Bicyclic compounds attachable to keratinous tissues

Abstract

The present disclosure relates to novel compounds and their various uses, said compounds being of formula (I), 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), after having covalently bound to the substrate, is providing color to the substrate; and / or wherein the compound of formula (I) comprises one or more active ingredients, wherein the one or more active ingredients are present, independently from each other, a) as the active ingredient or b) as a precursor moiety of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor moiety after the application of the compound of formula (I) to the substrate; and c) wherein one of A1, A2, A3, A4, A5, A6 and A7 represents said active ingredient or the corresponding precursor moiety thereof; wherein the dashed line is absent or wherein the dashed line represents a bond and L2-A2 and L5-A5 are absent; wherein L1, L2, L3, L4, L5, L6 and L7 are, independently from each other, absent or represent a linker group with the further proviso that one vicinal pair amongst L1, L2, L3, L4, L5, L6 and L7 forms an optionally substituted bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety, wherein the corresponding two moieties amongst A1, A2, A3, A4, A5, A6 and A7 are connected to said bicyclic linker group; wherein each of A1, A2, A3, A4, A5, A6 and A7 not representing an active ingredient or a corresponding precursor moiety thereof is defined as follows: A1, A4 and A5 represent, independently from each other, hydrogen, a C1-C30 moiety, hydroxyl, or a halogen; A2 and A3 are, independently from each other, defined as indicated for A1, or L2-A2 and L3-A3 jointly represent oxo; A6 and A7 represent, independently from each other, hydrogen or a C1-C30 moiety; and wherein R1 represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

Description

[0001] Bicyclic compounds attachable to keratinous tissues CROSS REFERENCE TO RELATED APPLICATIONS

[0002] 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 “Dimeric compounds attachable to keratinous tissues”, “1,5-Dicarbonylic 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.

[0003] TECHNICAL FIELD

[0004] The present disclosure relates to compounds which can be reliably and efficiently grafted onto substrates comprising amino groups, in particular 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 the substrate 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 the substrate, in particular skin or hair. The active ingredient may provide its effect while being bound to the substrate, or it can provide its effect after a precursor of the active ingredient has been cleaved from the anchored compound. In other instances, the anchored compound provides a noticeable color of its own and such compounds are particularly useful in semi-permanent tattoos or as markers to monitor the residual presence of an active ingredient (e.g. an insect repellent or a pesticide) on the substrate, e.g. the skin and / or hair of farm animals. The disclosure also relates to compounds as such, to topical compositions comprising these compounds and to various methods and applications for these compounds.

[0005] BACKGROUND

[0006] Genipin is the naturally occurring compound methyl (1R,4aS,7aS)-1-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]

[0008] 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:

[0009] R = lysine

[0010]

[0011] When bound to skin, genipin develops an intense blue color. For this reason, genipin is used as a colorant in semi-permanent inks.

[0012] WO 2023 / 102652 Al discloses that genipin and related seco-iridoids and iridoids can be hydrogenated to provide compounds which bind to skin without adding color of their own. The publication is incorporated herein in its entirety by reference thereto.

[0013] In their extensive research regarding genipin chemistry, the present inventors have further found that a broad range of synthetic 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:

[0014] HO

[0015]

[0016] 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.

[0017] 4

[0018]

[0019] 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 this moiety. This will in the following be explained using genipin as an example. Genipin exists in a number of tautomers, including the ring-opened 1,5-dialdehydic tautomer which has some similarity to the well-known crosslinking agent glutaraldehyde:

[0020]

[0021] Ring-open dialdehydic tautomer Glutaraldehyde 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:

[0022] R = lysine

[0023]

[0024] 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:

[0025]

[0026] The coupling to keratinous tissues is also irreversible due to the high stability of the generated 1,4-dihydropyridine moiety and due to the fact that its formation involves the elimination of two equivalents of water.

[0027] 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. Moreover, a similar reaction pathway is available for the 2H-pyran derivatives after tautomerization.

[0028] Utilizing the robustness of this coupling chemistry, the present inventors have made available a reliable and effective platform 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 WO 2024 / 250111 Al and WO 2024 / 250112 Al which are incorporated herein in their entirety by reference thereto. A representative example of how an active ingredient is attached to keratinous tissue via such an anchoring compound is shown below:

[0029]

[0030] R moiety representing the active ingredient

[0031] The broken bond indicates attachment to the keratinous tissue

[0032] However, the aforementioned 3,4-saturated 2H-pyran derivatives, such as genipin, oleuropein, aucubin and other seco-iridoids, are natural compounds which are difficult to source in larger quantities and in consistent quality.

[0033] SUMMARY OF THE INVENTION

[0034] In a first aspect, the present disclosure relates to a compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety,

[0035]

[0036] or a tautomer and / or a pharmaceutically acceptable salt thereof. The compound is suitable for covalently binding to a substrate comprising amino groups, in particular skin and / or hair. It is capable of covalently binding to the substrate by the reaction of its 3,4-saturated 2H-pyran moiety with an amino group comprised by the substrate.

[0037] After having covalently bound to the substrate, the compound of formula (I), may provide color to the substrate. Additionally or alternatively, the compound of formula (I) comprises one or more active ingredients, 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, a UVA- and / or UVB-absorbing moiety, a colorimparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair. The one or more active ingredients are present, independently from each other, a) as the active ingredient, or b) as a precursor moiety of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor moiety after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor moiety thereof’). If present, one or more of Ai, A2, A3, A4, As, As and A7 represents said one or more active ingredient or the corresponding precursor moiety thereof.

[0038] In formula (I), Li, L2, L3, L4, Ls, Lg and L7 are, independently from each other, absent or represent a linker group with the further proviso that

[0039] i) one vicinal pair amongst Li, L2, L3, L4, Ls, Lg and L7 forms an optionally substituted bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H- pyran moiety, wherein the corresponding two moieties amongst Ai, A2, A3, A4, As, As and Ai are connected to said bicyclic linker group; and that ii) optionally one or two further vicinal pairs amongst Li, L2, L3, L4, Ls, Le and L7 form an optionally substituted further cyclic linker group which is different from said bicyclic linker group and which is ortho-fused to the 3,4-saturated 2H-pyran moiety, wherein the corresponding two moieties amongst Ai, A2, A3, A4, As, As and A7 are connected to said further cyclic linker group.

[0040] In formula (I), the dashed line is absent or the dashed line represents a bond. In the latter case, L2-A2 and L5-A5 are absent.

[0041] In formula (I), each of Ai, A2, A3, A4, As, As and A7 not representing an active ingredient or a corresponding precursor moiety thereof is defined as follows: A1, A4 and A5 represent, independently from each other, hydrogen, a C1-C30 moiety, hydroxyl, or a halogen; A2 and As are, independently from each other, defined as indicated for Ai, or L2-A2 and L3-A3 jointly represent oxo; As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety.

[0042] In formula (I), R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0043] In a second aspect, the present disclosure provides a topical composition comprising a compound according to the first aspect, wherein the topical composition further comprises an excipient that is suitable for topical administration.

[0044] In a third aspect, the present disclosure relates to the use of the compound or the topical composition according to the first and second aspect respectively for covalently binding a compound according to the first aspect to a substrate comprising amino groups, more specifically keratinous tissue, and, in particular, to (mammalian and more specifically human) skin and / or hair or to a process of covalently binding a compound or the topical composition according to the first and second aspect respectively to a substrate, more specifically keratinous tissue, and, in particular, to (mammalian and more specifically human) skin and / or hair, the process comprising administering the compound or topical composition to the substrate. In a fourth aspect, the present disclosure provides the compounds and / or topical compositions disclosed herein for use in medicine, in particular for treating a skin-associated disease and / or a hair-associated disease. In some embodiments, said use includes topically administering the compound or composition to the skin of (mammalian, more specifically human) subject to be treated.

[0045] In a fifth aspect, the present disclosure provides a process for preparing for preparing a topical composition according to the second aspect, the process comprising providing a compound according to the first aspect of the present disclosure and mixing it with an excipient suitable for topical administration.

[0046] DESCRIPTION OF DRAWINGS

[0047] Figs 1 to 9 disclose synthetical approaches to compounds according to the present disclosure.

[0048] DETAILED DESCRIPTION

[0049] The present inventors set out to find more cost-efficient and more easily obtainable alternatives to the naturally occurring 3,4-saturated 2H-pyran derivatives and have realized that such compounds are conveniently accessible using bicyclic terpenoid-based or alkaloid-based derivatives which are much more readily available at a fraction of the price. For instance, the bicyclic terpenoids a-pinene and P-pinene, myrtenal, perillaldehyde, pinocarvone, camphor and nopinone are available at less than, and sometimes substantially less than, 10% of the open market price of genipin and oleuropein. The same applies to the bicyclic alkaloid-based compounds such as tropinone and heliotridine.

[0050] Moreover, the present synthetic approaches are particularly efficient since the bicyclic structure of the naturally occurring starting materials induce stereoselectivity which facilitates the purification of the intermediates and final products. This further helps in reducing costs. As an illustrative example, Fig. 1 shows a synthetic route starting from the bicyclic terpenoid myrtenal which is reacted in an 1,4-Michael addition reaction with methyl acetoacetate to a 1,5-dicarbonylic intermediate. Marínez-Ramos et al., Tetrahedron: Asymmetry, 12 (2001), 3095-3103, found that similar 1,4-thia Michael addition reactions with myrtenal proceeded in yields of 95-98% with >99% diastereomeric excess. As shown in Fig. 1, the reason for this stereoselectivity is the highly preferential nucleophilic attack of the Michael donor from the sterically less constrained side of the bicyclic ring structure of myrtenal. The resulting 1,5-dicarbonylic intermediate can then undergo a series of tautomerizations and a stereoselective ring-closure, yielding the shown 3,4-saturated 2H-pyran derivative as the predominant isomer.

[0051] Unlike genipin which is a 1,5-dialdehyde in its ring-opened form, the myrtenal -based 3,4-saturated 2H-pyran derivative shown in Fig. 1 is a mixed keto-aldehydic compound, i.e. a 1-aldehyde-5-keto compound in its ring-opened form. The present inventors have further found in their research work that not only 1,5-dialdehydic compounds like genipin are effective and reliable in coupling to skin and hair, but that 3,4-saturated 2H-pyran derivatives which are ring-opened to 1,5-diketonic tautomers and mixed ketoaldehydic tautomers (i.e. to l-keto-5-aldehyde tautomers or l-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. Therefore, the present inventors have concluded that 3,4-saturated 2H-pyran derivatives which ring-open to 1,5-diketonic tautomers and mixed ketoaldehydic tautomers (or, more generally, to 1,5-dicarbonyl tautomers) also represent an attractive and often more accessible platform of compounds which are suitable for topically coupling a very diverse range of active ingredients to keratinous tissues such as skin or hair.

[0052] Finally, being naturally derived compounds, the compounds of the present disclosure can also be expected to be well-tolerated. For instance, bicyclic terpenoids are typically well-tolerated and, in fact, have a long history of topical administration, for instance as essential oils or, in their derivatized form, as UV-protecting agents (e.g. the benzylidene-camphor family). The same applies to alkaloid-based bicyclic derivatives which are typically well-tolerated by the skin (although some alkaloids may provide a pharmaceutical effect on their own which can be expected to be lost once the alkaloids are fused to a 3,4-saturated 2H-pyran moiety).

[0053] Therefore, the present inventors have concluded that the bicyclic 3,4-saturated 2H-pyran derivatives of the present disclosure represent an attractive platform of compounds which are suitable for coupling a very diverse range of active ingredients to substrates comprising amino groups, in particular keratinous tissues such as skin and hair and more specifically mammalian skin, in particular human skin. In addition, the present inventors have also realized that the colored embodiments of the bicyclic 3,4-saturated 2H-pyran 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 bicyclic 3,4-saturated 2H-pyran compounds being both colored after having bound to the substrate and comprising an active ingredient.

[0054] Accordingly, in a first aspect, the present disclosure relates to a compound of formula (I) comprising a cyclic (hemi)acetal moiety, in particular a 3,4-saturated 2H-pyran moiety,

[0055]

[0056] for covalently binding to a substrate comprising amino groups. The compound of formula (I) may also be present as a tautomer and / or a pharmaceutically acceptable salt thereof.

[0057] 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. Formula (I) contains a cyclic (hemi)acetal moiety which is the aforementioned 3,4-saturated 2H-pyran moiety in case the dashed bond is absent. For sake of simplicity, the following disclosure refers to this moiety as a 3,4-saturated 2H-pyran moiety. However, it should be understood that, in case the dashed bond is present, the 2H pyran moiety is no longer 3,4-saturated and a 3,4-unsaturated 2H-pyran moiety (or, more generally, a cyclic (hemi)acetal moiety) is meant. 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. The principal reaction pathway is analogous to the reaction pathway discussed above in the background section for the hydrogenated genipin. Accordingly, the 3,4-saturated 2H-pyran moiety is converted to a 1,4-dihydropyridine 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.

[0058] 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 3,4-saturated 2H-pyran 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 or pharmaceutical effect or activity to the substrate, in particular in case the substrate is a keratinous tissue such as skin and / or hair.

[0059] The type of the one or more active ingredients is not particularly limited, but such active ingredients are advantageously selected from a moisturizer, a pesticide, a fragrance, a pharmaceutical, a skin whitening agent, a UVA- and / or UVB-absorbing moiety, a colorimparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair.

[0060] 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.

[0061] The term “pesticide” refers to its common meaning in the art and in particular refers to 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.

[0062] 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.

[0063] 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).

[0064] 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. 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.

[0065] The term “color-imparting moiety” refers to the common meaning in the art and in particular refers to a moiety which imparts a color-impression perceivable by the human eye.

[0066] 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.

[0067] 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.

[0068] In some embodiments, the compound of formula (I) comprises one or more active ingredients which are, independently from each other, present in the compound

[0069] a) as the active ingredient, or

[0070] b) as a precursor moiety of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor moiety (or the compound of formula (I) in the form as it is bound to the substrate) after the application of the compound of formula (I) to the substrate.

[0071] 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, in case the substrate is skin, a polyhydroxy-based skin moisturizer is able to provide its moisturizing effect while being bound to the skin (via the 1,4-dihydropyridine moiety) 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 the substrate. For instance, in the above example, 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 subsequently be hydrolyzed or cleaved by esterase enzymes which are natively present on skin such that the polyhydroxy-based skin moisturizer provides, over time, its moisturizing effect as a chemically modified active ingredient.

[0072] 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 such a precursor is a moiety of the compound of formula (I) and, thus, can synonymously be referred to as “precursor moiety”. For brevity, the precursor (moiety) corresponding to an active ingredient will in the following also be referred to as “the corresponding precursor (moiety) thereof’ or simply as “precursor” or “precursor moiety”. However, it should be understood that, unless specified otherwise, the terms “precursor” and “precursor moiety” are 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.

[0073] Moreover, it should be understood that the compound of formula (I) comprising a precursor (moiety) 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 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.

[0074] In the compound of formula (I), the substituents are defined as follows:

[0075] 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, As, A4, As, Ae and A7. In other words: In case the compound of formula (I) comprises one active ingredient, one of Ai, A2, As, A4, As, Ae and A7 represents said active ingredient. In case the compound of formula (I) comprises one precursor moiety, one of Ai, A2, A3, A4, As, As and A7 represents said precursor moiety. 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 A7 represents the second active ingredient. In case the compound of formula (I) comprises one active ingredient and one precursor moiety 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 moiety, and so on.

[0076] 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 linkers groups Li to L7 connect the corresponding substituents Ai to A7 to the 3,4-saturated 2H-pyrane 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 3,4-saturated 2H-pyran 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. For the purposes of the present disclosure, a reference to a linker or substituent being “attached” to another moiety is supposed to mean that said linker or substituent is directly attached to said other moiety by a covalent bond. For the purposes of the present disclosure, a reference to a linker or substituent being “connected” to another moiety is supposed to mean that said linker or substituent is not directly attached to said other moiety by a covalent bond but attached by a covalent bond to its linker and said linker is directly attached to said other moiety by a covalent bond.

[0077] In formula (I), the dashed line may be absent or the dashed line may represent a bond, i.e. the two carbon atoms carrying L3-A3 and L4-A4 are attached to each other by a double bond. In this case, L2-A2 and L5-A5 are absent.

[0078] As will be discussed in the following in more detail, vicinal pairs amongst Li, L2, L3, L4, L5, Le and L7 form cyclic linker groups which are fused to the 3,4-saturated 2H-pyran moiety. In these cases, the two corresponding substituents of Ai to A7 are attached to the respective cyclic linker group and connected to the 3,4-saturated 2H-pyran moiety. It should be further understood that said two substituents of Ai to A7 may be attached or connected to any atom of said cyclic linker group except for those atoms which are shared with the 3,4-saturated 2H-pyran moiety.

[0079] According to the present disclosure, the linker groups Li, L2, L3, L4, Ls, Le and L7 have to meet the following further provisos:

[0080] i) one vicinal pair amongst Li, L2, L3, L4, L5, Le and L7 forms an optionally substituted bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H- pyran moiety, wherein the corresponding two moieties amongst Ai, A2, A3, A4, As, Ae and Ai are connected to said bicyclic linker group; and

[0081] ii) optionally one or two further vicinal pairs amongst Li, L2, L3, L4, Ls, Le and L7 form an optionally substituted further cyclic linker group which is different from said bicyclic linker group and which is ortho-fused to the 3,4-saturated 2H-pyran moiety, wherein the corresponding two moieties amongst Ai, A2, A3, A4, As, Ae and Ai are connected to said further cyclic linker group;

[0082] The proviso under item (i) is mandatory and the proviso under item (ii) is optional in nature. In other words, one vicinal pair amongst Li, L2, L3, L4, Ls, Le and L7 must form an optionally substituted bicyclic tinker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety whereas one or more vicinal pairs amongst the remainder of Li, L2, L3, L4, Ls, Lg and L7 may optionally form an optionally substituted further cyclic linker group. In this way, the aforementioned benefits regarding stereoselectivity and reduced need for purification may be realized.

[0083] The present disclosure relates to polycyclic compounds and the following nomenclature will be used to distinguish between the individual rings:

[0084] The term “bicyclic linker group” refers to the mandatory bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety. The term “ortho-fused” is to be understood as defined in the IUPAC recommendation 1998, published in Pure & Appl. Chem, Vol. 70, No. 1, pp. 143-216, 1998, i.e. as referring to two rings which are fused together and have only two atoms and one bond in common. For sake of clarity, it should be understood that the bicyclic linker group is a ring system which is provided in addition to and distinct from the cyclic 3,4-saturated 2H-pyran moiety.

[0085] The term “further cyclic linker group” refers to a further linker ring formed by a further vicinal pair amongst Li, L2, L3, L4, Ls, Lg and L7. For sake of clarity, it should be understood that said further cyclic linker group is a ring which is provided in addition to and different from the bicyclic linker group that is ortho-fused to the 3,4-saturated 2H-pyran moiety (and also different from the cyclic 3,4-saturated 2H-pyran moiety). It should further be understood that the lUPAC-definition of “ortho-fused” excludes that a linker group is jointly part of two neighboring vicinal pairs amongst Li, L2, L3, L4, L5, Lg and L7 since the resulting rings would then be peri-fused (according to the aforementioned IUPAC recommendation) and are no longer ortho-fused. To give an example, in case L3 and L4 form a first vicinal pair, L3 may not form a second vicinal pair with Li and L4 may not form a second vicinal pair with L5.

[0086] An illustrative non-limiting example of a further cyclic linker group will be given below. In this example, based on the myrtenal-based synthetical approach shown in Fig. 1, cyclohexane-1, 3-dione replaces methyl acetoacetate as the Michael donor and the resulting compound comprises a further cyclic linker group. Referring to formula (I), L3 and L4 represent a first vicinal pair forming the bicyclic linker group (with A3 and A4 representing hydrogen) and Li and Lg represent a second vicinal pair forming a further linker group (with Ai and As representing hydrogen):

[0087]

[0088] In the above example, both Ai and As represent hydrogen which are each directly attached to the further cyclic linker group.

[0089] As said, the further cyclic linker groups of the present disclosure may optionally be further substituted. For instance, and returning to the above example, Ai and As may also be connected to the further cyclic linker group via connecting linker groups L which each are attached to the further cyclic linker group and connect Ai and As to said further cyclic linker group:

[0090]

[0091] A more comprehensive disclosure of such optional linkers will be given below. With respect to the cyclic nature of the further cyclic linker group, it should be understood that the further cyclic linker group may also be a further polycyclic linker group, i.e. the further cyclic linker group comprises more than one cycle, wherein the further cycle(s) is / are fused to the aforementioned (first) cycle. To give an illustrative non-limiting example, and this time replacing the Michael acceptor myrtenal with the Michael acceptor pinocarvone and the Michael donor cyclohexane-1, 3-dione with the Michael donor lawsone in the above Michael addition reaction and subsequent cyclization cascade, the further cyclic linker group is, in its entirety, a further polycyclic linker group, more specifically a further bicyclic linker group: o o

[0092]

[0093] (-)-pinocarvone lawsone

[0094] In this example, and referring to formula (I), L4 and L7 represent a first vicinal pair forming the bicyclic linker group and Li and Ls represent a second vicinal pair forming a further linker group, more specifically a further linker group and both Ai and As represent hydrogen.

[0095] Again, the further polycyclic linker group may optionally be further substituted. For instance, and returning to the above example, Ai and As may also be connected to the further bicyclic linker group via connecting linker groups L which each are attached to any of the rings of the further bicyclic linker group and connect Ai and As to said further cyclic linker group:

[0096]

[0097] Returning to the definition of the individual substituents of formula (I), and again irrespective of the presence or absence of an active ingredient, each of Ai, A2, A3, A4, As, As and A7 not representing an active ingredient or a corresponding precursor moiety thereof is defined as follows:

[0098] A1, A4 and A5 represent, independently from each other, hydrogen, a C1-C30 moiety, hydroxyl, or a halogen;

[0099] A2 and A3 are, independently from each other, defined as indicated for A1, or L2-A2 and L3- A3 jointly represent oxo; and

[0100] Ag and A7 represent, independently from each other, hydrogen or a C1-C30 moiety.

[0101] 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 hydrolysed to the more reactive hemi-acetal which then binds to the substrate.

[0102] In some embodiments, R1represents a protective group hydrolysable under physiological conditions after application of the compound to the skin and / or the hair. As said, the primary purpose of providing a protective group hydrolysable under physiological conditions 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 skin or hair with their lower pH environment, R1should be hydrolysed to the more reactive hemi-acetal which then binds to the skin and / or the hair. Therefore, 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 according to the second aspect is supposed to bind to (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 amino-acids, and in particular those with nucleophilic side chains such as lysine, will further facilitate hydrolysis.

[0103] Accordingly, a group qualifies as “protective group hydrolysable under physiological conditions after application of the compound to the skin and / or the hair”, if the compound 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 for 24 hours at 37°C in any one of the following three solutions: a) a phosphate buffer solution, pH 5.5; b) 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 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.

[0104] As said, in some embodiments, the compounds of the present disclosure are intended to 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.

[0105] The compound, 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 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 (or a topical composition comprising said compound) on the respective porcine skin or hair sample at 37°C for 24 hours, the compound 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 achieve this feature if it passes a suitable in-vitro test, in particular placing 0.1 mol / L of the compound 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 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 and its oxidation products (if any) such as an aromatized pyridinium 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 the first aspect 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 according to the present disclosure in which R1does not represent hydrogen, also alternatively be performed with the corresponding derivative in which R1represents hydrogen.

[0106] The choice of specific embodiments for the aforementioned 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:

[0107] a) 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.

[0108] b) 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.

[0109] c) Protective groups which themselves can be hydrolysed or decompose under the conversion of the ether bond to the 3,4-saturated 2H-pyran moiety can also be utilized. Examples include silyl groups.

[0110] In some embodiments, R1represents hydrogen; Ci-6 acyl, in particular C1-3 acyl or trifluoracetyl; C1-6 alkyl, in particular methyl or ethyl; or a silyl group, in particular trimethoxysilyl, triethoxysilyl, and tert-butyldimethylsilyl; and in particular hydrogen. In some embodiments, the compound of formula (I) is suitable for covalently binding to skin and / or hair and R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the skin and / or hair. The bicyclic linker group

[0111] In some embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety comprises: a) a bridged linker ring; or b) a cis-ortho-fused bicyclic linker group comprising a first ring and a second ring, wherein the first ring is orthofused to the 3,4-saturated 2H-pyran moiety and the second ring is cis-ortho-fused to the first ring.

[0112] The term “bridged linker ring” is not particularly limited and attributed its ordinary meaning in the art. Additionally or alternatively, the term “bridged linker ring” refers to a 4- to 8-membered ring wherein two of its ring atoms which are not shared with the 3,4-saturated 2H-pyran moiety are connected to each other by a single atom or a chain of more than one atoms, more specifically by one, two, three or four atoms, in particular by one or two atoms.

[0113] The term “cis-ortho-fused bicyclic linker group” is not particularly limited and attributed its ordinary meaning in the art. Additionally or alternatively, the term “cis-ortho-fused bicyclic linker group” refers to a 4- to 8-membered first ring and a 4- to 8-membered second ring, wherein the second ring is cis-ortho-fused to the first ring at two of its ring atoms which are not shared with the 3,4-saturated 2H-pyran moiety. The term “cis-ortho-fused” is to be understood as meaning ortho-fused, again as defined in the IUPAC recommendation 1998, published in Pure & Appl. Chem, Vol. 70, No. 1, pp. 143-216, 1998, i.e. as referring to two rings which are fused together and have only two atoms and one bond in common, and additionally also in cA-configuration, i.e. meaning that the second ring is ortho-fused to the first ring with the second ring attaching to the first ring on the same ring side (as opposed to / ram-configuration).

[0114] In some embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety comprises a bridged linker ring, in particular a 5 -membered, 6-membered or 7-membered ring with a bridge consisting of one or two bridging atoms. It should be understood that the bridged linker ring may optionally be further substituted. Examples of such substituents will be given below. In some alternative embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety comprises a cis-ortho-fused bicyclic linker group comprising a first ring and a second ring, wherein the first ring is ortho-fused to the 3,4-saturated 2H-pyran moiety and the second ring is cis-ortho-fused to the first ring, in particular a cis-ortho-fused bicyclic linker group comprising a 5 -membered or 6-membered first ring and a 4-membered, 5 -membered or 6-membered second ring. It should be understood that said cis-ortho-fused bicyclic linker group may optionally be further substituted. Examples of such substituents will be given below.

[0115] In some embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is the bridged linker ring, more specifically a bridged linker ring wherein:

[0116] the ring of the bridged linker ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is an optionally substituted 5 -membered, 6-membered or 7-membered carbocycle or an optionally substituted 5-membered, 6-membered or 7-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O, N and S;

[0117] more specifically an optionally substituted saturated or unsaturated 5-membered, 6- membered or 7-membered carbocycle or an optionally substituted saturated or unsaturated 5-membered, 6-membered or 7-membered heterocycle comprising one or two heteroatoms which are, independently from each other, selected from O and N; and, in particular,

[0118] a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted cycloheptane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyran; or a saturated or unsaturated and optionally substituted morpholine.

[0119] Additionally or alternatively, in some embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is the bridged linker ring wherein the bridge of the bridged linker ring consists of one or two bridging atoms which are, independently from each other, selected from C, N, O and S, more specifically from C, N and O, and in particular from C and N; more specifically wherein the bridge is an optionally substituted methylene bridge, an optionally substituted ethylene bridge, an oxa-bridge, a thiabridge or an optionally substituted aza-bridge.

[0120] In some embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is a bridged linker ring comprising a) an optionally substituted saturated or mono-unsaturated 5-membered, 6-membered or 7-membered carbocycle, or b) an optionally substituted saturated or mono-unsaturated 5 -membered, 6-membered or 7-membered heterocycle comprising one or two heteroatoms selected from N or O, and in particular N; and having a bridge consisting of one or two bridging atoms selected from C, O andN.

[0121] In some embodiments, it may be particularly advantageous that the bridged linker ring is represented by one of the following moieties,

[0122]

[0123] wherein the broken bonds indicate the attachment of the bridged linker ring to the 3,4-saturated 2H-pyran moiety; wherein the dashed bond between the broken bonds represents a double bond in case the bridged linker ring is formed by L1 and L6 or in case the bridged linker ring is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein X1 represents a moiety selected from CH2, C(CH3)2, NH, NR, O and S; wherein X2 represents a moiety selected from CH2, C(CH3)2, and NH; wherein R represents a C1-C30 moiety, the active ingredient, or a precursor thereof, or an ancillary linker group connecting the active ingredient, or the precursor thereof, to the nitrogen atom; and wherein each ring atom of the bridged linker ring may optionally be further substituted. Compounds according to the aforementioned embodiments are particularly advantageous since they are derivatives of readily available terpenoids such as pinene-derivatives or alkaloids such as tropinone and / or endowed with a secondary or tertiary amine which do not irreversibly react with the 3,4-saturated 2H-pyran moiety but may be protonated in an aqueous environment to impart improved water-solubility to the compound.

[0124] In some embodiments, it may be particularly advantageous that Xi represents a moiety selected from CH2 and C(CH3)2; and X2 represents a moiety selected from CH2 and C(CH3)2.

[0125] Here and elsewhere in the present disclosure, the term “ancillary linker group” is meant to refer to a linker group which is involved in connecting one of the moieties Ai to A? to the 3,4-saturated 2H-pyran moiety but which is neither part of the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety nor part of a further cyclic linker group (but it is part of the entirety of the respective linker group of Li to L7). To give a non-limiting illustrative example of an ancillary linker group: Tropinone is readily functionalized at its bridge head nitrogen atom and is in the following example substituted with an ethylene linker (-CH2-CH2-) which connects moiety A4 to the tropinone nitrogen. This tropinone derivative can then be converted to a Michael acceptor with benzaldehyde and subsequently converted to a compound of the present disclosure by reaction with methyl 3,3-dimethoxypropanoate, followed by intramolecular cyclization.

[0126]

[0127] In this example, with reference to formula (I), the vicinal pair of linker groups L4 and L7 form a bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety and ethylene linker mentioned above represents the aforementioned ancillary linker group that connects the corresponding moiety A4 to the 3,4-saturated 2H-pyran moiety. In other words, the vicinal pair of linker groups L4 and L7 forms said bicyclic linker group and the ethylene linker is part of L4 as its ancillary linker group. In some embodiments, the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is the cis-ortho-fused bicyclic linker group.

[0128] In some embodiments, the bicyclic linker group is a cis-ortho-fused bicyclic linker group wherein the first ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is an optionally substituted 5-membered, 6-membered or 7-membered carbocycle or an optionally substituted 5-membered, 6-membered or 7-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O, N and S. In some embodiments, it may be particularly advantageous that said first ring is an optionally substituted saturated or unsaturated 5-membered, 6-membered or 7-membered carbocycle or an optionally substituted saturated or unsaturated 5-membered, 6-membered or 7-membered heterocycle comprising one or two heteroatoms which are, independently from each other, selected from O and N; and, in particular, a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted cycloheptane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyran; or a saturated or unsaturated and optionally substituted morpholine. In some embodiments, it may be particularly advantageous that the second ring which is cis-ortho-fused to the said first ring is an optionally substituted 4-membered, 5-membered or 6-membered carbocycle or an optionally substituted 4-membered, 5-membered or 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O, N and S; more specifically an optionally substituted saturated or unsaturated 5-membered or 6-membered carbocycle or an optionally substituted saturated or unsaturated 5-membered or 6-membered heterocycle comprising one or two heteroatoms which are, independently from each other, selected from O and N; and, in particular, a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyran; or a saturated or unsaturated and optionally substituted morpholine. Compounds according to these embodiments are particularly advantageous since they are derivatives of readily available alkaloids such as pyrrolizidine alkaloids or Diels Alder reactions and / or endowed with a secondary or tertiary amine which do not irreversibly react with the 3,4-saturated 2H-pyran moiety but may be protonated in an aqueous environment to impart improved water-solubility to the compound. It should be understood that, due to the ring fusion, heteroatoms can also be shared between the rings. In this instance, for the purposes of counting heteroatoms per heterocycle, the shared heteroatom is considered to be a heteroatom of each of the heterocycle sharing said heteroatom.

[0129] In some embodiments, it may be advantageous that the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is a cis-ortho-fused bicyclic linker group wherein a) the first ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is an optionally substituted saturated or mono-unsaturated 5 -membered or 6-membered carbocycle or an optionally substituted saturated or mono-unsaturated 5 -membered or 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O and N; and b) the second ring which is cis-ortho-fused to the first ring is an optionally substituted saturated or mono-unsaturated 5 -membered or 6-membered carbocycle or an optionally substituted saturated or mono-unsaturated 5 -membered or 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O and N.

[0130] In some of the embodiments of the preceding paragraph, it may be particularly advantageous that the first ring is an optionally substituted saturated or mono-unsaturated 5-membered or 6-membered carbocycle and the second ring is an optionally substituted mono-unsaturated 6-membered carbocycle or an optionally substituted mono-unsaturated 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O and N. Such moieties are readily available utilizing Dierls-Alder-type reactions. In some of the embodiments of the preceding paragraph, it may be particularly advantageous that the first ring is an optionally substituted saturated or mono-unsaturated 5-membered or 6-membered heterocycle and the second ring is an optionally substituted saturated or mono-unsaturated 5-membered or 6-membered heterocycle, wherein the first and second heterocycle share a nitrogen atom. Such moieties are readily available starting from pyrrolizidine alkaloids.

[0131] In some embodiments, the cis-ortho-fused bicyclic linker group is represented by one of the following moieties,

[0132]

[0133] wherein the broken bonds indicate the attachment of the cis-ortho-fused bicyclic linker group to the 3,4-saturated 2H-pyran moiety; wherein the dashed bond between the broken bonds represents a double bond in case the cis-ortho-fused bicyclic linker group is formed by Li and Lg or in case the bicyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; and wherein each ring atom of the cis-ortho-fused bicyclic linker group may optionally be further substituted.

[0134] Compounds according to the aforementioned embodiments are particularly advantageous since they are derivatives of readily available bicyclic alkaloids such as heliotridine, hyacinthacine, epilupinine labumine, isoretronecanol, tashiromine, and others; and / or are endowed with a tertiary amine which does not irreversibly react with the 3,4-saturated 2H-pyran moiety but is protonated in an aqueous environment to impart improved watersolubility; and / or are readily synthetically accessible by inverse electron demand Diels-Alder reactions.

[0135] The position of the bicyclic linker group on the 3,4-saturated 2H-pyran moiety

[0136] The position of the ortho-fused bicyclic linker group on the 3,4-saturated 2H-pyran moiety is not particularly limited. In some embodiments, it may be particularly beneficial from a synthetical perspective that the bicyclic linker group is formed by L3 and L4; L4 and L7; Li and Lg; or tautomers thereof. Various illustrative examples will be discussed below:

[0137] In some embodiments, L3 and L4 form the bicyclic linker group. This configuration resembles the ring arrangement of genipin which is well-known to reliably couple to skin without causing cytotoxicity. It is synthetically accessible by e.g. utilizing a Michael addition reaction using a bicyclic Michael acceptor comprising an endocyclic ene group and exocyclic carbonyl group, in particular an exocyclic aldehyde, and a Michael donor. This synthetical pathway was already exemplarily discussed above for the bicyclic Michael acceptor myrtenal with reference to Fig. 1.

[0138] In some embodiments, it may be particularly advantageous that L3 and L4 form the bicyclic linker group, that Lg is absent and Ag represents hydrogen and / or that L7 is absent and A7 represents hydrogen. It may be most advantageous that L3 and L4 form the bicyclic linker group, that Lg is absent and Ag represents hydrogen and / or that L7 is absent and A7 represents hydrogen, and that the combined substituent L1-A1 does not represent hydrogen. Such embodiments resemble genipin closer still and are endowed with high reactivity towards amino groups.

[0139] In some embodiments, L4 and L7 form the bicyclic linker group. This configuration is synthetically accessible by e.g. utilizing a Michael addition reaction using a Michael acceptor and a bicyclic Michael donor such as camphor, norcamphor, nopinone, tropinone and 3-quinuclidone. An example of such a synthesis is shown in Fig. 2. In Fig. 2, perillaldehyde is used as the Michael acceptor whereas camphor is used as a bicyclic Michael donor. The ring-opened 1,5-dicarbonyl intermediate may cyclize to a 3,4-saturated 2H-pyran moiety wherein, in the terms of formula (I), L4 and L7 form the bicyclic linker group. Alternatively, a Michael addition reaction can be used in which a bicyclic Michael acceptor is synthesized by a condensation reaction of bicyclic ketones, such as camphor and its derivatives, nopinone, tropinone and 3-quinuclidone, with aldehydes or ketones. An example of such a synthesis is shown in Fig. 3. In Fig. 3, camphor is condensed with benzaldehyde, a reaction which is commercially used in the production of UV-protecting agents. The resulting 3-benzylidene camphor is then reacted in a Michael addition with methyl 3,3-diethoxypropanoate to a ring- opened 1,5-dicarbonyl intermediate which may cyclize to a 3,4-saturated 2H-pyran moiety wherein, in the terms of formula (I), L4 and L7 form the bicyclic linker group.

[0140] In some embodiments, it may be particularly advantageous that L4 and L7 form the bicyclic linker group and that the combined substituent L1-A1 does not represent hydrogen. It may be most advantageous that L4 and L7 form the bicyclic linker group and that the combined substituent L1-A1 comprises a carbonyl group which is attached to the 3,4-saturated 2H-pyran moiety. Such embodiments may favor the ring-closed tautomer due to the conjugation of the carbonyl group to the enolether group of the 3,4-saturated 2H-pyran moiety, thus, facilitating purification.

[0141] In some alternative embodiments, it may be particularly advantageous that L4 and L7 form the bicyclic linker group and L2 and L3 jointly represent oxo. Such embodiments may favor the ring-closed tautomer due to the conjugation of the carbonyl group at L2 and L3 to the enol ether group of the 3,4-saturated 2H-pyran moiety, thus, facilitating purification. Moreover, such compounds may also be particularly efficient in linking to the amino group of a substrate such as skin or hair since the resulting 4-pyridone is particularly stable. Finally, the compounds of this embodiment are readily synthetically available from bicyclic ketones, such as camphor and its derivatives, nopinone, tropinone and 3-quinuclidone, by reaction with an acid chloride or an activated carboxylic acid. An exemplary synthesis is shown in Fig. 4. In Fig. 4, starting from benzyl hydrogen 2-formylmalonate which is obtainable from Meldrum’s acid as disclosed by Sato et al. in Chem Pharm. Bull., 37(3), 665-669, 1989, pinocarvon is acylated to yield the cyclized 3,4-saturated 2H-pyran derivative. This compound can be functionalized further as desired, for instance by hydrogenolysis of the benzyl ether, followed by introduction of an active ingredient (shown in Fig. 4 as moiety “R”) to the to the generated carboxylic acid, or by functionalization of the exocyclic double bond to further increase the reactivity of the 3,4-saturated 2H-pyran moiety towards the amino groups of the substrate.

[0142] In some embodiments, it may be particularly advantageous that L4 and L7 form the bicyclic linker group, that L2 and L3 jointly represent oxo, that L6 is absent and that A6 represents hydrogen; and in particular that L4 and L7 form the bicyclic linker group, that L2 and L3 jointly represent oxo, that L6 is absent and A6 represents hydrogen, and that the combined substituent L1-A1 does not represent hydrogen. Such embodiments may favor the ring-closed tautomer due to the conjugation of the carbonyl group to the enol ether group of the 3,4-saturated 2H-pyran moiety, thus, facilitating purification.

[0143] As further shown in Fig. 4, and depending on the substituents, the compounds of the aforementioned embodiment may also be present in an alternative tautomeric form in which L1 and L6 form the bicyclic linker group. Accordingly, in some embodiments, it may also be particularly advantageous that L1 and L6 form the bicyclic linker group, that L2 and L3 jointly represent oxo, that L7 is absent and that A7 represents hydrogen; and in particular that L1 and L6 form the bicyclic linker group, that L2 and L3 jointly represent oxo, that L7 is absent and A7 represents hydrogen, and that the combined substituent L4-A4 does not represent hydrogen. Such embodiments may favor the ring-closed tautomer due to the conjugation of the carbonyl group to the enol ether group of the 3,4-saturated 2H-pyran moiety, thus, facilitating purification.

[0144] The further cyclic linker group

[0145] Coming back to a vicinal pair of L1 to L7 forming a further cyclic linker group:

[0146] In some embodiments, the compound of the present disclosure comprises a further cyclic linker group, wherein the further cyclic linker group is a monocyclic linker group selected from the group consisting of: an optionally substituted monocyclic carbocycle; and an optionally substituted monocyclic heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S.

[0147] In some embodiments, it may be advantageous that the further cyclic linker group is a monocyclic linker group selected from the group consisting of: an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered carbocycle; an optionally substituted monocyclic aromatic 5- or 6-membered carbocycle; an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; and an optionally substituted monocyclic 5- or 6-membered heteroaromatic comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S. In some embodiments, it may be particularly advantageous that the further cyclic linker group is a monocyclic linker group selected from the group consisting of: an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered carbocycle; and an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S.

[0148] Exemplary embodiments of such a further cyclic linker group may be selected from the group consisting of: a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyrane; or a saturated or unsaturated and optionally substituted morpholine.

[0149] As explained above, the further cyclic linker group may optionally also comprise further rings, i.e. be a further polycyclic linker group. Accordingly, in some embodiments, the further cyclic linker group is a polycyclic linker group comprising two or more, more specifically two, three, four, or five, and in particular two, three or four, (hetero)cycles which are, independently from each other, selected from the group consisting of: an optionally substituted carbocycle; and an optionally substituted heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S.

[0150] In some embodiments, it may be advantageous that the further cyclic linker group is a polycyclic linker group comprising two, three or four (hetero)cycles which are, independently from each other, selected from the group consisting of: an optionally substituted saturated or unsaturated 5- or 6-membered carbocycle; an optionally substituted aromatic 5- or 6-membered carbocycle; an optionally substituted saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; and an optionally substituted 5- or 6-membered heteroaromatic comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S. In some embodiments, it may be particularly advantageous that the further cyclic linker group is a polycyclic linker group comprising two, three or four (hetero)cycles which are, independently from each other, selected from the group consisting of: an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered carbocycle; and an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S.

[0151] In some embodiments, the further cyclic linker group is represented by one of the following moieties,

[0152]

[0153] wherein the broken bonds indicate the attachment of the further cyclic linker group to the 3,4-saturated 2H-pyran moiety; wherein the dashed bond between the broken bonds represents a double bond in case the further cyclic linker group is formed by L1 and L6 or in case the further cyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein the remainder of the dashed bonds represents a single bond or a double bond; wherein X1 represents a moiety selected from CH2, NH, O and S; wherein X2 represents a moiety selected from CH2, NH, O and S in case the dashed bond represents a single bond, and selected from CH and N in case the dashed bond represents a double bond; and wherein each ring atom of the further cyclic linker group may optionally be further substituted.

[0154] In some embodiments, it may be advantageous that, after the compound of formula (I) has covalently bound to the substrate, converting the 3,4-saturated 2H-pyran moiety to a dihydropyridine or pyridinium moiety, the further cyclic linker group and the dihydropyridine or pyridinium moiety form a conjugated π-electron system. In such embodiments, the compound of formula (I) may provide intense and vibrant color after having bound to the substrate due to the extensive conjugation of the formed π-electron system. In some embodiments, the further cyclic linker group is substituted by at least one oxo group, in particular by at least one oxo group which is present on a carbon atom which is in alpha-position to one of the carbon atoms of the 3,4-saturated 2H-pyran moiety. Such oxo groups will generally introduce polarity into the molecule and be beneficial for improving water-solubility of the compounds. In case the oxo groups(s) is / are in alpha-position to one of the carbon atoms of the 3,4-saturated 2H-pyran moiety, the oxo group(s) will additionally be in conjugation to the enol ether group of the 3,4-saturated 2H-pyran moiety increasing the stability of the ring-closed tautomer and / or to the 1,4-dihydropyridine derivative obtained from the 3,4-saturated 2H-pyran moiety after linking to the substrate and, thus, facilitate the coupling reaction to the substrate. An example of such an oxo group (in this case present on the linker group L1) is shown below. In the example, further substituents are truncated by broken bonds. The example illustrates an oxo group which is in alpha-position to a carbon atom of the 3,4-saturated 2H-pyran moiety and stabilizes – by way of conjugation – both the 3,4-saturated 2H-pyran moiety and the resulting 1,4-dihydropyridine.

[0155]

[0156] In some embodiments, it may be particularly advantageous that the further cyclic linker group is formed by Li and Lg and is substituted by at least one oxo group which is present on a carbon atom which is in alpha-position to the carbon atom to which Li is attached or in cilpha-position to the carbon atom to which Lg is attached; more specifically that the further cyclic linker group is formed by Li and Lg and is substituted by at least two oxo groups, one of which is present on a carbon atom which is in alpha-position to the carbon atom to which Li is attached and the other one of which is present on a carbon atom which is in alpha-position to the carbon atom to which Lg is attached.

[0157] In some embodiments, it may be particularly advantageous that the further cyclic linker group is formed by L4 and L7 and is substituted by at least one oxo group which is present on a carbon atom which is in alpha-position to the carbon atom to which L5 is attached or in alpha-position to the carbon atom to which L7 is attached; or that the further cyclic linker group is formed by L4 and L7 and is substituted by at least two oxo groups, one of which is present on a carbon atom which is in alpha-position to the carbon atom to which L4 is attached and the other one of which is present on a carbon atom which is in alpha-position to the carbon atom to which L7 is attached.

[0158] In some embodiments, it may be advantageous that the further cyclic linker group is an optionally substituted 1,4-naphthoquinone moiety, an optionally substituted 1,2-naphtho-quinone moiety or an optionally substituted acridine moiety. Such embodiments are readily available from lawsone or lawsone derivatives or reaction products with aromatic ortho-diamines which are obtainable from lawsone and said diamines in excellent (often quantitative) yields. An example of such a derivative starting from lawsone and myrtenal is indicated below:

[0159]

[0160] In some embodiments, it may be advantageous that the further cyclic linker group is represented by one of the following moieties, o o

[0161]

[0162] wherein the broken bonds indicate the attachment of said moiety to the 3,4-saturated 2H-pyran moiety; wherein the dashed bond between the broken bonds represents a double bond in case the further cyclic linker group is formed by L1 and L6 or in case the further cyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein the remainder of the dashed bonds represents a single bond or a double bond; and wherein each ring atom of said moiety may optionally be further substituted. The position of the further cyclic linker group on the 3,4-saturated 2H-pyran moiety

[0163] The position of the further cyclic linker group on the 3,4-saturated 2H-pyran moiety is also not particularly limited.

[0164] In some embodiments, it may be particularly beneficial, from a synthetical perspective, that the further cyclic linker group is formed by L1 and L6 or L4 and L7 since, in these positions, the further cyclic linker group is forcing the enol-tautomer to assume the Z-stereoisomeric configuration required for the cyclization to the 3,4-saturated 2H-pyran derivative. Moreover, the presence of a further cyclic linker group in these positions restricts the conformational freedom of the ring-opened 1,5-dicarbonyl tautomer and favors the close proximity of the 1,5-dicarbonyl positions and, thus, may facilitate the ring-closing reaction to form the 1,4-dihydropyridine that ultimately binds the compound to the substrate. Therefore, providing the further cyclic linker group on L1 and L6 or L4 and L7 facilitates the formation of the 3,4-saturated 2H-pyran derivative and, thus, purification.

[0165] Ancillary linker groups as optional substituents on any of the rings formed by L1-L7

[0166] As indicated above, the term “ancillary linker group” is meant to refer to a linker group which is involved in connecting one of the moieties A1 to A7 to the 3,4-saturated 2H-pyran moiety but which is neither part of the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety nor part of a further cyclic linker group (but it is part of the entirety of the respective linker group of L1 to L7). It should also be understood that the presence of such ancillary linker groups is optional and that different linker groups amongst L1 to L7 forming the bicyclic linker group or the optional further cyclic linker group may be provided with different ancillary linker groups.

[0167] Accordingly, in some embodiments, and independently from each other, the moieties amongst A1, A2, A3, A4, A5, A6 and A7 which correspond to those linker groups amongst L1, L2, L3, L4, L5, L6 and L7 which form the bicyclic linker group and the optional further cyclic linker group are either attached to their respective (bi)cyclic linker group by a bond, or are alternatively connected to their respective (bi)cyclic linker group by an ancillary linker group. In some embodiments, and independently from each other, each instance of the ancillary linker group comprises 1 to 12, more specifically 1 to 10, 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 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 6, more specifically 0 to 4, and in particular 0 to 3 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms. In some embodiments, it may be particularly advantageous that one or more of the ancillary linker groups is selected from the group consisting of: -O-, -S-, -C(O)-, -CO2-, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2)1-4-, -(CH2)1-4-O- and -O-(CH2)1-4-, or combinations thereof. In case that a plurality of ancillary linker groups is present, each selection from said group may be done independently from each other.

[0168] Alternatively, the total size, more specifically the total number of atoms, of the vicinal pair of linker groups forming the bicyclic linker group and their respective optional ancillary linker groups as well as the other optional substituents on the bicyclic moiety may also be defined starting from the bicyclic moiety. The same applies to the vicinal pair of linker groups forming the further cyclic linker group.

[0169] Accordingly, in some embodiments, a) the bicyclic linker group, together with its optional substituent(s) and its optional ancillary linker group(s), and b) the optional further cyclic linker group(s), together with its(their) optional substituent(s) and its(their) optional ancillary linker group(s), each comprise, independently from each other and excluding the two carbon atoms shared with the 3,4-saturated 2H-pyran moiety: less than 30, more specifically less than 24, and in particular less than 16 carbon atoms; less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms. Additionally or alternatively, in some embodiments, a) the bicyclic linker group, together with its optional substituent(s) and its optional ancillary linker group(s), and b) the optional further cyclic linker group(s), together with its(their) optional substituent(s) and its(their) optional ancillary linker group(s), each comprise, independently from each other and excluding the two carbon atoms shared with the 3,4-saturated 2H-pyran moiety: between 3 and 29, more specifically between 4 and 23, and in particular between 5 and 15 carbon atoms; between 0 and 11, more specifically between 0 and 7, and in particular between 0 and 5 oxygen atoms; between 0 and 7, more specifically between 0 and 5, and in particular between 0 and 3 nitrogen atoms; between 0 and 5, more specifically between 0 and 3, and in particular between 0 and 2 sulfur atoms; between 0 and 5, more specifically between 0 and 3, and in particular between 0 and 2 phosphor atoms; between 0 and 5, more specifically between 0 and 3, and in particular between 0 and 2 boron atoms; and between 0 and 9, more specifically between 0 and 7, and in particular between 0 and 6 halogen atoms.

[0170] The linking groups L1 to L7 in general, in particular when not forming a (bi)cyclic linker group

[0171] In some embodiments, L1 to L7 and, in particular L1 to L7 not part of a vicinal pair of linker groups forming a (bi)cyclic linker group, are defined as follows:

[0172] 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

[0173] 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

[0174] 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

[0175] 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

[0176] 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 L6is 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

[0177] L7is 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.

[0178] Additionally, in some embodiments, it may be particularly advantageous that, independently from each other, each of the optionally substituted hydrocarbon moieties L1to L7comprises, together with its optional substituents, less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms.

[0179] It should be understood that the aforementioned term “optionally substituted hydrocarbon moiety” is not meant to exclude the presence of heteroatoms (i.e. atoms besides C and H).

[0180] 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, one or more of L1to L7represents a polymeric moiety or represents a moiety which comprises a polymeric moiety (e.g. as an ancillary linker group) or forms together with one its adjacent linker groups a moiety which comprises a polymeric moiety (e.g. as an ancillary linker group). In some embodiments, none of L1to L7represents a polymeric moiety.

[0181] In some embodiments, none of the substituent combinations L1-A1 and L4-A4 represent hydrogen. Like glutardialdehyde, 3,4-saturated 2H-pyran derivatives may undergo sidereactions which result in oligomerized or polymerized side-products 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.

[0182] Cleavable and non-cleavable functional groups linking the active ingredients to the remainder of the compound

[0183] 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 and in particular to the 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 skin and / or the hair, can be broken such that the active ingredient is released.

[0184] 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.

[0185] It should be understood that the aforementioned functional group serves to attach 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, L6-A6and L7-A7comprising 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.

[0186] 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: 1 to 12 carbon atoms, more specifically 1 to 8 carbon atoms, and in particular 1 to 4 carbon atoms; 1 to 4 oxygen atoms, more specifically 1 to 3 oxygen atoms, and in particular 1 or 2 oxygen atoms; 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; 1 to 3 phosphorus atoms, more specifically 1 or 2 phosphorus atoms, and in particular 1 phosphorus atom; 1 or 2 boron atoms, and in particular 1 boron atom.

[0187] 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 up to 14 days which is a typical time span before the natural desquamation of the skin removes any bound compounds from the skin.

[0188] 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 and / or after its covalent attachment 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.

[0189] 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.

[0190] 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; b) 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.

[0191] 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 the 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.

[0192] 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.

[0193] 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.

[0194] 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 / or 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).

[0195] In some embodiments, the functional group comprises a carbon ester, in particular a monoester, 1,1 -di ester, 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.

[0196] 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.

[0197] Specific embodiments of the present disclosure

[0198] Specific embodiments of the present disclosure will be described in more detail in the following:

[0199] In some embodiments, the compound of formula (I) is a compound of formula (Ila),

[0200]

[0201] The compound may be present as a tautomer and / or a pharmaceutically acceptable salt thereof. R1, A1, A2, A3, A4, A5, A6, A7, L1, L2, L3, L4, L5, L6, and L7are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the preceding embodiments.

[0202] In some embodiments, the compound of formula (I) is a compound of formula (IIb),

[0203]

[0204] (lib)

[0205] The compound may be present as a tautomer and / or a pharmaceutically acceptable salt thereof. R1, A1, A2, A3, A4, A6, A7, L1, L2, L3, L4, L6, and L7are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the preceding embodiments.

[0206] In some embodiments, the compound of formula (I) is a compound of formula (III),

[0207]

[0208] The compound may be present as a tautomer and / or a pharmaceutically acceptable salt thereof. R1, A1, A2, A3, A4, A6, A7, L2, L3, L4, L6, and L7are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the preceding embodiments. X represents O or S, and in particular O; and Lxis absent or represents -O-, -S-, -NH-, or 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 10 carbon atoms, 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 sulfur atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 phosphorous atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms; and the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfur atom. Compounds of formula (III) may be particularly advantageous since the (thio-)carbonyl group facilitates the ring-opening to the more reactive 1,5 -dicarbonyl tautomer. Moreover, it blocks the C-5 position in the 3,4-saturated 2H-pyran moiety and allows to delocalize charge in the cascade of reactions towards the 1,4-dihydropyridine derivative, both of which are beneficial in suppressing the formation of oligomers and polymers which may be facilitated in case the C-5 position is substituted with hydrogen.

[0209] In some embodiments, it may be advantageous that the substituent combination C(=X)-Lx-Ai represents 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 Ra represents a moiety comprising 1 to 16 carbon atoms, and optionally one or more of: 1 to 8 oxygen atoms, 1 to 6 nitrogen atoms, 1 to 3 sulfur atoms, 1 or 2 phosphorous atoms, 1 or 2 boron 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, 1 or 2 phosphorous atoms, 1 or 2 boron atoms, and 1 to 3 halogen atoms; 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.

[0210] In some embodiments, it may be particularly advantageous that -C(=X)-Lx-Ai represents -COORa as defined immediately above; more specifically -COORa, wherein Ra represents a hydrocarbon moiety comprising 1 to 8 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 4 nitrogen atoms, 1 or 2 sulfur atoms, 1 or 2 phosphorous atoms, 1 or 2 boron atoms, and 1 to 3 halogen atoms; and in particular -COORa, wherein Ra represents Ci-C4-alkyl, such as methyl or ethyl. Compounds of this embodiment may be particularly beneficial since they are essentially structurally genipin, oleuropein and elenolic acid which are generally regarded as safe.

[0211] In some embodiments, in particular in embodiments according to formulae (lib) and (III), both L6and L7are absent and A6and A7represent hydrogen. These embodiments may be particularly advantageous since the respective 3,4-saturated 2H -pyran moiety may ring-open to a reactive 1,5-diadehyde and, thus, may couple to the amino group of the substrate in a fast manner. This may be beneficial in industrial applications in which machine time is of importance and it may be beneficial in skin- and / or hair-oriented consumer applications due to the increased convenience for the user.

[0212] In some alternative embodiments, in particular in embodiments according to formulae (lib) and (III), L6is absent and A6represents hydrogen or L7is absent and A7represents hydrogen. In other words, the respective 3,4-saturated 2H-pyran moiety may ring-open to a reactive mixed 1,5-ketoaldehyde which is still more reactive towards primary amines than the 1,5-diketones but is also more readily synthetically available than the 1, 5-dial dehy des.

[0213] In some embodiments, it may be particularly advantageous that the compound of formula (I) is a compound of formula (IV),

[0214] / A1

[0215]

[0216] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, A1, A6, A7, L1, L6, and L7are defined as indicated above for formula (I) and are, in particular, defined as indicated in any further of the preceding embodiments. Compounds of this embodiment may be particularly beneficial since they are structurally close to genipin and can be conveniently and stereo-selectively obtained from the chiral terpenoid myrtenal which is generally considered to be safe and is available at low cost. Moreover, when attached to a substrate such as skin and / or hair, compounds of this embodiment will be colorless or nearly colorless (such as faintly yellow), i.e. attach to a substrate such as skin and / or hair in an unobtrusive fashion.

[0217] In some embodiments, it may be particularly advantageous that L7 is absent and A7 represents hydrogen. Additionally or alternatively, in some embodiments, it may be particularly advantageous that R1represents hydrogen. Such substitution patterns will facilitate linking the 3,4-saturated 2H-pyran moiety to the substrate since both the initial ring-opening to the 1,5-dicarbonyl derivative as well as the formation of the 1,4-dihydropyridine moiety are facilitated.

[0218] In some embodiments, it may be particularly advantageous that the compound of formula (I) is a compound of formula (V),

[0219]

[0220] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, A1, A6, A7, L6, and L7are defined as indicated above for formula (I) and Lxand X, are defined as indicated above for formula (III); and are, in particular, defined as indicated in any of the further preceding embodiments.

[0221] In some embodiments, it may be particularly advantageous that L7 is absent and A7 represents hydrogen. Additionally or alternatively, in some embodiments, it may be particularly advantageous that R1represents hydrogen. Again, such substitution patterns will facilitate linking the 3,4-saturated 2H-pyran moiety to the substrate since both the initial ring-opening to the 1,5-dicarbonyl derivative as well as the formation of the 1,4-dihydropyridine moiety are facilitated.

[0222] In some embodiments, it may be particularly advantageous that the compound of formula (I) is a compound of formula (VI),

[0223]

[0224] (VI)

[0225] 5

[0226] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, A1, A2, A3, A6, L1, L2, L3, and L6are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the further preceding embodiments.

[0227] An exemplary synthetical approach is shown in Fig. 5, starting from camphor, 4-(di-methylamino) benzaldehyde and an acetoacetate ester. Moreover, the synthetical approach is highly flexible and can be readily adapted. All components are readily available at low cost and generally regarded as safe. The chiral camphor derivative will further provide stereoselectivity to the synthesis (not shown) which will facilitate purification and, thus, also overall yields. In some embodiments, it may be particularly advantageous that L2-A2 or L3-A3 represents an optionally substituted phenyl. The intermediate benzylidene camphor derivative shown in Fig. 5 can be reliably and robustly obtained in high yields from a larger number of aldehydes. Changing the aromatic aldehyde allows conveniently introducing further functionalities: For instance, the 4-(dimethyl-amino)benzaldehyde provides a group that is protonated at a physiological pH, i.e. improves water solubility. A hydroxybenzaldehyde derivative could provide a further functional group for attaching compounds of interest. Moreover, in case L2-A2 or L3-A3 represents an optionally substituted phenyl, the compounds will further provide a UV-absorbing effect. In some embodiments, it may be particularly advantageous that L2 is absent and A2 represents hydrogen and that L3 is absent and A3 represents phenyl or a phenyl which, in combination with its optional substituents, comprises 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 4, more specifically 0 to 3, and in particular 0 to 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; and in particular phenyl or phenyl mono- or disubstituted with (a) hydroxyl group(s). In some embodiments, it may be particularly advantageous that Lg is absent and As represents hydrogen. Additionally or alternatively, in some embodiments, it may be particularly advantageous that R1represents hydrogen. Such substitution patterns will facilitate linking the 3,4-saturated 2H-pyran moiety to the substrate since both the initial ring-opening to the 1,5-dicarbonyl derivative as well as the formation of the 1,4-dihydropyridine moiety are facilitated.

[0228] In some embodiments, it may be advantageous that the substituent combination L1-A1 represents the substituent combination C(=X)-Lx-Ai as defined above with respect to the compound of formula (III) and the related embodiments. Compounds of these embodiments introduce polarity into the molecule and may be beneficial for their increased hydrophilicity. Moreover, the (thio)carbonyl group may stabilize the 3,4-saturated 2H-pyran moiety since it is in alpha -position to a carbon atom of the 3,4-saturated 2H-pyran moiety and, as explained above, stabilizes - by way of conjugation - both the 3,4-saturated 2H-pyran moiety and the resulting 1,4-dihydropyridine. Finally, like for the compounds of formula (III), compounds of this embodiment may be particularly beneficial since they are structurally close to genipin, oleuropein and elenolic acid which are generally regarded as safe.

[0229] In some embodiments, it may be particularly advantageous that the compound of formula (I) is a compound of formula (VII),

[0230]

[0231] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, A1, A2, A3, A4, A6, L1, L2, L3, and L6are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the further preceding embodiments; and wherein Lyrepresents an ancillary linker group, in particular an ancillary linker group as indicated above in the context of formula (I), and, in particular, as defined as indicated in any of the preceding embodiments. An exemplary synthetical approach is shown in Fig. 6, starting from tropinone, benzaldehyde and an acetoacetate ester, the latter of which can be further functionalized to provide the compounds according to the present disclosure. Moreover, the synthetical approach is highly flexible and can be readily adapted. All components are readily available at low cost and generally regarded as safe. Tropinone will also improve water-solubility since the amine group will be protonated. In case L2-A2 or L3-A3 represents an optionally substituted phenyl, the compounds will further provide a UV-absorbing effect. In some embodiments, it may be particularly advantageous that L2 is absent and A2 represents hydrogen and that L3 is absent and A3 represents phenyl or a phenyl which, in combination with its optional substituents, comprises 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 4, more specifically 0 to 3, and in particular 0 to 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; and in particular phenyl or phenyl mono- or disubstituted with (a) hydroxyl group(s).

[0232] In some embodiments, Lycomprises, together with its optional substituents, less than 12, more specifically less than 8, and in particular less than 6 carbon atoms; less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms. In some embodiments, it may be particularly advantageous that Lyrepresents an ancillary linker group is selected from the group consisting of: -O-, -S-, -C(O)-, -CO2-, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2)1-4-, -(CH2)1-4-O- and -O-(CH2)1-4-, or combinations thereof.

[0233] In some embodiments, it may be particularly advantageous that L6is absent and A6represents hydrogen. Additionally or alternatively, in some embodiments, it may be particularly advantageous that R1represents hydrogen. Such substitution patterns will facilitate linking the 3,4-saturated 2H-pyran moiety to the substrate since both the initial ring-opening to the 1,5- dicarbonyl derivative as well as the formation of the 1,4-dihydropyridine moiety are facilitated.

[0234] In some embodiments, it may be advantageous that the substituent combination L1-A1 represents the substituent combination C(=X)-Lx-Ai as defined above with respect to the compound of formula (III) and the related embodiments. Compounds of these embodiments introduce polarity into the molecule and may be beneficial for their increased hydrophilicity. Moreover, the (thio)carbonyl group may stabilize the 3,4-saturated 2H-pyran moiety since it is in alpha -position to a carbon atom of the 3,4-saturated 2H-pyran moiety and, as explained above, stabilizes - by way of conjugation - both the 3,4-saturated 2H-pyran moiety and the resulting 1,4-dihydropyridine. Finally, like for the compounds of formula (III), compounds of this embodiment may be particularly beneficial since they are structurally close to genipin, oleuropein and elenolic acid which are generally regarded as safe.

[0235] In some embodiments, it may be particularly advantageous that the compound of formula (I) is a compound of formula (VIII),

[0236]

[0237] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, A1, A2, A3, A6, L1, L2, L3, and L6are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the further preceding embodiments.

[0238] In some embodiments, it may be particularly advantageous that L2 and L3 are absent and A2 and A3 both represent hydrogen. Such embodiments are available starting from the chiral pinene derivative pinocarvone which is readily obtained from the cheapest available pinenederivative, a-pinene. a-Pinene can be quantitatively converted at room temperature and ambient pressure into pinocarvone by a visible-light photooxidation with singlet oxygen which is produced in-situ using tetraphenyl porphyrin as a photosensitizer (Miyaji et al., Angew. Chem. Int. Ed., 2016, 55, 1372 -1376; incorporated in its entirety by reference thereto). Starting from pinocarvone, an exemplary synthetical approach to compounds of this embodiment is shown in Fig. 7.

[0239] In some alternative embodiments, it may be particularly advantageous that L2-A2 and L3-A3 jointly represent oxo. An exemplary synthetical approach is shown in Fig. 8 starting from the chiral pinene derivative nopinone and a formylated monoester of malonic acid, the latter of which can e.g. be further functionalized to provide the compounds according to the present disclosure. All components are readily available at low cost and generally regarded as safe. The chiral nopinone will further provide stereoselectivity to the synthesis which will facilitate purification and, thus, also improve overall yields. The formylated monoester of malonic acid can be obtained as disclosed by Sato et al. in Chem. Pharm. Bull 37(3), 665-669 (1989), herein incorporated in its entirety by reference thereto.

[0240] Additionally or alternatively, in some embodiments, it may be particularly advantageous that Lg is absent and As represents hydrogen. Additionally or alternatively, in some embodiments, it may be particularly advantageous that R1represents hydrogen. Such substitution patterns will facilitate linking the 3,4-saturated 2H-pyran moiety to the substrate since both the initial ring-opening to the 1,5-dicarbonyl derivative as well as the formation of the 1,4-dihydropyridine moiety are facilitated.

[0241] Additionally or alternatively, in some embodiments, it may be further advantageous that the substituent combination L1-A1 represents the substituent combination C(=X)-Lx-Ai as defined above with respect to the compound of formula (III) and the related embodiments. Compounds of these embodiments introduce polarity into the molecule and may be beneficial for their increased hydrophilicity. Moreover, the (thio)carbonyl group may stabilize the 3,4-saturated 2H-pyran moiety since it is in alpha -position to a carbon atom of the 3,4-saturated 2H-pyran moiety and, as explained above, stabilizes - by way of conjugation - both the 3,4-saturated 2H-pyran moiety and the resulting 1,4-dihydropyridine. Finally, like for the compounds of formula (III), compounds of this embodiment may be particularly beneficial since they are structurally close to genipin, oleuropein and elenolic acid which are generally regarded as safe. In some embodiments, there is provided a compound of formula (I), wherein L3 and L4 form the bicyclic linker group, L2-A2 is absent and L3 comprises a carbon atom which is attached to the 3,4-saturated 2H-pyran moiety by a double bond. In some embodiments, L3 and L4 form the bicyclic linker group, L2-A2 and L5-A5 are absent and the dashed line in formula (I) represents a bond. Compounds of this embodiment may, for instance, be formed by oxidative dehydrogenation and / or rearrangement reaction of related compounds of formula (I). An illustrative example is given below for the Michael addition product of myrtenal and 1,3- cyclohexadione. A reaction pathway can be formulated in which the compound undergoes an oxidative dehydrogenation via a stable allylic tertiary carbo-radical, to yield an exocyclic double bond:

[0242]

[0243] This dehydrogenated compound may undergo a rearrangement to an endocyclic double bond, e.g. by a sequence of sigmatropic rearrangements of its ring-opened tautomer:

[0244]

[0245] In some embodiments, it may be particularly advantageous that the compound of any one of formulae (I) to (VIII) is also a compound of formulae (IX) or (X),

[0246]

[0247] or a tautomer and / or a pharmaceutically acceptable salt thereof; wherein R1, A1, A2, A3, A4, A6, A7, L2, L3, L4, and L7are defined as indicated above for formula (I) and are, in particular, defined as indicated in any of the further preceding embodiments; and wherein each instance of Lyrepresents independently from each other an ancillary linker group as indicated above for formula (VII), and, in particular, as defined as indicated in any of the preceding embodiments.

[0248] Compounds according to formula (IX) may be particularly beneficial since the cyclic structure of the cyclohexan-l,3-dione-derivative sterically constrains the ring-opened 1,5-dicarbonyl compound and, by allowing only the formation of the Z-enol, may facilitate ringclosure to the 3,4-saturated dihydropyran during synthesis, thus, shifting the overall equilibrium towards the product side. The compounds are generally available following the synthetical approach shown in Fig. 1 using a cyclohexan-l,3-dione-derivative as the Michael donor instead of the acetoacetate.

[0249] An exemplary synthetical approach is shown in Fig. 9 using a lawsone derivative as the Michael donor and benzylidene-camphor as the Michael acceptor. Compounds according to formula (X) may be particularly beneficial since the cyclic structure of the lawsone derivative sterically constrains the ring-opened 1,5-dicarbonyl compound and, by allowing only the formation of the Z-enol, may facilitate ring-closure to the 3,4-saturated dihydropyran during synthesis, thus, shifting the overall equilibrium towards the product side. This will be further facilitated by the extended conjugation of the 3,4-saturated dihydropyran with the lawsone moiety. Compounds according to formula (X) 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 indicator of the presence of residual active ingredient bound to the animal’s skin and / or fur.

[0250] In some embodiments, it may be particularly advantageous that L7 is absent and A7 represents hydrogen. Additionally or alternatively, in some embodiments, it may be particularly advantageous that R1represents hydrogen. Such substitution patterns will facilitate linking the 3,4-saturated 2H-pyran moiety to the substrate since both the initial ring-opening to the 1,5-dicarbonyl derivative as well as the formation of the 1,4-dihydropyridine moiety are facilitated.

[0251] Specific embodiments of the C1-C30 moiety in all aspects of the present disclosure

[0252] 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 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; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms.

[0253] 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-C30moiety is bound a) to the respective L1to L7via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or, b) if the respective L1to L7is 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-C30moiety is attached.

[0254] In some embodiments, it may be particularly advantageous that, again independently from each other, for each occurrence of the C1-C30moiety in the present disclosure, the C1-C30moiety is selected from a saturated or unsaturated, cyclic or acyclic (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 4, more specifically 0 to 3, and in particular 0 to 2 sulfur atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 phosphorous atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and, optionally, wherein the C1-C30moiety is bound a) to the respective L1to L7via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or, b) if the respective L1to L7is 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-C30moiety is attached.

[0255] In some embodiments, it may be particularly advantageous that, again independently from each other, for each occurrence of the C1-C30moiety in the present disclosure, the C1-C30moiety 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 atom; and 0 to 5, more specifically 0 to 4, and in particular 0 to 3 halogen atoms; and wherein the C1-C30moiety is bound a) to the respective L1to L7via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or, b) if the respective L1to L7is 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-C30moiety is attached.

[0256] Active ingredients of the present disclosure

[0257] 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 according to the present disclosure. It should be understood that this is to be interpretated as a reference to a moiety that is attached to the remainder of said compound, by e.g. elimination of a hydrogen atom from the active ingredient.

[0258] It should be further understood that the below disclosure regarding the active components is freely combinable with the above disclosure relating to the compounds the present disclosure. It should also be understood that the below disclosure of active ingredients also applies to the respective precursors thereof, unless expressly stated to the contrary.

[0259] In some embodiments, the active ingredient is 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. In some embodiments, it may be particularly advantageous that the active ingredient is a moisturizer, a skin moisturizer or a hair moisturizer.

[0260] The concrete structure and / or mass of the active ingredient or the precursor thereof is not particularly limited since the anchoring moieties are robustly linking to amino-functionalized substrates such as keratinous tissues such as skin and / or hair independently therefrom. In some embodiments, at least one of the one or more active ingredients or of the corresponding precursors thereof is a C1-C60moiety. In some embodiments, the C1-C60moiety 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 C1-C60moiety is a C10-C60moiety, a C15-C60moiety or a C20-C60moiety, all of which may optionally comprise the same aforementioned heteroatoms.

[0261] 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 as H, O, N and others may be contained in the polymeric moiety. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent either C1-C60 moieties or polymeric moieties. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent C1-C60 moieties. In some embodiments, all of the one or more active ingredients or of the corresponding precursors thereof represent polymeric moieties.

[0262] 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.

[0263] 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.

[0264] 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. 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.

[0265] 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.

[0266] In some embodiments, specifically those compounds of formula (I) capable of or 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.

[0267] In some embodiments, specifically those compounds of formula (I) capable of or 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.

[0268] The substituents Ai to A7, also in combination with their respective linker groups In some embodiments, L7-A7 represents hydrogen or the C1-C30 moiety. In some embodiments, L6-A6 represents hydrogen or the C1-C30 moiety. In some embodiments, L7-A7 represents hydrogen and L6-A6 represents the C1-C30 moiety. In some embodiments, L7-A7 represents the C1-C30 moiety and L6-A6 represents hydrogen. In some embodiments, L7-A7 represents the C1-C30 moiety and L6-A6 represents the C1-C30 moiety. It may be particularly advantageous, in some embodiments, that L7-A7 represents hydrogen and L6-A6 represents the C1-C30 moiety or that L7-A7 represents the C1-C30 moiety and L6-A6 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 L6-A6 represents the C1-C30 moiety.

[0269] 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.

[0270] 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.

[0271] In some embodiments, it may be particularly advantageous that, in the above formula (lib), L1-A1 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 (lib), it may further be particularly advantageous that L7-A7 represents hydrogen and L6-A6 represents the C1-C30 moiety or that L7-A7 represents the C1-C30 moiety and L6-A6 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 L6-A6 represents the C1-C30 moiety since this substitution pattern is conveniently synthetically accessible.

[0272] In some embodiments, in the above formula (lib), 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.

[0273] In some embodiments, 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.

[0274] 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, A3 represents the C1-C30 moiety, and A4 represents the C1-C30 moiety.

[0275] In some embodiments, A4 represents one of the one or more active ingredients or of the corresponding precursors thereof, and the compound is further provided with one of the following: i) A2 represents hydrogen and A3 represents hydrogen; ii) A2 represents the C1-C30 moiety and A3 represents hydrogen; iii) A2 represents hydrogen and A3 represents the C1-C30 moiety; or iv) A2 represents the C1-C30 moiety and A3 represents the C1-C30 moiety. In some embodiments, it may be particularly advantageous that L1-A1 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 side-products 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.

[0276] In some embodiments, 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.

[0277] In some embodiments, 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.

[0278] 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.

[0279] Humectants, Emollients, Occlusives In some embodiments, the active ingredient is a moisturizer, a skin moisturizer or a hair moisturizer.

[0280] 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:

[0281] 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;

[0282] 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;

[0283] a sugar, more specifically a triose, a tetrose, a pentose a hexose, a monosaccharide, a disaccharide, a trisaccharide, or an oligosaccharide;

[0284] 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

[0285] 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 C1-C4-alkylester thereof; or an amide thereof; or a water-soluble polymer is 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.

[0286] 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.

[0287] In some embodiments, the active ingredient is an emollient or an occlusive.

[0288] In some embodiments, the active ingredient comprises: a C10-C60 moiety, more specifically a C15-C60 moiety and in particular a C20-C60 moiety; or an oligo- or polysiloxane, in particular a poly(di-Ci-C4-alkyl)siloxane. In some embodiments, the active ingredient is the C1-C60 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 C15-C60 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 C1-C60 moiety is a sphingosine or a derivative thereof, in particular a ceramide or a sphingomyelin.

[0289] Pesticides

[0290] In some embodiments, the active ingredient is a pesticide.

[0291] 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.

[0292] 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.

[0293] 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.

[0294] Skin whitening agents

[0295] In some embodiments, the active ingredient is a skin whitening agent.

[0296] 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. 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-hydroxy-acids, in particular lactic and glycolic acid; and vitamin C.

[0297] Fragrances

[0298] In some embodiments, the active ingredient is the fragrance. It should be understood that the fragment is present in the form of its precursor. In some embodiments, 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. In some embodiments, the C1-C60 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 C1-C60 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.

[0299] Pharmaceuticals

[0300] In some embodiments, the active ingredient is a pharmaceutical.

[0301] 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.

[0302] 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. Cosmetic hair coating agents

[0303] In some embodiments, the active ingredient is a cosmetic hair coating agent.

[0304] 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.

[0305] 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.

[0306] 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.

[0307] 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 polycarboxylic acids or polycarboxylates, in particular a polyitaconate.

[0308] Accordingly, in some embodiments, the cosmetic hair coating agent may in particular be further characterized as follows:

[0309] 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.

[0310] In some embodiments, the cosmetic hair coating agent represents a C₁-C₆₀ moiety, in particular a C₁-C₆₀ 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.

[0311] 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 polyquaternium, in particular polyquaternium-16, polyquaternium-46, polyquaternium-11, polyquaternium-28, polyquaternium-6, polyquaternium-7, polyquaternium-22, polyquaternium-39, polyquaternium-2, polyquaternium-17, or polyquaternium-18. In some embodiments, the cosmetic hair coating agent is a polycarboxylic acid or a polycarboxylate, in particular a polyitaconate. In some embodiments, the cosmetic hair coating agent comprises a polyether, more specifically a poly-(C₁-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-C₁-C₄-alkyl)siloxane and derivatives thereof. In some embodiments, the cosmetic hair coating agent comprises a copolymer comprising polyether blocks and polysiloxane blocks.

[0312] Primers for attaching dyes to hair

[0313] 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.

[0314] 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. 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.

[0315] 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.

[0316] 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.

[0317] Accordingly, in some embodiments, in particular relating to uses of the compounds of the present disclosure for covalently binding the one or more active ingredients to hair, represents the active ingredient which is a primer for attaching dyes to the hair.

[0318] In some embodiments, the primer comprises one or more functional groups, in particular hydroxyl, 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.

[0319] 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.

[0320] 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.

[0321] 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.

[0322] In some embodiments, the primer is a C₁-C₆₀ moiety, in particular a C₁-C₆₀ 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.

[0323] 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.

[0324] 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.

[0325] In some embodiments, the dye precursor is selected from para-phenylenediamine and paraaminophenol. 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.

[0326] In some embodiments, the oxidizing agent is a peroxide, in particular hydrogen peroxide.

[0327] 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.

[0328] In some embodiments, the compound of the present disclosure 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.

[0329] UVA and / or UVB-absorbing moieties and color-imparting moieties

[0330] In some embodiments, the active ingredient is a color-imparting moiety or a UVA and / or UVB-absorbing moiety.

[0331] 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.

[0332] 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.

[0333] In some embodiments, the color-imparting 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.

[0334] In some embodiments, the UVA and / or UVB absorbing 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.

[0335] In some embodiments, at least one of A₁, A₂, A₃, A₄, A₅, A₆, and A₇ represents a chromophore (dye moiety), more specifically 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.

[0336] In some embodiments, the 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.

[0337] No or low color anchoring compound

[0338] The compounds of the present disclosure do not necessarily have to be colorless when bound to the substrate such as skin or hair. For instance, if the compounds are used to bind active ingredients to farm animals, color does not play a prominent role and may even be desirable. However, in particular in uses for humans, it may be beneficial that the compounds of the present disclosure, 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.

[0339] Accordingly, in some embodiments, the compound of the present disclosure, 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.

[0340] Suitable test conditions include a visual inspection, optionally by a test panel of 5 or 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 the present disclosure onto explanted porcine skin at a concentration of 1 μmol / in² (=0.156 μmol / cm²), followed by incubation at 25 °C and at 50% relative humidity for 24 hours. At the concentration of 1 μmol / in², hydrogenated genipin and oleuropein aglycone bind to skin without being visually perceivable whereas skin-bound genipin is still perceivable at about 0.07 μmol / in². For compounds of the present disclosure 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 (DOSY). Alternatively, for compounds of the present disclosure 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 the present disclosure 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.

[0341] Alternatively or additionally, a comparative test can be performed: The compound of the present disclosure can be considered to have bound to the skin and / or the hair as not observable to the human eye, if the compound of the present disclosure 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 or 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 μmol / in² (=0.780 μmol / cm² and 1.56 μmol / cm²), followed by incubation of each sample at 25 °C and at 50% relative humidity for 24 hours.

[0342] In some embodiments, the compound of the present disclosure, 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.

[0343] In some embodiments, the compound of the present disclosure, 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.

[0344] Specific embodiments of the C1-C30 moiety of the present disclosure

[0345] In any of the embodiments of the present disclosure, and independently from each other for each occurrence of the C1-C30 moiety, it may be 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; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms.

[0346] 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 bound a) to the respective L₁ to L₇ via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or, b) if the respective L₁ to L₇ is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of the ring to which the C₁-C₃₀ moiety is attached. In some 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, cyclic or acyclic (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 4, more specifically 0 to 3, and in particular 0 to 2 sulfur atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 phosphorous atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and, optionally, wherein the C1-C30 moiety is bound a) to the respective L₁ to L₇ via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or, b) if the respective L₁ to L₇ is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of the ring to which the C₁-C₃₀ moiety is attached.

[0347] In some 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 atom; 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 L₁ to L₇ via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or, b) if the respective L₁ to L₇ 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.

[0348] Topical Compositions

[0349] In a second aspect, the present disclosure provides a topical composition comprising a compound according to the first aspect, wherein the topical composition further comprises an excipient that is suitable for topical administration.

[0350] Any of the specific compounds disclosed above for the first aspect also represent specific embodiments according to this second aspect. The topical composition is not particularly limited and includes any such composition for topical administration. Topical administration in the sense of the present disclosure, specifically administration to skin and / or hair, in particular human skin and / or hair, 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 (mammalian and more specifically human) subject, including administration to skin appendages such as hair but excluding oral, rectal, intrapulmonary and intranasal administration.

[0351] As one form of topical composition, the present disclosure further pertains, in some embodiments, to cosmetic compositions.

[0352] In the present disclosure, 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 Regulation (EC) N° 1223 / 2009 of the European Union and / or with The Modernization of Cosmetics Regulation Act of 2022 of the USA.

[0353] 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).

[0354] 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.

[0355] 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.

[0356] 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 is liquid. In some embodiments, the excipient is a solid. In some embodiments, the excipient 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.

[0357] 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.

[0358] 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.

[0359] In some embodiments, the topical 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. 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.

[0360] In some embodiments, it may be particularly beneficial that the topical composition comprises a 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 anchor compounds into the deeper layers of the skin, thereby enhancing the attachment and long-lasting effect of the compounds of the present disclosure.

[0361] In some embodiments, the composition may also include a preservative; a thickening agent, more specifically a gelling agent, and in particular xanthan gum; a film-forming agent and / or a humectant.

[0362] As used herein, a “preservative” refers to an agent that protects the topical composition against decay, discoloration, and / or spoilage. Nonlimiting 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.

[0363] 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.

[0364] 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.

[0365] 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 / C12-22alkyl 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 poly glycol ester, VP / VA copolymer, polyester- 1, polyester-2, polyester-3, polyester-4, polyester-5, polyester-7, polyester-8, and polyester-10.

[0366] 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.

[0367] The topical compositions can be applied to the skin of the (mammalian, more specifically human) 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.

[0368] 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.

[0369] In some embodiments, the topical formulation comprising a compound of the first aspect is storage stable (i.e., the compound of first aspect 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.

[0370] In some embodiments, it may be particularly advantageous that the topical composition is not too “runny” in order to facilitate that the topical composition is retained locally on the substrate, more specifically skin or hair, 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.

[0371] 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.

[0372] In a third aspect, the present disclosure relates to the use of the compound or the topical composition according to the first and second aspect respectively for covalently binding a compound according to the first aspect to a substrate, more specifically keratinous tissue, and, in particular, to mammalian and more specifically human skin and / or hair. The third aspect further relates to a process of covalently binding a compound or the topical composition according to the first and second aspect respectively to a substrate, more specifically keratinous tissue, and, in particular, to (mammalian and more specifically human) skin and / or hair, the process comprising administering the compound or topical composition to the substrate.

[0373] Any of the specific compounds disclosed above for the first aspect also represent specific embodiments for the use according to this third aspect. Likewise, any of the specific topical compositions disclosed above for the second aspect also represent specific embodiments for the use according to this third aspect.

[0374] In some embodiments, the use is a cosmetic use. In some embodiments, the compound according to the first aspect does not comprise an active ingredient that is a pharmaceutical, or a corresponding precursor thereof. In some embodiments, the compound according to the first aspect comprises an active ingredient which is selected from the group consisting of: moisturizer, a pesticide, a fragrance, 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; or a corresponding precursor thereof. In a fourth aspect, the present disclosure provides the compounds and / or topical compositions disclosed herein for use in medicine, in particular for treating a skin-associated disease and / or a hair-associated disease. In some embodiments, said use includes topically administering the compound or composition to the skin of (mammalian, more specifically human) subject to be treated.

[0375] Any of the specific compounds disclosed above for the first aspect also represent specific embodiments for use according to this fourth aspect. Likewise, any of the specific topical compositions disclosed above for the second aspect also represent specific embodiments in this fourth aspect.

[0376] In a fifth aspect, the present disclosure provides a process for preparing a topical composition according to the second aspect, the process comprising providing a compound according to the first aspect of the present disclosure and mixing it with an excipient suitable for topical administration.

[0377] Any of the specific compounds disclosed above for the first aspect also represent specific embodiments for this fifth aspect. Likewise, any of the specific topical compositions, excipient and additives disclosed above for the second aspect also represent specific embodiments in this fifth aspect.

[0378] Methods of preparing the compounds of the present disclosure

[0379] The methods of preparing the compounds of the present disclosure are not particularly limited.

[0380] Particularly suitable are the syntheses disclosed in the detailed description and the figures. However, alternative approaches are readily available to the skilled person in view of the teaching of the present disclosure. Further Definitions

[0381] 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.

[0382] 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, Cs alkyl, and Ce alkyl.

[0383] 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 C1-4, Ci-6, and the like.

[0384] As used herein, the terms “Cn-Cmmoiety”, as it is used in e.g. C1-C30 moiety, C1-C16 moiety, Ci-Ceo moiety etc., refer 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.

[0385] 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 “Ci-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.

[0386] As used herein, the term “Cn-malkyl”, 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 moieties include, but are not limited to, chemical groups such as methyl, ethyl, «-propyl, isopropyl, «-butyl, / c / 7-butyl. isobutyl, sec-butyl; higher homologs such as 2-methyl-l -butyl, / 7-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.

[0387] As used herein, the term “Cn-macyl”, 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.

[0388] As used herein, the term “amino” refers to a group of formula -NH2.

[0389] As used herein, the term “halogen” refers in particular to F, Cl, Br and I.

[0390] 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.

[0391] 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.

[0392] As used herein, the term “tautomer” is attributed its ordinary meaning in the art and, in particular, comprises the corresponding ring-opened 1,5-dicarbonyls (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.

[0393] 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 paratoluenesulfonic 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, parabromophenylsulfonic 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, malonate, succinate, suberate, sebacate, fumarate, maleate, butyne- 1,4-dioate, hexyne-l,6-dioate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, hydroxybenzoate, methoxybenzoate, phthalate, terephthalate, sulfonate, xylene sulfonate, phenyl acetate, phenylpropionate, phenylbutyrate, citrate, lactate, f>-hydroxybutyrate, glycolate, maleate, tartrate, methanesulfonate, propanesulfonate, naphthal ene-1 -sulfonate, naphthalene-2- sulfonate, mandelate and other salts. In one embodiment, pharmaceutically acceptable acid addition salts include those formed with mineral acids such as hydrochloric acid 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; triethylamine; 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.

[0394] 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.

[0395] 3rd Ed., John Wiley & Sons, New York, N. Y, 1999, which is incorporated herein by reference in its entirety).

[0396] 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.

[0397] Methods of preparing the compounds of the present disclosure The methods of preparing the compounds of the present disclosure are not particularly limited.

[0398] Particularly suitable are the syntheses disclosed in the detailed description and the figures. However, alternative approaches are readily available to the skilled person in view of the teaching of the present disclosure.

[0399] OTHER EMBODIMENTS

[0400] 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.

[0401] The present disclosure also relates to the following embodiments which are supplementary to and freely combinable with the above specification:

[0402] 1. A compound of formula (I) comprising a 3,4-saturated 2H-pyran moiety,

[0403]

[0404] or a tautomer and / or a pharmaceutically acceptable salt thereof,

[0405] for covalently binding to a substrate comprising amino groups, in particular skin and / or hair;

[0406] 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 an amino group 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

[0407] wherein the compound of formula (I) comprises one or more active ingredients, 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, a UVA- and / or UVB-absorbing moiety, a color-imparting moiety, a cosmetic hair coating agent, and a primer for attaching dyes to hair;

[0408] wherein the one or more active ingredients are present, independently from each other, a) as the active ingredient, or

[0409] b) as a precursor moiety of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor moiety after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor moiety thereof’); and

[0410] c) wherein one of Ai, A2, A3, A4, As, As and A7 represents said active ingredient or the corresponding precursor moiety thereof;

[0411] wherein the dashed line is absent or wherein the dashed line represents a bond and L2-A2 and L5-A5 are absent;

[0412] wherein Li, L2, L3, L4, Ls, Ls and L7 are, independently from each other, absent or represent a linker group with the further proviso that

[0413] i) one vicinal pair amongst Li, L2, L3, L4, Ls, Ls and L7 forms an optionally substituted bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety, wherein the corresponding two moi eties amongst Ai, A2, A3, A4, As, As and A7 are connected to said bicyclic linker group;

[0414] ii) optionally one or two further vicinal pairs amongst Li, L2, L3, L4, Ls, Ls and L7 form an optionally substituted further cyclic linker group which is different from said bicyclic linker group and which is ortho-fused to the 3,4-saturated 2H- pyran moiety, wherein the corresponding two moieties amongst Ai, A2, A3, A4, As, As and A 7 are connected to said further cyclic linker group;

[0415] wherein each of Ai, A2, A3, A4, As, As and A7 not representing an active ingredient or a corresponding precursor moiety thereof is defined as follows:

[0416] A1, A4 and A5 represent, independently from each other, hydrogen, a C1-C30 moiety, hydroxyl, or a halogen; A2 and A3 are, independently from each other, defined as indicated for A1, or L2-A2 and L3-A3 jointly represent oxo;

[0417] As and A7 represent, independently from each other, hydrogen or a C1-C30 moiety; and

[0418] wherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

[0419] The compound according to embodiment 1, wherein each occurrence of the C1-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; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and / or wherein

[0420] the C1-C30 moiety is bound

[0421] a) to the respective Li to L7 via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or,

[0422] b) if the respective Li to L7 is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of 3,4-saturated 2H-pyran moiety to which the C1-C30 moiety is attached.

[0423] The compound according to embodiment 2, wherein each occurrence of the C1-C30 moiety is, independently from each other, selected from a saturated or unsaturated, cyclic or acyclic (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 4, more specifically 0 to 3, and in particular 0 to 2 sulfur atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 phosphorous atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms; and, optionally, wherein the C1-C30 moiety is bound: a) to the respective Li to L7 via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or,

[0424] b) if the respective Li to L7 is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of 3,4-saturated 2H-pyran moiety to which the C1-C30 moiety is attached.

[0425] The compound according to embodiment 3, 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 in particular 0 to 2 nitrogen atoms; 0 or 1 sulfur atom; and 0 to 5, maore specifically 0 to 4, and in particular 0 to 3 halogen atoms; and wherein the C1-C30 moiety is bound

[0426] a) to the respective Li to L7 via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom, or,

[0427] b) if the respective Li to L7 is absent, via a carbon atom, an oxygen atom, a nitrogen atom or a sulfur atom to the carbon atom of 3,4-saturated 2H-pyran moiety to which the C1-C30 moiety is attached.

[0428] The compound according to any preceding embodiment, wherein:

[0429] both Lg and L7 are absent and As and A7 represent hydrogen; or

[0430] Lg is absent and As represents hydrogen; or

[0431] L7 is absent and A7 represents hydrogen.

[0432] The compound according to any preceding embodiment, wherein Li to L7 are defined as follows:

[0433] 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

[0434] 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 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

[0435] 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

[0436] L5 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

[0437] Lg 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

[0438] 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.

[0439] The compound according to embodiment 6, wherein, independently from each other, each of the optionally substituted hydrocarbon moieties L1to L7comprises, together with its optional substituents, less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms.

[0440] The compound according to any one of embodiments 1 to 7, wherein the compound of formula (I) is a compound of formula (Ila) or of formula (lib),

[0441]

[0442] (lib)

[0443] or a tautomer and / or a pharmaceutically acceptable salt thereof;

[0444] wherein R1, Ai, A2, A3, A4, As, Ag, A7, Li, L2, L3, L4, Ls, Lg, and L7 are defined as in any preceding embodiment.

[0445] The compound according to any one of embodiments 1 to 8, wherein:

[0446] Lg is absent and As represents hydrogen;

[0447] L? is absent and A7 represents hydrogen; or

[0448] Lg is absent and As represents hydrogen and L7 is absent and A7 represents hydrogen.

[0449] The compound according to any one of embodiments 1 to 9, wherein the combined substituent L1-A1 does not represent hydrogen.

[0450] The compound according to any one of embodiments 1 to 10, wherein R1represents hydrogen; 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 tert- butyldimethylsilyl; and in particular hydrogen;

[0451] or

[0452] wherein the compound is suitable for covalently binding to skin and / or hair and R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the skin and / or hair.

[0453] The compound according to any one of embodiments 1 to 11, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety comprises: a) a bridged linker ring, in particular an optionally substituted 5-membered, 6- membered or 7-membered ring with a bridge consisting of one or two bridging atoms; or

[0454] b) a cis-ortho-fused bicyclic linker group comprising a first ring and a second ring, wherein the first ring is ortho-fused to the 3,4-saturated 2H-pyran moiety and the second ring is cis -ortho -fused to the first ring, in particular a cis-ortho-fused bicyclic linker group comprising an optionally substituted 5-membered or 6- membered first ring and an optionally substituted 4-membered, 5-membered or 6- membered second ring.

[0455] The compound according to embodiment 12, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is the bridged linker ring, more specifically a bridged linker ring wherein:

[0456] the ring of the bridged linker ring which is ortho-fused to the 3,4-saturated 2H- pyran moiety is an optionally substituted 5-membered, 6-membered or 7- membered carbocycle or an optionally substituted 5 -membered, 6-membered or 7- membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O, N and S;

[0457] more specifically an optionally substituted saturated or unsaturated 5- membered, 6-membered or 7-membered carbocycle or an optionally substituted saturated or unsaturated 5-membered, 6-membered or 7- membered heterocycle comprising one or two heteroatoms which are, independently from each other, selected from O and N; and, in particular, a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted cycloheptane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyrane; or a saturated or unsaturated and optionally substituted morpholine; and / or

[0458] wherein the bridge of the bridged linker ring consists of one or two bridging atoms which are, independently from each other, selected from C, N, O and S, more specifically from C, N and O, and in particular from C and N; more specifically wherein the bridge is an optionally substituted methylene bridge, an optionally substituted ethylene bridge, an oxa-bridge, a thia-bridge or an optionally substituted aza-bridge.

[0459] The compound according to embodiment 12 or 13, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is a bridged linker ring comprising

[0460] a) an optionally substituted saturated or mono-unsaturated 5-membered, 6- membered or 7-membered carbocycle, or

[0461] b) an optionally substituted saturated or mono-unsaturated 5-membered, 6- membered or 7-membered heterocycle comprising one or two heteroatoms selected from N or O, and in particular N; and

[0462] having a bridge consisting of one or two bridging atoms selected from C, O and N.

[0463] The compound according to any one of embodiments 12 to 14, wherein the bridged linker ring is represented by one of the following moieties,

[0464]

[0465] wherein the broken bonds indicate the attachment of the bridged linker ring to the 3,4-saturated 2H-pyran moiety;

[0466] wherein the dashed bond between the broken bonds represents a double bond in case the bridged linker ring is formed by Li and Le or in case the bridged linker ring is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein X1 represents a moiety selected from CH2, C(CH3)2, NH, NR, O and S;

[0467] X2 represents a moiety selected from CH2, C(CH3)2, and NH; wherein R represents a C1-C30 moiety, the active ingredient, or a precursor thereof, or an ancillary linker group connecting the active ingredient, or the precursor thereof, to the nitrogen atom; and

[0468] wherein each ring atom of the bridged linker ring may optionally be further substituted.

[0469] The compound according to any embodiment 15, wherein Xi represents a moiety selected from CH2, C(CHs)2, NH and NR; X2 represents a moiety selected from CH2 and C(CH3)2; wherein R represents a C1-C30 moiety, the active ingredient, or a precursor thereof, or an ancillary linker group connecting the active ingredient, or the precursor thereof, to the nitrogen atom; and in particular wherein X1 represents a moiety selected from CH2 and C(CH3)2 and wherein X2 represents a moiety selected from CH2 and C(CH3)2.

[0470] The compound according to embodiment 12, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is the cis-ortho-fused bicyclic linker group, more specifically a cis-ortho-fused bicyclic linker group wherein:

[0471] the first ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is an optionally substituted 5 -membered, 6-membered or 7-membered carbocycle or an optionally substituted 5 -membered, 6-membered or 7-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O, N and S;

[0472] more specifically an optionally substituted saturated or unsaturated 5- membered, 6-membered or 7-membered carbocycle or a saturated or an optionally substituted unsaturated 5-membered, 6-membered or 7-membered heterocycle comprising one or two heteroatoms which are, independently from each other, selected from O and N; and, in particular,

[0473] a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted cycloheptane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyrane; or a saturated or unsaturated and optionally substituted morpholine; and

[0474] the second ring which is cis-ortho-fused to the first ring is an optionally substituted 4-membered, 5-membered or 6-membered carbocycle or an optionally substituted 4-membered, 5-membered or 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O, N and S; more specifically

[0475] an optionally substituted saturated or unsaturated 5-membered or 6-membered carbocycle or an optionally substituted saturated or unsaturated 5 -membered or 6-membered heterocycle comprising one or two heteroatoms which are, independently from each other, selected from O and N; and, in particular, a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyrane; or a saturated or unsaturated and optionally substituted morpholine.

[0476] The compound according to embodiment 12 or 17, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is a cis-ortho-fused bicyclic linker group wherein:

[0477] a) the first ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is an optionally substituted saturated or mono-unsaturated 5-membered or 6- membered carbocycle or an optionally substituted saturated or monounsaturated 5-membered or 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O and N; and

[0478] b) the second ring which is cis-ortho-fused to the first ring is an optionally substituted saturated or mono-unsaturated 5-membered or 6-membered carbocycle or an optionally substituted saturated or mono-unsaturated 5- membered or 6-membered heterocycle comprising one or more heteroatoms which are, independently from each other, selected from O and N. The compound according to any one of embodiments 12, 17 and 18, wherein the cis-ortho-fused bicyclic linker group is represented by one of the following moieties,

[0479]

[0480] wherein the broken bonds indicate the attachment of the cis-ortho-fused bicyclic linker group to the 3,4-saturated 2H-pyran moiety;

[0481] wherein the dashed bond between the broken bonds represents a double bond in case the cis-ortho-fused bicyclic linker group is formed by L1 and L6 or in case the cis-ortho-fused bicyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; and

[0482] wherein each ring atom of the cis-ortho-fused bicyclic linker group may optionally be further substituted.

[0483] The compound according to any of embodiments 1 to 19, wherein L3 and L4 form the bicyclic linker group; more specifically

[0484] wherein L3 and L4 form the bicyclic linker group and wherein L6 is absent and A6 represents hydrogen and / or L7 is absent and A7 represents hydrogen; and in particular wherein L3 and L4 form the bicyclic linker group, wherein L6 is absent and A6 represents hydrogen and / or L7 is absent and A7 represents hydrogen, and the combined substituent L1-A1 does not represent hydrogen. The compound according to any of embodiments 1 to 19, wherein L4 and L7 form the bicyclic linker group; more specifically

[0485] wherein L4 and L7 form the bicyclic linker group and wherein the combined substituent L1-A1 does not represent hydrogen; and in particular

[0486] wherein L4 and L7 form the bicyclic linker group, wherein the combined substituent Li-Ai comprises a carbonyl group which is attached to the 3,4-saturated 2H-pyran moiety.

[0487] The compound according to any of embodiments 1 to 19, wherein L2 and L3 jointly represent oxo and L4 and L7 form the bicyclic linker group; more specifically wherein L2 and L3 jointly represent oxo, L4 and L7 form the bicyclic linker group and wherein L6 is absent and A6 represents hydrogen; and in particular wherein L4 and L7 form the bicyclic linker group, wherein L6 is absent and A6 represents hydrogen, and the combined substituent L1-A1 does not represent hydrogen.

[0488] The compound according to any preceding embodiment, wherein the bicyclic linker group, together with its optional substituents and its optional ancillary linker groups but excluding the two carbon atoms shared with the 3,4-saturated 2H-pyran moiety, comprises less than 30, more specifically less than 24, and in particular less than 16 carbon atoms; less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms.

[0489] The compound according to any preceding embodiment, wherein the compound comprises a further cyclic linker group.

[0490] The compound according to embodiment 24, wherein the further cyclic linker group is a monocyclic linker group selected from the group consisting of:

[0491] an optionally substituted monocyclic carbocycle; and an optionally substituted monocyclic heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; more specifically wherein the further cyclic linker group is a monocyclic linker group selected from the group consisting of:

[0492] an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered carbocycle;

[0493] an optionally substituted monocyclic aromatic 5- or 6-membered carbocycle; an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; and

[0494] an optionally substituted monocyclic 5- or 6-membered heteroaromatic comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; and,

[0495] in particular, wherein the further cyclic linker group is a monocyclic linker group selected from the group consisting of:

[0496] an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered carbocycle; and

[0497] an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S.

[0498] The compound according to embodiment 25, wherein the further cyclic linker group is a monocyclic linker group selected from the group consisting of: a saturated or unsaturated and optionally substituted cyclopentane; a saturated or unsaturated and optionally substituted cyclohexane; a saturated or unsaturated and optionally substituted pyrrolidine; a saturated or unsaturated and optionally substituted tetrahydrofuran; a saturated or unsaturated and optionally substituted piperidine; a saturated or unsaturated and optionally substituted tetrahydropyrane; or a saturated or unsaturated and optionally substituted morpholine.

[0499] The compound according to any one of embodiments 24 to 26, wherein the further cyclic linker group is represented by one of the following moieties,

[0500]

[0501] wherein the broken bonds indicate the attachment of the further cyclic linker group to the 3,4-saturated 2H-pyran moiety;

[0502] wherein the dashed bond between the broken bonds represents a double bond in case the further cyclic linker group is formed by L1 and L6 or in case the further cyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein the remainder of the dashed bonds represents a single bond or a double bond; wherein X1 represents a moiety selected from CH2, NH, O and S; wherein X2 represents a moiety selected from CH2, NH, O and S in case the dashed bond represents a single bond, and selected from CH and N in case the dashed bond represents a double bond; and

[0503] wherein each ring atom of the further cyclic linker group may optionally be further substituted.

[0504] The compound according to embodiment 24 or embodiment 27 (when referring back to embodiment 24), wherein the further cyclic linker group is a polycyclic linker group comprising two or more, more specifically two, three, four, or five, and in particular two, three or four, (hetero)cycles which are, independently from each other, selected from the group consisting of:

[0505] an optionally substituted carbocycle; and

[0506] an optionally substituted heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S;

[0507] more specifically wherein the further cyclic linker group is a polycyclic linker group comprising two, three or four (hetero)cycles which are, independently from each other, selected from the group consisting of:

[0508] an optionally substituted saturated or unsaturated 5- or 6-membered carbocycle; an optionally substituted aromatic 5- or 6-membered carbocycle; an optionally substituted saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; and

[0509] an optionally substituted 5- or 6-membered heteroaromatic comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S; and,

[0510] in particular, wherein the further cyclic linker group is a polycyclic linker group comprising two, three or four (hetero)cycles which are, independently from each other, selected from the group consisting of:

[0511] an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered carbocycle; and

[0512] an optionally substituted monocyclic saturated or unsaturated 5- or 6-membered heterocycle comprising one, two or three heteroatoms which are, independently from each other, selected from O, N and S.

[0513] The compound according to any one of embodiments 24 to 28, wherein the further cyclic linker group is substituted by at least one oxo group, in particular by at least one oxo group which is present on a carbon atom which is in alpha-position to one of the carbon atoms of the 3,4-saturated 2H-pyran moiety.

[0514] The compound according to any one of embodiments 24 to 29, wherein

[0515] the further cyclic linker group is formed by Li and Lg and is substituted by at least one oxo group which is present on a carbon atom which is in alpha-position to the carbon atom to which L1 is attached or in alpha-position to the carbon atom to which L6 is attached;

[0516] the further cyclic linker group is formed by Li and Lg and is substituted by at least two oxo groups, one of which is present on a carbon atom which is in alpha- position to the carbon atom to which Li is attached and the other one of which is present on a carbon atom which is in alpha-position to the carbon atom to which Lg is attached;

[0517] the further cyclic linker group is formed by Ls and L? and is substituted by at least one oxo group which is present on a carbon atom which is in alpha-position to the carbon atom to which Ls is attached or in alpha-position to the carbon atom to which L? is attached; or

[0518] the further cyclic linker group is formed by L5 and L7 and is substituted by at least two oxo groups, one of which is present on a carbon atom which is in alpha- position to the carbon atom to which L5 is attached and the other one of which is present on a carbon atom which is in alpha-position to the carbon atom to which L7 is attached.

[0519] The compound according to any one of embodiments 24 to 30, wherein, after the compound of formula (I) has covalently bound to the substrate converting the 3,4-saturated 2H-pyran moiety to a dihydropyridine or pyridinium moiety, the further cyclic linker group and the dihydropyridine or pyridinium moiety form a conjugated π-electron system.

[0520] The compound according to any one of embodiments 24 to 31, wherein the further cyclic linker group is represented by one of the following moieties,

[0521]

[0522] wherein the broken bonds indicate the attachment of said moiety to the 3,4-saturated 2H-pyran moiety;

[0523] wherein the dashed bond between the broken bonds represents a double bond in case the further cyclic linker group is formed by L1 and L6 or in case the further cyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein the remainder of the dashed bonds represents a single bond or a double bond; and wherein each ring atom of said moiety may optionally be further substituted.

[0524] The compound according to any one of embodiments 1 to 32, wherein, independently from each other, the moieties amongst Ai, A2, A3, A4, As, Ar, and A7 which are corresponding to those linker groups amongst Li, L2, L3, L4, Ls, Lg and L7 which are forming the bicyclic linker group and the optional further cyclic linker group are a) attached to their respective (bi)cyclic linker group by a bond, or

[0525] b) are connected to their respective (bi)cyclic linker group by an ancillary linker group.

[0526] The compound according to any of embodiments 1 to 33, wherein, independently from each other, each instance of the ancillary linker group comprises 1 to 12, more specifically 1 to 10, 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 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 6, more specifically 0 to 4, and in particular 0 to 3 boron atoms; and 0 to 10, more specifically 0 to 8, and in particular 0 to 6 halogen atoms.

[0527] The compound according to embodiment 34, wherein the ancillary linker group is selected from the group consisting of: -O-, -S-, -C(O)-, -CO2-, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, -(CH2)1-4-, -(CH2)1-4-O- and -O-(CH2)1-4-, or combinations thereof.

[0528] The compound according to any preceding embodiment, wherein a) the bicyclic linker group, together with its optional substituent(s) and its optional ancillary linker group(s), and

[0529] b) the optional further cyclic linker group(s), together with its(their) optional substituent(s) and its(their) optional ancillary linker group(s),

[0530] each comprise, independently from each other and excluding the two carbon atoms shared with the 3,4-saturated 2H-pyran moiety:

[0531] less than 30, more specifically less than 24, and in particular less than 16 carbon atoms;

[0532] less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms;

[0533] less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms;

[0534] less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms;

[0535] less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms;

[0536] less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and

[0537] less than 10, more specifically less than 8, and in particular less than 6 halogen atoms;

[0538] or, alternatively:

[0539] between 3 and 29, more specifically between 4 and 23, and in particular between 5 and 15 carbon atoms;

[0540] between 0 and 11, more specifically between 0 and 7, and in particular between 0 and 5 oxygen atoms;

[0541] between 0 and 7, more specifically between 0 and 5, and in particular between 0 and 3 nitrogen atoms;

[0542] between 0 and 5, more specifically between 0 and 3, and in particular between 0 and 2 sulfur atoms;

[0543] between 0 and 5, more specifically between 0 and 3, and in particular between 0 and 2 phosphor atoms;

[0544] between 0 and 5, more specifically between 0 and 3, and in particular between 0 and 2 boron atoms; and between 0 and 9, more specifically between 0 and 7, and in particular between 0 and 6 halogen atoms.

[0545] The compound according to any one of embodiments 1 to 36, wherein the compound of formula (I) is a compound of formula (III),

[0546]

[0547] or a tautomer and / or a pharmaceutically acceptable salt thereof;

[0548] wherein R1, A1, A2, A3, A4, A6, A7, L2, L3, L4, L6, and L7 are defined as indicated in any preceding embodiment;

[0549] X represents O or S, and in particular O; and

[0550] Lxis absent or represents -O-, -S-, -NH-, or 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 10 carbon atoms, 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 sulfur atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 phosphorous atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms; and the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfur atom.

[0551] The compound according to embodiment 37, wherein the substituent combination -C(=X)-Lx-Ai represents 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:

[0552] -COOH or a salt thereof; -COORa, -C(O)-Ra,

[0553] -C(O)-NH2, -C(O)NHRa, -C(O)NRa2,

[0554] wherein Ra represents a moiety comprising 1 to 16 carbon atoms, and optionally one or more of: 1 to 8 oxygen atoms, 1 to 6 nitrogen atoms, 1 to 3 sulfur atoms, 1 or 2 phosphorous atoms, 1 or 2 boron 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, 1 or 2 phosphorous atoms, 1 or 2 boron atoms, and 1 to 3 halogen atoms,

[0555] 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.

[0556] The compound according to embodiment 38, wherein -C(=X)-Lx-Ai represents -COORa as defined in embodiment 38; more specifically -COORa, wherein Ra represents a hydrocarbon moiety comprising 1 to 8 carbon atoms, and optionally one or more of: 1 to 4 oxygen atoms, 1 to 4 nitrogen atoms, 1 or 2 sulfur atoms, 1 or 2 phosphorous atoms, 1 or 2 boron atoms, and 1 to 3 halogen atoms; and in particular -COORa, wherein Ra represents Ci-C4-alkyl, such as methyl or ethyl.

[0557] The compound according to any one of embodiments 1 to 39, wherein the compound of formula (I) is a compound of formula (IV),

[0558] / A1

[0559]

[0560] or a tautomer and / or a pharmaceutically acceptable salt thereof; and wherein R1, Ai, Ag, A7, Li, Ls, and L7 are defined as indicated in any preceding embodiment.

[0561] The compound according to embodiment 40, wherein L7 is absent and A7 represents hydrogen.

[0562] The compound according to embodiment 40 or 41, wherein R1represents hydrogen.

[0563] The compound according to any one of embodiments 1 to 39, wherein the compound of formula (I) is a compound of formula (V),

[0564]

[0565] or a tautomer and / or a pharmaceutically acceptable salt thereof; and

[0566] wherein R1, Ai, As, A7, Lx, X, Lg, and L7 are defined as indicated in any preceding embodiment.

[0567] The compound according to embodiment 43, wherein L7 is absent and A7 represents hydrogen.

[0568] The compound according to embodiment 43 or 44, wherein R1represents hydrogen.

[0569] The compound according to any one of embodiments 1 to 39, wherein the compound of formula (I) is a compound of formula (V),

[0570]

[0571] or a tautomer and / or a pharmaceutically acceptable salt thereof; and

[0572] wherein R1, Ai, As, A7, Lx, X, Lg, and L7 are defined as indicated in any preceding embodiment.

[0573] The compound according to embodiment 46, wherein L7 is absent and A7 represents hydrogen; and / or wherein R1represents hydrogen.

[0574] The compound according to any one of embodiments 1 to 39, wherein the compound of formula (I) is a compound of formula (VI),

[0575]

[0576] or a tautomer and / or a pharmaceutically acceptable salt thereof; and

[0577] wherein R1, Ai, A2, A3, As, Li, L2, L3, and Ls are defined as indicated in any preceding embodiment.

[0578] The compound according to embodiment 48, wherein Ls is absent and As represents hydrogen.

[0579] The compound according to embodiment 48 or 49, wherein R1represents hydrogen. The compound according to any one of embodiments 48 to 50, wherein the substituent combination Li-Ai represents the substituent combination C(=X)-Lx-Ai as defined in any one of embodiments 37 to 39.

[0580] The compound according to any one of embodiments 1 to 39, wherein the compound of formula (I) is a compound of formula (VII),

[0581]

[0582] or a tautomer and / or a pharmaceutically acceptable salt thereof;

[0583] wherein R1, Ai, A2, A3, A4, As, Li, L2, L3, and Lg are defined as indicated in any preceding embodiment; and

[0584] wherein Lyrepresents an ancillary linker group.

[0585] The compound according to embodiment 52, wherein Lg is absent and As represents hydrogen.

[0586] The compound according to embodiment 52 or 53, wherein R1represents hydrogen.

[0587] The compound according to any one of embodiments 52 to 54, wherein the substituent combination L1-A1 represents the substituent combination C(=X)-Lx-Ai as defined in any one of embodiments 37 to 39.

[0588] The compound according to any one of embodiments 52 to 55, wherein L2 is absent and A2 represents hydrogen and wherein L3 is absent and A3 represents phenyl or a phenyl which, in combination with its optional substituents, comprises 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 4, more specifically 0 to 3, and in particular 0 to 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; and in particular phenyl or phenyl mono- or disubstituted with (a) hydroxyl group(s).

[0589] The compound according to any one of embodiments 52 to 56, wherein Lyrepresents an ancillary linker group which comprises, together with its optional substituents, less than 12, more specifically less than 8, and in particular less than 6 carbon atoms; less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than 3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms.

[0590] The compound according to any one of embodiments 52 to 57, wherein Lvrepresents an ancillary linker group which comprises, together with its optional substituents, between 1 and 6 carbon atoms; between 1 and 4 oxygen atoms; between 1 and 3 nitrogen atoms; between 1 and 3 sulfur atoms; and between 1 and 6 halogen atoms.

[0591] The compound according to embodiment 57 or embodiment 58, wherein Lyrepresents an ancillary linker group which is selected from the group consisting of: -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.

[0592] The compound according to any one of embodiments 1 to 39, wherein the compound of formula (I) is a compound of formula (VIII),

[0593]

[0594] or a tautomer and / or a pharmaceutically acceptable salt thereof;

[0595] wherein R1, Ai, A2, A3, As, Li, L2, L3, and Lg are defined as indicated in any preceding embodiment.

[0596] The compound according to embodiment 60, wherein Lg is absent and As represents hydrogen.

[0597] The compound according to embodiment 60 or 61, wherein R1represents hydrogen.

[0598] The compound according to any one of embodiments 60 to 62, wherein the substituent combination L1-A1 represents the substituent combination C(=X)-Lx-Ai as defined in any one of embodiments 37 to 39.

[0599] The compound according to any one of embodiments 60 to 63, wherein L2 and L3 are absent and A2 and A3 both represent hydrogen.

[0600] The compound according to any one of embodiments 60 to 63, wherein L2 and L3 jointly represent oxo.

[0601] The compound according to any one of embodiments 1 to 65, wherein the compound of any one of formulae (I) to (VIII) is also a compound of formulae (IX) or (X),

[0602]

[0603] or a tautomer and / or a pharmaceutically acceptable salt thereof;

[0604] wherein R1, Ai, A2, A3, A4, Ag, A7, L2, L3, L4, and L7 are defined as indicated in any preceding embodiment; and wherein each instance of Lyrepresents, independently from each other, an ancillary linker group, in particular as defined in any of embodiments 57 and 58.

[0605] The compound according to any one of embodiments 1 to 66, wherein the compound of formula (I) comprises one or more active ingredients and / or one or more precursor moieties corresponding to an active ingredient.

[0606] The compound according to any one of embodiments 1 to 67, 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 an amino group comprised by keratinous tissue, more specifically skin and / or hair, and in particular human skin and / or human hair.

[0607] The compound according to embodiment 67 or embodiment 68, wherein at least one, and in particular all, of the one or more active ingredients (or the corresponding precursor moieties thereof), are, independently from each other, 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.

[0608] The compound according to according to any one of embodiments 1 to 69, 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.

[0609] The compound according to any one of embodiments 1 to 70, wherein the compound of formula (I) comprises:

[0610] 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;

[0611] 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;

[0612] in total, two of the active ingredients and none of the precursors;

[0613] in total, one of the active ingredients and one of the precursors; or

[0614] in total, two of the precursors and none of the active ingredients;

[0615] and in particular:

[0616] 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

[0617] 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.

[0618] The compound according to any one of embodiments 1 to 71, wherein the compound is capable of 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.

[0619] The compound according to any one of the embodiments 1 to 71, wherein the compound is capable of 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.

[0620] The compound according to any one of the preceding embodiments, wherein L7-A7 represents hydrogen or the C1-C30 moiety or wherein Lg-Ag represents hydrogen or the C1-C30 moiety. The compound according to any one of the preceding embodiments, wherein L7-A7 represents hydrogen and Lg-Ag represents the C1-C30 moiety.

[0621] The compound according to any one of embodiments! to 74, wherein L7-A7 represents the C1-C30 moiety and Lg-Ag represents hydrogen.

[0622] The compound according to any one of embodiments 1 to 74, wherein L7-A7 represents the C1-C30 moiety and Lg-Ag represents the C1-C30 moiety.

[0623] The compound according to any one of the preceding embodiments, 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.

[0624] The compound according to any one of the preceding embodiments, wherein at least one of A2, A3 and A4 represents one of the one or more active ingredients or of the corresponding precursors thereof.

[0625] The compound according to any one of the preceding embodiments, 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.

[0626] The compound according to embodiment 80, 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: - 1 to 12 carbon atoms, more specifically 1 to 8 carbon atoms, and in particular 1 to 4 carbon atoms;

[0627] - 1 to 4 oxygen atoms, more specifically 1 to 3 oxygen atoms, and in particular 1 or 2 oxygen atoms;

[0628] - 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;

[0629] - 1 to 3 phosphorus atoms, more specifically 1 or 2 phosphorus atoms, and in particular 1 phosphorus atom

[0630] - 1 or 2 boron atoms, and in particular 1 boron atom.

[0631] The compound according to any one of the embodiments 80 and 81, wherein, when the compound of formula (I) has bound to the skin and / or the hair, the functional group is: (i) biostable; or

[0632] (ii) cleavable,

[0633] more specifically cleavable under physiological conditions encountered after its application to the skin and / or the hair, and / or

[0634] 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.

[0635] The compound according to any one of embodiments 80 to 82, 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.

[0636] The compound according to any one of embodiments 80 to 83, wherein 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.

[0637] The compound according to any one of embodiments 80 to 84, 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.

[0638] The compound according to any one of embodiments 80 to 85, 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.

[0639] The compound according to embodiment 86, wherein, after cleavage of the functional group:

[0640] 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 / or

[0641] 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).

[0642] The compound according to any one of embodiments 80 to 87, wherein the functional group comprises a carbon ester, in particular a monoester, 1,1 -di ester, 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 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.

[0643] A topical composition comprising a compound as defined in in any one of embodiments 1 to 88 and an excipient that is suitable for topical administration. The topical composition embodiment 89, wherein the topical composition has a dynamic viscosity of more than 2 mPa·s, more specifically more than 10 mPa·s, and in particular more than 50 mPa·s; or 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; wherein the dynamic viscosity is measured at 37°C according to 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.

[0644] The topical composition of embodiment 89 or 90 wherein the topical composition comprises trehalose.

[0645] The topical composition of any one of embodiments 89 to 91, wherein the topical composition is present in the form of a patch or in the form of an ink comprised in a pen-like applicator.

[0646] A process for preparing a topical composition according to any one of embodiments 89 to 92, the process comprising providing a compound as defined in any one of embodiments 1 to 88 and mixing it with an excipient suitable for topical administration.

[0647] Use of a compound according to any one of embodiments 1 to 88, in medicine, more specifically for treating a skin-associated disease and / or a hair-associated disease; in particular wherein the compound is administered topically to skin and / or hair.

[0648] Use of a compound according to any one of embodiments 1 to 88 or a topical composition according to any one of embodiments 89 to 92 for covalently binding said compound to a substrate comprising amino groups, more specifically keratinous tissue, and, in particular, to mammalian and more specifically human skin and / or hair.

[0649] A process of covalently binding a compound according to any one of embodiments 1 to 88 or a topical composition according to any one of embodiments 89 to 92 to a substrate comprising amino groups, more specifically keratinous tissue, and, in particular, to (mammalian and more specifically human) skin and / or hair, the process comprising administering the compound or topical composition to the substrate.

Claims

CLAIMS1. 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 skin and / or 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 an amino group comprised by the substrate;wherein the compound of formula (I), after having covalently bound to the substrate, is providing color to the substrate; and / orwherein the compound of formula (I) comprises one or more active ingredients, 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, a 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 one or more active ingredients are present, independently from each other, a) as the active ingredient, orb) as a precursor moiety of the active ingredient, wherein the compound of formula (I) is cleavable to release the active ingredient from the precursor moiety after the application of the compound of formula (I) to the substrate (in the following: “the corresponding precursor moiety thereof’); and c) wherein one of A1, A2, A3, A4, A5, A6 and A7 represents said active ingredient or the corresponding precursor moiety thereof;wherein the dashed line is absent or wherein the dashed line represents a bond and L2- A2 and L5-A5 are absent;wherein L1, L2, L3, L4, L5, L6 and L7 are, independently from each other, absent or represent a linker group with the further proviso thati) one vicinal pair amongst L1, L2, L3, L4, L5, L6 and L7 forms an optionally substituted bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety, wherein the corresponding two moieties amongst A1, A2, A3, A4, A5, A6 and A7 are connected to said bicyclic linker group;ii) optionally one or two further vicinal pairs amongst L1, L2, L3, L4, L5, L6 and L7 form an optionally substituted further cyclic linker group which is different from said bicyclic linker group and which is ortho-fused to the 3,4-saturated 2H-pyran moiety, wherein the corresponding two moieties amongst A1, A2, A3, A4, A5, A6 and A7 are connected to said further cyclic linker group;wherein each of A1, A2, A3, A4, A5, A6 and A7 not representing an active ingredient or a corresponding precursor moiety thereof is defined as follows:A1, A4 and A5 represent, independently from each other, hydrogen, a C1-C30 moiety, hydroxyl, or a halogen;A2 and A3 are, independently from each other, defined as indicated for A1, or L2-A2 and L3-A3 jointly represent oxo;A6 and A7 represent, independently from each other, hydrogen or a C1-C30 moiety; andwherein R1represents hydrogen or a protective group hydrolysable after application of the compound of formula (I) to the substrate.

2. The compound according to claim 1, wherein the compound of formula (I) is a compound of formula (Ila) or of formula (Uh),or a tautomer and / or a pharmaceutically acceptable salt thereof;wherein R1, A1, A2, A3, A4, A5, A6, A7, L1, L2, L3, L4, L5, L6, and L7 are defined as indicated in claim 1.

3. The compound according to claim 1 or claim 2, wherein R1represents hydrogen; C1-6 acyl, in particular C1-3 acyl or trifluoracetyl; C1-6 alkyl, in particular methyl or ethyl; or a silyl group, in particular trimethoxysilyl, triethoxysilyl, and tert-butyldimethylsilyl; and in particular hydrogen.

4. The compound according to any one of claims 1 to 3, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety comprises: a) a bridged linker ring, in particular an optionally substituted 5-membered, 6- membered or 7-membered ring with a bridge consisting of one or two bridging atoms; orb) a cis-ortho-fused bicyclic linker group comprising a first ring and a second ring, wherein the first ring is ortho-fused to the 3,4-saturated 2H-pyran moiety and the second ring is cis-ortho-fused to the first ring, in particular a cis-ortho-fused bicyclic linker group comprising an optionally substituted 5-membered or 6- membered first ring and an optionally substituted 4-membered, 5-membered or 6- membered second ring.

5. The compound according to claim 4, wherein the bicyclic linker group comprising a ring which is ortho-fused to the 3,4-saturated 2H-pyran moiety is a bridged linker ring comprisinga) an optionally substituted saturated or mono-unsaturated 5-membered, 6- membered or 7-membered carbocycle, orb) an optionally substituted saturated or mono-unsaturated 5-membered, 6- membered or 7-membered heterocycle comprising one or two heteroatoms selected from N or O, and in particular N; andhaving a bridge consisting of one or two bridging atoms selected from C, O and N.

6. The compound according to claim 4 or claim 5, wherein the bridged linker ring is represented by one of the following moieties,wherein the broken bonds indicate the attachment of the bridged linker ring to the 3,4- saturated 2H-pyran moiety;wherein the dashed bond between the broken bonds represents a double bond in case the bridged linker ring is formed by L1 and L6 or in case the bridged linker ring is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein X1 represents a moiety selected from CH2, C(CH3)2, NH, NR, O and S;X2 represents a moiety selected from CH2, C(CH3)2, and NH;wherein R represents a C1-C30 moiety, the active ingredient, or a precursor thereof, or an ancillary linker group connecting the active ingredient, or the precursor thereof, to the nitrogen atom; andwherein each ring atom of the bridged linker ring may optionally be further substituted.

7. The compound according to claim 4, wherein the cis-ortho-fused bicyclic linker group is represented by one of the following moieties,wherein the broken bonds indicate the attachment of the cis-ortho-fused bicyclic linker group to the 3,4-saturated 2H-pyran moiety;wherein the dashed bond between the broken bonds represents a double bond in case the cis-ortho-fused bicyclic linker group is formed by L1 and L6 or in case the cis-ortho-fused bicyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; andwherein each ring atom of the cis-ortho-fused bicyclic linker group may optionally be further substituted.

8. The compound according to any one of claims 1 to 7, wherein the compound comprises a further cyclic linker group, in particular a further cyclic linker group which is represented by one of the following moieties,wherein the broken bonds indicate the attachment of the further cyclic linker group to the 3,4-saturated 2H-pyran moiety;wherein the dashed bond between the broken bonds represents a double bond in case the further cyclic linker group is formed by L1 and L6 or in case the further cyclic linker group is formed by L3 and L4 and the dashed line in formula (I) represents a bond and wherein the dashed bond between the broken bonds represents a single bond in all other cases; wherein the remainder of the dashed bonds represents a single bond or a double bond; wherein X1 represents a moiety selected from CH2, NH, O and S; wherein X2 represents a moiety selected from CH2, NH, O and S in case the dashed bond represents a single bond, and selected from CH and N in case the dashed bond represents a double bond; andwherein each ring atom of the further cyclic linker group may optionally be further substituted.

9. The compound according to any one of claims 1 to 8, wherein the compound of formula (I) is a compound of formula (III),or a tautomer and / or a pharmaceutically acceptable salt thereof;wherein R1, A1, A2, A3, A4, A6, A7, L2, L3, L4, L6, and L7 are defined as indicated in any one of claims 1 to 8;X represents O or S, and in particular O; andLxis absent or represents -O-, -S-, -NH-, or 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 10 carbon atoms, 0 to 12, more specifically 0 to 8, and in particular 0 to 6 oxygen atoms; 0 to 6, more specifically 0 to 4, and in particular 0 to 3 nitrogen atoms; 0 to 4, more specifically 0 to 3, and inparticular 0 to 2 sulfur atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 phosphorous atoms; 0 to 4, more specifically 0 to 3, and in particular 0 to 2 boron atoms; and 0 to 8, more specifically 0 to 6, and in particular 0 to 5 halogen atoms; and the hydrocarbon moiety is attached to the (C=X)-moiety via a carbon atom, an oxygen atom, a nitrogen atom, or a sulfur atom.

10. The compound according to any one of claims 1 to 9, wherein the compound of formula (I) is a compound of formula (IV),or a tautomer and / or a pharmaceutically acceptable salt thereof; andwherein R1, A1, A6, A7, L1, L6, and L7 are defined as indicated in any of claims 1 to 9.

11. The compound according to any one of claims 1 to 9, wherein the compound of formula (I) is a compound of formula (VI),or a tautomer and / or a pharmaceutically acceptable salt thereof; andwherein R1, A1, A2, A3, A6, L1, L2, L3, and L6 are defined as indicated in any one of claims 1 to 9.

12. The compound according to any one of claims 1 to 9, wherein the compound of formula (I) is a compound of formula (VIII),or a tautomer and / or a pharmaceutically acceptable salt thereof;wherein R1, A1, A2, A3, A6, L1, L2, L3, and L6 are defined as indicated in any of claims 1 to 9.

13. The compound according to any one of claims 1 to 12, wherein the compound of any one of formulae (I) to (VIII) is also a compound of formulae (IX) or (X),or a tautomer and / or a pharmaceutically acceptable salt thereof;wherein R1, A1, A2, A3, A4, A6, A7, L2, L3, L4, and L7 are defined as indicated in any one of claims 1 to 12; andwherein each instance of Lyrepresents, independently from each other, an ancillary linker group, more specifically an ancillary linker group which comprises, together with its optional substituents, less than 12, more specifically less than 8, and in particular less than 6 carbon atoms; less than 12, more specifically less than 8, and in particular less than 6 oxygen atoms; less than 8, more specifically less than 6, and in particular less than 4 nitrogen atoms; less than 6, more specifically less than 4, and in particular less than 3 sulfur atoms; less than 6, more specifically less than 4, and in particular less than -ISO-3 phosphorus atoms; less than 6, more specifically less than 4, and in particular less than 3 boron atoms; and less than 10, more specifically less than 8, and in particular less than 6 halogen atoms; and in particular an ancillary linker group which is selected from the group consisting of: -O-, -S-, -C(O)-, -CO2-, -O-C(O)-, -NH-C(O)-, -C(O)-NH-, - (CH2)I-4-, -(CH2)1-4-O- and -O-(CH2)1-4-, or combinations thereof.

14. A topical composition comprising a compound as defined in in any one of claims 1 to 13 and an excipient that is suitable for topical administration.

15. Use of a compound as defined in any one of claims 1 to 13 or a topical composition as defined in claim 14 for covalently binding said compound to substrate comprising amino groups, more specifically to keratinous tissue, still more specifically to mammalian skin and / or hair, and in particular to human skin and / or hair.

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