (5.0 g, 27 mmol) and 2 (3.1 g, 27 mmol) were dissolved in ethanol (27 mL). Afterwards, piperidine (1.9 mL) followed by acetic acid (1.0 mL) were added to the reaction mixture. The reaction mixture was stirred at room temperature. After 18 h, the dark yellow solution was directly subjected to column chromatography (hexane / ethyl acetate) to obtain 3 (2.0 g, 26%) as a light yellow solid.

[0381] Step 2:

[0382] In a reaction flask, 11 (300 mg, 1.1 mmol), 5 (72 mg, 0.22 mmol) and acetic acid (0.06 mL) were taken in water and were cooled to 0 °C in an ice-bath. Afterwards, 4 (160 mg, 2.2 mmol) was added to the reaction mixture. The reaction was stirred at 0 °C for 1 h and was then warmed to room temperature and stirred overnight. After 48h, the reaction was quenched with sat. NaHCO3 (60 mL), extracted with ethyl acetate (3 x 30 mL). The combined organic extract was washed with brine (50 mL) and then dried over sodium sulfate. All solvents were evaporated to obtain a crude yellow oil, which was subjected to column chromatography (DCM / EtOAc) to obtain pure 12 (87 mg, 22%) as a light-yellow oil.

[0383] HRMS (DART ) m / z calculated for Ci6H2o04Br+[M+H]+: 355.0540 and 357.0519, found : 355.0540 and 357.05

[0384] 6. Reaction of compound 12 with n-hexylamine

[0385] Compound 12 was reacted with n-hexylamine as a model compound for a substrate comprising an amino group.

[0386] A reaction mixture of 12 (55 mg, 0.18 mmol) and n-hexylamine (150 mg, 1.5 mmol) was refluxed in toluene at 114 °C. After 20 h, it was then cooled to room temperature. After evaporating all solvents, the crude yellow oil was subjected to column chromatography (hexanes / ethyl acetate) to obtain the pure product.

[0387] HRMS (DART ) m / z calculated for C22H3iBrNO2+[M+H]+: 420.1533 and 422.1513, found : 420.1524 and 420.16

[0388] 7. Reaction kinetics with n-hexylamine in MeOH

[0389] This experiment compares the reaction rate of Compound 6 and Compound 9 with that of hydrogenated genipin 13 in a reaction with n-hexylamine as a model compound for a substrate comprising amino groups in methanol:

[0390]

[0391] 6 (12.0 mg, 0.05 mmol), 9 (15 mg, 0.05 mmol) and 13 (15 mg, 0.05 mmol) were dissolved separately in deuterated methanol (0.6 mL for each sample). To each of the three samples, 2 equivalents of n-hexylamine was added. Afterwards,1H NMR spectra were collected after 90 minutes, 8 h, 23 h, 50 h, 110 h and 160 h.

[0392] Based on the NMR data, the rate of the reaction of each of the samples with n-hexylamine indicated the following order : 9 > 13 > 6. The comparison of 6 and 9 suggests that the reaction rate depends on electronic nature of the phenyl ring. Of note, compound 9 reacts faster than dehydrogenated genipin 13 even though it is a mixed keto-aldo compound and not a 1,5- dialdehyde.

[0393] 8. Reaction under physiological conditions

[0394] This experiment reacts Compound 6 a with n-hexylamine under physiological conditions. rt

[0395] 6

[0396] 6 (9.0 mg, 0.03 mmol) and n-hexylamine (6.0 mg, 0.008 mmol) were taken in an acetate buffer (pH =5.0). After 48 h, the reaction mixture was diluted with water (5 mL) and extracted with EtOAc (10 mL). All organic solvents were evaporated to obtain the crude product. The 'H NMR spectrum of the crude product matched with the purified reference sample obtained in above Example 2.

[0397] This example demonstrates that even the slowest reacting derivative (according to Example 7) is able to reliably bind to a model compound for a substrate comprising amino groups.

[0398] 9. Skin Toxicity Assays

[0399] Genipin and Compound 6 were tested for cytotoxicity to two human keratinocyte cell lines, CCD 1106 KERTr and HEKa. Testing was conducted utilizing the CellTiter-Glo® 2.0 Luminescent Cell Viability Assay.

[0400] The compounds were dissolved in DMSO to a concentration of 40 mM. The reference compound, Staurosporine, was purchased from Sigma-Aldrich (Saint Louis, MI). CellTiter- Glo® 2.0 Luminescent Cell Viability Assay reagent was purchased from Promega (Madison, WI). CCD 1106 KERTr and HEKa cell lines were purchased from American Type Culture Collection (Manassas, VA) and Thermo Fisher Scientific respectively. Cell culture media are listed in the following table 1.

[0401] Table 1:

[0402] All media were supplemented with 100 pg / ml of penicillin and 100 pg / ml of streptomycin unless otherwise stated. Cultures were maintained at 37°C in a humidified atmosphere of 5% CO2 and 95% air. The highest dose of each compound was tested was at a concentration of 1.00X10'4M, with dose concentrations diminishing by factors of three for a total of 30 concentrations tested. Concentrations tested ranged from 1X10'4M to 5xlO'8M. Percentages of cell viability at each tested concentration were plotted against the log of the molar concentration to give cell viability curves. IC50 values were extrapolated from these cell viability curves. Staurosporine was used as a control (not shown). The IC50 values obtained for genipin and Compound 6 are given for both cell lines in the below table 3.

[0403] Table 3:

[0404] As can be seen from the above table, Compound 6 has low toxicity, on a level that is comparable to genipin.

[0405] OTHER EMBODIMENTS

[0406] It is to be understood that while the present application has been described in conjunction with the detailed description thereof, the description is intended to illustrate and not limit the scope of the present application, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims. The present disclosure also relates to the following embodiments which are supplementary to and freely combinable with the above specification:

[0407] 1. Use of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, L5, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0408] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0409] A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo;

[0410] A4 and As are, independently from each other, defined as indicated for Ai;

[0411] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate. The use according to embodiment 1, wherein the substrate is a keratinous tissue. The use according to embodiment 2, wherein the substrate is skin and / or hair. The use according to embodiment 1 , wherein the substrate is a textile fabric, in particular spun wool; amino-functionalized cotton; an amino-functionalized synthetic fiber, in particular an amino-functionalized polyester fiber; or a polyamide fiber, in particular a nylon-6 fiber or a nylon-6.6 fiber. Use, optionally according to any one of embodiments 1 to 4, of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for providing color to a substrate comprising amino groups; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate; wherein Li, L2, L3, L4, Ls, Le and L7 represent, independently from each other, a linker group or are absent; wherein Ai, A2, A3, A4, As, As and A7 are defined as follows:

[0412] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0413] A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo;

[0414] A4 and As are, independently from each other, defined as indicated for Ai;

[0415] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Ls-As and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate. Use, optionally according to any one of embodiments 1 to 4, of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding one or more active ingredients to a substrate comprising amino groups; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, binds the one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Ls and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0416] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0417] A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo;

[0418] A4 and As are, independently from each other, defined as indicated for Ai;

[0419] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Ls-As and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0420] Use, optionally according to any one of embodiments 1 to 6, of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety,

[0421] or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding the compound and, optionally, one or more active ingredients, to a substrate comprising amino groups; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) is applied to the substrate, and covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups present on the substrate; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); wherein one or more of Ai, A2, A3, A4, As, As and A7 represent one of the one or more active ingredients and precursors; wherein, if no active ingredient or corresponding precursor thereof is present, the covalently bound compound of formula (I) provides color to the substrate; wherein Li, L2, L3, L4, Ls, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, Ag and A7 not representing one of the one or more active ingredients and precursors is defined as follows: Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0422] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-

[0423] A2 and L3-A3 jointly represent oxo;

[0424] A4 and As are, independently from each other, defined as indicated for Ai;

[0425] Ae and A 7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Ls-As and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate. Use, optionally according to any one of embodiments 1 to 4 and 5, wherein the compound is a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding the compound to a substrate comprising amino groups; wherein the compound of formula (I) is applied to the substrate, and covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups present on the substrate; wherein the covalently bound compound of formula (I) provides color to the substrate; wherein Li, L2, L3, L4, L5, Lg and L7 represent, independently from each other, a linker group or are absent; wherein Ai, A2, A3, A4, As, As and A7 are defined as follows:

[0426] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0427] A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo; A4 and AS are, independently from each other, defined as indicated for Ai;

[0428] Ae and A? represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Le-Ae and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate. Use, optionally according to any one of embodiments 1 to 4 and 6, wherein the compound is a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding one or more active ingredients to a substrate comprising amino groups; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) is applied to the substrate and covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups present on the substrate; wherein the compound of formula (I) comprises the one or more active ingredients, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); wherein one or more of Ai, A2, A3, A4, As, As and A7 represent one of the one or more active ingredients and precursors; wherein Li, L2, L3, L4, Ls, Ls and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0429] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0430] A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo;

[0431] A4 and As are, independently from each other, defined as indicated for Ai;

[0432] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Ls-As and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate. The use according to embodiment 9, wherein the substrate is skin and / or hair and wherein the compound of formula (I) is topically applied to skin and / or hair and covalently binds to the skin and / or the hair by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups present on the skin and / or the hair. Use, optionally according to embodiment 1 , of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding one or more active ingredients to skin and / or hair; wherein the one or more active ingredients are independently from each other selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) is topically applied to skin and / or hair and covalently binds to the skin and / or the hair by the reaction of its 3,4-saturated 2H-pyran moiety with amino groups present on the skin and / or the hair; wherein the compound of formula (I) comprises the one or more active ingredients, independently from each other, a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the skin and / or the hair (in the following: “the corresponding precursor thereof’); wherein one or more of Ai, A2, As, A4, As, Ae and A7 represent one of the one or more active ingredients and precursors; wherein Li, L2, L3, L4, L5, Lr, and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, Ae and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0433] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0434] A2 and A3 are, independently from each other, defined as indicated for Ai or L2-A2 and L3-A3 jointly represent oxo;

[0435] A4 and As are, independently from each other, defined as indicated for Ai;

[0436] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable under physiological conditions after application of the compound of formula (I) to the skin and / or the hair. 12. The use according to any preceding embodiment, wherein at least one of the one or more active ingredients or of the corresponding precursors thereof is a Ci-Ceo moiety; or wherein at least one of the one or more active ingredients or of the corresponding precursors thereof is a polymeric moiety.

[0437] 13. The use according to any preceding embodiment, wherein the compound of formula (I) comprises: one or more of the active ingredients or of the corresponding precursors thereof; two or more of the active ingredients or of the corresponding precursors thereof; three or more of the active ingredients or of the corresponding precursors thereof; in total, one, two or three of the active ingredients or of the corresponding precursors thereof; in total, one or two of the active ingredients or of the corresponding precursors thereof; in total, one of the active ingredients or of the corresponding precursors thereof; in total, one of the active ingredients and none of the precursors; in total, two of the active ingredients and none of the precursors; in total, one of the active ingredients and one of the precursors; or in total, two of the precursors and none of the active ingredients; and in particular: a UVA- and / or UVB-absorbing moiety and one further active ingredient, or the corresponding precursor thereof, which is not a UVA and / or UVB-absorbing moiety; a moisturizer and one further active ingredient, or the corresponding precursor thereof, which is not a moisturizer; or a UVA- and / or UVB-absorbing moiety, a moisturizer, and one further active ingredient, or the corresponding precursor thereof, which is not a UVA and / or UVB-absorbing moiety and not a moisturizer.

[0438] 14. The use according to any one of embodiments 1 to 13 for covalently binding the one or more active ingredients to skin, wherein at least one of the one or more active ingredients or of the corresponding precursors thereof is selected from the group consisting of skin moisturizers, pesticides, skin whitening agents, fragrances, pharmaceuticals, UVA- and / or UVB-absorbing moieties, and color-imparting moieties. 15. The use according to any one of embodiments 1 to 13 for covalently binding the one or more active ingredients to hair, wherein at least one of the one or more active ingredients or of the corresponding precursors thereof is selected from the group consisting of hair moisturizers, fragrances, cosmetic hair coating agents, primers for attaching dyes to hair, UVA- and / or UVB- absorbing moieties, and color-imparting moieties.

[0439] 16. The use according to any preceding embodiment, wherein L7-A7 represents hydrogen or the C1-C30 moiety or wherein Lg-Ag represents hydrogen or the C1-C30 moiety.

[0440] 17. The use according to any preceding embodiment, wherein L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety.

[0441] 18. The use according to any one of embodiments 1 to 16, wherein L7-A7 represents the Ci- C30 moiety and Lg-Ag represents hydrogen.

[0442] 19. The use according to any one of embodiments 1 to 16, wherein L7-A7 represents the Ci- C30 moiety and Lg-Ag represents the C1-C30 moiety.

[0443] 20. The use according to any preceding embodiment, wherein at least one of Ai, A2, As and A4 represents one of the one or more active ingredients or of the corresponding precursors thereof.

[0444] 21. The use according to any preceding embodiment, wherein at least one of A2, A3 and A4 represents one of the one or more active ingredients or of the corresponding precursors thereof.

[0445] 22. The use according to any preceding embodiment, wherein the compound of formula (I) comprises a functional group which couples one of the one or more active ingredients or of the corresponding precursors thereof to the remainder of the compound of formula (I) and wherein the functional group comprises a carbon atom, an oxygen atom, a nitrogen atom, a sulfur atom, a phosphorus atom, a boron atom, or a combination thereof; more specifically a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof; and in particular a carbon atom and / or an oxygen atom. 23. The use according to embodiment 22, wherein the functional group comprises one or more of, two or more of, three or more of, four or more of, five or more, or all of:

[0446] 1 to 12 carbon atoms, more specifically 1 to 8 carbon atoms, and in particular 1 to 4 carbon atoms;

[0447] 1 to 4 oxygen atoms, more specifically 1 to 3 oxygen atoms, and in particular 1 or 2 oxygen atoms;

[0448] 1 to 4 nitrogen atoms, more specifically 1 to 3 nitrogen atoms, and in particular lor 2 nitrogen atoms;

[0449] 1 to 3 sulfur atoms, more specifically 1 or 2 sulfur atoms, and in particular 1 sulfur atom;

[0450] 1 to 3 phosphorus atoms, more specifically 1 or 2 phosphorus atoms, and in particular 1 phosphorus atom

[0451] 1 or 2 boron atoms, and in particular 1 boron atom.

[0452] 24. The use according to embodiment 22 or 23, wherein, after the compound of formula (I) has bound to the skin and / or the hair, the functional group is:

[0453] (i) biostable; or

[0454] (ii) cleavable, more specifically cleavable under physiological conditions encountered after its application to the skin and / or the hair, and / or cleavable under conditions preselected for said use, in particular cleavable upon elevation of temperature to higher than 42 °C, cleavable upon exposure to daylight, cleavable upon exposure to UVA- and / or UVB-light, cleavable upon exposure to acids, cleavable upon exposure to an oxidizing agent suitable for oxidizing said functional group, cleavable upon exposure to a reducing agent suitable for reducing said functional group, or cleavable upon exposure to salts.

[0455] 25. The use according to any one of embodiments 22 to 24, wherein the functional group is hydrolysable at the physiological pH of mammalian skin, more specifically of human skin, and in particular at a pH of between about 5 to about 6.

[0456] 26. The use according to any one of embodiments 22 to 25, wherein the functional group is enzymatically cleavable under physiological conditions after the compound of formula (I) or

[0457] -I OS- (la) is topically applied onto mammalian, more specifically human skin, in particular enzymatically cleavable by enzymes present in the mammalian, more specifically human skin.

[0458] 27. The use according to any one of embodiments 24 to 26, wherein the functional group provides a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime; or salts thereof; after cleavage of the functional group.

[0459] 28. The use according to any one of embodiments 24 to 27, wherein the functional group provides a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime; or salts thereof; to said active ingredient after cleavage of the functional group.

[0460] 29. The use according to embodiment 28, wherein, after cleavage of the functional group: the functional group provides a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime to said active ingredient; and the functional group provides a hydroxyl group, a primary or secondary amine group, a carboxylic acid, a thiol, an aldehyde, a ketone, a thiocarbonic acid, a sulfonic acid, a sulfinic acid, a phosphoric acid, a phosphonic acid, an olefine, a boronic acid, a borinic acid, a boric acid, or an oxime to the remainder of the compound of formula (I).

[0461] 30. The use according to any one of embodiments 32 to 29, wherein the functional group comprises a carbon ester, in particular a monoester, 1,1 -diester, a carbonate, or a carbamate; an ether or thioether, in particular an acetal, a hemi-acetal, a glycosidic group or a thioacetal; a disulfide; a carbon amide, in particular a peptide or aN-Mannich base; an enol; an enamine; an imine; an oxime; a sulfate ester; a sulfonic acid ester; a sulfonic acid amide; a phosphoric acid ester; a phosphonic acid ester; a phosphoric acid amide; a phosphonic acid amide; a boronic ester, a borinic ester, a boric ester; an oxazol, a triazole, a benzothiazole, or a coumarin. 31. The use according to any one of embodiments 1 to 30, wherein the compound of formula

[0462] (I) is a compound of formula (II), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg, and L7 are defined as in any preceding embodiment; and in particular wherein L1-A1 and L4-A4 do not represent hydrogen.

[0463] 32. The use according to any one of embodiments 1 to 31, wherein Ai represents one of the one or more active ingredients or of the corresponding precursors thereof and A2, A3 and A4 represent independently from each other hydrogen or the C1-C30 moiety.

[0464] 33. The use according to any one of embodiments 1 to 31, wherein Ai represents the C1-C30 moiety and A2, A3 or A4 represents one of the one or more active ingredients or of the corresponding precursors thereof.

[0465] 34. The use according to embodiment 33, wherein A2 represents one of the one or more active ingredients or of the corresponding precursors thereof, wherein A3 represents the C1-C30 moiety, and A4 represents the C1-C30 moiety.

[0466] 35. The use according to embodiment 33, wherein A4 represents one of the one or more active ingredients or of the corresponding precursors thereof, and wherein:

[0467] A2 represents hydrogen and A3 represents hydrogen; or

[0468] A2 represents the C1-C30 moiety and A3 represents hydrogen; or A2 represents hydrogen and A3 represents the C1-C30 moiety; or A2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety. 36. The use according to any preceding embodiment, wherein Li, L2, L3, L4, Ls Le and L7 independently from each other are absent or represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms.

[0469] 37. The use according to any preceding embodiment, wherein:

[0470] Li is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0471] L2 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0472] L3 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0473] L4 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0474] Ls is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms;

[0475] Lg is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1 to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms; and / or

[0476] L7 is present and represents an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 18 carbon atoms, more specifically 1

[0477] -I OS- to 12 carbon atoms, still more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms.

[0478] 38. The use according to any one of embodiments 1 to 37, wherein:

[0479] Li and Le are present and form a ring; and / or

[0480] Li and L2 are present and form a ring; and / or

[0481] L2 and L4 are present and form a ring; and / or

[0482] L4 and L7 are present and form a ring; and / or

[0483] L4 and R1are present and form a ring.

[0484] 39. The use according to embodiment 38, wherein the ring is a 5-, 6-, 7- or 8-membered ring, more specifically a 5-, 6-, or 7-membered ring, and in in particular a 5- or 6-membered ring.

[0485] 40. The use according to embodiment 38, wherein the ring is an optionally substituted cyclopentyl ring, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring.

[0486] 41. The use according to any preceding embodiment, wherein L3 and L4 are present and form an optionally substituted 5-, 6-, 7- or 8-membered ring comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, in particular an optionally substituted cyclopentyl, an optionally substituted cyclohexyl ring, an optionally substituted pyrrolidinyl ring, an optionally substituted piperidinyl ring, an optionally substituted tetrahydrofuranyl ring or an optionally substituted tetrahydropyranyl ring.

[0487] 42. The use according to any preceding embodiment, wherein L3 and L4 are present and form an optionally substituted 5-or 6-membered ring, in particular cyclopentyl, cyclopentenyl, tetrahydrofuranyl, cyclohexyl, or cyclohexenyl, to which A3 and A4 are attached, optionally via a group selected from: -O-, -S-, -C(O)-, -CO2-, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-, - (CH2)I-4-O- and -O-(CH2)I-4-, or combinations thereof. 43. The use according to any preceding embodiment, wherein each occurrence of the Ci- C30 moiety independently from each other comprises 1 to 30, more specifically 1 to 16, and in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg. L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0488] 44. The use according to embodiment 43, wherein each occurrence of the C1-C30 moiety is, independently from each other, selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl or (hetero)aryl, each comprising 1 to 30, more specifically 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Lg, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

[0489] 45. The use according to embodiment 44, wherein each occurrence of the C1-C30 moiety is, independently from each other, selected from a saturated or unsaturated (hetero)alkyl comprising 1 to 12, more specifically 1 to 8, and in particular 1 to 4, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 4, more specifically 0 to 3, and

[0490] -no- in particular 0 to 2 nitrogen atoms; 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, Ls, Le, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or b) if the respective Li, L2, L3, L4, Ls, Le, L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached

[0491] 46. The use according to any preceding embodiment, wherein Ai, A3, As, Ae and A7 do not represent one of the one or more active ingredients or of the corresponding precursors thereof, and wherein Li, L3, Ls, Le and L7 are absent.

[0492] 47. The use according to any preceding embodiment, wherein the compound of formula (I) is a compound of formula (III), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, As, A4, Ae, A7, L2, L3, L4, Le and L7 are defined as in any preceding embodiment; wherein X represents O or S, and in particular O; and wherein Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms, and wherein the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom.

[0493] 48. The use according to any preceding embodiment, and in particular embodiment 47, wherein Ai represents the C1-C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0494] 49. The use according to embodiment 47 or 48, wherein Lx-Ai represents a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from:

[0495] -COOH or a salt thereof;

[0496] -COORa, -C(O)-Ra,

[0497] -C(O)-NH2, -C(O)NHRa, -C(0)NRa2, wherein Rarepresents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0498] 50. The use according to any preceding embodiment, wherein R1represents hydrogen, C1-6 acyl, a silyl group, or C1-6 alkyl; and in particular hydrogen. 51. The use according to any preceding embodiment, wherein the compound of formula (I), after having covalently bound to the skin and / or the hair, is not observable to the human eye on the skin and / or hair when illuminated with artificial light of 3000 Kelvin and an intensity of 1000 Lux.

[0499] 52. The use according to any preceding embodiment, wherein the compound of formula (I), after having covalently bound to lysine, does not show absorption peaks having an extinction of more than 0.5 within the wavelength range of 380 to 790 nm in 2 mM methanolic solution.

[0500] 53. The use according to any preceding embodiment, wherein L2-A2, L3-A3 and L4-A4 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alphaposition to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0501] 54. The use according to any preceding embodiment, wherein L1-A1 and Lg-Ag do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alphaposition to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0502] 55. The use according to any preceding embodiment, wherein L4-A4 and L7-A7 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alphaposition to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0503] 56. The use according to any preceding embodiment, wherein L1-A1 and L2-A2 do not represent moieties (or form a moiety) comprising an unsaturated C-C or C-N bond in alphaposition to the respective carbon atom(s) of the 3,4-saturated 2H-pyran moiety to which they are bound.

[0504] 57. The use according to any of embodiments 21 to 46, wherein the 3,4-saturated 2H-pyran moiety of the compound of formula (I) covalently binds to the skin and / or the hair forming a compound of formulae (la) and / or (lb), or a tautomer and / or a salt thereof; wherein the broken bond represents the covalent bond to the skin and / or the hair; wherein Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg and L7 are defined as indicated in any of the preceding embodiments.

[0505] 58. The use according to embodiment 57, wherein no more than one, and in particular none, of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I) forms, after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formula (la) and / or (Ib), a conjugated 71-electron system comprising more than 6 double bonds, more specifically more than 5 double bonds, and in particular more than 4 double bonds, with the heterocycle marked by letters a to e in the formula (la) and more than 7 double bonds, more specifically more than 6 double bonds, and in particular more than 5 double bonds, with the heterocycle marked by letters a to e in the formula (Ib).

[0506] 59. The use according to embodiment 57 or 58, wherein the combination of all of L1-A1, L2-A2, L3-A3, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I), after the 3,4-saturated 2H-pyran moiety has covalently bound to the skin and / or hair forming a compound of formula (la) and / or (lb): does not form a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (la) and (lb); or forms a conjugated 71-electron system with the heterocycle marked by letters a to e in the formula (la) which comprises less than 7 double bonds, more specifically less than 6 double bonds, and in particular less than 5 double bonds, and forms a conjugated 71- electron system with the heterocycle marked by letters a to e in the formula (lb) which comprises less than 8 double bonds, more specifically less than 7 double bonds, and in particular less than 6 double bonds. 60. The use according to any one of embodiments 57 to 59, wherein no more than three, more specifically no more than two, and in particular no more than one, of Li-Ai, L2-A2, L4- A4, Lg-Ag and L7-A7 of the compound of formula (I) comprise a carbonyl group which forms or is part of a conjugated 71-electron system with the heterocycles marked by letters a to e in the formulae (la) and (lb).

[0507] 61. The use according to any one of embodiments 57 to 60, wherein L1-A1, L2-A2, L4-A4, Lg-Ag and L7-A7 of the compound of formula (I) are selected such that, after the compound has bound to skin or hair, they do not provide a combination of electron-withdrawing and electrondonating groups to the conjugated 71-electron system formed with the respective heterocycles marked by letters a to e in the formulae (la) and (lb).

[0508] 62. The use according to any preceding embodiment, wherein the compound of formula (I) is a compound of formula (IV), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Li, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; wherein R2represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; and wherein R3represents hydrogen or a Ci-Cie moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms.

[0509] 63. The use according to embodiment 62, wherein R2represents Ci-Ce alkyl or C6-C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms; and wherein R3represents hydrogen or Ci-Ce alkyl or C6-C12 aryl, both of which may be optionally further substituted with the proviso that the entirety of R3does not comprise more than 16 carbon atoms, 6 oxygen atoms, 4 nitrogen atoms, 3 sulfur atoms, and 5 halogen atoms.

[0510] 64. The use according to embodiment 62 or 63, wherein R2represents a Ci-Ce alkyl which may be optionally further substituted with the proviso that the entirety of R2does not comprise more than 12 carbon atoms, 4 oxygen atoms, 3 nitrogen atoms, 2 sulfur atoms, and 3 halogen atoms; and wherein R3represents hydrogen or C1-C4 alkyl.

[0511] 65. The use according to any one of embodiments 62 to 64, wherein R2represents an aliphatic C1-C4 moiety, optionally comprising a carboxylic acid or a salt thereof, a carboxylic acid ester, a ketone, an alcohol, an ether, or combinations thereof; and wherein R3represents hydrogen.

[0512] 66. The use according to any preceding embodiment, wherein the compound of formula (I) is a compound of formula (V),

[0513] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, A2, A3, A4, L2, L3 and L4 are defined as indicated in any of the preceding embodiments; and wherein R4represents hydrogen or a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone or an amide; more specifically a moiety selected from:

[0514] -COOH or a salt thereof;

[0515] -COORa, -C(O)-Ra,

[0516] -C(O)-NH2, -C(O)NHRa, -C(0)NRa2, wherein Rarepresents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0517] 67. The use according to embodiment 56, wherein R4represents COOH or a salt thereof, COORb, -C(O)-Rb, C(O)-NH2, -C(O)NHRb, -C(O)NRb2, wherein Rb represents a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, more specifically a moiety comprising 1 to 4 carbon atoms, and optionally one or more of: 1 to 3 oxygen atoms, 1 or 2 nitrogen atoms, and 1 to 3 halogen atoms..

[0518] 68. The use according to embodiment 67, wherein Rb represents -Ci-C4-alkyl, more specifically methyl or ethyl and in particular methyl.

[0519] 59. The use according to any preceding embodiment, wherein the compound of formula (I) is a compound of formula (Via) or (VIb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, and R4are defined as indicated in any of the preceding embodiments; wherein each of R5, independently from each other, represents hydrogen or a Ci-Ce moiety which optionally further comprises 1-3 oxygen atoms, 1-3 nitrogen atoms, and 1-2 sulfur atoms; wherein for formula (Via) Ls and As are defined as L2and A2in any of the preceding embodiments; and wherein for formula (VIb) Ls and As are defined as L4and A4in any of the preceding embodiments.

[0520] 70. The use according to embodiment 69, wherein Ls represents a saturated Ci-Ce-alkyl moiety which is optionally substituted with a group selected from: -O-, -C(O)-, -CO2-, -O-C(O)- , -NH-, -N(Ci-C4-alkyl)-, -NH-C(O)-, -C(O)-NH-, -(CH2)I-4-, -(CH2)I-4-O-, -O-(CH2)i-4-, - S(O)-, -SO2-, or combinations thereof.

[0521] 71. The use according to embodiment 69 or 70, wherein each of R5, independently from each other, represents hydrogen or a C1-C4 alkyl. 72. The use according to any one of embodiments 1 to 68, wherein the compound of formula (I) is a compound of formula (Vila) or (Vllb), or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4, and R5are defined as indicated in any of the preceding embodiments; wherein the dashed line represents a bond or is absent; wherein n is an integer between 0 and 6, more specifically between 0 and 4, and in particular between 0 and 3; and m is an integer between 0 and 8, more specifically between 0 and 4, and in particular between 0 and 3; and wherein Ls and As are defined as L4 and A4 in any of the preceding embodiments.

[0522] 73. The use according to embodiment 72 wherein

[0523] R2represents H or C1-C4 alkyl,

[0524] R3represents H or C1-C4 alkyl,

[0525] R4represents COOH or a salt thereof, COORa-C(O)-Ra, C(0)-NH2, -C(O)NHRa, - C(O)NRa2, wherein Ra is as defined in any preceding embodiment.

[0526] 74. The use according to any one of embodiments 1 to 73, wherein at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents the active ingredient or the precursor of the active ingredient, wherein the active ingredient is the moisturizer, the skin moisturizer or the hair moisturizer, respectively.

[0527] 75. The use according to embodiment 74, wherein the active ingredient comprises a plurality of hydrogen bonding groups selected from the group consisting of hydroxyl groups, ether groups, carboxylic acids, amines and amides; and their salts. 76. The use according to embodiment 75, wherein the plurality of hydrogen bonding groups comprises three or more, more specifically 4 or more, and in particular 6 or more hydrogen bonding groups.

[0528] 77. The use according to embodiment 74 or embodiment 75, wherein the ratio of C-atoms to the sum of hydrogen bonding groups comprised in the active ingredient is between about 4: 1 to 1 : 1, more specifically between about 3: 1 to about 1 : 1 and in particular between about 2: 1 to about 1:1.

[0529] 78. The use according to any one of embodiments 74 to 77, wherein the active ingredient has a molecular weight of at least 60 g / mol, more specifically at least 90 g / mol, and in particular at least 120 g / mol.

[0530] 79. The use according to any one of embodiments 74 to 78, wherein the ratio of C-atoms to the sum of heteroatoms comprised in the active ingredient is between about 4: 1 to 1:2, more specifically between about 3: 1 to about 1:1.5, and in particular between about 2:1 to about 1:1, wherein the heteroatoms are selected from nitrogen and oxygen.

[0531] 80. The use according to any one of embodiments 74 to 79, wherein the active ingredient comprises: a polyol, more specifically a polyol having n hydroxyl groups with n being 2 or more, 3 or more, 4 or more, 5 or more, 6 or more, 8 or more, 10 or more, 12 or more, or 16 or more; a mono- or polyvalent carboxylic acid comprising one or more hydroxyl groups, more specifically glycolic acid, lactic acid, malic acid, tartaric acid or citric acid; a sugar, more specifically a triose, a tetrose, a pentose a hexose, a monosaccharide, a disaccharide, a trisaccharide, or an oligosaccharide; a sugar alcohol, more specifically a sugar alcohol comprising between 2 and 24 carbon atoms, in particular ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, or maltotetraitol; a sugar acid, more specifically an aldonic acid, an ulosonic acid, an uronic acid or an aldaric acid; or a salt thereof; or an ester thereof, in particular a Ci-C4-alkylester thereof; or an amide thereof; or a polysaccharide; more specifically a glycosaminoglycan, such as chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid; and in particular hyaluronic acid; and copolymers thereof, in particular copolymers comprising polyethylene glycol; and, in particular, hyaluronic acid, more specifically a hyaluronic acid having a weight-average or a number-average, and in particular a number-average, molecular weight of between 3000 and 3 million kDa, more specifically between 5000 and 2 million kDa, and in particular between 10,000 and 1.5 million kDa.

[0532] 81. The use according to embodiment 80, wherein the active ingredient has a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol.

[0533] 82. The use according to embodiment 74, wherein the active ingredient is an emollient or an occlusive.

[0534] 83. The use according to embodiment 82, wherein the active ingredient comprises: a Cio-Ceo moiety, more specifically a Cis-Ceo moiety and in particular a C20-C60 moiety; or an oligo- or polysiloxane, in particular a poly(di-Ci-C4-alkyl)siloxane.

[0535] 84. The use according to embodiment 82, wherein the active ingredient is the C i-Ceo moiety and has a molecular weight of 140 g / mol to 2000 g / mol, more specifically 160 g / mol to 1600 g / mol, and in particular 180 g / mol to 1200 g / mol.

[0536] 85. The use according to embodiment 82 or embodiment 83, wherein the active ingredient has more than 30 carbon atoms. 86. The use according to any one of embodiments 82 to 85, wherein the active ingredient comprises a saturated or unsaturated Cio-Ceo aliphatic moiety, more specifically a Cis-Ceo aliphatic moiety, and in particular a C20-C60 aliphatic moiety.

[0537] 87. The use according to any one of embodiments 82 to 86, wherein the ratio of C-atoms to the sum of heteroatoms comprised in the active ingredient is between about 60:1 to 5:1, more specifically between about 50:1 to about 10:1, and in particular between about 40:1 to about 20: 1, wherein the heteroatoms are selected from nitrogen and oxygen.

[0538] 88. The use according to any one of embodiments 82 to 87, wherein the Ci-Ceo moiety is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin.

[0539] 89. The use according to any one of embodiments 74 to 88, wherein at least one of Ai, A2, A3, A4, A5, and As represents the moisturizer, the skin moisturizer or the hair moisturizer, respectively.

[0540] 90. The use according to any one of embodiments 74 to 89, wherein at least one of Ai, A2, A3, A4, As, and As represents the precursor of the moisturizer, the skin moisturizer or the hair moisturizer, respectively.

[0541] 91. The use according to any one of embodiments 1 to 73, wherein at least one of Ai, A2,

[0542] A3, A4, As, As, A7 and As represents the active ingredient or the precursor of the active ingredient, and wherein the active ingredient is the pesticide.

[0543] 92. The use according to embodiment 91, wherein the pesticide is an insect repellant.

[0544] 93. The use according to embodiment 91, wherein the pesticide is an insecticide.

[0545] 94. The use according to embodiment 92 or 93, wherein the insect repellant or insecticide acts against an ectoparasite and / or a hematophagous insect, in particular a hematophagous insect selected from the group consisting of mosquitoes, ticks, mites, gnats, fleas, chiggers, leeches and bugs. 95. The use according to embodiment 92 or embodiment 94, wherein the pesticide is an insect repellant which is selected from isoprenoids, tertiary amides, and phenylpropanoids.

[0546] 96. The use according to embodiment 95, wherein the insect repellant is an isoprenoid, more specifically a monoterpenoid, a diterpenoid or a triperpenoid, and in particular a terpineol or derivative thereof, a monoterpenoid aldehyde or a derivative thereof, a limonoid or a derivative thereof; or a pyrethrin or a derivative thereof.

[0547] 97. The use according to embodiment 96, wherein the isoprenoid is selected from citronellal, hydroxy citronellal, citronellol, citral A, citral B, or a derivative thereof; a necrodane, in particular a-necrodol, or a derivative thereof; a limonoid, in particular azadirachtine, or a derivative thereof; or a pyrethrin, in particular a jasmolin, a cinerin, or a derivative thereof.

[0548] 98. The use according to embodiment 96, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents a moiety of formula (Villa) or formula (Vlllb),

[0549] (Villa) (Vlllb).

[0550] 99. The use according to embodiment 96, wherein the insect repellant is a phenylpropanoid, in particular eugenol or a derivative thereof.

[0551] 100. The use according to embodiment 96, wherein the insect repellant is comprising a tertiary amide.

[0552] 101. The use according to embodiment 100, wherein the tertiary amide is selected from picaridine, an N,N-di(Ci-Ce-alkyl)-toluamide, in particular N,N-diethyl-meta-toluamide, p- menthane-3,8-diol, ethyl 3-(V-butylacetamido)propanoate; and derivatives thereof. 102. The use according to embodiment 100, wherein the insect repellant is selected from one of the following compounds and moieties / derivatives thereof: N,N-diethyl-meta-toluamide, diethyl phenyl acetamide, N-butylacetanilide, ethyl butylacetylaminopropionate, picaridine, N- (2-methylpiperidin-l-yl)cyclohex-3-ene-l -carboxamide, and l-[3-cyclo-hexen-l-ylcarbonyl]- 2-methylpiperidine or l-[3-cyclohexen-l-ylcarbonyl] piperidine.

[0553] 103. The use according to embodiment 100, wherein at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents a moiety of formula (IX),

[0554] (IX).

[0555] 104. The use according to embodiment! 00, wherein at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents a moiety of formula (X),

[0556] 105. The use according to embodiment 91, wherein the pesticide is a topical insecticide, in particular a topical insecticide which is selected from permethrine; cypermethrin; deltamethrin; ivermectin; amidines, in particular amitraz; bendiocarb; malathion; carbaryl; diazinon; DDT; fenthion; fipronil; imidacloprid; nitenpyram; and propoxur. 106. The use according to any one of embodiments 91 to 105, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents the pesticide, in particular the insect repellant.

[0557] 107. The use according to any one of embodiments 91 to 106, wherein at least one of Ai, A2, A3, A4, As, Ae, A7 and As represents the precursor of the pesticide, in particular the insect repellant.

[0558] 108. The use according to any one of embodiments 1 to 73 for covalently binding the one or more active ingredients to the skin, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents the active ingredient of the active ingredient, and wherein the active ingredient is the skin whitening agent.

[0559] 109. The use according to any of embodiments 1 to 73, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents the precursor of the active ingredient, and wherein the active ingredient is the skin whitening agent.

[0560] 110. The use according to embodiment 108 or 109, wherein the skin whitening agent acts by chemically or metabolically whitening the skin, in particular by providing a bleaching effect or decreasing melanin production.

[0561] 111. The use according to any one of embodiments 108 to 110, wherein the skin whitening agent is selected from corticosteroids, in particular clobetasol derivatives, fluocinolone derivative, or betamethasone; a vitamin A derivative, in particular tretinoin, isotretinoin, alitretinoin, retinol or retinal; a hydroxyphenol derivative, in particular hydroquinone; an aliphatic dicarboxylic acid, in particular azelaine; alpha-hydroxy-acids, in particular lactic and glycolic acid; and vitamin C.

[0562] 112. The use according to any of embodiments 1 to 73, wherein at least one of Ai, A2, A3, A4, A5, As, A7 and As represents the precursor of the active ingredient, and wherein the active ingredient is the fragrance.

[0563] 113. The use according to embodiment 112, wherein the precursor is a Ci-Cso moiety comprising a functional group which couples the Ci-Cso moiety to the corresponding Li, L2, L3, L4, L5, Lg, L7, or Ls moiety or, if the corresponding Li, L2, L3, L4, L5, Lg or L7 moiety is absent, to the 3,4-saturated-2H-pyran moiety, or, if the corresponding Ls moiety is absent, to the respective cycloalkane moiety.

[0564] 114. The use according to embodiment 113, wherein the Ci-Cgo moiety is cleaved under physiological conditions on skin and / or hair to an aldehyde, a ketone, a thiol, a hydroxy, a carboxy, or an amine.

[0565] 115. The use according to embodiment 113, wherein the functional group is an imine, an acetal, a 1,1 -diester, an enolether, an ester, an amide, a thioester, or a thioacetal.

[0566] 116. The use according to embodiment 114, wherein the Ci-Cgo moiety has a molecular weight after being cleaved off of less than 400 g / mol, more specifically less than 300 g / mol, and in particular less than 200 g / mol.

[0567] 117. The use according to any one of embodiments 1 to 73, wherein at least one of Ai, A2, A3, A4, A5, As, A7 and As represents the active ingredient or the precursor of the active ingredient, and wherein the active ingredient is the pharmaceutical.

[0568] 118. The use according to embodiment 117, wherein the pharmaceutical is suitable for treating a skin-associated disease and / or a hair-associated disease.

[0569] 119. The use according to embodiment 118, wherein the skin-associated disease is selected from acneiform eruptions, autoinflammatory syndromes, chronic blistering, conditions of the mucus membranes, conditions of the skin appendages, conditions of the subcutaneous fat, congenital anomalies, connective tissue diseases, abnormalities of dermal fibrous and elastic tissue, dermal and subcutaneous growths, dermatitis, eczema, seborrheic dermatitis, disturbances of pigmentation, endocrine-related skin conditions, eosinophilic cutaneous conditions, skin lesions, skin cancer, erythemas, genodermatoses, infection-related cutaneous conditions, lichenoid eruptions, lymphoid-related cutaneous condition, melanocytic nevi and neoplasms, monocyte- and macrophage-related cutaneous conditions, mucinoses, neurocutaneous conditions, Noninfectious immunodeficiency-related cutaneous conditions, Nutrition-related cutaneous conditions, Papulosquamous hyperkeratotic cutaneous conditions, Palmoplantar keratodermas, pruritus, psoriasis, reactive neutrophilic cutaneous conditions, skin conditions resulting from errors in metabolism, skin conditions resulting from physical factors, urticaria, dandruff, desquamation disorders, and vascular-related cutaneous conditions; and / or the hair-associated disease is selected from dandruff and alopecia.

[0570] 120. The use according to any of embodiments 117 to 119, wherein the active ingredient is an agonist of a retinoid receptor, more specifically a retinoic acid receptor, a retinoid X receptor and / or a RAR-related orphan receptor.

[0571] 121. The use according to any of embodiments 117 to 120, wherein the active ingredient comprises a vitamin A vitamer, more specifically a vitamer selected from the group of retinol, tretinoin, isotretinoin, alitretinoin, etretinate, acitretin, adapalene and / or bexarotene, in particular retinol, retinal and / or adapalene.

[0572] 122. The use according to any of embodiments 117 to 119, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents a moiety of formula (XI), wherein R6represents H, OH, Ci-C4-alkyl, NH2, N(Ci-C4-alkyl)2, N-morpholino-l-yl, or piperi din-1 -yl; and wherein Lyrepresents group selected from -C(O)-, -C(O)-(CH2)I-4-, -C(O)-O-, -C(O)-O-(CH2)I-4-, -C(O)-NRYC(O)-, -C(O)-NRYC(O)-(CH2)I-4-, -S(O)2-O-, and -S(O)2-O-(CH2)I-4; and wherein Lyis part of the linker Li, L2, L3, L4, L5, Lg, L7, or Ls corresponding to the Ai, A2, A3, A4, As, As, A7, or As which represents the moiety of formula (XI) and wherein RYrepresents H or C1-C4 alkyl.

[0573] 123. The use according to embodiments 122, wherein R6represents H (i.e. kopexil) or piperi din- 1-yl (i.e. minoxidil). 124. The use according to any of embodiments 117 to 119, wherein at least one of Ai, A2, A3, A4, As, Ag, A7 and As represents a moiety of formula (XII), (XII), wherein Lxrepresents group selected from -C(O)-, -C(O)-(CH2)I-4-, -C(O)-O-, -C(O)-O-(CH2)I-4-, -C(O)-NRYC(O)-, -C(O)-NRYC(O)-(CH2)I-4-, -S(O)2-O-, and -S(O)2-O-(CH2)I-4; wherein RYrepresents H or C1-C4 alkyl; and wherein Lxis part of the linker group Li, L2, L3, L4, L5, Lg, L7, or Ls corresponding to the Ai, A2, As, A4, As, Ag, A7, or As which represents the moiety of formula (XII).

[0574] 125. The use according to any one of embodiments 117 to 124, wherein at least one of Ai, A2, As, A4, As, Ag, A7 and As represents the pharmaceutical.

[0575] 126. The use according to any one of embodiments 117 to 125, wherein at least one of Ai, A2, A3, A4, As, Ag, A7 and As represents the precursor of the pharmaceutical.

[0576] 127. The use according to any of embodiments 1 to 73 for covalently binding the one or more active ingredients to the hair, wherein at least one of Ai, A2, A3, A4, As, Ag, A7 and As represents one of the one or more active ingredients or of the corresponding precursors thereof, and wherein the active ingredient is the cosmetic hair coating agent.

[0577] 128. The use according to embodiment 127, wherein the cosmetic hair coating agent is providing a conditioning effect to the hair.

[0578] 129. The use according to embodiment 127 or embodiment 128, wherein the cosmetic hair coating agent is providing a gloss effect to the hair. 130. The use according to any of embodiments 137 to 139, wherein the cosmetic hair coating agent is providing an anti-frizz effect to the hair.

[0579] 131. The use according to any of embodiments 127 to 130, wherein the cosmetic hair coating agent is providing a reinforcing effect to the hair.

[0580] 132. The use according to any of embodiments 127 to 131, wherein the cosmetic hair coating agent represents a Ci-Ceo moiety, in particular a Ci-Ceo moiety having a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol; or a polymeric moiety.

[0581] 133. The use according to any one of embodiments 127 to 132, wherein the cosmetic hair coating agent is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin.

[0582] 134. The use according to any one of embodiments 127 to 133, wherein the cosmetic hair coating agent is positively charged and / or comprises a cation, in particular a quaternary cation.

[0583] 135. The use according to any one of embodiments 127 to 133, wherein the cosmetic hair coating agent is negatively charged and / or comprises anion, in particular a sulfate ion or a carboxylate ion.

[0584] 136. The use according to any one of embodiments 127 to 134, wherein the cosmetic hair coating agent is a polymeric moiety, in particular a polymeric moiety that is positively charged and / or comprises a cation, in particular a quaternary cation.

[0585] 137. The use according to embodiment 134 or embodiment 136, wherein the cosmetic hair coating agent is a polyquatemium, in particular polyquatemium-16, polyquatemium-46, polyquatemium-11, polyquatemium-28, polyquatemium-6, polyquatemium-7, polyquatemium-22, polyquatemium-39, polyquatemium-2, polyquatemium- 17, or polyquatemium-18. 138. The use according to embodiment 135, wherein the cosmetic hair coating agent is a poly carboxylic acid or a poly carboxylate, in particular a polyitaconate.

[0586] 139. The use according to any of embodiments 127 to 131, wherein the cosmetic hair coating agent comprises a poly ether, more specifically a poly-(Ci-Ce)ether, and in particular polymers of ethylene oxide and / or propylene oxide.

[0587] 140. The use according to any of embodiments 127 to 131, wherein the cosmetic hair coating agent comprises a poly siloxane, more specifically a poly(di-Ci-C4-alkyl)siloxane and derivatives thereof.

[0588] 141. The use according to any of embodiments 127 to 131, 139 and 140, wherein the cosmetic hair coating agent comprises a copolymer comprising polyether blocks and polysiloxane blocks.

[0589] 142. The use according to any one of embodiments 1 to 73 for covalently binding the one or more active ingredients to the hair, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents the active ingredient which is the primer for attaching dyes to the hair.

[0590] 143. The use according to embodiment 142, wherein the primer is a Ci-Cso moiety, in particular a Ci-Cso moiety having a molecular weight of 60 g / mol to 2000 g / mol, more specifically 90 g / mol to 1600 g / mol, and in particular 120 g / mol to 1200 g / mol.

[0591] 144. The use according to embodiments 142 or 143, wherein the primer comprises hydroxyl groups and / or amino groups.

[0592] 145. The use according to embodiment 144, wherein the primer reacts in the presence of an oxidizing agent with a dye precursor under formation of a dye.

[0593] 146. The use according to embodiment 145, wherein the primer is an aromatic moiety comprising two or more functional groups selected from hydroxyls, primary, secondary or tertiary amines, and ethers.

[0594] -I SO- 147. The use according to embodiment 146, wherein the primer is selected from resorcinol, m-aminophenol, 2-methyl-5-aminophenol, p-phenylenediamine, 2,4-diaminoanisole, 1,5- dihydroxynaphthalene, 4-methoxy-3-aminophenol, 2,4-diaminophenoxyethanol, nidi ethylaminophenol and p-amino-o-cresol; and derivatives thereof.

[0595] 148. The use according to embodiment 145, wherein the dye precursor is selected from paraphenylenediamine and para-aminophenol.

[0596] 149. The use according to embodiment 145, wherein the oxidizing agent is a peroxide, in particular hydrogen peroxide.

[0597] 150. The use according to any preceding embodiment, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents the active ingredient which is the color-imparting moiety or the UVA and / or UVB-absorbing moiety.

[0598] 151. The use according to embodiment 150, wherein the color-imparting moiety has at least one absorption peak within the wavelength range of 380 to 790 nm, more specifically at least one absorption peak within the wavelength range of 380 to 790 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0599] 152. The use according to embodiment 151, wherein the UVA- and / or UVB-absorbing moiety has at least one absorption peak within the wavelength range of 280 to 379 nm, more specifically at least one absorption peak within the wavelength range of 280 to 379 nm having an absorbance value of more than 0.5 when measured at a concentration of 2 mM.

[0600] 153. The use according to any one of embodiments 1 to 73 and 150 to 152, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents the color-imparting moiety, and wherein said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 40 carbon atoms, or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 6 to 40 carbon atoms and at least 3 conjugated C-C double bonds. 154. The use according to any one of embodiments 1 to 73 and 150 to 152, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents a UVA and / or UVB absorbing moiety, wherein said moiety is: a) an optionally substituted (hetero)aromatic moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms, or b) an optionally substituted conjugated moiety comprising, in combination with its optional substituents, 4 to 36 carbon atoms, and at least 2 conjugated C-C double bonds.

[0601] 155. The use according to any one of embodiments 1 to 73 and 150 to 154, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents a chromophore (dye moiety) selected from an azo group; a diazo group; a diphenylamine group; a nitroarylamine group; an azine group; an oxazine group; an acridine group; an indoline group; a sulfur dye group, in particular a thiazine group, a thiazole group, a thiazone group, a thianthrene group, or a phenothiazonethioanthrone group; a quinoid or quinone group; an anthraquinoid or anthraquinone group; a xanthene group; a naphthostyryl group; a diaryl methyl or triarylmethyl group; a benzodifuranone-based group; a formazan group; a phthalocyanine group; or a metal complex.

[0602] 156. The use according to any preceding embodiment, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents a UVA- and / or UVB-absorbing moiety which is being selected / derived from: a benzophenone group, a benzotriazole group, a benzone group, salicylic acid or a salicylic acid derivative, a benzocaine group, an esculin or an esculin derivative, a ferulic acid or a ferulic acid derivative, octinoxate or an octinoxate derivative, or octocrylene or an octocrylene derivative.

[0603] 157. The use according to any preceding embodiment, wherein at least one of Ai, A2, A3, A4, As, As, A7 and As represents a moiety which is selected from the following group of moieties: A compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety, or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair; wherein the compound of formula (I) is capable of covalently binding to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein the compound of formula (I) comprises the one or more active ingredients, if present, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor thereof; wherein Li, L2, L3, L4, Ls, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, Ag and A7 not representing one of the one or more active ingredients and precursors is defined as follows:

[0604] Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;

[0605] A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo;

[0606] A4 and As are, independently from each other, defined as indicated for Ai;

[0607] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0608] 159. The compound according to embodiment 158, wherein the compound of formula (I) is a compound as defined in any of the embodiments 2 to 157.

[0609] 160. A topical composition comprising the compound according to embodiment 158 or embodiment 159 and an excipient that is suitable for topical administration.

[0610] 161. A method of preparing a topical composition comprising combining the compound according to embodiment 158 or embodiment 159 with an excipient that is suitable for topical administration.

[0611] 166. Use, compound, composition comprising the compound or method of preparing the composition according to any one of embodiments 1 to 61 and 74-155, wherein the compound of formula (I) is a compound of formula (XIII),

[0612] (XIII), or a tautomer and / or a pharmaceutically acceptable salt thereof, wherein R1, Ai, As, A4, Ag, A7, Lg and L7 are defined as in any preceding embodiment; X represents O or S, and in particular O;

[0613] Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms; wherein said hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom; wherein one moiety selected from L3 and L4 represents an optionally substituted (hetero)aromatic C3-C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and wherein the other moiety amongst L3 and L4 represents a C1-C30 moiety, more specifically a Ci- Ci6 moiety selected from a saturated or unsaturated, acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0614] 167. Use, compound, composition comprising the compound or method of preparing the composition according to embodiment 166, wherein L3 represents the optionally substituted (hetero)aromatic C3-C12 moiety, more specifically an optionally substituted (hetero)aromatic C4-C12 moiety comprising, in combination with its optional substituents, 4 to 16, more specifically 4 to 12, and in particular 4 to 10, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0615] 168. Use, compound, composition comprising the compound or method of preparing the composition according to embodiment 167, wherein L3 represents an optionally substituted phenyl moiety comprising, in combination with its optional substituents, 6 to 12, more specifically 6 to 10, and in particular 6 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0616] 169. Use, compound, composition comprising the compound or method of preparing the composition according to embodiment 168, wherein the phenyl moiety is optionally substituted with -OH; -O-Ci-C4-alkyl; -N(Ci-C4-alkyl)2; one or more halogen atoms, each independently from each other selected from Cl, Br, and F; -NO2; and -CF3.

[0617] 170. Use, compound, composition comprising the compound or method of preparing the composition according to any one of embodiments 166 to 169, wherein L4 represents an optionally substituted aliphatic moiety comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0618] 171. Use, compound, composition comprising the compound or method of preparing the composition according to embodiment 170, wherein the aliphatic moiety is a Ci-Ce-alkyl, more specifically a linear or branched Ci-C4-alkyl; and in particular a linear Ci-C4-alkyl.

[0619] 172. Use, compound, composition comprising the compound or method of preparing the composition according to any one of embodiments 166 to 171, wherein Ai represents the Ci- C30 moiety, more specifically a C1-C16 moiety selected from a saturated or unsaturated, cyclic or acylic (hetero)alkyl comprising 1 to 16, more specifically 1 to 12, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 6, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

[0620] 173. Use, compound, composition comprising the compound or method of preparing the composition according to any one of embodiments 166 to 172, wherein Lx-Ai represents a Ci- Ci6 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof; -COORa, -C(O)-Ra, -C(O)- NH2, -C(O)NHRa, -C(O)NRa2, wherein Rarepresents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

Claims

CLAIMS1. Use of a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety,or a tautomer and / or a pharmaceutically acceptable salt thereof, for covalently binding to a substrate comprising amino groups, in particular to skin and / or to hair; wherein the compound of formula (I) covalently binds to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with the amino groups comprised by the substrate; wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate, and / or binds one or more active ingredients to the substrate; wherein the one or more active ingredients are, in particular and independently from each other, selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair; wherein, if present, the compound of formula (I) comprises the one or more active ingredients, independently from each other: a) as the active ingredient, or b) as a precursor of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor thereof’); and c) wherein one of Ai, A2, A3, A4, As, Ae and A 7 represents said active ingredient or the corresponding precursor thereof;wherein Li, L2, L3, L4, L5, Lg and L7 represent, independently from each other, a linker group or are absent; wherein each of Ai, A2, A3, A4, As, As and A7 not representing one of the one or more active ingredients and precursors is defined as follows:Ai represents hydrogen, a C1-C30 moiety, hydroxyl, amino, or a halogen;A2 and A3 are, independently from each other, defined as indicated for Ai or L2- A2 and L3-A3 jointly represent oxo;A4 and As are, independently from each other, defined as indicated for Ai;As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety, with the proviso that at least one of Lg-Ag and L7-A7 does not represent hydrogen; and wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

2. The use according to claim 1, wherein at least one of the one or more active ingredients or of the corresponding precursors thereof is a Ci-Cgo moiety; or wherein at least one of the one or more active ingredients or of the corresponding precursors thereof is a polymeric moiety.

3. The use according to claim 1 or claim 2, wherein L7-A7 represents the C1-C30 moiety and Lg-Ag represents hydrogen or wherein L7-A7 represents the C1-C30 moiety and Lg- Ag represents the C1-C30 moiety.

4. The use according to any preceding claim, wherein at least one of Ai, A2, A3 and A4 represents one of the one or more active ingredients or of the corresponding precursors thereof; and / or wherein at least one of A2, A3 and A4 represents one of the one or more active ingredients or of the corresponding precursors thereof.

5. The use according to any preceding claim, wherein the compound of formula (I) comprises a functional group which couples one of the one or more active ingredients or of the corresponding precursors thereof to the remainder of the compound of formula (I) and wherein the functional group comprises a carbon atom, an oxygen atom, anitrogen atom, a sulfur atom, a phosphorus atom, a boron atom, or a combination thereof; more specifically a carbon atom, an oxygen atom, a nitrogen atom, or a combination thereof; and in particular a carbon atom and / or an oxygen atom; optionally wherein, after the compound of formula (I) has bound to the skin and / or the hair, the functional group is:(i) biostable; or(ii) cleavable, more specifically cleavable under physiological conditions encountered after its application to the skin and / or the hair, and / or cleavable under conditions preselected for said use, in particular cleavable upon elevation of temperature to higher than 42 °C, cleavable upon exposure to daylight, cleavable upon exposure to UVA- and / or UVB-light, cleavable upon exposure to acids, cleavable upon exposure to an oxidizing agent suitable for oxidizing said functional group, cleavable upon exposure to a reducing agent suitable for reducing said functional group, or cleavable upon exposure to salts.

6. The use according to any one of claims 1 to 5, wherein the compound of formula (I) is a compound of formula (II),or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, As, A7, Li, L2, L3, L4, Lg, and L7 are defined as in any preceding claim; and in particular wherein L1-A1 and L4-A4 do not represent hydrogen.

7. The use according to any one of claims 1 to 6, wherein Ai represents one of the one or more active ingredients or of the corresponding precursors thereof and A2, A3 and A4 represent independently from each other hydrogen or the C1-C30 moiety; or wherein Airepresents the C1-C30 moiety and A2, A3 or A4 represents one of the one or more active ingredients or of the corresponding precursors thereof.

8. The use according to any preceding claim, wherein A4 represents one of the one or more active ingredients or of the corresponding precursors thereof, and wherein:A2 represents hydrogen and A3 represents hydrogen; or A2 represents the C1-C30 moiety and A3 represents hydrogen; orA2 represents hydrogen and A3 represents the C1-C30 moiety; orA2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety.

9. The use according to any preceding claim, wherein Li, L2, L3, L4, Ls Lr> and L7 independently from each other are absent or represent an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms.

10. The use according to any preceding claim, wherein:Li and Le are present and form a ring; and / orLi and L2 are present and form a ring; and / or L2 and L4 are present and form a ring; and / or L4 and L7 are present and form a ring; and / or L4 and R1are present and form a ring.

11. The use according to any preceding claim, wherein each occurrence of the C 1-C30 moiety independently from each other comprises 1 to 30, more specifically 1 to 16, and in particular 1 to 12 carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 phosphorus atoms, and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein the C1-C30 moiety is bound a) to the respective Li, L2, L3, L4, L5, Lg, L7 and Ls, if it is present, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, orb) if the respective Li, L2, L3, L4, L5, Lg. L7 and Ls, is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of ring to which the C1-C30 moiety is attached.

12. The use according to any preceding claim, wherein the compound of formula (I) is a compound of formula (III),or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, Ai, A2, A3, A4, Ag, A7, L2, L3, L4, Lg and L7 are defined as in any preceding claim; wherein X represents O or S, and in particular O; and wherein Lxis absent or represents -O-, -NH-, or an optionally substituted hydrocarbon moiety comprising, in combination with its optional substituents, 1 to 12 carbon atoms, more specifically 1 to 10 carbon atoms, and in particular 1 to 8 carbon atoms, 0 to 8, more specifically 0 to 6, and in particular 0 to 4 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms, and wherein the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfide atom; and, in particular, wherein Lx-Ai represents a Ci-Cig moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone; more specifically a moiety selected from: -COOH or a salt thereof;-COORa, -C(O)-Ra,-C(O)-NH2, -C(O)NHRa, -C(O)NRa2,wherein Rarepresents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2 nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms.

13. The use according to any preceding claim, wherein R1represents hydrogen, Ci-6 acyl, in particular C1-3 acyl or trifluoracetyl; C1-6 alkyl, in particular methyl or ethyl; or a silylgroup, in particular trimethoxy silyl triethoxysilyl, and fert-butyldimethylsilyl; and represents in particular hydrogen.

14. The use according to any preceding claim, wherein the compound of formula (I), after having covalently bound to the skin and / or the hair, is not observable to the human eye on the skin and / or hair when illuminated with artificial light of 3000 Kelvin and an intensity of 1000 Lux; or wherein the compound of formula (I), after having covalently bound to lysine, does not show absorption peaks having an extinction of more than 0.5 within the wavelength range of 380 to 790 nm in 2 mM methanolic solution.

15. The use according to any one of claims 1 to 14, wherein the compound of formula (I) is a compound of formula (Vila) or (Vllb),(Vllb),or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1is defined as indicated in any of the preceding claims; wherein R2represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; wherein R3represents hydrogen or a C1-C16 moiety; more specifically hydrogen or a C1-C16 moiety comprising 1 to 16, and in particular 1 to 12, carbon atoms; 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 8, more specifically 0 to 6, and in particular 0 to 4 nitrogen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 sulfur atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and in particular hydrogen or a saturated or unsaturated, cyclic or acylic (hetero)alkyl or a (hetero)aryl moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms; wherein R4represents hydrogen or a C1-C16 moiety selected from a carboxylic acid or a salt thereof, a carboxylic acid ester; a ketone or an amide; more specifically a moiety selected from: -COOH or a salt thereof;-COORa, -C(O)-Ra,-C(O)-NH2, -C(O)NHRa, -C(O)NRa2, wherein Rarepresents a moiety comprising 1 to 10 carbon atoms, and optionally one or more of: 1 to 6 oxygen atoms, 1 to 4 nitrogen atoms, 1 to 3 sulfur atoms, and 1 to 5 halogen atoms, more specifically a moiety comprising 1 to 6 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 3 nitrogen atoms, 1 or 2 sulfur atoms, and 1 to 3 halogen atoms, and in particular Ci-Ce-alkyl or phenyl; and wherein NRa2 may alternatively represent an optionally substituted saturated or unsaturated nitrogen heterocycle comprising, in combination with its optional substituents, 1 to 12, more specifically 1 to 10, and in particular 1 to 8, carbon atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 oxygen atoms; 1 to 4, more specifically 1 to 3, and in particular 1 or 2nitrogen atoms; 0 to 3, more specifically 0 to 2, and in particular 0 or 1 sulfur atoms; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; wherein each of R5, independently from each other, represents hydrogen or a Ci-Ce moiety which optionally further comprises 1-3 oxygen atoms, 1-3 nitrogen atoms, and 1-2 sulfur atoms; wherein the dashed line represents a bond or is absent; wherein n is an integer between 0 and 6, more specifically between 0 and 4, and in particular between 0 and 3; wherein m is an integer between 0 and 8, more specifically between 0 and 4, and in particular between 0 and 3; and wherein Ls and As are defined as L4 and A4 in any of the preceding claims.

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